Miracle-dz/UniFAR-FTUs huggingface dataset:
The Emergence of Japanese Encephalitis in Australia and the Implications for a Vaccination Strategy

Japanese encephalitis (JE) is the leading cause of viral encephalitis in Asia. Until 2022, only six locally transmitted human JE cases had been reported in Australia; five in northern Queensland and one in the Northern Territory. Thus, JE was mainly considered to be a disease of travellers. On 4 March 2022, JE was declared a ‘Communicable Disease Incident of National Significance’ when a locally acquired human case was confirmed in southern Queensland. By 11 May 2022, 41 human JE cases had been notified in four states in Australia, in areas where JE has never been detected before. From this perspective, we discuss the potential reasons for the recent emergence of the JE virus in Australia in areas where JE has never been previously reported as well as the implications of and options for mass immunisation programs if the outbreak escalates in a JE virus-immunologically naïve population.
Association of insurance types and outcomes in acute promyelocytic leukemia

Abstract Understanding the association between insurance status and survival in an evolving US healthcare system remains a challenge but is essential to address healthcare disparities. We utilized National Cancer Database to evaluate the effects of insurance type on one-month mortality and overall survival (OS) in patients with acute promyelocytic leukemia. Among patients <65 years, one-month mortality was worse for uninsured patients and patients with Medicare compared to patients with private insurance. OS was similar between patients with private insurance and uninsured patients but worse for patients with Medicare and Medicaid/other government insurance. In multivariate analysis, older age and greater comorbidity burden conferred worse OS. For patients ≥65 years, insurance type did not affect one-month mortality and OS. Older age, greater comorbidity burden, and treatment at non-academic centers conferred worse one-month mortality and OS. Our results highlight healthcare disparities based on insurance types for both younger and older patients.
A novel, essential trans-splicing protein connects the nematode SL1 snRNP to the CBC-ARS2 complex

Abstract Spliced leader trans-splicing is essential for gene expression in many eukaryotes. To elucidate the molecular mechanism of this process, we characterise the molecules associated with the Caenorhabditis elegans major spliced leader snRNP (SL1 snRNP), which donates the spliced leader that replaces the 5′ untranslated region of most pre-mRNAs. Using a GFP-tagged version of the SL1 snRNP protein SNA-1 created by CRISPR-mediated genome engineering, we immunoprecipitate and identify RNAs and protein components by RIP-Seq and mass spectrometry. This reveals the composition of the SL1 snRNP and identifies associations with spliceosome components PRP-8 and PRP-19. Significantly, we identify a novel, nematode-specific protein required for SL1 trans-splicing, which we designate SNA-3. SNA-3 is an essential, nuclear protein with three NADAR domains whose function is unknown. Mutation of key residues in NADAR domains inactivates the protein, indicating that domain function is required for activity. SNA-3 interacts with the CBC-ARS2 complex and other factors involved in RNA metabolism, including SUT-1 protein, through RNA or protein-mediated contacts revealed by yeast two-hybrid assays, localisation studies and immunoprecipitations. Our data are compatible with a role for SNA-3 in coordinating trans-splicing with target pre-mRNA transcription or in the processing of the Y-branch product of the trans-splicing reaction.
Airway Pressure Release Ventilation for Acute Respiratory Failure Due to Coronavirus Disease 2019: A Systematic Review and Meta-Analysis

