Every year cervical cancer affects more than 300,000 people, and on average one woman is diagnosed with cervical cancer every minute. Early diagnosis and classification of cervical lesions greatly ...boosts up the chance of successful treatments of patients, and automated diagnosis and classification of cervical lesions from Papanicolaou (Pap) smear images have become highly demanded. To the authors' best knowledge, this is the first study of fully automated cervical lesions analysis on whole slide images (WSIs) of conventional Pap smear samples. The presented deep learning-based cervical lesions diagnosis system is demonstrated to be able to detect high grade squamous intraepithelial lesions (HSILs) or higher (squamous cell carcinoma; SQCC), which usually immediately indicate patients must be referred to colposcopy, but also to rapidly process WSIs in seconds for practical clinical usage. We evaluate this framework at scale on a dataset of 143 whole slide images, and the proposed method achieves a high precision 0.93, recall 0.90, F-measure 0.88, and Jaccard index 0.84, showing that the proposed system is capable of segmenting HSILs or higher (SQCC) with high precision and reaches sensitivity comparable to the referenced standard produced by pathologists. Based on Fisher's Least Significant Difference (LSD) test (P < 0.0001), the proposed method performs significantly better than the two state-of-the-art benchmark methods (U-Net and SegNet) in precision, F-Measure, Jaccard index. For the run time analysis, the proposed method takes only 210 seconds to process a WSI and is 20 times faster than U-Net and 19 times faster than SegNet, respectively. In summary, the proposed method is demonstrated to be able to both detect HSILs or higher (SQCC), which indicate patients for further treatments, including colposcopy and surgery to remove the lesion, and rapidly processing WSIs in seconds for practical clinical usages.
Purpose
To survey adenoid cystic carcinoma of lacrimal glands in Asian population and investigate the predictability in prognosis following the 8
th
edition American Joint Committee on Cancer (AJCC) ...staging guideline.
Study design
Retrospective study.
Methods
The clinical entities and surgical outcomes of the patients who were histologically confirmed with a diagnosis of lacrimal adenoid cystic carcinoma in National Taiwan University Hospital between January 1995 and December 2015 were retrospectively reviewed.
Results
Enrolled were 11 patients. The median follow-up was 7.2 years. Eight patients (72.7%) were diagnosed as T1 or T2 disease, and three patients (27.3%) were diagnosed as T3 or T4 disease according to the AJCC 8
th
edition guideline. Eye-sparing surgery with radiotherapy was performed in nine patients. Local recurrence was noted in six patients (54.5%) with median disease-free interval of 23.5 months. Six patients (54.5%) developed distant metastases, including lung, bone, and cranial invasions. Overall survival rate during the study period was 54.6%. Five-year overall survival was 81.8% and ten-year overall survival was 68.2%. The Log-rank test for overall survival and disease-free survival between patients with less than T3 disease (p=0.001) and patients with T3 or T4 disease (p=0.006) revealed significant differences.
Conclusion
This study highlighted the aggressive nature of adenoid cystic carcinoma of lacrimal glands. Eye-sparing surgery with adjunctive radiotherapy may achieve relatively optimal disease control in diseases staged T1 or T2, but in advanced disease metastasis and mortality are usually inevitable.
Aim
The COVID‐19 outbreak in Taiwan had a significant impact on medical services. These changes posed a threat to nurses' mental health. Resilience may protect nurses from the psychological impact of ...COVID‐19. This study aimed to understand nurses' resilience and its relationship with nurses' characteristics (life and work situations) and mental health (depression, anxiety and stress) during the outbreak.
Design
A cross‐sectional study.
Methods
This study surveyed the nurses at a hospital from 9 August 2021, to 20 August 2021. The content of the questionnaire included nurses' characteristics, resilience and mental health.
Results
There was an association between higher resilience and lower mental health problems. We also found that some nurses' characteristics were positively correlated with mental health problems.
Conclusion
Some nurses' life and work situations predicted high levels of mental health problems during the pandemic. Additionally, higher levels of resilience were associated with lower levels of mental health problems.
