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Background Cisplatin, the first-line drug for chemotherapy, often has limited treatment efficacy because of resistance and cancer recurrence mechanisms. Tetrandrine is a unique secondary metabolite of Stephania tetrandra. As a traditional Chinese medicine agent, tetrandrine has been reported to have antioxidant, anti-inflammatory, antitumor, and antiangiogenesis activities and has been shown to inhibit the proliferation and angiogenesis of colorectal, lung, and breast cancer cells; potential mechanisms underlying its activities include the promotion of tumor cell apoptosis, promotion of cell cycle arrest, and intensification of reactive oxygen species (ROS) production. Objectives The main treatments for oral cancer are chemotherapy, surgery, and radiotherapy; these treatments are often used in combination. Cancer cells easily develop cisplatin resistance; therefore, we investigated tetrandrine’s potential as a therapy for overcoming resistance to oral cancer drugs. Materials and Methods We used the cisplatin-resistant oral cancer CAR cell line (CAL27) as a research objected and applied inhibitor treatment to clarify the role of tetrandrine in cell death and mitochondrial dysfunction. Results Tetrandrine could effectively inhibit CAR cell proliferation and induce apoptosis, with a corresponding increase in ROS production in mitochondria. Moreover, tetrandrine increased caspase-9 and caspase-3 activity in CAR cells and induced apoptotic mRNA, caspase-3/-9, AIF, and Endo G overexpression. Our results indicate that tetrandrine induces apoptosis in CAR cells through a mitochondrial-dependent signaling pathway.

BACKGROUND Identification and referral of at-risk patients from primary care practitioners (PCPs) to eye care professionals remains problematic. Approximately 1.9 million Americans suffer from vision loss as a result of undiagnosed or untreated ophthalmic conditions. Artificial intelligence modeling of 1,486,078 patients identifies individuals at higher risk for glaucoma, age-related macular degeneration, diabetic retinopathy, visually significant cataracts, and ocular surface disease. OBJECTIVE To build and compare artificial intelligence (AI) strategies, applicable to Electronic Health Records of primary care physicians (PCPs), capable of triaging patients for referral to eyecare specialists. METHODS From the Optum® de-identified Electronic Health Record dataset, 743,039 patients with age-related macular degeneration (AMD), visually significant cataract, diabetic retinopathy, glaucoma, or ocular surface disease (OSD) were exact matched on age and gender to 743,039 controls without eye conditions. Between 142-182 non-ophthalmic parameters per patient were inputted into five AI models: Generalized Linear Model (GLM), L1-regularized logistic regression, random forest, XGBoost, and J-48 decision trees. Model performance was compared for each pathology to select the most predictive algorithm. Area under the curve (AUC) was assessed for all algorithms for each outcome. RESULTS XGBoost demonstrated the best performance, showing, respectively, prediction accuracy and AUC of 78.6% and 0.878 for visually significant cataract, 77.4% and 0.858 for exudative AMD, 79.2% and 0.879 for non-exudative AMD, 72.2% and 0.803 for OSD requiring medication, 70.8% and 0.785 for glaucoma, 85.0% and 0.924 for type 1 nonproliferative diabetic retinopathy (NPDR), 82.2% and 0.911 for type 1 proliferative diabetic retinopathy (PDR), 81.3% and 0.891 for type 2 NPDR, and 82.1% and 0.900 for type 2 PDR. CONCLUSIONS The five AI strategies deployed were able to successfully identify patients with elevated odds ratios (ORs [95% CI]), thus capable of patient triage, for ocular pathology ranging from 2.4 [2.4-2.5] (glaucoma) to 5.7 [5.0-6.4] (type 1 NPDR), with an average OR of 3.9. The application of these models could enable PCPs to better identify and triage patients at risk for ophthalmic pathology. CLINICALTRIAL N/A

