Determination of Mouth Width for Facial Reconstruction Based on Statistical Regression Model.

INTRODUCTION: It is important to generate predictable statistical models by increasing the number of variables on the human skeletal and soft tissue structures on the face to increase the accuracy of human facial reconstructions. The purpose of this study was to determine mouth width 3-dimensionally based on statistical regression model. MATERIAL AND METHODS: Cone-beam computed tomography scan data from 130 individuals were used to measure the horizontal and vertical dimensions of orbital and nasal structures and intercanine width. The correlation between these hard tissue variables and the mouth width was evaluated using the statistical regression model. RESULTS: Orbital width, nasal width, and intercanine width were found to be strong predictors of the mouth width determination and were used to generate the regression formulae to find the most approximate position of the mouth. CONCLUSION: These specific variables may contribute to improving the accuracy of mouth width determination for oral and maxillofacial reconstructions.

Prediction of TKI response in EGFR-mutant lung cancer patients-derived organoids using malignant pleural effusion.

Patient-derived organoids (PDOs) are valuable in predicting response to cancer therapy. PDOs are ideal models for precision oncologists. However, their practical application in guiding timely clinical decisions remains challenging. This study focused on patients with advanced EGFR-mutated non-small cell lung cancer and employed a cancer organoid-based diagnosis reactivity prediction (CODRP)-based precision oncology platform to assess the efficacy of EGFR inhibitor treatments. CODRP was employed to evaluate EGFR-tyrosine kinase inhibitors (TKI) drug sensitivity. The results were compared to those obtained using area under the curve index. This study validated this index by testing lung cancer-derived organoids in 14 patients with lung cancer. The CODRP index-based drug sensitivity test reliably classified patient responses to EGFR-TKI treatment within a clinically suitable 10-day timeline, which aligned with clinical drug treatment responses. This approach is promising for predicting and analyzing the efficacy of anticancer, ultimately contributing to the development of a precision medicine platform.

Vacuum-Processed Propylene Urea Additive: A Novel Approach for Controlling the Growth of CH3NH3PbI3 Crystals in All Vacuum-Processed Perovskite Solar Cells.

In this study, we present a novel method for controlling the growth of perovskite crystals in the vacuum thermal evaporation process by utilizing a vacuum-processable additive, propylene urea (PU). By coevaporation of perovskite precursors with PU to form the perovskite layer, PU, acting as a Lewis base additive, retards the direct reaction between the perovskite precursors. This facilitates a larger domain size and reduced defect density. Following the removal of the residual additive, the perovskite layer, exhibiting improved crystallinity, demonstrates reduced charge recombination, as confirmed by a time-resolved microwave conductivity analysis. Consequently, there is a notable enhancement in open-circuit voltage and power conversion efficiency, increasing from 1.05 to 1.15 V and from 17.17 to 18.31%, respectively. The incorporation of a vacuum-processable and removable Lewis base additive into the fabrication of vacuum-processed perovskite solar cells offers new avenues for optimizing these devices.

Ursodeoxycholic acid may protect from severe acute respiratory syndrome coronavirus 2 Omicron variant by reducing angiotensin-converting enzyme 2.

The SARS-CoV-2 caused COVID-19 pandemic has posed a global health hazard. While some vaccines have been developed, protection against viral infection is not perfect because of the urgent approval process and the emergence of mutant SARS-CoV-2 variants. Here, we employed UDCA as an FXR antagonist to regulate ACE2 expression, which is one of the key pathways activated by SARS-CoV-2 Delta variant infection. UDCA is a well-known reagent of liver health supplements and the only clinically approved bile acid. In this paper, we investigated the protective efficacy of UDCA on Omicron variation, since it has previously been verified for protection against Delta variant. When co-housing with an Omicron variant-infected hamster group resulted in spontaneous airborne transmission, the UDCA pre-supplied group was protected from weight loss relative to the non-treated group at 4 days post-infection by more than 5%-10%. Furthermore, UDCA-treated groups had a 3-fold decrease in ACE2 expression in nasal cavities, as well as reduced viral expressing genes in the respiratory tract. Here, the data show that the UDCA serves an alternative option for preventive drug, providing SARS-CoV-2 protection against not only Delta but also Omicron variant. Our results of this study will help to propose drug-repositioning of UDCA from liver health supplement to preventive drug of SARS-CoV-2 infection.

PRMT5 is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer.

CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Through a genome-wide CRISPR screen, we identify protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout breast cancer cells. Inhibition of PRMT5 blocks the G1-to-S transition in the cell cycle independent of RB, leading to growth arrest in RB1-knockout cells. Proteomics analysis uncovers fused in sarcoma (FUS) as a downstream effector of PRMT5. Inhibition of PRMT5 results in dissociation of FUS from RNA polymerase II, leading to hyperphosphorylation of serine 2 in RNA polymerase II, intron retention, and subsequent downregulation of proteins involved in DNA synthesis. Furthermore, treatment with the PRMT5 inhibitor pemrametostat and a selective ER degrader fulvestrant synergistically inhibits growth of ER+/RB-deficient cell-derived and patient-derived xenografts. These findings highlight dual ER and PRMT5 blockade as a potential therapeutic strategy to overcome resistance to CDK4/6i in ER+/RB-deficient breast cancer.

Towards optimal design of patient isolation units in emergency rooms to prevent airborne virus transmission: From computational fluid dynamics to data-driven modeling.

BACKGROUND: Patient isolation units (PIUs) can be an effective method for effective infection control. Computational fluid dynamics (CFD) is commonly used for PIU design; however, optimizing this design requires extensive computational resources. Our study aims to provide data-driven models to determine the PIU settings, thereby promoting a more rapid design process. METHOD: Using CFD simulations, we evaluated various PIU parameters and room conditions to assess the impact of PIU installation on ventilation and isolation. We investigated particle dispersion from coughing subjects and airflow patterns. Machine-learning models were trained using CFD simulation data to estimate the performance and identify significant parameters. RESULTS: Physical isolation alone was insufficient to prevent the dispersion of smaller particles. However, a properly installed fan filter unit (FFU) generally enhanced the effectiveness of physical isolation. Ventilation and isolation performance under various conditions were predicted with a mean absolute percentage error of within 13%. The position of the FFU was found to be the most important factor affecting the PIU performance. CONCLUSION: Data-driven modeling based on CFD simulations can expedite the PIU design process by offering predictive capabilities and clarifying important performance factors. Reducing the time required to design a PIU is critical when a rapid response is required.

CYR61 confers chemoresistance by upregulating survivin expression in triple-negative breast cancer.

Cysteine-rich angiogenic inducer 61 (CYR61) is a protein from the CCN family of matricellular proteins that play diverse regulatory roles in the extracellular matrix. CYR61 is involved in cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence. Here, we show that CYR61 induces chemoresistance in triple-negative breast cancer (TNBC). We observed that CYR61 is overexpressed in TNBC patients, and CYR61 expression correlates negatively with the survival of patients who receive chemotherapy. CYR61 knockdown reduced cell migration, sphere formation, and the cancer stem cell (CSC) population and increased the chemosensitivity of TNBC cells. Mechanistically, CYR61 activated Wnt/ß-catenin signaling and increased survivin expression, which are associated with chemoresistance, the epithelial-mesenchymal transition, and CSC-like phenotypes. Altogether, our study demonstrates a novel function of CYR61 in chemotherapy resistance in breast cancer.

Comparative efficacy of vericiguat to sacubitril/valsartan for patients with heart failure reduced ejection fraction: Systematic review and network meta-analysis.

BACKGROUND: Despite the established efficacy of vericiguat compared to placebo, uncertainties remain regarding its comparative efficacy to sacubitril/valsartan for patients with heart failure reduced ejection fraction (HFrEF). This study aimed to assess the relative efficacy of vericiguat and sacubitril/valsartan through a systematic review, network meta-analysis, and non-inferiority tests. METHODS: A systematic review was conducted to identify the randomized phase 3 clinical trials involving vericiguat and sacubitril/valsartan. The hazard ratios (HRs) with 95% confidence intervals (CI) for cardiovascular death (CVD) and hospitalization due to HF (hHF) were extracted from these trials and synthesized via network meta-analysis. Non-inferiority testing of vericiguat was performed using a fixed-margin method with a predefined non-inferiority margin (1.24). Sensitivity analyses explored the impact of the time from hHF to screening. RESULTS: Among the 1366 studies, two trials (VICTORIA and PARADIGM-HF) met the inclusion criteria. Network meta-analysis demonstrated that the HR for CVD or hHF with vericiguat did not significantly differ from that for sacubitril/valsartan (HR: 0.88, 95% CI:0.62-1.23). The upper limit of the 95% CI was less than the predefined margin of 1.24, confirming vericiguat's non-inferiority to sacubitril/valsartan. Sensitivity analyses affirmed the robustness of the base-case results. CONCLUSION: Vericiguat exhibited a comparable risk of CVD or hHF when contrasted with sacubitril/valsartan. Importantly, in patients with HFrEF, vericiguat's efficacy was not statistically inferior to that of sacubitril/valsartan. These findings reinforce the potential of vericiguat as a viable treatment option for this patient population.

