Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation ...signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B
:89A3B
:27A3B
), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.
Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation ...potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan’s Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.
During laparoscopic surgery, surgical gauze is usually inserted into the body cavity to help achieve hemostasis. Retention of surgical gauze in the body cavity may necessitate reoperation and ...increase surgical risk. Using deep learning technology, this study aimed to propose a neural network model for gauze detection from the surgical video to record the presence of the gauze. The model was trained by the training group using YOLO (You Only Look Once)v5x6, then applied to the testing group. Positive predicted value (PPV), sensitivity, and mean average precision (mAP) were calculated. Furthermore, a timeline of gauze presence in the video was drawn by the model as well as human annotation to evaluate the accuracy. After the model was well-trained, the PPV, sensitivity, and mAP in the testing group were 0.920, 0.828, and 0.881, respectively. The inference time was 11.3 ms per image. The average accuracy of the model adding a marking and filtering process was 0.899. In conclusion, surgical gauze can be successfully detected using deep learning in the surgical video. Our model provided a fast detection of surgical gauze, allowing further real-time gauze tracing in laparoscopic surgery that may help surgeons recall the location of the missing gauze.
It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the ...pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction.
This research continues the research of Deng et al. (2022) 1, using Discrete Element Method (DEM) coupled with Finite Element Analysis to solve shotgun exterior ballistics. The simulation examples in ...this research are using an Italian-made 24 gm #9½ birdshot with 433 pellets fired from 30” long, 12-gauge cylinder and full choke barrels. The simulations of shotgun exterior ballistics of this research included pellet swarm velocity and the pellet dispersion at different distances until 50 yards away from the muzzle. The ballistics simulation of the pellet swarm is completed from interior to exterior consecutively after the shotshell is fired inside the chamber so all ballistics performances can be calculated at one time. Three forces were applied to the pellets for exterior ballistics simulation: the contact force between pellets, the aerodynamic separation force between pellets, and the drag force. Because of the complexity of the aerodynamic forces exerted on pellets, this research used an equivalent aerodynamic force to simulate this complex phenomenon. Two birdshot models with different pellet formations were created; the first one was simulated to calibrate the separation scale factor defined in aerodynamic separation force, and the second one was used for validation and sensitivity of the model. The simulation results show that for #9½ birdshots fired by cylinder barrel, the average Effective Shot Dispersion (ESD) of pellet dispersion of both birdshots inside the 30” diameter of the target circle at 40 yards from the muzzle is 398.53, which is remarkably close to 396.98 of the experiment result. The simulation of the average pellets' target hit rate is 77.14% (inside the 30” diameter of the target circle), which is also remarkably close to the experiment hit rate of 77.57%. The same birdshot fired from a full choke barrel shows that ESD and hit rate rose to 406.34 and 83.14%, respectively. These results demonstrate the effectiveness of using the discrete element method in conjunction with the proposed equivalent aerodynamic force to predict the shotgun's interior and exterior ballistics.
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•The equivalent aerodynamic forces were formulated from experiments of two pellets flying near to each other.•An Italian made 12-gauge 24 gm. #9½ birdshot with 433 pellets fired from 30-in long cylinder and full choke barrels were simulated.•Two birdshot models with different pellet formations were created to validate the sensitivity of the model.•Average simulated pellet dispersion at 40 yards fired by cylinder has only 0.43% error compared to the experiment.•Birdshot fired by full-choke barrel has 6.0% higher target hit rate compared to cylinder barrel did.
Globo H (GH), a hexasaccharide, is expressed at low levels in normal tissues but is highly expressed in multiple cancer types, rendering it a promising target for cancer immunotherapy. OBI-999, a ...novel antibody-drug conjugate, is derived from a conjugation of a GH-specific mAb with a monomethyl auristatin E (MMAE) payload through a site-specific ThioBridge and a cleavable linker. OBI-999 high homogeneity with a drug-to-antibody ratio of 4 (>95%) was achieved using ThioBridge. OBI-999 displayed GH-dependent cellular internalization and trafficked to endosome and lysosome within 1 and 5 hours, respectively. Furthermore, OBI-999 showed low nanomolar cytotoxicity in the assay with high GH expression on tumor cells and exhibited a bystander killing effect on tumor cells with minimal GH expression. Tissue distribution indicated that OBI-999 and free MMAE gradually accumulated in the tumor, reaching maximum level at 168 hours after treatment, whereas OBI-999 and free MMAE decreased quickly at 4 hours after treatment in normal organs. Maximum MMAE level in the tumor was 16-fold higher than in serum, suggesting that OBI-999 is stable during circulation and MMAE is selectively released in the tumor. Excellent tumor growth inhibition of OBI-999 was demonstrated in breast, gastric, and pancreatic cancer xenograft or lung patient-derived xenograft models in a dose-dependent manner. The highest nonseverely toxic dose in cynomolgus monkeys is 10 mg/kg determined by a 3-week repeated-dose toxicology study demonstrating an acceptable safety margin. Taken together, these results support further clinical development of OBI-999, which is currently in a phase I/II clinical study in multiple solid tumors (NCT04084366). OBI-999, the first GH-targeting ADC, displayed excellent tumor inhibition in animal models across multiple cancer types, including breast, gastric, pancreatic, and lung cancers, warranting further investigation in the treatment of solid tumors.
