Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparison of Digital and Screen-Film Mammography for Breast-Cancer Screening: A Systematic Review and Meta-Analysis

Purpose Digital mammography (DM) has replaced screen-film mammography (SFM). However, findings of comparisons between the performance indicators of DM and SFM for breast-cancer screening have been inconsistent. Moreover, the summarized results from studies comparing the performance of screening mammography according to device type vary over time. Therefore, this study aimed to compare the performance of DM and SFM using recently published data. Methods The MEDLINE, Embase, and Cochrane Library databases were searched for paired studies, cohorts, and randomized controlled trials published through 2018 that compared the performance of DM and SFM. All studies comparing the diagnostic accuracy of DM and SFM in asymptomatic, average-risk women aged 40 years and older were included. Two reviewers independently assessed the study quality and extracted the data. Results Thirteen studies were included in the meta-analysis. The pooled sensitivity (DM, 0.76 [95% confidence interval {CI}, 0.70–0.81]; SFM, 0.76 [95% CI, 0.70–0.81]), specificity (DM, 0.96 [95% CI, 0.94–0.97]; SFM, 0.97 [95% CI, 0.94–0.98]), and area under the receiver-operating characteristic curve (DM, 0.94 [95% CI, 0.92–0.96]; SFM, 0.92 [95% CI, 0.89–0.94]) were similar for both DM and SFM. The pooled screening performance indicators reinforced superior accuracy of full-field DM, which is a more advanced type of mammography, than SFM. The advantage of DM appeared greater among women aged 50 years or older. There was high heterogeneity among studies in the pooled sensitivity, specificity, and overall diagnostic accuracy estimates. Stratifying by study design (prospective or retrospective) and removing studies with a 2-year or greater follow-up period resulted in homogeneous overall diagnostic accuracy estimates. Conclusion The breast-cancer screening performance of DM is similar to that of SFM. The diagnostic performance of DM depends on the study design, and, in terms of performance, full-field DM is superior to SFM, unlike computed radiography systems.
Cell Division Cycle Associated 8 Is a Key Regulator of Tamoxifen Resistance in Breast Cancer

Purpose Breast cancer (BC) is one of the most common malignancies globally, and millions of women worldwide are diagnosed with BC every year. Up to 70% of BC patients are estrogen receptor (ER)-positive. Numerous studies have shown that tamoxifen has a significant therapeutic effect on both primary and metastatic ER-positive BC patients. Although tamoxifen is currently one of the most successful therapeutic agents for BC, a significant proportion of patients will eventually become resistant to tamoxifen, leading to tumor recurrence and metastasis. Knowledge about the development of tamoxifen resistance in BC patients is still limited. Methods We applied a loss-and-gain method to study the biological functional role of cell division cycle associated 8 (CDCA8) in tamoxifen resistance in BC cells. Results We found that CDCA8 was significantly elevated in tamoxifen-resistant BC cells. Knockdown of CDCA8 expression significantly inhibited the proliferation of tamoxifen-resistant BC cells and reduced their resistance to tamoxifen. In contrast, overexpression of CDCA8 promoted the growth of tamoxifen-sensitive BC cells and induced their resistance to tamoxifen. Conclusion In this study, we reported that CDCA8 is a key regulator of tamoxifen resistance in BC, suggesting that CDCA8 may serve as a potential therapeutic target for BC treatment.
A heritable subset of the core rumen microbiome dictates dairy cow productivity and emissions

Cow genes dictate environmentally friendly microbiomes: a step towards reducing greenhouse gas emissions. A 1000-cow study across four European countries was undertaken to understand to what extent ruminant microbiomes can be controlled by the host animal and to identify characteristics of the host rumen microbiome axis that determine productivity and methane emissions. A core rumen microbiome, phylogenetically linked and with a preserved hierarchical structure, was identified. A 39-member subset of the core formed hubs in co-occurrence networks linking microbiome structure to host genetics and phenotype (methane emissions, rumen and blood metabolites, and milk production efficiency). These phenotypes can be predicted from the core microbiome using machine learning algorithms. The heritable core microbes, therefore, present primary targets for rumen manipulation toward sustainable and environmentally friendly agriculture.
Plasma Biomarkers to Detect Prevalent or Predict Progressive Tuberculosis Associated With Human Immunodeficiency Virus–1

Abstract Background The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1–infected individuals are likely to progress to active disease is unknown. Methods Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations. Results Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly. Conclusions Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.
Osteoblastic lysosome plays a central role in mineralization

