Miracle-dz/UniFAR-FTUs huggingface dataset:
Double Low-Dose Dual-Energy Liver CT in Patients at High-Risk of HCC

Supplemental digital content is available in the text. Objectives The aim of this study was to investigate the clinical feasibility of the simultaneous reduction of radiation and contrast doses using spectral computed tomography (CT) in patients at high-risk for hepatocellular carcinoma. Materials and Methods Between May 2017 and March 2018, this prospective study recruited participants at risk of hepatocellular carcinoma with body mass indexes less than 30 and randomly assigned them to either the standard-dose group or the double low-dose group, which targeted 30% reductions in both radiation and contrast media (NCT03045445). Lesion conspicuity as a primary endpoint and lesion detection rates were then compared between hybrid iterative reconstruction (iDose) images of standard-dose group and low monoenergetic (50 keV) images of double low-dose group. Qualitative and quantitative image noise and contrast were also compared between the 2 groups. Participants and reviewers were blinded for scan protocols and reconstruction algorithms. Lesion conspicuity was analyzed using generalized estimating equation analysis. Lesion detection was evaluated using weighted jackknife alternative free-response receiver operating characteristic analysis. Results Sixty-seven participants (male-to-female ratio, 59:8; mean age, 64 ± 9 years) were analyzed. Compared with the standard-dose group (n = 32), significantly lower CTDIvol (8.8 ± 1.7 mGy vs 6.1 ± 0.6 mGy) and contrast media (116.9 ± 15.7 mL vs 83.1 ± 9.9 mL) were utilized in the double low-dose group (n = 35; P < 0.001). Comparative analysis demonstrated that lesion conspicuity was significantly higher on 50 keV images of double low-dose group than on iDose images of standard dose on both arterial (2.62 [95% confidence interval (CI), 2.31–2.93] vs 2.02 [95% CI, 1.73–2.30], respectively, P = 0.004) and portal venous phases (2.39 [95% CI, 2.11–2.67] vs 1.88 [95% CI, 1.67–2.10], respectively, P = 0.005). No differences in lesion detection capability were observed between the 2 groups (figure of merit: 0.63 in standard-dose group; 0.65, double low-dose group; P = 0.52). Fifty kiloelectronvolt images of double low-dose group showed better subjective image noise and contrast than iDose image of standard-dose group on arterial and portal venous phases (P < 0.001 for all). Contrast-to-noise ratio of the aorta and portal vein was also higher in double low-dose group than in standard-dose group (P < 0.001 for all), whereas there was no significant difference of quantitative image noise between the 2 groups on arterial and portal phases (P = 0.4~0.5). Conclusions Low monoenergetic spectral CT images (50 keV) can provide better focal liver lesion conspicuity than hybrid iterative reconstruction image of standard-dose CT in nonobese patients while using lower radiation and contrast media doses.
Diagnostic performance of serum interferon gamma, matrix metalloproteinases, and periostin measurements for pulmonary tuberculosis in Japanese patients with pneumonia

Serum markers that differentiate between tuberculous and non-tuberculous pneumonia would be clinically useful. However, few serum markers have been investigated for their association with either disease. In this study, serum levels of interferon gamma (IFN-γ), matrix metalloproteinases 1 and 9 (MMP-1 and MMP-9, respectively), and periostin were compared between 40 pulmonary tuberculosis (PTB) and 28 non-tuberculous pneumonia (non-PTB) patients. Diagnostic performance was assessed by analysis of receiver-operating characteristic (ROC) curves and classification trees. Serum IFN-γ and MMP-1 levels were significantly higher and serum MMP-9 levels significantly lower in PTB than in non-PTB patients (p < 0.001, p = 0.002, p < 0.001, respectively). No significant difference was observed in serum periostin levels between groups. ROC curve analysis could not determine the appropriate cut-off value with high sensitivity and specificity; therefore, a classification tree method was applied. This method identified patients with limited infiltration into three groups with statistical significance (p = 0.01), and those with MMP-1 levels < 0.01 ng/mL and periostin levels ≥ 118.8 ng/mL included only non-PTB patients (95% confidence interval 0.0–41.0). Patients with extensive infiltration were also divided into three groups with statistical significance (p < 0.001), and those with MMP-9 levels < 3.009 ng/mL included only PTB patients (95% confidence interval 76.8–100.0). In conclusion, the novel classification tree developed using MMP-1, MMP-9, and periostin data distinguished PTB from non-PTB patients. Further studies are needed to validate our cut-off values and the overall clinical usefulness of these markers.
A subcellular proteome atlas of the yeast Komagataella phaffii

