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Abstract Background Monitoring pyruvate metabolism in the spleen is important for assessing immune activity and achieving successful radiotherapy for cervical cancer due to the significance of the abscopal effect. We aimed to explore the feasibility of utilizing hyperpolarized (HP) [1-13C]-pyruvate magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to evaluate pyruvate metabolism in the human spleen, with the aim of identifying potential candidates for radiotherapy in cervical cancer. Methods This prospective study recruited six female patients with cervical cancer (median age 55 years; range 39–60) evaluated using HP [1-13C]-pyruvate MRI/MRS at baseline and 2 weeks after radiotherapy. Proton (1H) diffusion-weighted MRI was performed in parallel to estimate splenic cellularity. The primary outcome was defined as tumor response to radiotherapy. The Student t-test was used for comparing 13C data between the groups. Results The splenic HP [1-13C]-lactate-to-total carbon (tC) ratio was 5.6-fold lower in the responders than in the non-responders at baseline (p = 0.009). The splenic [1-13C]-lactate-to-tC ratio revealed a 1.7-fold increase (p = 0.415) and the splenic [1-13C]-alanine-to-tC ratio revealed a 1.8-fold increase after radiotherapy (p = 0.482). The blood leukocyte differential count revealed an increased proportion of neutrophils two weeks following treatment, indicating enhanced immune activity (p = 0.013). The splenic apparent diffusion coefficient values between the groups were not significantly different. Conclusions This exploratory study revealed the feasibility of HP [1-13C]-pyruvate MRS of the spleen for evaluating baseline immune potential, which was associated with clinical outcomes of cervical cancer after radiotherapy. Trial registration ClinicalTrials.gov NCT04951921 , registered 7 July 2021. Relevance statement This prospective study revealed the feasibility of using HP 13C MRI/MRS for assessing pyruvate metabolism of the spleen to evaluate the patients’ immune potential that is associated with radiotherapeutic clinical outcomes in cervical cancer. Key points • Effective radiotherapy induces abscopal effect via altering immune metabolism. • Hyperpolarized 13C MRS evaluates patients’ immune potential non-invasively. • Pyruvate-to-lactate conversion in the spleen is elevated following radiotherapy. Graphical Abstract

Abstract Background Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18F‐fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. Methods Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III‐IVA or stage I–II with positive pelvic or para‐aortic lymph node (PALN) on PET/CT from AGOG09‐001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer‐specific survival (CSS) using multivariate Cox regression. Results Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p

Abstract Background Older patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non‐small cell cancer (NSCLC) in Taiwan. Methods This study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan–Meier survival curves were drawn. Results A total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan–Meier survival curves showed significant differences across the three treatment options (log‐rank p

Edoxaban, a once-daily, direct-acting oral anticoagulant, is approved to prevent stroke or systemic embolism in non-valvular atrial fibrillation (NVAF) and treat venous thromboembolism. The clinical benefit of edoxaban for stroke prevention in Asian patients with NVAF has been demonstrated in clinical and real-world studies. We share early clinical experiences with once-daily edoxaban and discuss its evidence-based use in patients with NVAF in Southeast Asia through several cases of patients at high risk, including frail patients, elderly patients with multiple comorbidities and patients with increased bleeding risk. These cases demonstrate the effectiveness and safety of once-daily edoxaban in patients with NVAF in Southeast Asia.

Research trend analysis gives the research community an essential chance to learn the past to support sustainable development. The topic of evolution analysis presents a chance to position the current research, linkages among research topics, and identify the research gap. In this study, the authors revisit a known mechanism, namely Girvan-Newman (GN) algorithm, and propose a new approach for research topic analysis. Based on the GN algorithm, author-keywords analysis approach, one-mode cluster, and duo GN algorithm analysis were suggested and applied to research topic analysis of Library and Information Science studies. The results show that the suggested approach could process major quantity materials and be able to avoid the possible distorted results gained by taking the small size of samples, or two-mode cluster, to ensure the validity of the results. The topics’ hierarchy structure also suggests a different approach that could be used to deconstruct the linkages among research topics for future study.

