Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling and estimating a threshold effect: An application to improving cardiac surgery practices

Estimating thresholds when a threshold effect exists has important applications in biomedical research. However, models/methods commonly used in the biomedical literature may lead to a biased estimate. For patients undergoing coronary artery bypass grafting (CABG), it is thought that exposure to low oxygen delivery (DO2) contributes to an increased risk of avoidable acute kidney injury. This research is motivated by estimating the threshold of nadir DO2 for CABG patients to help develop an evidence-based guideline for improving cardiac surgery practices. We review several models (sudden-jump model, broken-stick model, and the constrained broken-stick model) that can be adopted to estimate the threshold and discuss modeling assumptions, scientific plausibility, and implications in estimating the threshold. Under each model, various estimation methods are studied and compared. In particular, under a constrained broken-stick model, a modified two-step Newton–Raphson algorithm is introduced. Through comprehensive simulation studies and an application to data on CABG patients from the University of Michigan, we show that the constrained broken-stick model is flexible, more robust, and able to incorporate scientific knowledge to improve efficiency. The two-step Newton–Raphson algorithm has good computational performances relative to existing methods.
Projecting turbidity levels in future river flow: a mathematical modeling approach

Climate and land use change impacts on river flow were evaluated in this study with emphasis placed on turbidity. Turbidity levels for the year 2020 were projected for Gin River, one of the prime sources of drinking water in Southern Sri Lanka. Future land use in the Gin catchment was predicted using a GIS based statistical regression approach. Regional Climate Modelling system generated the future rainfall for the SRES A2 and SRES A1B emission scenarios. Streamflow simulations were carried out using a distributed hydrologic model, and turbidity values were determined using rating curve based relationship developed between river discharge and TSS (Total Suspended Solid) concentration followed by Turbidity-TSS linear regression correlation. Increased turbidity levels are clearly evident under the SRES A2 scenario, following more pronounced increased stream flows. Projected 75th percentile monthly turbidity values in year 2020 are expected to increase during May to November compared to the baseline, and in certain months, about 100%increase is noted. 60% of the time, year 2020 turbidity levels have indicated exceedance of the water quality standards set for the potable water as well the inland waters of Sri Lanka, which would lead to exert extra challenge on future drinking water production in Southern region of Sri Lanka. ENGINEER, Vol. 48, No.01, pp. 61-70, 2015
The Sediment Transport of the Siret River during the Floods from 2010

Beginning with 2004 in the Siret River Catchment there occurred exceptional flash floods that exceeded the maximum historical values recorded, on the main river and on its tributaries (2004, the Trotus River; 2005, the Siret River, the Trotus River, the Bistriţa River, the Putna River; 2006 - the Clit River from the Suceava River Catchment; 2008, the Siret River, the Suceava River). The 2010 summer flood from the Siret River also falls in this category. This paper uses hydrological data (water discharge, suspended sediment discharge) between the 20 th of June and 10 th of July 2010 from 5 gauging stations located on the Siret River: Siret, Hutani, Lespezi, Dragesti, Lungoci, and also meteorological data (rainfall) measured at different gauging stations from the Siret River Catchment. The rainfall recorded in this time of the year in the catchment was very high, with values up to 210 l/m 2 in approximately 10 days. The hydrographs of the flash flood indicate the fact that the transit of the water trough the reservoirs system from the Siret River (Rogojesti - Bucecea and Răcăciuni – Beresti –Călimănesti - Movileni) reduced the maximum water discharge with values between 7-27%. The values of the maximum sediment discharge also recorded a reduction while transiting this reservoirs system with approximately 60%. The evolution of the Siret river bed channel during this flood (aggradations with values between 15-100 cm and degradations starting from 65 cm until 200 cm, in different moments of the flood) is influenced by the high values of the water and sediment discharge and by anthropogenic interventions on the river bed (pit-ballast, regularization of the river bed, reservoirs). Processing the hydrological and meteorological data recorded during the flood (20th of June – 10th of July 2010) indicates two important features of this event: the climatic variability – exemplified by the big values of precipitations from the catchment and the anthropogenic impact revealed by the transit of the flood wave and the evolution of the river bed.
Intrapartum transperineal ultrasound: angle of progression to evaluate and predict the mode of delivery and labor progression