ABSTRACT The compartmentalization of metabolic and regulatory pathways is a common pattern of living organisms. Eukaryotic cells are subdivided into several organelles enclosed by lipid membranes. Organelle proteomes define their functions. Yeasts, as simple eukaryotic single cell organisms, are valuable models for higher eukaryotes and frequently used for biotechnological applications. While the subcellular distribution of proteins is well studied in Saccharomyces cerevisiae, this is not the case for other yeasts like Komagataella phaffii (syn. Pichia pastoris). Different to most well-studied yeasts, K. phaffii can grow on methanol, which provides specific features for production of heterologous proteins and as a model for peroxisome biology. We isolated microsomes, very early Golgi, early Golgi, plasma membrane, vacuole, cytosol, peroxisomes and mitochondria of K. phaffii from glucose- and methanol-grown cultures, quantified their proteomes by liquid chromatography-electrospray ionization-mass spectrometry of either unlabeled or tandem mass tag-labeled samples. Classification of the proteins by their relative enrichment, allowed the separation of enriched proteins from potential contaminants in all cellular compartments except the peroxisomes. We discuss differences to S. cerevisiae, outline organelle specific findings and the major metabolic pathways and provide an interactive map of the subcellular localization of proteins in K. phaffii.
Increased intracellular survival of Salmonella Typhimurium ST313 in HIV‐1‐infected primary human macrophages is not associated with Salmonella hijacking the HIV compartment

Non‐typhoidal Salmonella (NTS) causes a severe invasive syndrome (iNTS disease) described in HIV‐positive adults. The impact of HIV‐1 on Salmonella pathogenesis and the molecular basis for the differences between these bacteria and classical diarrhoeal S. Typhimurium remains unclear.
Moderate hyperoxia plays a protective role in lung bronchial epithelial cells.

PURPOSE Oxygen therapy is commonly used in clinical settings, but several problems may result from improper use. Oxygen poisoning involves the initiation of a series of inflammatory reactions. In this study, we compared the effects of moderate hyperoxia (40% O2) and extreme hyperoxia (85% O2) on pulmonary bronchial epithelial cells. METHODS Normal human tracheobronchial epithelium (NHBE) cells were exposed to hyperoxia (40% and 85%) for 24 hours, and their survival rates were determined by the colorimetic assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide). The protein and mRNA levels of RelA, RelB, ASK1, TNF-α and secretory component (SC) were detected by immunohistochemical staining, western blot, and real-time polymerase chain reaction. RESULTS The NHBE cell survival increased in the presence of moderate hyperoxia. RelA, RelB, ASK1, TNF-α and SC expressions were significantly higher in the 85% O2 group in comparison with the control group and the 40% O2 group. In the 40% O2 group, RelA, RelB, ASK1 and TNF-α were upregulated, but SC expression was not significantly different than that of the control group. However, compared with the 85% O2 group, SC expression was significantly lower in the 40% O2 group. CONCLUSION These results suggest that moderate hyperoxia promotes proliferation in NHBE cells and activates TNF-α and downstream ASK1. Then TNF-α activates NF-κB and SC to play a protective role.
Simple risk models to predict cardiovascular death in patients with stable coronary artery disease