Psoriatic disease is a chronic inflammatory disorder with skin and joint manifestations. Due to the persistent inflammatory state exhibited by patients with psoriasis, multiple systemic comorbidities occur more frequently in patients with psoriasis than in the general population, and the risk of cardiovascular (CV) diseases is significantly increased. As the pathophysiology of psoriatic disease is becoming better understood, the sharing of underlying pathogenic mechanisms between psoriatic and CV diseases is becoming increasingly apparent. Consequently, careful attention to CV comorbidities that already exist or may potentially develop is needed in the management of patients with psoriasis, particularly in the screening and primary prevention of CV disease and in treatment selection due to potential drug–drug and drug-disease interactions. Furthermore, as the use of effective biologic therapy and more aggressive oral systemic treatment for psoriatic disease is increasing, consideration of the potential positive and negative effects of oral and biologic treatment on CV disease is warranted. To improve outcomes and quality of care for patients with psoriasis, the Taiwanese Dermatological Association, the Taiwanese Association for Psoriasis and Skin Immunology, and the Taiwan Society of Cardiology established a Task Force of 20 clinicians from the fields of dermatology, cardiology, and rheumatology to jointly develop consensus expert recommendations for the management of patients with psoriatic disease with attention to CV comorbidities.

BackgroundThe risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.MethodsThe database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death.ResultsPatients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20–8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30–3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases.ConclusionsThe machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.

Abstract Background The risk of ischemic heart disease (IHD) due to the impact of gonadotropin‐releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy. Methods Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new‐onset IHD diagnosis, death, or December 31, 2018. A Kaplan–Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD. Results A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan–Meier survival curves showed a significant difference between patients with and without GnRH therapy (log‐rank p

Key points 1. Transfer learning (TL) improves performance of tumor segmentation on diffusion-weighted imaging (DWI) especially in limited case numbers. 2. Training a model by combining sufficient data of different cancers exhibited the highest performance for segmenting mixed cervical and uterine datasets and also improved the pretrained cervical model. 3. The TL model with fine-tuning the early layers of the encoder part outperformed those by fine-tuning the other layers.

Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0–89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8–170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10–0.71) or chemotherapy (HR 0.41, 95% CI: 0.24–0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15–0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67–9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.

Although it is commonly considered that, in birds, there is a trend towards reduced dentition, teeth persisted in birds for 90 Ma and numerous macroscopic morphologies are observed. However, the extent to which the microstructure of bird teeth differs from other lineages is poorly understood. To explore the microstructural differences of the teeth of birds in comparison with closely related non-avialan dinosaurs, the enamel and dentine-related features were evaluated in four Mesozoic paravian species from the Yanliao and Jehol biotas. Different patterns of dentinal tubular tissues with mineralized extensions of the odontoblast processes were revealed through the examination of histological sectioning under electron microscopy. Secondary modification of the tubular structures, forming reactive sclerotic dentin of Longipteryx, and the mineralization of peritubular dentin of Sapeornis were observed in the mantle dentin region. The new observed features combined with other dentinal-associated ultrastructure suggest that the developmental mechanisms controlling dentin formation are quite plastic, permitting the evolution of unique morphologies associated with specialized feeding behaviours in the toothed birds. Proportionally greater functional stress placed on the stem bird teeth may have induced reactive dentin mineralization, which was observed more often within tubules of these taxa. This suggests modifications to the dentin to counteract potential failure.

The circulation of money in the global pharmaceutical market is substantial and has been increasing annually. Moreover, the high requirements for new drugs and the procedures for verifying the quality of drugs are increasingly complex; thus, successful drug research and development are critical for drug companies. To identify fluctuations in stock prices during the drug research and development process, the event study model is adopted to capture abnormal returns in Pfizer stock resulting from the public announcement of various relevant events. The study aims to (a) examine whether events publicized by official databases or the media during drug research and development affect Pfizer’s stock price; (b) examine whether these events affect the stock price of Pfizer’s competitors; and (c) compare price fluctuations around the dates of these events. The event data are collected from official databases, including the US Food and Drug Administration’s Orange Book; clinicaltrials.gov; Web of Science; and media sources, such as the Wall Street Journal. The collected data span from the first date in each data source to December 31, 2018. The results reveal that Pfizer’s stock price is affected by drug approval dates and trial judgment dates prior to media reports. However, the stock prices of other competitors are not correlated with Pfizer’s stock price. Notably, a time gap between reporting from the Wall Street Journal and other data sources is identified. The results of this study can be useful for investors in the global stock market and for pharmaceutical companies exploring resource allocation in drug research and development strategies.