According to the United Nations Sustainable Development Goal (SDG) 4, “achieving inclusive and quality education for all”, foreign language learning has come to be seen as a process of integrating ...sustainable development into the socio-cultural aspects of education and learning. The aim of this study was to employ virtual reality (VR) eye tracker to examine how students with different levels of prior knowledge process visual behaviors for Japanese Mimicry and Onomatopoeia (MIO) while learning Japanese as a second foreign language. A total of 20 students studying at the Department of Applied Japanese at the university of Southern Taiwan were recruited. Based on the Japanese language proficiency test (JLPT) level, 20 participants were divided into high prior knowledge group (levels N1–N3) with 7 participants, and low prior knowledge group (level N4 or below) with 13 participants. The learning stimuli materials were created by Unreal Engine 4 (UE4) development tool to design a 3D virtual MIO paradise, including 5 theme amusement parks. Through a VR eye tracker, participants’ visual behaviors were tracked and recorded based on 24 different regions of interest (ROIs) (i.e., ROI1–ROI24). This was done to discuss the distribution of visual attention in terms of different ROIs of each theme amusement park based on four eye movement indicators, including latency of first fixation (LFF), duration of first fixation (DFF), total fixation durations (TFD), and fixation counts (FC). Each ROI of the two groups were then compared. In addition, a heat zone map was also generated to show the overall visual distribution of each group. After the experiment, based on the eye movement indicators and test scores in the pre-test and post-test phases, statistical analysis was used to examine and evaluate the differences in visual attention and learning outcomes. The results revealed that the gaze sequences of the two prior knowledge groups gazing at the ROIs in theme parks were different, except for the gaze sequence in the circus theme park. Different prior knowledge groups exhibited differences in visual attention in the ROIs fixated on in each amusement park. Additionally, in terms of TFD and FC of different groups in each amusement park, there was no significant difference except in ROI10, ROI16, and ROI18. Moreover, after receiving cognitive comprehension processes introduced in the VR-simulated MIO scenes, students from both groups achieved higher post-test scores compared with pre-test scores, and such differences had statistical significance. In conclusion, the implications of VR eye movement analysis on developing students’ competence related to learning Japanese and cross-cultural aspects, compatible with sustainable development, were presented.
Repetitive transcranial magnetic stimulation (rTMS) is the current treatment option for major depression (MD). Theta-burst stimulation (TBS), a variation of rTMS, affords a short stimulation ...duration, low stimulation pulse intensity, and possibility to improve rTMS efficiency. This systematic review and meta-analysis examined the studies on efficacy and tolerability of TBS in patients with MD.
This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature from 1990 until May 24, 2020, and performed a random-effects meta-analysis by including response and remission rates of depression and dropout rates as main outcome measures.
In total, 10 studies including 6 randomized controlled trials (RCTs; n = 294) and 4 uncontrolled clinical trials (non-RCTs; n = 297) were included. The overall effect size of response rate and remission rates were 0.38 (95% confidence interval CI: 0.29–0.48) and 0.20 (95% CI: 0.13–0.29), respectively. Notably, the TBS group showed favorable efficacy without major adverse events.
TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.
•TBS applied to the dorsolateral prefrontal cortex is associated with significant antidepressant effects and favorable tolerability.•TBS showed medium treatment effect of response rates and remission rates.•Low stimulation intensities, high number of pulses per session, short treatment periods, and iTBS might be the optimal parameters of TBS protocols.
That intensity-modulated radiotherapy (IMRT) plus antiandrogen therapy (IMRT-ADT) and radical prostatectomy (RP) are the definitive optimal treatments for relatively young patients (aged ≤ 65 years) ...with high- or very high-risk localized prostate cancer (HR/VHR-LPC), but remains controversial. We conducted a national population-based cohort study by using propensity score matching (PSM) to evaluate the clinical outcomes of RP and IMRT-ADT in relatively young patients with HR/VHR-LPC. Methods: We used the Taiwan Cancer Registry database to evaluate clinical outcomes in relatively young (aged ≤ 65 years) patients with HR/VHR-LPC, as defined by the National Comprehensive Cancer Network risk strata. The patients had received RP or IMRT-ADT (high-dose, ≥72 Gy plus long-term, 1.5–3 years, ADT). Head-to-head PSM was used to balance potential confounders. A Cox proportional hazards regression model was used to analyze oncologic outcomes. Results: High-dose IMRT-ADT had a higher risk of biochemical failure (adjusted hazard ratio aHR = 2.03, 95% confidence interval CI 1.56–2.65, p < 0.0001) compared with RP; IMRT-ADT did not have an increased risk of all-cause death (aHR = 1.2, 95% CI 0.65–2.24, p = 0.564), locoregional recurrence (aHR = 0.88, 95% CI 0.67–1.06, p = 0.3524), or distant metastasis (aHR = 1.03, 95% CI 0.56–1.9, p = 0.9176) compared with RP. Conclusion: In relatively young patients with HR/VHR-LPC, RP and IMRT-ADT yielded similar oncologic outcomes and RP reduced the risk of biochemical failure compared with IMRT-ADT.