Abstract Aims Risk estimation is important to motivate patients to adhere to treatment and to identify those in whom additional treatments may be warranted and expensive treatments might be most cost effective. Our aim was to develop a simple risk model based on readily available risk factors for patients with stable coronary artery disease (CAD). Methods and results Models were developed in the CLARIFY registry of patients with stable CAD, first incorporating only simple clinical variables and then with the inclusion of assessments of left ventricular function, estimated glomerular filtration rate, and haemoglobin levels. The outcome of cardiovascular death over ∼5 years was analysed using a Cox proportional hazards model. Calibration of the models was assessed in an external study, the CORONOR registry of patients with stable coronary disease. We provide formulae for calculation of the risk score and simple integer points-based versions of the scores with associated look-up risk tables. Only the models based on simple clinical variables provided both good c-statistics (0.74 in CLARIFY and 0.80 or over in CORONOR), with no lack of calibration in the external dataset. Conclusion Our preferred model based on 10 readily available variables [age, diabetes, smoking, heart failure (HF) symptom status and histories of atrial fibrillation or flutter, myocardial infarction, peripheral arterial disease, stroke, percutaneous coronary intervention, and hospitalization for HF] had good discriminatory power and fitted well in an external dataset. Study registration The CLARIFY registry is registered in the ISRCTN registry of clinical trials (ISRCTN43070564).
General mechanism of JQ1 in inhibiting various types of cancer

Bromodomain-containing 4 (BRD4) is a histone modification reader and transcriptional regulator that has been reported to interact with acetylated lysine histone motifs transcription factors (TFs), transcription co-activators and RNA polymerase II. The selective small molecule inhibitor JQ1, which binds competitively to bromodomains, has been reported to exhibit anti-proliferative effects in various types of cancer. Previous studies on the mechanism of action of JQ1 mostly focused on a specific tumor type or disease; however, the general mechanism through which JQ1 affects various tumors remains to be determined. In the present study, chromatin immunoprecipitation sequencing data for BRD4 and its expression profiles in six cancer cell lines were integrated and analyzed systematically. The results indicated that BRD4 binds to enhancers with histone H3 acetylated at lysine 27 (H3K27Ac) and mediator complex subunit 1 in a cell type-specific manner, as well as binds to promoter regions with the oncogenic TFs MYC and E2F1 in a cell type-common manner. The cell type-common sites across the six cell types investigated were found to be functionally important for tumorigenesis, whereas the cell type-specific sites were functionally enriched with the cell identity, all of which were sensitive to JQ1 treatment. Furthermore, a core set of JQ1-regulated BRD4 binding genes were obtained, which were significantly inhibited by JQ1 in various cancer cell lines and contributed to hallmarks of cancer. These results implied a common mechanism underlying the therapeutic effects of JQ1 and suggested its potential suitability as an anti-cancer drug targeting BRD4-mediated transcriptional regulation.
Friends over Doctors? The Influences of Source and Perceived Customization on College Drinking

ABSTRACT College drinking, often associated with college binge drinking, is a critical issue in the United States and may lead to harmful consequences such as academic failure, injury, sexual assault, and even death. Health interventions targeted at reducing problematic drinking are needed to help prevent these harmful behaviors among college students. The current work explores the intersection of different types of information sources (e.g., authority and peer) and perceived customization on various health-related outcomes related to college drinking (e.g., trust, attitudes, and behavioral intentions). Undergraduate students (N = 448) were presented with health information regarding college drinking in a 2 (perceived customization or non-customization) × 3 (authority, peer, or technology source) between-subjects experimental design. We found a strong effect of peer source of health information, somewhat surprisingly more effective than information from a professional source (i.e., a medical physician). Moreover, the results underscore the importance of not only promoting perceived customization but also fostering a sense of agency with such interface features. Theoretical and practical implications for health-related outcomes are discussed.
Inorganic nanoparticles for the theranostics of cancer

Abstract Theranostics are a multifunctional approach using nanoparticles for combined diagnostic and therapeutic purposes. The hybrid nanoparticles that are applied for these purposes are composed of an inorganic core and an organic shell. The inorganic core acts as a contrast enhancer and the organic shell acts as a drug releaser. Hybrid nanoparticles can be conjugated with targeting moieties and systematically administered to patients to direct the nanoparticles to specific cells such as cancer cells. Theranostics have the potential to significantly improve early stage cancer diagnostics and patient survival. This review discusses preclinical and clinical advances in applications of inorganic nanoparticles for the theranostics of cancer.
MicroRNA-936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway

MicroRNA-936 (miR-936) has been reported to play important roles in the progression of non-small cell lung cancer and glioma. However, the expression and functions of miR-936 in retinoblastoma (RB) remain elusive and need to be further elucidated. Herein, the aims were to measure miR-936 expression in RB, identify the functional importance of miR-936 in the oncogenicity of RB, and investigate the underlying molecular mechanisms. Reverse-transcription quantitative PCR was carried out to determine miR-936 expression in RB tissues and cell lines. Cell proliferation, colony formation, apoptosis, migration, and invasion in vitro and tumor growth in vivo were examined respectively by Cell Counting Kit-8, colony formation, flow cytometric, and Transwell migration and invasion assays and a subcutaneous heterotopic xenograft experiment. The potential target of miR-936 was predicted by bioinformatic analysis and was subsequently validated by luciferase reporter assay, reverse-transcription quantitative PCR, and western blotting. miR-936 expression was weak in both RB tissues and cell lines and was correlated with differentiation, lymph node metastasis and TNM staging in RB. RB cell proliferation, colony formation, migration, and invasion in vitro and tumor growth in vivo were attenuated by exogenous miR-936, whereas apoptosis was enhanced by miR-936 overexpression. Further molecular investigation identified histone deacetylase 9 (HDAC9) as a direct target gene of miR-936 in RB cells. HDAC9 depletion had effects similar to those of miR-936 overexpression in RB cells. Recovery of HDAC9 expression counteracted the tumor-suppressive action of miR-936 on the oncogenicity of RB cells. Ectopic miR-936 expression deactivated the PI3K/AKT pathway in RB cells in vitro and in vivo by decreasing HDAC9 expression. Downregulated miR-936 is related to poor prognosis in RB, and its upregulation inhibits RB aggressiveness via direct targeting of HDAC9 mRNA and thereby inactivation of the PI3K/AKT pathway.
CHALLENGES AND OPPORTUNITIES FOR WILDLIFE DISEASE SURVEILLANCE IN SRI LANKA

Abstract: The Sri Lanka Wildlife Health Centre was created in 2011 as an intersectoral surveillance system intended to address gaps in emerging and zoonotic disease preparedness in the country. This study, which was conducted during August 2015 to November 2015, examined perceived obstacles and opportunities to undertake wildlife disease surveillance in Sri Lanka. Responses to a pretested postal questionnaire by 315 field officers from the Department of Wildlife Conservation (DWC) and Department of Animal Production and Health (livestock development instructors [LDIs] and field veterinary surgeons [FVSs]) were used in the analysis. Responses came from all 25 administrative districts in the country. The reported obstacles (and proportion of respondents) included lack of transport facilities (80%), skilled staff (75%), infrastructure (65%), human resources (62%), training (67%), and a mandate for getting involved in wildlife disease surveillance (28%). These obstacles have resulted in rare or sporadic collection and submission of samples and their testing for surveillance purposes. A focus on rabies surveillance found that 84 (78%) DWC officers whose mandate was to deal with wild animals and 41 (40%) LDIs whose mandate was to deal with agricultural animals had inadequate knowledge to inform rabies surveillance activities and actions. Despite being outside of their mandate, 68% of FVSs and 72% of LDI s were willing to contribute to wild animal disease surveillance. Overcoming legal impediments to handling wildlife was cited as an essential step to establishing a multisectoral surveillance system involving government branches, universities, and citizens.
Computer simulation study on the effect of electrode–tissue contact force on thermal lesion size in cardiac radiofrequency ablation

Abstract Purpose In cardiac radiofrequency (RF) ablation, RF energy is often used to create a series of transmural lesions for blocking accessory conduction pathways. Electrode–tissue contact force (CF) is one of the key determinants of lesion formation during RF ablation. Low electrode–tissue CF is associated with ineffective RF lesion formation, whereas excessive CF may increase the risk of steam pop and perforation. By using finite element analysis, we studied lesion size and features at different values of electrode–tissue CF in cardiac RF ablation. Materials and methods A computer-model-coupled electrode–tissue CF field, RF electric field, and thermal field were developed to study temperature distribution and lesion dimensions in cardiac tissue subjected to CF of 2, 5, 10, 20, 30, and 40 g with identical RF voltage and duration. Results Increasing CF was associated with an increase in lesion depth, width, and cross-section area. The lesion cross-section area exhibited a linear increase, and the lesion width was significantly greater than lesion depth under the identical ablation condition. The relationship between CF value and lesion size is a power function: Lesion Size = a × CFb (Lesion Depth = 3.17 × CF0.14 and Lesion Width = 5.17 × CF0.14). Conclusions This study confirmed that CF is a major determinant of RF lesion size and that electrode–tissue CF affects the amount of power dissipated in tissue. At a constant RF voltage and application time, RF lesion size increases as CF increases.
Evaluation of Stem Cell-Derived Cellular Therapy Products