IntroductionAnaplastic lymphoma kinase (ALK) fusion mutation is more common in younger and never-smoking lung cancer patients. The association of smoking and ALK-tyrosine kinase inhibitors (TKIs) on overall survival (OS) of treatment-naïve ALK-positive advanced lung adenocarcinoma remains unclear in real-world.MethodsThis retrospective study evaluated all 33170 lung adenocarcinoma patients registered in the National Taiwan Cancer Registry from 2017 to 2019, of whom 9575 advanced stage patients had ALK mutation data.ResultsAmong the 9575 patients, 650 (6.8%) patients had ALK mutation with the median follow-up survival time 30.97 months (median age, 62 years; 125 [19.2%] were aged ≥75 years; 357 (54.9%) females; 179 (27.5) smokers, 461 (70.9%) never-smokers, 10 (1.5%) with unknown smoking status; and 544 (83.7%) with first-line ALK-TKI treatment). Overall, of 535 patients with known smoking status who received first-line ALK-TKI treatment, never-smokers and smokers had a median OS of 40.7 months (95% confidence interval (CI), 33.1-47.2 months) and 23.5 months (95% CI, 11.5-35.5 months) (P=0.015), respectively. Among never-smokers, those who received first-line ALK-TKI treatment had a median OS of 40.7 months (95% CI, 22.7-57.8 months), while those ALK-TKI not as first-line treatment had a median OS of 31.7 months (95% CI, 15.2-42.8 months) (P=0.23). In smokers, the median OS for these patients was 23.5 months (95% CI, 11.5-35.5 months) and 15.6 months (95% CI, 10.2-21.1 months) (P=0.026), respectively.Conclusions and relevanceFor patients with treatment-naïve advanced lung adenocarcinoma, the ALK test should be performed irrespective of smoking status and age. Smokers had shorter median OS than never-smokers among treatment-naïve-ALK-positive patients with first-line ALK-TKI treatment. Furthermore, smokers not receiving first-line ALK-TKI treatment had inferior OS. Further investigations for the first-line treatment of ALK-positive smoking advanced lung adenocarcinoma patients are needed.

BackgroundLeft ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.MethodsThis retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF

IntroductionAs one of the megadiverse countries, the effectiveness of wildlife protection in China is of great significance to global biodiversity conservation. With continued evolution and revisions, China’s Wildlife Protection Law has listed over 140 marine species; however, it is still inclined toward terrestrial animals.MethodsTo narrow the gap between compliance and enforcement, we collected 1,309 effective responses from various coastal cities of China through an anonymous online questionnaire survey, to investigate their exposure, understanding and attitudes toward Wildlife Protection Law for marine species (mWPL).ResultsMost respondents demonstrated an overall good understanding about the context, necessity and effectiveness of mWPL. The fisher communities were found to be more aware of the dissemination and implementation of mWPL. However, they understood less of the penal system, and exhibited negative attitudes toward the necessity and punishment of the legislation, probably due to the conflicts between resource utilizations and legislative interventions. The participants also indicated that seahorses, horseshoe crabs and corals were commonly subjected to illegal exploitations.DiscussionWhile most respondents suggested greater fines, tighter laws and better public enforcement, we advocate the exploration of bottom-up options such as community engagement and environmental education to improve compliance and implementation of mWPL for the benefit of marine wildlife conservation in China.