Intrapartum ultrasonography serves as a valuable tool for the objective evaluation of labor progression and effectively identifies underlying factors, such as asynclitism, in cases of abnormal labor progression. Among the various ultrasound measurement techniques, the angle of progression (AOP) demonstrates favorable reproducibility and accuracy in assessing fetal head descent. In the context of abnormal labor, interventions differ across different stages of labor, emphasizing the importance of investigating the utility of AOP according to labor stages in this review article. Pre-labor assessment of AOP can be beneficial in terms of counseling for the timing of induction of labor, while a wider AOP value during the prolonged first stage of labor has demonstrated a positive correlation with successful vaginal delivery and shorter time to delivery. In the second stage of labor, the AOP has exhibited efficacy in predicting the mode of delivery and complicated operative deliveries. Furthermore, it has assisted in predicting the duration of labor, thereby highlighting its potential as a decision-making model for labor progression. However, further research is needed to investigate aspects, such as the determination of cutoff values, of AOP, considering the multifaceted characteristics of labor progression, which are influenced by complex interactions among maternal, fetal, and other contributing factors.
Halocline water formation in the Barents Sea

Hydrographic data from the first phase of the Coordinated Eastern Arctic Experiment (CEAREX) are analyzed. The data consist of temperature and salinity measurements made by a ship-based conductivity-temperature-depth (CTD) instrument and by a drifting SALARGOS buoy. These data were collected in the autumn and early winter of 1988–1989 in the northern Barents Sea, mostly in ice-covered conditions and then across the marginal ice zone (MIZ). The data show that relatively warm, salty water of Atlantic origin is modified by air cooling and ice melting to produce lighter water that has properties identical to (lower) halocline water found in the Arctic Ocean. This occurs mostly at the MIZ and to a lesser degree within the ice pack itself. At the MIZ the halocline water subducts underneath the lighter meltwater that resides directly under the ice pack; geostrophic velocity calculations indicate that it then turns eastward and flows toward the Kara Sea, in keeping with previous chemical tracer analyses. A rough calculation reveals that the amount of halocline water formed in this way in the Barents Sea and Fram Strait is 30–50% of that formed by ice growth in eastern Arctic polynyas.
Mineralogy and geochemical properties of some upland soils from different sedimentary formations in south-eastern Nigeria

Geochemical and mineralogical properties of soil can be used to assess their agricultural productivity potential. Ten soils from 4 geological formations in the south-eastern Nigeria were studied. Soil samples were taken from typical A and B horizons from each soil. The soil properties assessed were the free forms of Fe and Al, particle size distribution, total elements, and clay mineralogy. The soils are deep and highly weathered. Crystalline Fe and Al were more dominant than amorphous or less crystalline forms. The geochemical properties of the soils are dominated by SiO2, Al2O3, and Fe2O3, whereas MgO, TiO2, and ZrO2 occur in moderate to low quantities. Other basic elements such as Na2O, K2O, and CaO are very low in the soils, with an insignificant role in their genesis. The low contents of these elements in the soil may be the cause of their low nutrient release and storage in the soil. Ferritisation, laterisation, and kaolinitisation are the major pedogenic processes in the soil. The dominant clay mineral in all the soils was kaolinite; other minerals present though less common were illite, vermiculite, and smectites. Based on elemental contents and clay mineralogy, the soils can be grouped into 3 distinct groups: those with only kaolinite, illite, and vermiculites; and those that also contain smectite. These groupings can indicate the agricultural fertility potential.
Prognostic Value and the Immune Microenvironment-associated Role of SMAD4 in Pancreatic Adenocarcinoma