Although there is an increase in the development of new cellular therapies, few guidelines have been published to assist in the design of preclinical studies. As no product and therapeutic intention is entirely alike regulators and Contract Research Organizations need to treat each project on a case-by-case basis. One of the most important considerations in study design is to retain all tissues from the study, thereby allowing for further analysis of tissues should unexpected effects be seen in clinical studies. Input from the pathologist at the earliest stages of study design regarding animal selection, cell markers, and phased tissue examination improves the scientific integrity of the study.
FIT, a regulatory hub for iron deficiency and stress signaling in roots, and FIT-dependent and -independent gene signatures

Abstract Iron (Fe) is vital for plant growth. Plants balance the beneficial and toxic effects of this micronutrient, and tightly control Fe uptake and allocation. Here, we review the role of the basic helix–loop–helix (bHLH) transcription factor FIT (FER-LIKE FE DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) in Fe acquisition. FIT is not only essential, it is also a central regulatory hub in root cells to steer and adjust the rate of Fe uptake by the root in a changing environment. FIT regulates a subset of root Fe deficiency (–Fe) response genes. Based on a combination of co-expression network and FIT-dependent transcriptome analyses, we defined a set of FIT-dependent and FIT-independent gene expression signatures and co-expression clusters that encode specific functions in Fe regulation and Fe homeostasis. These gene signatures serve as markers to integrate novel regulatory factors and signals into the –Fe response cascade. FIT forms a complex with bHLH subgroup Ib transcription factors. Furthermore, it interacts with key regulators from different signaling pathways that either activate or inhibit FIT function to adjust Fe acquisition to growth and environmental constraints. Co-expression clusters and FIT protein interactions suggest a connection of –Fe with ABA responses and root cell elongation processes that can be explored in future studies.
Structural insight into T cell coinhibition by PD-1H (VISTA)

Significance Programmed death-1 homolog (PD-1H) is a cell surface molecule that coinhibits T cells, with important roles in regulating immune responses in mouse models of tumor, autoimmune, and inflammatory diseases. Monoclonal antibodies (mAbs) or small-molecule reagents targeting PD-1H are being tested for therapeutic effect in clinical trials. However, efforts to uncover molecular details of PD-1H function have been hampered by the lack of structural information. We have solved the atomic structure of PD-1H to 1.9-Å resolution, revealed unique structural features, and investigated how these features contribute to coinhibitory function. Our results will guide the design of future studies and agents targeting this important immune signaling molecule. Programmed death-1 homolog (PD-1H), a CD28/B7 family molecule, coinhibits T cell activation and is an attractive immunotherapeutic target for cancer and inflammatory diseases. The molecular basis of its function, however, is unknown. Bioinformatic analyses indicated that PD-1H has a very long Ig variable region (IgV)-like domain and extraordinarily high histidine content, suggesting that unique structural features may contribute to coinhibitory mechanisms. Here we present the 1.9-Å crystal structure of the human PD-1H extracellular domain. It reveals an elongated CC′ loop and a striking concentration of histidine residues, located in the complementarity-determining region-like proximal half of the molecule. We show that surface-exposed histidine clusters are essential for robust inhibition of T cell activation. PD-1H exhibits a noncanonical IgV-like topology including an extra “H” β-strand and “clamping” disulfide, absent in known IgV-like structures, that likely restricts its orientation on the cell surface differently from other IgV-like domains. These results provide important insight into a molecular basis of T cell coinhibition by PD-1H.