Deep Learning-based Assessment of Facial Asymmetry Using U-Net Deep Convolutional Neural Network Algorithm.

OBJECTIVES: This study aimed to evaluate the diagnostic performance of a deep convolutional neural network (DCNN)-based computer-assisted diagnosis (CAD) system to detect facial asymmetry on posteroanterior (PA) cephalograms and compare the results of the DCNN with those made by the orthodontist. MATERIALS AND METHODS: PA cephalograms of 1020 patients with orthodontics were used to train the DCNN-based CAD systems for autoassessment of facial asymmetry, the degree of menton deviation, and the coordinates of its regarding landmarks. Twenty-five PA cephalograms were used to test the performance of the DCNN in analyzing facial asymmetry. The diagnostic performance of the DCNN-based CAD system was assessed using independent t -tests and Bland-Altman plots. RESULTS: Comparison between the DCNN-based CAD system and conventional analysis confirmed no significant differences. Bland-Altman plots showed good agreement for all the measurements. CONCLUSIONS: The DCNN-based CAD system might offer a clinically acceptable diagnostic evaluation of facial asymmetry on PA cephalograms.

Investigation and assessment of natural radioactivity in commercial animal feeds in Texas.

Commercial animal feed in Texas was characterized by determining natural gamma emitters including 40K,137Cs, and Uranium (235U and 238U) and Thorium (232Th) series to obtain basic radioactivity values. The measured activity concentration of natural radionuclides in animal feed was low enough for safe consumption by animal and largely depended on the type of animal feed.40K was the predominant radionuclide showing the highest activity concentration in animal feed. The radioactivity concentration of 214 Bi and 214Pb in 238U decay series was 1.39 and 1.33 Bq/kg in corn, respectively, lower than in other animal feed types. On the other hand, the vitamin/mineral mix samples showed higher concentrations of 214 Bi (9.04 Bq/kg) and 214Pb (10.19 Bq/kg). Beef cattle feed, poultry feed, and vitamin/mineral mix exhibited higher activity concentration of 228Ac and 212Pb in 232Th decay series. Gamma radionuclides appeared to be highly and significantly correlated within each decay series. 235U was present at low levels in all feed samples while the anthropogenic radionuclide of 137Cs was not detected irrespective of the type of animal feed. This study highlights an importance of establishing a current baseline of radioactivity concentration in animal feed in Texas in which the largest animal feed consumption in the US exists.

Digital application of three-dimensional diagnosis and treatment with a virtual articulator.

OBJECTIVE: The purpose of this article was to introduce a method for the digital application of three-dimensional (3D) diagnosis and treatment with a virtual articulator and 3D data. CLINICAL CONSIDERATION: With the use of cone-beam computed tomography (CBCT) and intraoral and facial scans, we can create a virtual articulator and evaluate the mandibular position in maximum intercuspation and centric-related occlusion for the patient with an unstable occlusion and temporomandibular disorders (TMD). Based on this, we treated a case using a digital mandibular position indicator (MPI) and fabricated a stabilization splint using a 3D printer. This approach eliminates the traditional impression or model mounting process and the analog face bow transfer. Furthermore, the design of the stabilization splint is accomplished using software. CONCLUSIONS: The approach outlined in this article offers the potential for a digital diagnosis and treatment process by seamlessly integrating CBCT, intraoral scans, and facial scans with a high degree of accuracy. This may enhance precision in diagnosis and treatment planning, especially for patients with complicated TMD, in addition to facilitating effective communication with orthodontic patients who require thorough attention. CLINICAL SIGNIFICANCE: Utilizing a virtual articulator and digital MPI for the occlusal evaluation of patients with TMD and unstable occlusion makes it possible to diagnose and analyze the occlusal condition accurately. This approach also allows for precision and efficiency in treatment.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Detection of aflatoxins in ground maize using a compact and automated Raman spectroscopy system with machine learning.