OBJECTIVES/HYPOTHESIS Evaluation of the clinical outcomes after 6 months of treatment with a novel adjustable implant, the APrevent® Vocal-Implant-System (VOIS), in conjunction with medialization thyroplasty (MT) in patients with unilateral vocal fold paralysis. STUDY DESIGN Prospective case series study at single tertiary referral center. METHODS Preoperative and 1 week, 7 weeks, and 6 months postoperative glottal efficiency (maximum phonation time [MPT]), voice quality (including GRBAS-scores and acoustic parameters) and self-perceived voice-related handicap (voice handicap index [VHI-30]) were measured and analyzed, whereas type of vocal fold closure was evaluated and determined by flexible videolaryngoscopy based on Sodersten and Lindestad classification (Wilcoxon signed-rank test). RESULTS Thirteen patients underwent MT with VOIS under local anesthesia. Six months after surgery, the VHI-30 and MPT had improved from a preoperative mean of 75.0 ± 22.9 and 2.7 ± 2.1 s to a postoperative mean of 20.6 ± 19.7 and 6.3 ± 4.0 s, respectively. The mean GRBAS score improved from preoperative scores of Gpreop = 2.7, Rpreop = 2.6, Bpreop = 2.6, Apreop = 2.2, and Spreop = 2.0 to Gpostop = 0.3, Rpostop = 0.3, Bpostop = 0.2, Apostop = 0.2, and Spostop = 0.3 at 6 months postoperatively. Improved glottal closure was achieved in all patients (n = 13). Five patients received postoperative adjustment for the optimization of voice quality and glottal closure. No intra- or postoperative complications were observed. Significant improvements in acoustic parameters, including percentage jitter, percentage shimmer, and signal-to-noise ratio, were also observed after MT. All results were statistically significant (P .8). CONCLUSIONS APrevent® VOIS-Implantation is a safe procedure with good voice outcomes. Postoperative adjustments can be performed smoothly to optimize voice quality and glottal closure. LEVEL OF EVIDENCE III Laryngoscope, 2021.

In seed plants, phospho-base N-methyltransferase (PMT) catalyzes a key step in the biosynthesis pathway of phosphatidylcholine (PC), the most abundant phospholipid class. Arabidopsis thaliana possesses three copies of PMT, with PMT1 and PMT3 play a primary role because the pmt1 pmt3 double mutant shows considerably reduced PC content with a pale seedling phenotype. Although the function of PMT1 and PMT3 may be redundant because neither of the parental single mutants showed a similar mutant phenotype, major developmental defects and possible functional divergence of these PMTs underlying the pale pmt1 pmt3 seedling phenotype are unknown. Here, we show the major developmental defect of the pale seedlings in xylem of the hypocotyl with partial impairments in chloroplast development and photosynthetic activity in leaves. Although PMT1 and PMT3 are localized at the endoplasmic reticulum, their tissue-specific expression pattern was distinct in hypocotyls and roots. Intriguingly, the function of PMT3 but not PMT1 requires its characteristic N-terminal sequence in addition to the promoter because truncation of the N-terminal sequence of PMT3 or substitution with PMT1 driven by the PMT3 promoter failed to rescue the pale pmt1 pmt3 seedling phenotype. Thus, PMT3 function requires the N-terminal sequence in addition to its promoter, whereas the PMT1 function is defined by the promoter.

Patients who fail to commit suicide by hanging often end up with laryngotracheal injuries, which may lead to a compromised airway, swallowing dysfunction, and dysphonia. Previous studies have mainly focused on airway management after near-hanging attempts. Few have shed light on the treatment of swallowing dysfunction after laryngotracheal injuries. Here, we present a near-hanging patient who developed complete dysphagia shortly afterward. We used a Montgomery T-tube as an endolaryngeal stent, combined with swallowing rehabilitation. The patient’s swallowing ability was gradually restored one month after the surgery, and the stent was removed six months later. The present case report exemplifies the unique way of using the Montgomery T-tubes in clinical practice. Among the patients with airway stenosis affecting the larynx and extending to the vocal cords, Montgomery T-tube may be the only stent that can help manage strictures at the level of the vocal cords and in the supraglottic region, restoring swallowing function and maintaining the airway.

This paper introduces a concept named ‘signaling re-interpretation,’ which aims to improve the decision-making quality and keep the decision maker from losses ex-ante. Signaling re-interpretation includes the essence of signaling theory and systems thinking by taking the idea of signaling effect and other essential components in the system sequentially into consideration. Thus, signaling re-interpretation may overcome the obstacles signaling effect confronts in the application, such as the deferred correction of interpretation and the blind spots from an objective perspective. The expected contribution for practitioners lies in providing a perspective which tallies with decision makers’ needs, and the logic is easier for practitioners to understand. Thus, it increases the convenience for practitioners to apply and the decision is made from a well-thought-out consideration. As for researchers, signaling re-interpretation shows a more comprehensive framework which may reveal more crucial components affecting the decision quality. Applying signaling re-interpretation into empirical testing may also help the result become more representative and answer more to the research context. Accordingly, signaling re-interpretation will extend the application of the signaling effect.