Background/Purpose: Genetic and environmental factors play significant roles in the pathogenesis of Parkinson's disease (PD). Recently, 17 novel risk loci of PD were identified in a meta-analysis of genome-wide association study (GWAS) in the European populations. In order to clarify if these risk loci are associated with PD in Taiwanese population, we conducted a case–control study including 14 of the novel risk loci and analyzed the genetic distribution and allele frequency. Methods: A total of 2798 subjects were recruited in this study. Genotyping was performed in 672 PD patients and 609 healthy controls by using Mass ARRAY, and data of another 1517 healthy controls from Taiwan Biobank were also examined. Results: Our results show that the dominant models of ITPKB rs4653767 (OR (95% CI) = 0.832 (0.699, 0.990), p = 0.038), IL1R2 rs34043159 (OR (95% CI) = 0.812 (0.665, 0.992), p = 0.041) and COQ7 rs11343 (OR (95% CI) = 0.304 (0.180, 0.512), p

Background/Purpose: The present study was designed to evaluate the local cardiology infrastructure and services for heart failure (HF) care in Taiwan hospitals and to compare the HF care with the hospitals in European countries. Methods: Available data from a total of 98 medical centers and regional hospitals in Taiwan were analyzed. Each facility was given a single copy of the questionnaire between September and December 2019, and service records were extracted from the National Health Insurance Database. European data were adopted from the 2017 European Society of Cardiology Atlas. Results: The number of cardiologists per million populations in Taiwan was 57.4, and it was lower than the European median (72.8). The median percentages of interventional and electrophysiologists among cardiologists were 64% and 15% in Taiwan, which were both higher than the European median values (12% and 5%, respectively). The accessibility rates to implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) in Taiwan were both higher (3.4 and 3.0 centers per million populations) comparing to those in European countries (median 1.6 and 1.5 centers per million populations). Comparing to 67 hospitals without HF care teams in Taiwan, 31 hospitals (31.6%) with HF teams have significantly more cardiology staff, enhanced procedural capabilities with more alternatives on oral or intravenous HF relevant medications. Conclusion: Our analysis clearly demonstrated discrepancies in cardiology subspecialties and CRT/ICD accessibilities between European countries and Taiwan. Variations in HF-focused services and facilities plus HF-directed medications have demonstrated significant differences among Taiwanese hospitals with or without HF care team.

Objective A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson’s disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling. Methods A total of 2,418 individuals were enrolled in our Taiwanese cohort for analysis of the genotypic and allelic frequency. Polymerase chain reaction–restriction fragment length polymorphism analysis was employed for rs13337493 genotyping, and the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA) was used for rs758033 and rs2361988 genotyping in 672 patients with PD and 392 controls. Taiwan Biobank data of another 1,354 healthy controls were subjected to whole-genome sequencing performed using Illumina platforms at approximately 30× average depth. Results Our results revealed that rs758033 {odds ratios [OR] (95% confidence interval [CI]) = 0.267 [0.064, 0.795], p = 0.014} was associated with the risk of PD, and there was a trend toward a protective effect of rs2361988 (OR [95% CI] = 0.296 [0.071, 0.884], p = 0.026) under the recessive model. The TT genotype of rs758033 (OR [95% CI] = 0.271 [0.065, 0.805], p = 0.015) and the CC genotype of rs2361988 (OR [95% CI] = 0.305 [0.073, 0.913], p = 0.031) were less common in the PD group than in the non-PD group. Conclusion Our findings indicate that the rs758033 and rs2361988 polymorphisms of AXIN1 may affect the risk of PD in the Taiwanese population.

Purpose: To investigate the prognostic factors and impact of adjuvant treatment on uterine carcinosarcoma (UCS). Methods: A retrospective review of UCS patients treated between 2005 and 2019 was conducted. International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system was used. Multivariate stepwise Cox proportional hazard regression models were used to identify the independent predictors of overall survival (OS) and progression-free survival (PFS). Results: A total of 138 patients were eligible for descriptive analysis. Excluding 12 patients without surgery, 126 patients with adequate clinicopathologic data were included for prognostic analysis. The median follow-up for survivors was 51.8 months. 5-year OS and PFS rates for FIGO stage I, II, III, IV were 64.5% and 51.8%, 60.8% and 57.7%, 47.7% and 45.9%, 5.1% and 4.1%, respectively. By multivariate analysis, six models each for PFS and OS were formulated including highly correlated variables alternatively. Adjuvant chemoradiation was consistently selected as an independent prognostic factor for OS (hazard ratio [HR] 0.10–0.22, all p