MTX-211 is a first-in-class dual inhibitor of epidermal growth factor receptor (EGFR) and phosphoinositide-3 kinase (PI3K) signaling pathways with a compelling pharmaceutical profile and could ...enhance the effectiveness of mitogen-activated protein kinase kinase (MEK) inhibitor therapy in colorectal tumors with KRAS mutations. However, the specific mechanisms contributing to the acquired resistance to MTX-211 in human cancers remain elusive. Here, we discovered that the overexpression of the ATP-binding cassette (ABC) drug transporter ABCG2, a prevalent mechanism associated with multidrug resistance (MDR), could diminish the effectiveness of MTX-211 in human cancer cells. We showed that the drug efflux activity of ABCG2 substantially decreased the intracellular accumulation of MTX-211 in cancer cells. As a result, the cytotoxicity and effectiveness of MTX-211 in suppressing the activation of the EGFR and PI3K pathways were significantly attenuated in cancer cells overexpressing ABCG2. Moreover, the enhancement of the MTX-211-stimulated ATPase activity of ABCG2 and the computational molecular docking analysis illustrating the binding of MTX-211 to the substrate-binding sites of ABCG2 offered a further indication for the interaction between MTX-211 and ABCG2. In summary, our findings indicate that MTX-211 acts as a substrate for ABCG2, underscoring the involvement of ABCG2 in the emergence of resistance to MTX-211. This finding carries clinical implications and merits further exploration.
In recent years, the COVID-19 pandemic has led to the development of a new business model, “Live Streaming + Ecommerce”, which is a new method for commercial sales that shares the goal of sustainable ...economic growth (SDG 8). As information technology finds its way into the digital lives of internet users, the real-time and interactive nature of live streaming has overturned the traditional entertainment experience of audio and video content, moving towards a more nuanced division of labor with multiple applications. This study used a portable eye tracker to collect eye movement information from participants watching Facebook Live, with 31 participants who had experience using the live streaming platform. The four eye movement indicators, namely, latency of first fixation (LFF), duration of first fixation (DFF), total fixation durations (TFD), and the number of fixations (NOF), were used to analyze the distribution of the visual attention in each region of interest (ROI) and explore the study questions based on the ROIs. The findings of this study were as follows: (1) the fixation order of the ROIs in the live ecommerce platform differed between participants of different sexes; (2) the DFF of the ROIs in the live ecommerce platform differed among participants of different sexes; and (3) regarding the ROIs of participants on the live ecommerce platform, participants of different sexes showed the same attention to the live products according to the TFD and NOF eye movement indicators. This study explored the visual search behaviors of existing consumers watching live ecommerce and provides the results as a reference for operators and researchers of live streaming platforms.
Genome-wide association studies (GWASs) have linked RRBP1 (ribosomal-binding protein 1) genetic variants to atherosclerotic cardiovascular diseases and serum lipoprotein levels. However, how RRBP1 ...regulates blood pressure is unknown.
To identify genetic variants associated with blood pressure, we performed a genome-wide linkage analysis with regional fine mapping in the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) cohort. We further investigated the role of the RRBP1 gene using a transgenic mouse model and a human cell model.
In the SAPPHIRe cohort, we discovered that genetic variants of the RRBP1 gene were associated with blood pressure variation, which was confirmed by other GWASs for blood pressure. Rrbp1- knockout (KO) mice had lower blood pressure and were more likely to die suddenly from severe hyperkalemia caused by phenotypically hyporeninemic hypoaldosteronism than wild-type controls. The survival of Rrbp1-KO mice significantly decreased under high potassium intake due to lethal hyperkalemia-induced arrhythmia and persistent hypoaldosteronism, which could be rescued by fludrocortisone. An immunohistochemical study revealed renin accumulation in the juxtaglomerular cells of Rrbp1-KO mice. In the RRBP1-knockdown Calu-6 cells, a human renin-producing cell line, transmission electron and confocal microscopy revealed that renin was primarily retained in the endoplasmic reticulum and was unable to efficiently target the Golgi apparatus for secretion.
RRBP1 deficiency in mice caused hyporeninemic hypoaldosteronism, resulting in lower blood pressure, severe hyperkalemia, and sudden cardiac death. In juxtaglomerular cells, deficiency of RRBP1 reduced renin intracellular trafficking from ER to Golgi apparatus. RRBP1 is a brand-new regulator of blood pressure and potassium homeostasis discovered in this study.
The gut microbiota plays a critical role in chronic kidney disease (CKD) and hypertension. Trimethylamine-N-oxide (TMAO) and trimethylamine (TMA) are gut microbiota-derived metabolites, and both are ...known uraemic toxins that are implicated in CKD, atherosclerosis, colorectal cancer and cardiovascular risk. Therefore, the detection and quantification of TMAO, which is a metabolite from gut microbes, are important for the diagnosis of diseases such as atherosclerosis, thrombosis and colorectal cancer. In this study, a new “colour-switch” method that is based on the combination of a plasma separation pad/absorption pad and polyallylamine hydrochloride-capped manganese dioxide (PAH@MnO2) nanozyme was developed for the direct quantitative detection of TMAO in whole blood without blood sample pretreatment. As a proof of concept, a limit of quantitation (LOQ) of less than 6.7 μM for TMAO was obtained with a wide linear quantification range from 15.6 to 500 μM through quantitative analysis, thereby suggesting potential clinical applications in blood TMAO monitoring for CKD patients.
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