Background/Aim: SMAD4 is a well-known cancer suppressor gene that regulates cell proliferation, differentiation, autoimmunity, pluripotency, and immune responses in pancreatic adenocarcinoma (PAAD). We herein investigated a novel involvement of SMAD4 within the PAAD microenvironment. Materials and Methods: Transcriptome data, derived from The Cancer Genome Atlas and Genotype-Tissue Expression Using TIMER 2.0, CIBERSORT, and ImmuCellAI, were used to identify the immune cell infiltration pattern of PAAD. We then knocked-down SMAD4 in the PANC-1 cell line and acquired RNA-seq data through the Illumina microarray technology. Kyoto Encyclopedia of Genes and Genomes was utilized along with Gene Ontology enrichment analyses, and protein–protein interaction network analysis to screen for genes that were differentially expressed. We constructed a miRNA–mRNA regulatory network and analyzed SMAD4 copy number variation (CNV) data. Results: In PAAD, decreased levels of SMAD4 expression were found to be connected to an unfavorable prognosis. There was a significantly higher infiltration level of DC cells, CD8+ T cells, TgD, Tc, and Tex cells and a lower level of B cells and Th2 in the SMAD4-high group. The expression of SMAD4 and immune cell infiltration including CD8+ T cells, myeloid dendritic cells, neutrophils, and macrophages are significantly positively correlated. DEGs were found enriched in the hypoxia response pathway. The six hypoxia-related genes exhibited a significant correlation with immune cell infiltration and survival rates. SMAD4 CNV levels were associated with MSI, stemness, infiltration of immune cells, and survival rates. Conclusion: A statistically significant correlation was found between SMAD4 expression and immune cell infiltration. SMAD4 could mediate hypoxia response in pancreatic cancer. The CNV levels of SMAD4 were associated with prognosis. SMAD4 has potential as a prognostic biomarker and provides a new orientation for the immunotherapy of PAAD.
Treatment Failure in a UK Malaria Patient Harboring Genetically Variant Plasmodium falciparum From Uganda With Reduced In Vitro Susceptibility to Artemisinin and Lumefantrine

Abstract Background Recent cases of clinical failure in malaria patients in the United Kingdom (UK) treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide. Methods Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at 6 resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor. Results A traveler, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival, 17.3% [95% confidence interval {CI}, 13.6%–21.1%]; P < .0001) and lumefantrine (effective concentration preventing 50% of growth = 259.4 nM [95% CI, 130.6–388.2 nM]; P = .001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V nonpropeller variant. In vitro susceptibility testing of 6 other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in 1 additional line, also from a 2022 treatment failure case. These parasites did not harbor a pfk13 propeller domain variant but rather the novel nonpropeller variant T349I. Variant alleles of pfubp1, pfap2mu, and pfcoronin were also identified among the 7 parasite lines. Conclusions We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda.
Mixed Reality Surgical Navigation System; Positional Accuracy Based on Food and Drug Administration Standard

Background Computer assisted surgical navigation systems are designed to improve outcomes by providing clinicians with procedural guidance information. The use of new technologies, such as mixed reality, offers the potential for more intuitive, efficient, and accurate procedural guidance. The goal of this study is to assess the positional accuracy and consistency of a clinical mixed reality system that utilizes commercially available wireless head-mounted displays (HMDs), custom software, and localization instruments. Methods Independent teams using the second-generation Microsoft HoloLens© hardware, Medivis SurgicalAR© software, and localization instruments, tested the accuracy of the combined system at different institutions, times, and locations. The ASTM F2554-18 consensus standard for computer-assisted surgical systems, as recognized by the U.S. FDA, was utilized to measure the performance. 288 tests were performed. Results The system demonstrated consistent results, with an average accuracy performance that was better than one millimeter (.75 ± SD .37 mm). Conclusion Independently acquired positional tracking accuracies exceed conventional in-market surgical navigation tracking systems and FDA standards. Importantly, the performance was achieved at two different institutions, using an international testing standard, and with a system that included a commercially available off-the-shelf wireless head mounted display and software.
Network pharmacology combined with molecular docking and experimental validation to explore the potential mechanism of Cinnamomi ramulus against ankylosing spondylitis