Abstract Background To examine the association between teeth loss and nasogastric tube feeding dependency in older people. Methods The National Health Interview Survey (NHIS) 2005, 2009, and 2013 in Taiwan. Participants were selected by a multistage stratified sampling method and baseline characteristics, including socioeconomic status and health habits, were obtained by well-trained interviewers. The NHIS was linked with the National Health Insurance research database 2000–2016 and the National Deaths Dataset, which contains all the medical information of ambulatory and inpatient care. Cox regression was used to examine the association between the number of teeth lost and nasogastric tube feeding dependency. Results There were 6165 adults older than 65 years old enrolled in the analysis, with 2959 male (48%) and the mean (SD) age was 73.95(6.46) years old. The mean follow-up duration was 6.5(3.3) years. Regarding the teeth loss categories, 1660 (26.93%), 2123 (34.44%), and 2382 (38.64%) of participants were categorized as having no teeth loss, loss of 1–9 teeth, and loss of 10–28 teeth, respectively. During 39,962 person-years of follow-up, new-onset nasogastric feeding dependency was recognized in 220(13.25%), 256(12.06%), and 461(19.35%) participants who were categorized as having no teeth loss, loss of 1–9 teeth, and loss of 10–28 teeth, respectively. Kaplan-Meier curves demonstrated significant findings (Log-rank P

Background An enhanced understanding of larval ecology is fundamental to improve the management of locally depleted horseshoe crab populations in Asia. Recent studies in the northern Beibu Gulf, China demonstrated that nesting sites of Asian horseshoe crabs are typically close to their nursery beaches with high-density juveniles distributed around mangrove, seagrass and other structured habitats. Methods A laboratory Y-maze chamber was used to test whether the dispersal of early-stage juvenile tri-spine horseshoe crab Tachypleus tridentatus is facilitated by chemical cues to approach suitable nursery habitats. The juvenile orientation to either side of the chamber containing controlled seawater or another with various vegetation cues, as well as their movement time, the largest distance and displacement were recorded. Results The juveniles preferred to orient toward seagrass Halophila beccarii cues when the concentration reached 0.5 g l−1, but ceased at 2 g l−1. The results can be interpreted as a shelter-seeking process to get closer to the preferred settlement habitats. However, the juveniles exhibited avoidance behaviors in the presence of mangrove Avicennia marina and invasive saltmarsh cordgrass Spartina alterniflora at 2 g l−1. The juveniles also spent less time moving in the presence of the A. marina cue, as well as reduced displacement in water containing the S. alterniflora cue at 1 and 2 g l−1. These results may explain the absence of juvenile T. tridentatus within densely vegetated areas, which have generally higher organic matter and hydrogen sulfide. Conclusion Early-stage juvenile T. tridentatus are capable of detecting and responding to habitat chemical cues, which can help guide them to high-quality settlement habitats. Preserving and restoring seagrass beds in the intertidal areas should be prioritized when formulating habitat conservation and management initiatives for the declining horseshoe crab populations.

Objective: Recurrent cervical cancer is hard to treat when occurring in a previous radiated area and unresectable or distant metastasis. We present three such cases who achieved complete remission (CR) after chemoradiotherapy and pembrolizumab. Case Report: Case 1 was diagnosed with cervical adenocarcinoma, stage IVB. She obtained CR after concurrent chemoradiotherapy (CCRT) and post-CCRT adjuvant chemotherapy and bevacizumab. Recurrence at previous irradiated sacral bone was controlled with pembrolizumab and CCRT using proton therapy (PT). Case 2 was diagnosed with stage IVB squamous cell carcinoma. First recurrence occurred at inguinal lymph node (LN). Secondary recurrence occurred at paraaortic LN ten years later. PT with chemotherapy and pembrolizumab achieved CR. Case 3 had a small cell carcinoma (stage IVB) with bone metastasis. She had CR to CCRT with etoposide-cisplatin. Liver metastasis was salvaged with CCRT and pembrolizumab. Conclusion: CCRT with pembrolizumab is potentially curative for recurrent cervical cancer conventionally amenable for palliation.