Objective: To explore the evidence surrounding the use of Airway Pressure Release Ventilation (APRV) in patients with coronavirus disease 2019 (COVID-19). Methods: A Systematic electronic search of PUBMED, EMBASE, and the WHO COVID-19 database. We also searched the grey literature via Google and preprint servers (medRxive and research square). Eligible studies included randomised controlled trials and observational studies comparing APRV to conventional mechanical ventilation (CMV) in adults with acute hypoxemic respiratory failure due to COVID-19 and reporting at least one of the following outcomes; in-hospital mortality, ventilator free days (VFDs), ICU length of stay (LOS), changes in gas exchange parameters, and barotrauma. Two authors independently screened and selected articles for inclusion and extracted data in a pre-specified form. Results: Of 181 articles screened, seven studies (one randomised controlled trial, two cohort studies, and four before-after studies) were included comprising 354 patients. APRV was initiated at a mean of 1.2-13 days after intubation. APRV wasn’t associated with improved mortality compared to CMV (relative risk [RR], 1.20; 95% CI 0.70-2.05; I2, 61%) neither better VFDs (ratio of means [RoM], 0.80; 95% CI, 0.52-1.24; I2, 0%) nor ICU LOS (RoM, 1.10; 95% CI, 0.79-1.51; I2, 57%). Compared to CMV, APRV was associated with a 33% increase in PaO2/FiO2 ratio (RoM, 1.33; 95% CI, 1.21-1.48; I2, 29%) and a 9% decrease in PaCO2 (RoM, 1.09; 95% CI, 1.02-1.15; I2, 0%). There was no significant increased risk of barotrauma compared to CMV (RR, 1.55; 95% CI, 0.60-4.00; I2, 0%). Conclusions: In adult patients with COVID-19 requiring mechanical ventilation, APRV is associated with improved gas exchange but not mortality nor VFDs when compared with CMV. The results were limited by high uncertainty given the low quality of the available studies and limited number of patients. Adequately powered and well-designed clinical trials to define the role of APRV in COVID-19 patients are still needed. Registration: PROSPERO; CRD42021291234.
Multitrend Conditional Value at Risk for Portfolio Optimization

Trend representation has been attracting more and more attention recently in portfolio optimization (PO) via machine learning methods. It adopts concepts and phenomena from the field of empirical and behavioral finance when little prior knowledge is obtained or strict statistical assumptions cannot be guaranteed. It is used mostly in estimating the expected asset returns, but hardly in measuring risk. To fill this gap, we propose a novel multitrend conditional value at risk (MT-CVaR), which embeds multiple trends and their influences in CVaR. Besides, we propose a novel PO model with this MT-CVaR as the risk metric and then design a solving algorithm based on the interior point method to compute the portfolio. Extensive experiments on six benchmark datasets from diverse financial markets with different frequencies show that MT-CVaR achieves the state-of-the-art investing performance and risk management.
Metformin and vitamin D modulate adipose-derived stem cell differentiation towards the beige phenotype

ABSTRACT Adipose-derived stem cells (ADSCs) represent an ideal stem cell population for regenerative medicine. ADSC adipogenic differentiation is controlled by the activation of a specific transcriptional program, including epigenetic factors and key adipogenic genes. Under certain conditioned media, ADSCs can differentiate into several phenotypes. We previously demonstrated that bioactive molecules could counteract lipid accumulation and regulate adipogenesis, acting on inflammation and vitamin D metabolism. In the present paper, we aimed at evaluating the effect of metformin and vitamin D in targeting ADSC differentiation towards an intermediate phenotype, as beige adipocytes. We exposed ADSCs to different conditioned media and then we evaluated the levels of expression of main markers of adipogenesis, aP2, LPL and ACOT2. We also analysed the gene and protein expression of thermogenic UCP1 protein, and the expression of PARP1 and the beige specific marker TMEM26. Our results showed a novel effect of metformin and vitamin D not only in inhibiting adipogenesis, but also in inducing a specific ‘brown-like’ phenotype. These findings pave the way for their possible application in the control of de novo lipogenesis useful for the prevention of obesity and its related metabolic disorders.
Presence and Multi-Species Spatial Distribution of Oropouche Virus in Brazil within the One Health Framework