Abstract Background Cinnamomi ramulus (C. ramulus) is frequently employed in the treatment of ankylosing spondylitis (AS). However, the primary constituents, drug targets, and mechanisms of action remain unidentified. Methods In this study, various public databases and online tools were employed to gather information on the compounds of C. ramulus, drug targets, and disease targets associated with ankylosing spondylitis. The intersection of drug targets and disease targets was then determined to identify the common targets, which were subsequently used to construct a protein-protein interaction (PPI) network using the STRING database. Network analysis and the analysis of hub genes and major compounds were conducted using Cytoscape software. Furthermore, the Metascape platform was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking studies and immunohistochemical experiments were performed to validate the core targets. Results The network analysis identified 2-Methoxycinnamaldehyde, cinnamaldehyde, and 2-Hydroxycinnamaldehyde as the major effective compounds present in C. ramulus. The PPI network analysis revealed PTGS2, MMP9, and TLR4 as the most highly correlated targets. GO and KEGG analyses indicated that C. ramulus exerts its therapeutic effects in ankylosing spondylitis through various biological processes, including the response to hormones and peptides, oxidative stress response, and inflammatory response. The main signaling pathways involved were IL-17, TNF, NF-kappa B, and Toll-like receptor pathways. Molecular docking analysis confirmed the strong affinity between the key compounds and the core targets. Additionally, immunohistochemical analysis demonstrated an up-regulation of PTGS2, MMP9, and TLR4 levels in ankylosing spondylitis. Conclusions This study provides insights into the effective compounds, core targets, and potential mechanisms of action of C. ramulus in the treatment of ankylosing spondylitis. These findings establish a solid groundwork for future fundamental research in this field.
Combination of fenchone and sodium hyaluronate ameliorated constipation‐predominant irritable bowel syndrome and underlying mechanisms

We sought to explore the protective effect of the combination of fenchone (FE) and sodium hyaluronate (SH) on ice water‐induced IBS‐C rats and the potential mechanism. The neurotransmitter levels, including substance P (SP), motilin (MTL), 5‐hydroxytryptamine (5‐HT), and vasoactive intestinal peptide (VIP), were determined by ELISA methods. The stem cell factors (SCF)/c‐Kit signaling pathway‐related protein and mRNA levels were determined by western blot and reverse transcription quantitative polymerase chain reaction (RT‐qPCR) analyses, respectively. The expressions of tight ZO‐1, Occludin, and Claudin‐1 were also measured by western blot assay and immunofluorescence staining. The 16S rRNA gene sequence was used to measure the composition of gut microbiota. The co‐administration of FE and SH improved the body weight, number of fecal pellets, fecal moisture, abdominal with drawal reflex score, and gastrointestinal transit rate in IBS‐C rats. The unique efficacy of combination depended on the regulation of balance between excitatory and inhibitory neurotransmitters, enhancement of intestinal barrier function, and activation of SCF/c‐Kit pathway. The gut microbiota structure was also restored. The ability of FE combined with SH to regulate SCF/c‐Kit signaling pathway, enhance intestinal barrier function, and modulate gut microbiota contributes to their efficacy in managing IBS‐C in rats.
Transcriptional Profiles of Non-neuronal and Immune Cells in Mouse Trigeminal Ganglia