Additional file 6: Figure S6. Decreased of p62 protein level and enhanced of the proteasome activities in the spinal cord, but not the forebrain, of symptomatic N390D/+ mice.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset degenerative disorder of motor neurons. The diseased spinal cord motor neurons of more than 95% of amyotrophic lateral sclerosis (ALS) patients are characterized by the mis-metabolism of the RNA/DNA-binding protein TDP-43 (ALS-TDP), in particular, the presence of cytosolic aggregates of the protein. Most available mouse models for the basic or translational studies of ALS-TDP are based on transgenic overexpression of the TDP-43 protein. Here, we report the generation and characterization of mouse lines bearing homologous knock-in of fALS-associated mutation A315T and sALS-associated mutation N390D, respectively. Remarkably, the heterozygous TDP-43 (N390D/+) mice but not those heterozygous for the TDP-43 (A315T/+) mice develop a full spectrum of ALS-TDP-like pathologies at the molecular, cellular and behavioral levels. Comparative analysis of the mutant mice and spinal cord motor neurons (MN) derived from their embryonic stem (ES) cells demonstrates that different ALS-associated TDP-43 mutations possess critical ALS-causing capabilities and pathogenic pathways, likely modified by their genetic background and the environmental factors. Mechanistically, we identify aberrant RNA splicing of spinal cord Bcl-2 pre-mRNA and consequent increase of a negative regulator of autophagy, Bcl-2, which correlate with and are caused by a progressive increase of TDP-43, one of the early events associated with ALS-TDP pathogenesis, in the spinal cord of TDP-43 (N390D/+) mice and spinal cord MN derived from their ES cells. The TDP-43 (N390D/+) knock-in mice appear to be an ideal rodent model for basic as well as translational studies of ALS- TDP.

Purpose Set in an emerging economy context, the purpose of this paper is to examine the determinants of green consumers’ purchase behavior on organic food by analyzing the impact of word-of-mouth (WOM) effects (i.e. tie strength, sender’s green expertise, receiver’s green expertise), conformity behaviors (i.e. normative interpersonal influence and informational interpersonal influence) on green purchase intention, and the relationship between green purchase intention and green purchase behavior. Design/methodology/approach Data were collected by self-administered questionnaire completed by respondents who had purchase experience of organic food in the last six months. The specific context of this study is green consumption for organic food in Taiwan. Data collection was implemented in a convenience sampling method. Among the 578 consumers who had filled the questionnaire, 147 did not have any purchase history of organic food, resulting in a final usable sample of 431 (response rate 74.57 percent) in Taiwan. The data were collected during a five-week period in late 2015. Findings Through structural equation modeling analysis, data were analyzed and the empirical results indicate that tie strength, sender’s green expertise, and receiver’s green expertise have a positive influence on green consumer’s susceptibility to informational interpersonal influences and normative interpersonal influences, separately. In addition, informational interpersonal influences and normative interpersonal influences both have a positive relationship on green purchase intention, which will further positively influence the green purchase behavior. Originality/value This study reminds marketers of the impact of WOM effects as well as interpersonal influences on consumers. It examines the impact of tie strength, senders’ green expertise, and receivers’ green expertise on green purchase intention and green purchase behavior. This study also explores the mediation effects of green consumers’ susceptibility to interpersonal influences. Consumers’ susceptibility to interpersonal influence is discussed in the marketing literature. However, few prior studies have explored its effect in the green setting. Last, few attempts have discussed the relationship between green purchase intention and green purchase behavior. This study contributes to the literature by examine the relationship between green purchase intentions and green purchase behavior.