Lysosome transports mineralizing nanovesicle in osteoblasts. Mineralization is the most fundamental process in vertebrates. It is predominantly mediated by osteoblasts, which secrete mineral precursors, most likely through matrix vesicles (MVs). These vesicular structures are calcium and phosphate rich and contain organic material such as acidic proteins. However, it remains largely unknown how intracellular MVs are transported and secreted. Here, we use scanning electron-assisted dielectric microscopy and super-resolution microscopy for assessing live osteoblasts in mineralizing conditions at a nanolevel resolution. We found that the calcium-containing vesicles were multivesicular bodies containing MVs. They were transported via lysosome and secreted by exocytosis. Thus, we present proof that the lysosome transports amorphous calcium phosphate within mineralizing osteoblasts.
p62 Negatively Regulates TLR4 Signaling via Functional Regulation of the TRAF6-ECSIT Complex

Sequestosome 1 (SQSTM1, p62), a ubiquitin binding protein, plays a role in cell signaling, oxidative stress, and autophagy. However, its functional role in inflammatory signaling is controversial. Recent studies have shown that p62 is negatively implicated in inflammatory responses. But, the precise molecular mechanisms by which p62 regulates inflammatory responses remain unclear. In this study, we report on a new regulatory role for p62 in TLR4-mediated signaling. p62 overexpression led to the suppression of NF-κB activation and the production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1β in response to TLR4 stimulation. In contrast, p62−/− mouse embryonic fibroblast (MEF) cells exhibited marked enhancement of NF-κB activation and production of pro-inflammatory cytokines by TLR4 stimulation, compared to p62+/+ MEF cells. Additionally, the TLR4-induced activation of signal transduction was significantly augmented in p62−/− MEF cells, indicating that p62 was negatively implicated in TLR4-mediated signaling. Biochemical studies revealed that p62 interacted with the internal domain of evolutionarily conserved signaling intermediate in Toll pathways (ECSIT), which is critical for associating with the TNF receptor associated factor 6 (TRAF6)-ECSIT complex to activate NF-κB in TLR4 signaling. Interestingly, p62-ECSIT interaction inhibited the interaction between TRAF6 and ECSIT and attenuated the ubiquitination of ECSIT. Furthermore, upon LPS challenge, the mortality of p62−/− (p62-knockout) mice was markedly enhanced compared to p62+/+ (p62 wild-type) mice. Taken together, our data demonstrate that p62 negatively regulated TLR4 signaling via functional regulation of the TRAF6-ECSIT complex.
Circulating miR-338 Cluster activities on osteoblast differentiation: Potential Diagnostic and Therapeutic Targets for Postmenopausal Osteoporosis

MicroRNAs (miRNAs) are the most abundant RNA species found in serum, and recently, several miRNAs have been found to be associated with osteoporosis. However, the development of such associated miRNAs into diagnostic and therapeutic targets remains unaddressed, mostly because of a lack of functional validation. Here, we identified circulating miR-338 associated with postmenopausal osteoporosis, and performed functional validation in vivo and in vitro. Methods: We collected the serum from postmenopausal osteoporosis patients (N=15) and female volunteers of the same age but with normal bone density (N=15) and examined the enrichment of miR-338 cluster. We also confirmed such enrichment using mice subjected to ovariectomy at different stages. We employed primary bone marrow stromal cells from mice and the MC-3T3 cell line along with CRISPR, RNA-seq and ChIP-qPCR to validate the biological function of secreted miR-338 cluster on osteoblastic differentiation and their upstream regulators. Moreover, we generated miR-338 knockout mice and OVX mice injected with an inhibitor against miR-338 cluster to confirm its biological function in vivo. Results: We observed a significant enrichment of miR-338 cluster in postmenopausal osteoporosis patients. Such enrichment was also prominent in serum from mice subjected to ovariectomy and was detected much earlier than bone density decreases revealed by micro-CT. We also confirmed the presence of an estrogen-dependent Runx2/Sox4/miR-338 positive feedback loop that modulated osteoblast differentiation, providing a possible explanation for our clinical findings. Moreover, deletion of the miR-338 cluster or direct intravenous injection of an miR-338 cluster inhibitor significantly prevented osteoporosis after ovariectomy. Conclusion: Circulating miR-338 cluster in the serum could serve as a promising diagnostic and therapeutic target for postmenopausal osteoporosis patients.
Hippocampal theta phases organize the reactivation of large-scale electrophysiological representations during goal-directed navigation

Hippocampal theta cycles provide a means to maintain and segregate different goal representations during human wayfinding. Humans are adept in simultaneously following multiple goals, but the neural mechanisms for maintaining specific goals and distinguishing them from other goals are incompletely understood. For short time scales, working memory studies suggest that multiple mental contents are maintained by theta-coupled reactivation, but evidence for similar mechanisms during complex behaviors such as goal-directed navigation is scarce. We examined intracranial electroencephalography recordings of epilepsy patients performing an object-location memory task in a virtual environment. We report that large-scale electrophysiological representations of objects that cue for specific goal locations are dynamically reactivated during goal-directed navigation. Reactivation of different cue representations occurred at stimulus-specific hippocampal theta phases. Locking to more distinct theta phases predicted better memory performance, identifying hippocampal theta phase coding as a mechanism for separating competing goals. Our findings suggest shared neural mechanisms between working memory and goal-directed navigation and provide new insights into the functions of the hippocampal theta rhythm.
Molecularly annotation of mouse avatar models derived from patients with colorectal cancer liver metastasis