Numerous patients suffer from chronic wounds and wound infections nowadays. Until now, the care for wounds after surgery still remain a tedious and challenging work for the medical personnel and ...patients. As a result, with the help of the hand-held mobile devices, there is high demand for the development of a series of algorithms and related methods for wound infection early detection and wound self monitoring.
This research proposed an automated way to perform (1) wound image segmentation and (2) wound infection assessment after surgical operations. The first part describes an edge-based self-adaptive threshold detection image segmentation method to exclude nonwounded areas from the original images. The second part describes a wound infection assessment method based on machine learning approach. In this method, the extraction of feature points from the suture area and an optimal clustering method based on unimodal Rosin threshold algorithm that divides feature points into clusters are introduced. These clusters are then merged into several regions of interest (ROIs), each of which is regarded as a suture site. Notably, a support vector machine (SVM) can automatically interpret infections on these detected suture site.
For (1) wound image segmentation, boundary-based evaluation were applied on 100 images with gold standard set up by three physicians. Overall, it achieves 76.44% true positive rate and 89.04% accuracy value. For (2) wound infection assessment, the results from a retrospective study using confirmed wound pictures from three physicians for the following four symptoms are presented: (1) Swelling, (2) Granulation, (3) Infection, and (4) Tissue Necrosis. Through cross-validation of 134 wound images, for anomaly detection, our classifiers achieved 87.31% accuracy value; for symptom assessment, our classifiers achieved 83.58% accuracy value.
This augmentation mechanism has been demonstrated reliable enough to reduce the need for face-to-face diagnoses. To facilitate the use of this method and analytical framework, an automatic wound interpretation app and an accompanying website were developed.
201505164RIND , 201803108RSB .
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aldosterone-to-renin ratio (ARR) is the standard screening test for primary aldosteronism (PA). Because of the poor reproducibility of the ARR, repeat testing is recommended if the result is not ...compatible with the clinical condition. Various methods to measure renin are used in different hospitals in Taiwan, and the ARR cutoff values also differ among laboratories. The Task Force of Taiwan PA recommend using plasma renin activity (PRA) to calculate ARR instead of direct renin concentration (DRC) unless PRA is unavailable, because PRA is widely used in international guidelines and most studies.
Atrial fibrillation (AF) detection is crucial for stroke prevention. We investigated the potential of quantitative analyses of photoplethysmogram (PPG) waveforms to identify AF. Continuous ...electrocardiogram (EKG) and fingertip PPG were recorded simultaneously in acute stroke patients (n = 666) admitted to an intensive care unit. Each EKG was visually labeled as AF (n = 150, 22.5%) or non-AF. Linear and nonlinear features from the pulse interval (PIN) and peak amplitude (AMP) of PPG waveforms were extracted from the first 1, 2, and 10 min of data. Logistic regression analysis revealed six independent PPG features feasibly identifying AF rhythm, including three PIN-related (mean, mean of standard deviation, and sample entropy), and three AMP-related features (mean of the root mean square of the successive differences, sample entropy, and turning point ratio) (all p < 0.01). The performance of the PPG analytic program comprising all 6 features that were extracted from the 2-min data was better than that from the 1-min data (area under the receiver operating characteristic curve was 0.972 (95% confidence interval 0.951-0.989) vs. 0.949 (0.929-0.970), p < 0.001 and was comparable to that from the 10-min data 0.973 (0.953-0.993) for AF identification. In summary, our study established the optimal PPG analytic program in reliably identifying AF rhythm.
According to pigeon racing rules in Taiwan, the pigeon raiser must decide which juveniles will be chosen as soon as possible. Differentiating the sex of young pigeons based on appearances, and other ...traditional methods, can be time-consuming and require several pieces of equipment. Recombinase polymerase amplification (RPA) combined with a lateral-flow dipstick (LFD) could further simplify the presentation of amplification results. A designed reverse primer and probe were labeled with biotin and FAM (fluorescein), respectively, to serve as ligands in the LFD. With the addition of a designed forward primer, the RPA-LFD can be used to perform sex identification of pigeon DNA. The optimal conditions were determined to require at least 6.3 pg of the DNA template, a temperature of 37 °C, and a reaction time of at least 20 min. Under these conditions, the test band area on the strip appeared as a dark color if the sample contained female template DNA, whereas the male DNA samples did not produce any test signal in any of the conditions. The results of random samples using RPA-LFD under the optimal conditions agreed with the results of the same samples determined by PCR-agarose gel electrophoresis. The approach in this study represents a rapid and accurate method for pigeon sexing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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