We conducted a retrospective study to evaluate the short-term effect of uvulopalatopharyngoplasty (UPPP) on changes in the nasalance of five vowels: /a/, /ε/, /i/, /Ɔ/, and /u/. Our study group was made up of 20 patients—15 males and 5 females, aged 16 to 57 years (mean: 37.3 ± 11.5)—who had undergone UPPP as a treatment for mild to moderate obstructive sleep apnea. Nasometry was used to obtain nasalance scores in all patients on the morning of the operation (day 1) and subsequently on day 4 or 5 (mean: 4.5 ± 0.5). Preoperatively, nasalance scores were highest for /i/ (mean: 29.8 ± 12.6) and /a/ (mean: 24.1 ± 10.3). After the operation, nasalance scores for all five studied vowels increased; they were highest for /i/ (mean: 40.7 ± +17.8) and /ε/ (mean: 30.0 ± 10.8). The increases in the nasalance of /i/, /ε/, and /u/ were statistically significant (p < 0.05). Our findings indicate that UPPP has a significant impact on nasalance immediately after surgery.

Research has demonstrated that trusting belief in one's ability is critical to coproducer selection; however, the importance of trusting belief in dedication has been ignored. This study aims to explore how reputation (i.e., word-of-mouth, certification, and recommendation) affects trusting belief in a potential coproducer's ability and dedication and examines its mediating effects in coproducing with a potential partner.Empirical results show significant mediating effects of trusting belief in a potential coproducer's ability from certification, word-of-mouth, and recommendation, which in turn motivate coproduction, whereas certification leads to the motivation for coproduction through trusting belief in a potential coproducer's dedication. The findings refer to a unitary acceptance of ability but a divergent recognition of dedication. The focal party may regard certification as factual without personal distortion, while the recommendation is an evaluation worth considering. In considering dedication, the focal party may be unable to assess the extent of distortion from second-hand information (e.g., word-of-mouth).

A series of PIs were first derived from 4,4′-oxydianiline (ODA) and various dianhydrides, including pyromellitic dianhydride (PMDA), 4,4′-oxydiphthalic dianhydride (ODPA), and 4,4′-(4,4′-isopropylidenediphenoxy) bis(phthalic anhydride) (IDPA), to produce PI matrix with various degrees of rigidity. In order to reduce the water-vapor-transmission-rate (WVTR) of PI, a moisture barrier was deposited on each PI substrate by an RF magnetron sputtering system and the WVTR was investigated as a function of rigidity of PI matrix. The deposited thin film (SiN x O y ) with the thickness of 100 nm on PI is an excellent moisture barrier that the WVTR of all PI thin films is significantly reduced. The relatively rigid PI matrix leads to a denser packing of barrier layer, and thus exhibits lower WVTR than other two PI systems. The WVTR of ODA–PMDA/SiN x O y declines to 5 g/m 2 -day compared with 123 g/m 2 -day for parent PI film. On the other hand, the moisture barrier on a flexible PI matrix (ODA–IDPA) shows a higher reliability on the WVTR after bending treatment to 15,000 cycles. In addition to the moisture barrier feature, the SiNxOy-deposited PI thin films maintain favorable thermal stability and mechanical strength for practical applications.

The Drosophila melanogaster anterior–posterior axis is established during oogenesis by the localization of bicoid and oskar mRNAs to the anterior and posterior poles of the oocyte. Although genetic screens have identified some trans-acting factors required for the localization of these transcripts, other factors may have been missed because they also function at other stages of oogenesis. To circumvent this problem, we performed a screen for revertants and dominant suppressors of the bicaudal phenotype caused by expressing Miranda–GFP in the female germline. Miranda mislocalizes oskar mRNA/Staufen complexes to the oocyte anterior by coupling them to the bicoid localization pathway, resulting in the formation of an anterior abdomen in place of the head. In one class of revertants, Miranda still binds Staufen/oskar mRNA complexes, but does not localize to the anterior, identifying an anterior targeting domain at the N terminus of Miranda. This has an almost identical sequence to the N terminus of vertebrate RHAMM, which is also a large coiled-coil protein, suggesting that it may be a divergent Miranda ortholog. In addition, we recovered 30 dominant suppressors, including multiple alleles of the spectroplakin, short stop, a lethal complementation group that prevents oskar mRNA anchoring, and a female sterile complementation group that disrupts the anterior localization of bicoid mRNA in late oogenesis. One of the single allele suppressors proved to be a mutation in the actin nucleator, Cappuccino, revealing a previously unrecognized function of Cappuccino in pole plasm anchoring and the induction of actin filaments by Long Oskar protein.