Consumption of aflatoxin-contaminated food can cause severe illness when consumed by humans or livestock. Because the mycotoxin frequently occurs in cereal grains and other agricultural crops, it is crucial to develop portable devices that can be used non-destructively and in real-time to identify aflatoxin-contaminated food materials during early stages of harvesting or processing. In this study, an aflatoxin detection method was developed using a compact Raman device that can be used in the field. Data were obtained using maize samples naturally contaminated with aflatoxin, and the data were analyzed using a machine learning method. Of the multiple classification models evaluated, such as linear discriminant analysis (LDA), linear support vector machines (LSVM), quadratic discriminant analysis (QDA), and quadratic support vector machines and spectral preprocessing methods, the best classification accuracy was achieved at 95.7% using LDA in combination with Savitzky-Golay 2nd derivative (SG2) preprocessing. Partial least squares regression (PLSR) models demonstrated a close-range accuracy within the scope of standard normal variate (SNV) and multiplicative scatter correction (MSC) preprocessing methods, with determination of coefficient values of R2C and R2V of 0.9998 and 0.8322 respectively for SNV, and 0.9916 and 0.8387 respectively for MSC. This study demonstrates the potential use of compact and automated Raman spectroscopy, coupled with chemometrics and machine learning methods, as a tool for rapidly screening food and feed for hazardous substances at on-site field processing locations.

Defining a TCF1-expressing progenitor allogeneic CD8+ T cell subset in acute graft-versus-host disease.

Graft-versus-host disease (GvHD) is a severe complication of hematopoietic stem cell transplantation driven by activated allogeneic T cells. Here, we identify a distinct subset of T cell factor-1 (TCF1)+ CD8+ T cells in mouse allogeneic and xenogeneic transplant models of acute GvHD. These TCF1+ cells exhibit distinct characteristics compared to TCF1- cells, including lower expression of inhibitory receptors and higher expression of costimulatory molecules. Notably, the TCF1+ subset displays exclusive proliferative potential and could differentiate into TCF1- effector cells upon antigenic stimulation. Pathway analyses support the role of TCF1+ and TCF1- subsets as resource cells and effector cells, respectively. Furthermore, the TCF1+ CD8+ T cell subset is primarily present in the spleen and exhibits a resident phenotype. These findings provide insight into the differentiation of allogeneic and xenogeneic CD8+ T cells and have implications for the development of immunotherapeutic strategies targeting acute GvHD.

Simulation of the optical system in the GroundBIRD telescope.

GroundBIRD is a ground-based telescope for measuring the polarization of cosmic microwave background radiation, and it is soon to be operational at the Teide Observatory. The GroundBIRD telescope employs Mizuguchi-Dragone dual reflectors and 161 kinetic inductance detectors coupled with single polarization antennas as photon detectors. We present the results of our optical simulation on the pointing direction, stray light response, and influence of the blackbody radiation from the baffle. We also find that the power of the baffle radiation incident on the detectors is reduced by 99.95% when corrugated feed horns are coupled to the detectors.

Protein arginine methyltransferase 5 (PRMT5) is an actionable therapeutic target in CDK4/6 inhibitor-resistant ER+/RB-deficient breast cancer.

CDK4/6 inhibitors (CDK4/6i) have improved survival of patients with estrogen receptor-positive (ER+) breast cancer. However, patients treated with CDK4/6i eventually develop drug resistance and progress. RB1 loss-of-function alterations confer acquired resistance to CDK4/6i, but the optimal therapy for these patients is unclear. Using a genome-wide CRISPR screen, we identified protein arginine methyltransferase 5 (PRMT5) as a molecular vulnerability in ER+/RB1-knockout (RBKO) breast cancer cells. PRMT5 inhibition blocked cell cycle G1-to-S transition independent of RB, thus arresting growth of RBKO cells. Proteomics analysis uncovered fused in sarcoma (FUS) as a downstream effector of PRMT5. Pharmacological inhibition of PRMT5 resulted in dissociation of FUS from RNA polymerase II (Pol II), Ser2 Pol II hyperphosphorylation, and intron retention in genes that promote DNA synthesis. Treatment with the PRMT5i inhibitor pemrametostat and fulvestrant synergistically inhibited growth of ER+/RB-deficient patient-derived xenografts, suggesting dual ER and PRMT5 blockade as a novel therapeutic strategy to treat ER+/RB-deficient breast cancer.