Visual disabilities affect more than 250 million people, with 43 million suffering from irreversible blindness. The eyes are an extension of the central nervous system which cannot regenerate. Neural tissue engineering is a potential method to cure the disease. Injectability is a desirable property for tissue engineering scaffolds which can eliminate some surgical procedures and reduce possible complications and health risks. We report the development of the anisotropic structured hydrogel scaffold created by a co-injection of cellulose nanofiber (CNF) solution and co-polypeptide solution. The positively charged poly (L-lysine)-r-poly(L-glutamic acid) with 20 mol% of glutamic acid (PLLGA) is crosslinked with negatively charged CNF while promoting cellular activity from the acid nerve stimulate. We found that CNF easily aligns under shear forces from injection and is able to form hydrogel with an ordered structure. Hydrogel is mechanically strong and able to support, guide, and stimulate neurite growth. The anisotropy of our hydrogel was quantitatively determined in situ by 2D optical microscopy and 3D X-ray tomography. The effects of PLLGA:CNF blend ratios on cell viability, neurite growth, and neuronal signaling are systematically investigated in this study. We determined the optimal blend composition for stimulating directional neurite growth yielded a 16% increase in length compared with control, reaching anisotropy of 30.30% at 10°/57.58% at 30°. Using measurements of calcium signaling in vitro, we found a 2.45-fold increase vs. control. Based on our results, we conclude this novel material and unique injection method has a high potential for application in neural tissue engineering.

Anode-free lithium metal battery is one of the most promising candidates for next-generation high energy density battery but suffer from poor cycle life. Here the authors present an integrated protocol to dissect and quantify the irreversible coulombic efficiencies for better understanding of the battery.

Abstract Objectives To investigate the prognostic value of the preoperative systemic immune‐inflammation index (SII) in patients with oral cavity squamous cell carcinoma (OC‐SCC) treated with curative surgery followed by adjuvant radiotherapy (RT) or chemoradiotherapy (CCRT). Materials and Methods We retrospectively reviewed the clinical records of patients with OC‐SCC who received surgery and postoperative adjuvant RT/CCRT between January 2005 and December 2012. Blood samples were drawn in the 2 weeks preceding surgery. SII was calculated by multiplying the absolute neutrophil and platelet counts, and then, divided by the absolute lymphocyte count, and its optimal cutoff value was identified using the Youden’s index. The study endpoints included overall survival (OS), local control (LC), regional control (RC), and distant control (DC). Results The study sample consisted of 993 patients (58.8% of them treated with CCRT). The optimal cutoff value for SII was 810.6. A total of 347 (34.9%) study participants had high preoperative SII values. After allowance for potential confounders in multivariable analysis, high SII values were independently associated with less favorable DC (adjusted hazard ratio [HR] = 1.683, p = 0.001) and OS (adjusted HR = 1.466, p

Abstract Single-session stereotactic radiosurgery (SSRS) is recognized as a safe and efficient treatment for meningioma. We aim to compare the long-term efficacy and safety of fractionated stereotactic radiotherapy (FSRT) with SSRS in the treatment of grade I meningioma. A total of 228 patients with 245 tumors treated with radiosurgery between March 2006 and June 2017were retrospectively evaluated. Of these, 147 (64.5%) patients were treated with SSRS. The remaining 81 patients (35.5%) were treated with a fractionated technique. Protocols to treat meningioma were classified as 12–16 Gy per fraction for SSRS and 7 Gy/fraction/day for three consecutive days to reach a total dose of 21 Gy for FSRT. In univariate and multivariate analyses, tumor volume was found to be associated with local control rate (hazard ratio = 4.98, p = 0.025). The difference in actuarial local control rate (LCR) between the SSRS and FSRT groups after propensity score matching (PSM) was not statistically significant during the 2-year (96.86% versus 100.00%, respectively; p = 0.175), 5-year (94.76% versus 97.56%, respectively; p = 0.373), and 10-year (74.40% versus 91.46%, respectively; p = 0.204) follow-up period. FSRT and SSRS were equally well-tolerated and effective for the treatment of intracranial benign meningioma during the10-year follow-up period.