Cutaneous red blood cell velocity in vivo can be measured by using capillaroscopy with image processing techniques. However, unlike simulated blood flow images, there is no standard to determine the accuracy of the techniques for computing blood flow velocities. In this paper, we quantitatively evaluated the accuracy of previously proposed optical flow method for measuring red blood cell velocity in nail-fold capillaries. Blood flow images of subjects under normal and occlusion-release conditions were examined by a capillaroscope. To obtain velocity values, the images were further analyzed by using optical flow, cross-correlation and visual inspection methods, respectively. Visual inspection method was taken as the golden standard to determine the accuracy of blood flow velocity measurement using optical flow and cross-correlation techniques. Results showed that optical flow estimation provided superior accuracy to cross-correlation when assessing real blood flow velocity in nail-fold capillaries. Optical flow estimation is able to measure red blood cell velocity with a high accuracy of 91% and 86% when the observed velocity is less than 0.5mm/s under normal and occlusion-release conditions, respectively. In addition, optical flow method showed good agreement with visual inspection in determining blood flow velocity in both normal and occlusion-release conditions when the high-velocity zone is excluded.

Objective The aim of this study was to investigate the acoustic characteristics of target vowels phonated in normal voice persons while performing laryngeal telescopy. The acoustic characteristics are compared to show the extent of possible difference to speculate their impact on phonation function. Methods Thirty-four male subjects aged 20–39 years with normal voice were included in this study. The target vowels were /i/ and /ɛ/. Recording of voice samples was done under natural phonation and during laryngeal telescopy. The acoustic analysis included the parameters of fundamental frequency, jitter, shimmer and noise-to-harmonic ratio. Results The sound of a target vowel /ɛ/ was perceived identical in more than 90% of the subjects by the examiner and speech language pathologist during the telescopy. Both /i/ and /ɛ/ sounds showed significant difference when compared with the results under natural phonation. There was no significant difference between /i/ and /ɛ/ during the telescopy. Conclusion The present study showed that change in target vowels during laryngeal telescopy makes no significant difference in the acoustic characteristics. The results may lead to the speculation that the phonation mechanism was not affected significantly by different vowels during the telescopy. This study may suggest that in the principle of comfortable phonation, introduction of the target vowels /i/ and /ɛ/ is practical.

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is used as an alternative method for the rapid diagnosis of albuminuria. This technique requires no further sample pretreatment than simply mixing the urine sample with a MALDI matrix and drying under ambient conditions. The resulting MALDI mass spectra reveal albumin ions having charges ranging from +1 to +5. The detection of albumin is possible using any of the three most common MALDI matrices - sinapinic acid (SA), 2,5-dihydroxybenzoic acid (2,5-DHB), or 4-hydroxy-alpha-cyanocinnamic acid (alpha-CHC). Using this analytical approach, the limit of detection for albumin in urine is 10(-6) M, approximately 5 to 10 times lower than that detectable through conventional chemical testing.

Viridians streptococcal shock syndrome is a subtype of toxic shock syndrome. Frequently, the diagnosis is missed initially because the clinical features are nonspecific. However, it is a rapidly progressive disease, manifested by hypotension, rash, palmar desquamation, and acute respiratory distress syndrome within a short period. The disease course is generally fulminant and rarely presents initially as a purpura over the plantar region. We present a case of a 54-year-old female hospital worker diagnosed with viridians streptococcal shock syndrome caused byStreptococcus gordonii. Despite aggressive antibiotic treatment, fluid hydration, and use of inotropes and extracorporeal membrane oxygenation, the patient succumbed to the disease. Early diagnosis of the potentially fatal disease followed by a prompt antibiotic regimen and appropriate use of steroids are cornerstones in the management of this disease to reduce the risk of high morbidity and mortality.