Oropouche virus (OROV) is an emerging vector-borne arbovirus with high epidemic potential, causing illness in more than 500,000 people. Primarily contracted through its midge and mosquito vectors, OROV remains prevalent in its wild, non-human primate and sloth reservoir hosts as well. This virus is spreading across Latin America; however, the majority of cases occur in Brazil. The aim of this research is to document OROV’s presence in Brazil using the One Health approach and geospatial techniques. A scoping review of the literature (2000 to 2021) was conducted to collect reports of this disease in humans and animal species. Data were then geocoded by first and second subnational levels and species to map OROV’s spread. In total, 14 of 27 states reported OROV presence across 67 municipalities (second subnational level). However, most of the cases were in the northern region, within the tropical and subtropical moist broadleaf forests biome. OROV was identified in humans, four vector species, four genera of non-human primates, one sloth species, and others. Utilizing One Health was important to understand the distribution of OROV across several species and to suggest possible environmental, socioeconomic, and demographic drivers of the virus’s presence. As deforestation, climate change, and migration rates increase, further study into the spillover potential of this disease is needed.
A Novel Probiotic Bacillus subtilis Strain Confers Cytoprotection to Host Pig Intestinal Epithelial Cells during Enterotoxic Escherichia coli Infection

ETEC remains one of the leading causes of postweaning diarrhea and mortality in swine production. Due to the rising concerns with the antibiotic use in livestock, alternative interventions need to be developed. ABSTRACT Enteric infections caused by enterotoxic Escherichia coli (ETEC) negatively impact the growth performance of piglets during weaning, resulting in significant economic losses for the producers. With the ban on antibiotic usage in livestock production, probiotics have gained a lot of attention as a potential alternative. However, strain specificity and limited knowledge on the host-specific targets limit their efficacy in preventing ETEC-related postweaning enteric infections. We recently isolated and characterized a novel probiotic Bacillus subtilis bacterium (CP9) that demonstrated antimicrobial activity. Here, we report anti-ETEC properties of CP9 and its impact on metabolic activity of swine intestinal epithelial (IPEC-J2) cells. Our results showed that pre- or coincubation with CP9 protected IPEC-J2 cells from ETEC-induced cytotoxicity. CP9 significantly attenuated ETEC-induced inflammatory response by reducing ETEC-induced nitric oxide production and relative mRNA expression of the Toll-like receptors (TLRs; TLR2, TLR4, and TLR9), proinflammatory tumor necrosis factor alpha, interleukins (ILs; IL-6 and IL-8), augmenting anti-inflammatory granulocyte-macrophage colony-stimulating factor and host defense peptide mucin 1 (MUC1) mRNA levels. We also show that CP9 significantly (P < 0.05) reduced caspase-3 activity, reinstated cell proliferation and increased relative expression of tight junction genes, claudin-1, occludin, and zona occludens-1 in ETEC-infected cells. Finally, metabolomic analysis revealed that CP9 exposure induced metabolic modulation in IPEC J2 cells with the greatest impact seen in alanine, aspartate, and glutamate metabolism; pyrimidine metabolism; nicotinate and nicotinamide metabolism; glutathione metabolism; the citrate cycle (TCA cycle); and arginine and proline metabolism. Our study shows that CP9 incubation attenuated ETEC-induced cytotoxicity in IPEC-J2 cells and offers insight into potential application of this probiotic for ETEC infection control. IMPORTANCE ETEC remains one of the leading causes of postweaning diarrhea and mortality in swine production. Due to the rising concerns with the antibiotic use in livestock, alternative interventions need to be developed. In this study, we analyzed the cytoprotective effect of a novel probiotic strain in combating ETEC infection in swine intestinal cells, along with assessing its mechanism of action. To our knowledge, this is also the first study to analyze the metabolic impact of a probiotic on intestinal cells. Results from this study should provide effective cues in developing a probiotic intervention for ameliorating ETEC infection and improving overall gut health in swine production.
Effectiveness and safety of ultrasound-guided high-intensity focused ultrasound ablation for the treatment of colorectal cancer liver metastases