Reconstruction of Range-Doppler Map Corrupted by FMCW Radar Asynchronization.

Frequency-modulated continuous wave (FMCW) radar system synchronization using external clock signals can cause repeated Range-Doppler (R-D) map corruption when clock signal asynchronization problems occur between the transmitter and receiver. In this paper, we propose a signal processing method for the reconstruction of the corrupted R-D map owing to the FMCW radar's asynchronization. After calculating the image entropy for each R-D map, the corrupted ones are extracted and reconstructed using the normal R-D maps acquired before and after the individual maps. To verify the effectiveness of the proposed method, three target detection experiments were conducted: a human target detection in an indoor environment and a wide place and a moving bike-rider target detection in an outdoor environment. The corrupted R-D map sequence of observed targets in each case was reconstructed properly and showed the validity by comparing the map-by-map range and speed changes in the detected target with the ground-truth information of the target.

Rapid Detection of Single- and Co-Contaminant Aflatoxins and Fumonisins in Ground Maize Using Hyperspectral Imaging Techniques.

Aflatoxins and fumonisins, commonly found in maize and maize-derived products, frequently co-occur and can cause dangerous illness in humans and animals if ingested in large amounts. Efforts are being made to develop suitable analytical methods for screening that can rapidly detect mycotoxins in order to prevent illness through early detection. A method for classifying contaminated maize by applying hyperspectral imaging techniques including reflectance in the visible and near-infrared (VNIR) and short-wave infrared (SWIR) regions, and fluorescence was investigated. Machine learning classification models in combination with different preprocessing methods were applied to screen ground maize samples for naturally occurring aflatoxin and fumonisin as single contaminants and as co-contaminants. Partial least squares-discriminant analysis (PLS-DA) and support vector machine (SVM) with the radial basis function (RBF) kernel were employed as classification models using cut-off values of each mycotoxin. The classification performance of the SVM was better than that of PLS-DA, and the highest classification accuracies for fluorescence, VNIR, and SWIR were 89.1%, 71.7%, and 95.7%, respectively. SWIR imaging with the SVM model resulted in higher classification accuracies compared to the fluorescence and VNIR models, suggesting that as an alternative to conventional wet chemical methods, the hyperspectral SWIR imaging detection model may be the more effective and efficient analytical tool for mycotoxin analysis compared to fluorescence or VNIR imaging models. These methods represent a food safety screening tool capable of rapidly detecting mycotoxins in maize or other food ingredients consumed by animals or humans.

IL-15 promotes self-renewal of progenitor exhausted CD8 T cells during persistent antigenic stimulation.

In chronic infections and cancer, exhausted CD8 T cells exhibit heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) can self-renew and give rise to Tim-3+PD-1+ terminally differentiated CD8 T cells that retain their effector functions. Tpex cells are thus essential to maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation, and only they respond to PD-1-targeted therapy. Despite their potential as a crucial therapeutic target for immune interventions, the mechanisms controlling the maintenance of virus-specific Tpex cells remain to be determined. We observed approximately 10-fold fewer Tpex cells in the spleens of mice chronically infected with lymphocytic choriomeningitis virus (LCMV) one-year post-infection (p.i.) than at three months p.i. Similar to memory CD8 T cells, Tpex cells have been found to undergo self-renewal in the lymphoid organs, prominently the bone marrow, during chronic LCMV infection. Furthermore, ex vivo treatment with IL-15 preferentially induced the proliferation of Tpex cells rather than the terminally differentiated subsets. Interestingly, single-cell RNA sequencing analysis of LCMV-specific exhausted CD8 T cells after ex vivo IL-15 treatment compared with those before treatment revealed increased expression of ribosome-related genes and decreased expression of genes associated with the TCR signaling pathway and apoptosis in both Tpex and Ttex subsets. The exogenous administration of IL-15 to chronically LCMV-infected mice also significantly increased self-renewal of Tpex cells in the spleen and bone marrow. In addition, we assessed the responsiveness of CD8 tumor-infiltrating lymphocytes (TILs) from renal cell carcinoma patients to IL-15. Similar to the data we obtained from chronic viral infection in mice, the expansion of the Tpex subset of PD-1+ CD8 TILs upon ex vivo IL-15 treatment was significantly higher than that of the terminally differentiated subset. These results show that IL-15 could promote self-renewal of Tpex cells, which has important therapeutic implications.