Current breast cancer risk assessment models have moderate discriminatory ability. We evaluated whether microRNA (miRNA) expression profiles in peripheral blood mononuclear cells (PBMC) could be a useful biomarker of risk in high-risk women.Next-generation sequencing evaluated miR expression in PBMCs of 20 women who were unaffected at the time of recruitment and later diagnosed with breast cancer and 20 unaffected women.Out of the 5 miRNAs identified as potential risk markers, miR-144-3p, miR-451a, miR-144-5p and miR-183-5p were up-regulated, while miR-708-5p was down-regulated. We then evaluated these miRs in 28 additional case/control pairs using quantitative reverse transcription polymerase chain reaction (PCR). None of the results in the validation sample were statistically significant possibly due to the much longer interval between blood collection and diagnosis in the validation set.Differentially expressed miRNAs from PBMCs may be potential non-invasive biomarkers for breast cancer prediction. Larger prospective studies are required to confirm whether our findings with specific miRNA loci were related to timing before diagnosis.

The double-stranded RNA binding protein Staufen is required for the microtubule-dependent localization of bicoid and oskar mRNAs to opposite poles of the Drosophila oocyte and also mediates the actin-dependent localization of prospero mRNA during the asymmetric neuroblast divisions. The posterior localization of oskar mRNA requires Staufen RNA binding domain 2, whereas prospero mRNA localization mediated the binding of Miranda to RNA binding domain 5, suggesting that different Staufen domains couple mRNAs to distinct localization pathways. Here, we show that the expression of Miranda during mid-oogenesis targets Staufen/oskar mRNA complexes to the anterior of the oocyte, resulting in bicaudal embryos that develop an abdomen and pole cells instead of the head and thorax. Anterior Miranda localization requires microtubules, rather than actin, and depends on the function of Exuperantia and Swallow, indicating that Miranda links Staufen/oskar mRNA complexes to the bicoid mRNA localization pathway. Since Miranda is expressed in late oocytes and bicoid mRNA localization requires the Miranda-binding domain of Staufen, Miranda may play a redundant role in the final step of bicoid mRNA localization. Our results demonstrate that different Staufen-interacting proteins couple Staufen/mRNA complexes to distinct localization pathways and reveal that Miranda mediates both actin- and microtubule-dependent mRNA localization.

In this paper, the edge current phenomena of on-board antenna, PIFA, are simulated by full 3D EM simulator, GEMS of 2COMU. The simulation of current density interprets the current crowed effect which makes a sensible explanation for the occurring of EMI noise even if the differential PCB layout topology is obtained for signal trace routing. Bridge connection, a solution for diverting this EMI current under this circumstance is also presented by simulation and real case verification in this paper.

This paper portrays the effect and solution of radiation interference from antenna to the base-band audio circuit. The 217 Hz TDMA modulation of GSM module constitutes a form of switching noise and causes the EMI problem in audio frequency. Differential and single-end PCB layout architectures are simulated and compared by full 3D EM simulator, GEMS, for observing the appearance of common mode noise cancellation mechanism. The actual two-way voice communication testing is also operated to verify the efficacy of noise cancellation by this differential architecture.

This paper presents a research and development of airborne InGaAs infra image module in Taiwan. This article will discuss the study of electromagnetic interference testing to meet requirement with RE and CE session of RTCA/DO160E. Those measurement results of airborne InGaAs infrared image module provided one successfully example of the category M of RTCA/DO-160E.

In this paper, two methods of microscopic image analysis were presented to classify the abnormal cells in Papanicolaou(Pap) smear for cervical cancer screening. Our goal is to extract those cell nuclei which are abnormally large size, bizarre shape as well as hyper density and we hope to apply this method to the different kinds of abnormal cells. The global information of the image and the local image condition were meantime considered. The reported method searched whole picture by scanning on different axes and determined the locations of abnormal cell nuclei with high contrast This developed method is also able to find cell nuclei, those were almost as bright as the background. Using the reported cytological image analysis, we successfully recognized the abnormal cells such as squamous intraepithelial neoplasia (SIL) and differentiated them from the normal epithelial cells.

The purpose of this study was to investigate early radiation effects on tongue function for patients with nasopharyngeal carcinoma (NPC) and to provide a scientific database for early intervention plans. Twelve subjects with NPC and 12 age- and sex-matched normal subjects were included. Tongue maximum isometric strength and endurance at 50% of maximum strength were obtained once from normal subjects with the Iowa Oral Performance Instrument (IOPI) and twice from the NPC subjects: before and 2 months after radiation treatment. No significant differences were found in tongue function evaluation for normal or NPC groups in either pre- or post-treatments. However, this study showed that significant decreases in tongue function may not start until 2 months after treatment.