Abstract Objective To investigate the effectiveness and safety of high-intensity focused ultrasound (HIFU) ablation for patients with colorectal liver metastases (CRLMs) who were unsuitable for hepatectomy. Methods This is a multicenter retrospective study. 238 CRLM patients underwent ultrasound-guided HIFU (USgHIFU) ablation in three medical centers from October 2014 to December 2020. Patients who had complete colorectal cancer resection, but exhibited extra-hepatic metastasis were excluded from this study. HIFU ablation procedure was performed, and contrast-enhanced MR imaging and/or contrast-enhanced CT examinations were conducted and mRECIST was used for the assessment of tumor ablation effectiveness before and after treatment, and every 3 months thereafter. Adverse events and complications were recorded. Results 43 CRML patients (27 male, 16 female, aged 29–82 years) were enrolled and underwent a USgHIFU ablation procedure. CR (complete response) was achieved in 21 patients, while PR (partial response) was observed in 21 patients and SD (stable disease) was achieved in one patient, respectively. The objective response rate was 97.7%. Median OS (overall survival) was estimated to be 31 months, and1-year and 18-month overall survival was 90.7% (39/43) and 72.1% (31/43), respectively. For CR and PR patients, the median OS was 35 months and 23 months, respectively (p = 0.00). The majority of adverse events were pain in 22 cases (51.2%) and local skin edema in 33 cases (76.7%). No severe adverse events or complications were reported and recorded. Conclusions USgHIFU ablation is a safe and effective treatment option for CRLM patients, especially for patients who are unsuitable for hepatectomy.
Consumer Central Energy Flexibility in Office Buildings

: Energy flexibility in buildings will play an important role in the smart energy system. Office buildings have more potentials to provide energy flexibility to the grid compared to other types of buildings, due to the existing building management, control systems and large energy consumption. Consumers in office buildings (building owners/managers and occupants) take a main role for adopting and engaging in building energy flexibility. This paper provides a systematic review of consumer central energy flexibility in office buildings with the discussion of social, technical and business aspects. This paper clarifies the correlations of consumers‟ concerns, external influential factors, energy flexibility resources and technology with eight hypotheses. This paper suggests that technical solutions with the integration of distributed energy resources, building management and control system can boost energy flexibility in the office buildings.
AtNusG, a chloroplast nucleoid protein of bacterial origin linking chloroplast transcriptional and translational machineries, is required for proper chloroplast gene expression in Arabidopsis thaliana

Abstract In Escherichia coli, transcription-translation coupling is mediated by NusG. Although chloroplasts are descendants of endosymbiotic prokaryotes, the mechanism underlying this coupling in chloroplasts remains unclear. Here, we report transcription-translation coupling through AtNusG in chloroplasts. AtNusG is localized in chloroplast nucleoids and is closely associated with the chloroplast PEP complex by interacting with its essential component PAP9. It also comigrates with chloroplast ribosomes and interacts with their two components PRPS5 (uS5c) and PRPS10 (uS10c). These data suggest that the transcription and translation machineries are coupled in chloroplasts. In the atnusg mutant, the accumulation of chloroplast-encoded photosynthetic gene transcripts, such as psbA, psbB, psbC and psbD, was not obviously changed, but that of their proteins was clearly decreased. Chloroplast polysomic analysis indicated that the decrease in these proteins was due to the reduced efficiency of their translation in this mutant, leading to reduced photosynthetic efficiency and enhanced sensitivity to cold stress. These data indicate that AtNusG-mediated coupling between transcription and translation in chloroplasts ensures the rapid establishment of photosynthetic capacity for plant growth and the response to environmental changes. Therefore, our study reveals a conserved mechanism of transcription-translation coupling between chloroplasts and E. coli, which perhaps represents a regulatory mechanism of chloroplast gene expression. This study provides insights into the underlying mechanisms of chloroplast gene expression in higher plants.
The Role of R&D in an Acquisition Program

The U.S. Army has a poor reputation for bringing new ground vehicles from the Science and Technology (S&T) phase to deployment. However, a counterexample is the Joint Light Tactical Vehicle (JLTV), which successfully passed through the acquisition gauntlet. The Research and Development (R&D) forerunner to the JLTV was the Future Tactical Truck System (FTTS) Advanced Concept Technology Demonstration (ACTD) that was initiated with TARDEC serving in the role of Technology Developer. Two utility variant prototypes were built as part of that program and were evaluated in a Military User Assessment in 2007. PM JLTV was stood up in 2006 and adopted technologies and personnel from the FTTS program. Both the organizational construct and the use of prototypes early on in the vehicle development cycle are considered key successes of the JLTV program, particularly the close collaboration of the PM with other groups including the OSD, TRADOC, and ASA(ALT) as well as their counterparts in the USMC. This paper documents the important role of R&D in the acquisition process.
Characterization of the pathogenicity of a Bacillus cereus isolate from the Mariana Trench