Background: Liver is the most common metastatic site in advanced colorectal cancer. Most patients with colorectal cancer liver metastasis (CRLM) do not benefit from current treatment. Patient-derived xenografts (PDXs) with defined molecular signatures are attractive models for preclinical studies. Methods: Successfully established PDXs were evaluated to elucidate their fidelity of patients' biologic characteristics (pathologic, genetic and protein properties, together with chemosensitivity). The genomic variations of PDXs were analyzed by next-generation sequencing to explore the underlying molecular mechanism of metastasis and potential therapeutic targets. Results: CRLM (N=73) showed a significantly higher successful PDX establishment rate than primary specimens (N=26; 76.7% vs. 57.7%). CRLM PDXs recapitulated the pathologic, genetic and protein properties of parental tumors, as well as chemosensitivity. Frequent altered genes in PDXs showed high consistency compared to patients' genomic alterations and were enriched in MAPK, ErbB, cell cycle, focal adhesion pathways for CRLM PDXs, whereas primary tumor-derived PDXs only exhibited genomic variations involving ErbB and cell cycle. The genetic alterations showed high concordance between paired PDXs from primary and metastatic tissues, except for recurrent gene mutations (ARID1A, CDK8, ETV1, STAT5B and WNK3) and common copy number gains in chromosomes 20q (e.g., SRC/AURKA). Several potential drug targets such as KRAS, HER2, and FGFR2 were validated using corresponding inhibitors. Additionally, PDX models could also be used in screening efficient regimens for patients with no druggable alterations. Conclusion: This study has successfully established and validated a large panel of molecularly annotated platforms from patients with CRLM for preclinical studies.
CATACOMB: An endogenous inducible gene that antagonizes H3K27 methylation activity of Polycomb repressive complex 2 via an H3K27M-like mechanism

CATACOMB is a catalytic antagonist PRC2 subunit whose expression is induced upon DNA demethylation. Using biochemical characterization of fusion proteins associated with endometrial stromal sarcoma, we identified JAZF1 as a new subunit of the NuA4 acetyltransferase complex and CXORF67 as a subunit of the Polycomb Repressive Complex 2 (PRC2). Since CXORF67’s interaction with PRC2 leads to decreased PRC2-dependent H3K27me2/3 deposition, we propose a new name for this gene: CATACOMB (catalytic antagonist of Polycomb; official gene name: EZHIP). We map CATACOMB’s inhibitory function to a short highly conserved region and identify a single methionine residue essential for diminution of H3K27me2/3 levels. Remarkably, the amino acid sequence surrounding this critical methionine resembles the oncogenic histone H3 Lys27-to-methionine (H3K27M) mutation found in high-grade pediatric gliomas. As CATACOMB expression is regulated through DNA methylation/demethylation, we propose CATACOMB as the potential interlocutor between DNA methylation and PRC2 activity. We raise the possibility that similar regulatory mechanisms could exist for other methyltransferase complexes such as Trithorax/COMPASS.
Development of a stem cell tracking platform for ophthalmic applications using ultrasound and photoacoustic imaging

Glaucoma is the second leading cause of blindness in the world. Disease progression is associated with reduced cellularity in the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising therapy seeks to deliver stem cells to the TM to regenerate the tissue and restore its function. However, like many stem cell-based regenerative therapies, preclinical development relies heavily on histology to evaluate outcomes. To expedite clinical translation, we are developing an ultrasound/photoacoustic (US/PA) imaging platform for longitudinal tracking of stem cells in the anterior eye. Methods: Mesenchymal stem cells (MSCs) were labeled with gold nanospheres in vitro and injected through the cornea into the anterior chamber of ex vivo porcine eyes. Physiological pressure was imposed to mimic in vivo conditions. AuNS-labeled MSCs were injected through the cornea while single-wavelength US/PA images were acquired. At 5 hours post-injection, three-dimensional multi-wavelength US/PA datasets were acquired and spectroscopic analysis was used to detect AuNS-labeled MSCs. US/PA results were compared to fluorescent microscopy. Results: The US/PA imaging platform was able to provide real-time monitoring of the stem cell injection and distinguish AuNS-labeled MSCs from highly absorbing background tissues in the anterior segment. Conclusion: Our US/PA imaging approach can inform preclinical studies of stem cell therapies for glaucoma treatment, motivating further development of this theranostic imaging tool for ophthalmic applications.
Generating partially synthetic geocoded public use data with decreased disclosure risk by using differential smoothing

When collecting geocoded confidential data with the intent to disseminate, agencies often resort to altering the geographies before making data publicly available. An alternative to releasing aggregated and/or perturbed data is to release synthetic data, where sensitive values are replaced with draws from models designed to capture distributional features in the data collected. The issues associated with spatially outlying observations in the data, however, have received relatively little attention. Our goal here is to shed light on this problem, to propose a solution—referred to as ‘differential smoothing’—and to illustrate our approach by using sale prices of homes in San Francisco.
Chinese readers extract semantic information from parafoveal words during reading.