Non-neuronal cells constitute 90-95% of sensory ganglia. These cells play critical roles in modulation of nociceptive signal transmissions by sensory neurons. Accordingly, the aim of this review-study was to identify, profile and summarize TG non-neuronal cell types in naïve male mice using published and our own data generated by single-cell RNA sequencing (scRNA-seq), flow cytometry (FC) and immunohistochemistry (IHC). TG contains 5 types of non-neuronal cells: glial, fibroblasts, smooth muscle, endothelial and immune cells. There is agreement among publications for glial, fibroblasts, smooth muscle and endothelial cells. Based on gene profiles, glial cells were classified as Schwann cells and satellite glial cells (SGC). Mpz had dominant expression in Schwann cells, and Fabp7 is specific for SCG. Two types of Col1a2+ fibroblasts located throughout TG were distinguished using gene profiles. TG smooth muscle and endothelial cells representing blood vessels were detected with well recognized markers. Our study split reported single TG immune cell group into 3 types of macrophages and 4 types of neutrophils. Macrophages were located among neuronal bodies and nerve fibers, and were sub-grouped by unique transcriptomic profiles and using Ccr2, Cx3cr1 and Iba1 as markers. S100a8+ neutrophils were located in dura surrounding TG and were sub-grouped by clustering and expressions of Csf3r, Ly6G, Ngp, Elane and Mpo. Overall, generated and summarized here dataset on non-neuronal TG cells could provide essential and fundamental information for studies on cell plasticity, interactomic network between neurons and non-neuronal cells and function during variety of pain conditions in the head and neck region.
Analysis of Domestic and Foreign Contributions using DDM in CMAQ during Particulate Matter Episode Period of February 2014 in Seoul

This study was carried out to understand the regional contribution of Particulate Matter (PM) emissions from East Asia (82° ~ 149°E, 18° ~ 53°N) to Seoul during high concentration period in February 2014. The Community Multi-scale Air Quality (CMAQ) version 5.0. 2 with Decoupled Direct Method (DDM) was used to analyze levels of contributions over Seoul. In order to validate model performance of the CMAQ, predicted PM and its chemical species concentrations were compared to observations in China and Seoul. Model predictions could depict the daily and hourly variations of observed PM. The calculated PM concentrations, however, had a tendency of underestimation. The discrepancies are due to uncertainties of meteorological data, emission inventories and CMAQ model itself. The high PM concentration in Seoul was induced by stationary anticyclone over the West Coast of Korea during 24 to 27 February. The DDM in CMAQ was used to analyze the contributions of emissions from East Asia on Seoul during this PM episode. PM 10 concentration in Seoul is contributed by 39.77% ~ 53.19% from China industrial and urban region, 15.37% ~ 37.10% from South Korea, and 9.03% ~ 18.05% North Korea. These indicate that PM 10 concentrations in Seoul during the episode period are dominated by long-range transport from China region as well as domestic sources. It was also found that the largest contribution region in China were Shandong peninsula during the PM event period.
PHRF1 Promotes Cell Invasion by Modulating SOX4 Expression in Colorectal Cancer HCT116-p53−/− Cells

Background/Aim: PHD and RING finger domain-containing protein 1 (PHRF1) ubiquitinates TGIP (TG-interacting protein) and redistributes cPML (cytoplasmic variant of PML) to the cytoplasm to enhance TGF-β signaling by. It is unclear whether PHRF1 affects invasion and survival when both mutations of the activated oncogene Kras and inactivation of the tumor suppressor p53 are present. Materials and Methods: We knockout PHRF1 expression using Crispr-Cas9 editing in HCT116-p53−/− (KrasG13D/p53−/−) cells and analyzed the expression profile in HCT116-p53−/−PHRF1−/− cells. Results: In contrast to lung cancer A549 (KrasG12S/p53wt) cells, the expression of Zeb1, a transcription factor for epidermal-mesenchymal transition (EMT), was not affected in PHRF1-knockout HCT116 p53−/− cells. Instead, SOX4 displayed a significant contribution to the impaired invasion in HCT116-p53−/−PHRF1−/− cells. Mechanistically, the C-terminal SRI domain of PHRF1 was required for both transwell invasion and SOX4 expression. The reintroduction of SOX4 into HCT116-p53−/− PHRF1−/− cells partially restored their invasive capability. Conclusion: This study sheds light on the role of PHRF1 in the invasion of colorectal cancer HCT116-p53−/− cells, which harbor the oncogenic KrasG13D mutation and lack p53. These findings provide novel insights regarding the role of PHRF1 in invasion by modulating SOX4 expression in colorectal cancer HCT116-p53−/− cells.