ABSTRACT Bacillus cereus is an important opportunistic pathogen widely distributed in the environment. In this study, we reported the isolation and characterization of a B. cereus isolate, MB1, from the Challenger Deep of the Mariana Trench. MB1 is aerobic, motile, and able to form endospores. It possesses 5966 genes distributed on a circular chromosome and two plasmids. The MB1 genome contains 14 sets of 23S, 5S, and 16S ribosomal RNA operons, 106 tRNA genes, 4 sRNA genes, 12 genomic islands, 13 prophages, and 302 putative virulence genes, including enterotoxins and cytolysins. Infection studies showed that MB1 was able to cause acute and lethal infection in fish and mice, and was highly toxic to mammalian cells. MB1 induced, in a dose-dependent manner, pyroptotic cell death, characterized by activation of caspase-1, cleavage of gasdermin D, and release of IL-1β and IL-18. MB1 spores exhibited swimming and haemolytic capacity, but were severely attenuated in pathogenicity, which, however, was regained to the full extent when the spores germinated under suitable conditions. Taken together, these results provide new insights into the biological and pathogenic mechanism of deep sea B. cereus.
Antibiotic Overuse and Its Effects on our Planet.

BACKGROUND The development of antibiotic agents has revolutionized the treatment of infectious diseases and clinical practice. However, antibiotic overuse, together with biologic evolution, has resulted in escalating antibiotic resistance of bacteria; with the One Health concept, it affects our planet including animals, aquatic wildlife, rivers, groundwater, lakes, sea water, aqua farming, and soil. This situation threatens our ability to treat infections effectively in the near future and raises the alarming question of whether we are getting close to the post-antibiotic era. Several measures are suggested to prevent the apocalyptic consequence of antibiotic overuse, few of which are novel with thinking outside the box.
Point Cloud Completion Via Skeleton-Detail Transformer

Point cloud shape completion plays a central role in diverse 3D vision and robotics applications. Early methods used to generate global shapes without local detail refinement. Current methods tend to leverage local features to preserve the observed geometric details. However, they usually adopt the convolutional architecture over the incomplete point cloud to extract local features to restore the diverse information of both latent shape skeleton and geometric details, where long-distance correlation among the skeleton and details is ignored. In this work, we present a coarse-to-fine completion framework, which makes full use of both neighboring and long-distance region cues for point cloud completion. Our network leverages a Skeleton-Detail Transformer, which contains cross-attention and self-attention layers, to fully explore the correlation from local patterns to global shape and utilize it to enhance the overall skeleton. Also, we propose a selective attention mechanism to save memory usage in the attention process without significantly affecting performance. We conduct extensive experiments on the ShapeNet dataset and real-scanned datasets. Qualitative and quantitative evaluations demonstrate that our proposed network outperforms current state-of-the-art methods.
Presynaptic cGMP sets synaptic strength in the striatum and is important for motor learning

The striatum is a subcortical brain region responsible for the initiation and termination of voluntary movements. Striatal spiny projection neurons receive major excitatory synaptic input from neocortex and thalamus, and cyclic nucleotides have long been known to play important roles in striatal function. Yet, the precise mechanism of action is unclear. Here, we combine optogenetic stimulation, 2‐photon imaging, and genetically encoded scavengers to dissect the regulation of striatal synapses in mice. Our data show that excitatory striatal inputs are tonically depressed by phosphodiesterases (PDEs), in particular PDE1. Blocking PDE activity boosts presynaptic calcium entry and glutamate release, leading to strongly increased synaptic transmission. Although PDE1 degrades both cAMP and cGMP, we uncover that the concentration of cGMP, not cAMP, controls the gain of striatal inputs. Disturbing this gain control mechanism in vivo impairs motor skill learning in mice. The tight dependence of striatal excitatory synapses on PDE1 and cGMP offers a new perspective on the molecular mechanisms regulating striatal activity.