Evidence for semantic preview benefit (PB) from parafoveal words has been elusive for reading alphabetic scripts such as English. Here we report semantic PB for noncompound characters in Chinese reading with the boundary paradigm. In addition, PBs for orthographic relatedness and, as a numeric trend, for phono- logical relatedness were obtained. Results are in agreement with other research suggesting that the Chinese writing system is based on a closer association between graphic form and meaning than is alphabetic script. We discuss implications for notions of serial attention shifts and parallel distributed processing of words during reading. Yan, M. , Richter, E. , Shu, H. , & Kliegl, R. (2009). Chinese readers extract semantic information from parafoveal words during reading. Psychonomic Bulletin & Review, 16, 561-566.
The Effect of Stimulus Audibility on the Relationship between Pure-Tone Average and Speech Recognition in Noise Ability

Abstract Background: The literature presents conflicting reports on the relationship between pure-tone threshold average and speech recognition in noise ability. Purpose: The purpose of this retrospective study and meta-analysis was to determine the effect of stimulus audibility on the relationship between speech recognition in noise ability and bilateral pure-tone average (BPTA). Research Design: Pure-tone threshold and Hearing in Noise Test (HINT) data from two data sets were evaluated. The HINT data from both data sets were divided into groups with complete and partial audibility of the HINT stimuli delivered at 65 dBA. Study Sample: Normal and hearing-impaired participants were included in this retrospective study. For data set 1 (n = 215), a relatively weak relationship had been found between HINT thresholds and BPTA. For data set 2 (n = 55), a relatively strong relationship had been found between HINT thresholds and BPTA. For data set 1, only 10% of the participants had partial audibility of the HINT stimuli. For data set 2, 16% of the participants had partial audibility of the HINT stimuli. Data Collection and Analysis: Pure-tone thresholds and HINT data were obtained from published and unpublished studies. HINT data were collected in a simulated soundfield environment under headphones using the standard HINT protocol. Statistical analyses included descriptive statistics, correlations, and a two-way analysis of variance (ANOVA), and multiple regression. Results: A two-way ANOVA followed by post hoc analyses revealed a greater difference between the data sets for the Noise Front thresholds obtained with partial rather than complete audibility of the stimuli. A weak and nonsignificant relationship was found between BPTA(0.5, 1.0, 2.0, 3.0, 6.0 kHz) versus HINT Noise Front thresholds for complete audibility data (r = 0.060, p = 0.356) and a strong relationship was found for the partial audibility data (r = 0.863, p < 0.001). Conclusions: The proportion of partial audibility data in a given data set may influence the relative strength of the relationship between BPTA and HINT Noise Front thresholds. This brings into question the convention of using pure-tone average as a predictor of speech recognition in noise ability.
Biomass growth variation and phytoextraction potential of four Salix varieties grown in contaminated soil amended with lime and wood ash

Abstract In a greenhouse experiment, plant growth and copper (Cu) and zinc (Zn) uptake by four Salix cultivars grown in Cu and Zn contaminated soils collected from a mining area in Finland were tested to assess their suitability for phytoextraction. The cultivars displayed tolerance to heavily contaminated soils throughout the experiment. After uptake, total mean Cu concentrations in the leaves, shoots and roots in all cultivars and treatments ranged from 163 to 474 mg kg−1 and mean Zn concentrations ranged from 776 to 1823 mg kg−1. Lime and wood ash addition increased dry biomass growth (25–43%), chlorophyll fluorescence (Fv/Fm) values (3–6%), the translocation factor (TF) (15–60% for Cu; 10–25% for Zn), the bio-concentration factor (BCF) (40–85% for Cu; 70–120% for Zn), and metal uptake (55–70% for Cu; 50–65% for Zn) compared to unamended treatment across all cultivars. The results revealed that Salix cultivars have the potential to take up and accumulate significant amounts of Cu and Zn. Cultivar Klara (Salix viminalis × S. schwerinii × S. dasyclados) was found to be the most effective cultivar for phytoextraction since it displayed greater dry biomass production, Fv/Fm, TF, BCF values and uptake percentage rates of Cu and Zn compared to the other three cultivars. This study indicates that further research is needed to clarify the wider phytoextraction capabilities of different Salix cultivars.