Cr and Mn play intriguing roles in determining the magnetic properties of CoFeNi-based high-entropy alloys (HEA). In this study, we tune the stoichiometric Mn composition to systematically explore the magnetic properties of (CoCrFeNi)1−xMnx HEAs. We observe a change from ferro-to ferrimagnetism due to the incorporation of Mn atoms into the CoCrFeNi HEA. In addition, we measure an 81% reduction in magnetization with the incorporation of 7.6 (2)% Mn atoms. Such a significant reduction in magnetization cannot be solely explained by the effect of the inversed moments on the Mn atoms. Hence, we propose a mechanism whereby the Mn atoms flip the moments of neighboring atoms, which results in the magnetization reduction observed in the CoFeNi-based HEAs.

Abstract Background Tooth morphology within theropod dinosaurs has been extensively investigated and shows high disparity throughout the Cretaceous. Changes or diversification in feeding ecology, i.e., adoption of an herbivorous diet (e.g., granivorous), is proposed as a major driver of tooth evolution in Paraves (e.g., Microraptor, troodontids and avialans). Here, we studied the microscopic features of paravian non-avian theropod and avialan teeth using high-spatial-resolution synchrotron transmission X-ray microscopy and scanning electron microscopy. Results We show that avialan teeth are characterized by the presence of simple enamel structures and a lack of porous mantle dentin between the enamel and orthodentin. Reduced internal structures of teeth took place independently in Early Cretaceous birds and a Microraptor specimen, implying that shifts in diet in avialans from that of closely related dinosaurs may correlate with a shift in feeding ecology during the transition from non-avian dinosaurs to birds. Conclusion Different lines of evidence all suggest a large reduction in biting force affecting the evolution of teeth in the dinosaur-bird transition. Changes in teeth microstructure and associated dietary shift may have contributed to the early evolutionary success of stemward birds in the shadow of other non-avian theropods.

Background/purpose: Ovarian clear cell carcinoma (OCCC) with recurrence/progression after treatment has dismal prognosis. We aimed to investigate the management and outcomes of such patients. Methods: OCCC patients who were treated between 2000 and 2013 with cancer recurrence or progression after primary treatment were analyzed. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Results: A total of 64 patients experienced treatment failure (49 recurred after remission and 15 progressed without remission). The 5-year CSS rates of recurrent/progressive OCCC patients were 22.9% (progression group: median CSS 5.9 months [range, 0.8–25.2] vs recurrence group: 43.6 months [range, 7.1–217.8]; p 12 months (HR: 0.22–0.40, p = 0.001 and p = 0.023), CA125

The Okhotsk Sea, which connects the high latitude Asian continent and the North Pacific, plays an important role in modern and past climate changes due to seasonal sea ice coverage and as a precursor of the North Pacific Intermediate Water. The long-term glacial-interglacial changes of sea ice coverage and its impacts on terrigenous transport and surface primary productivity in the Okhotsk Sea remain, however, not well constrained. Base on the paleomagnetic, rock magnetic, micropaleontological (diatom), and geochemical studies of the marine sediment core MD01-2414 (53°11.77′N, 149°34.80′E, water depth: 1,123 m) taken in the central Okhotsk Sea, we reconstruct the terrigenous sediment transport and paleoceanographic variations during the past 1550 thousand years (kyr). Seventeen geomagnetic excursions are identified from the paleomagnetic directional record. Close to the bottom of the core, an excursion was observed, which is proposed to be the Gilsa event ∼1550 thousand years ago (ka). During glacial intervals, our records reveal a wide extension of sea ice coverage and low marine productivity. We observed ice-rafted debris from mountain icebergs composed of coarse and high magnetic terrigenous detritus which were derived from the Kamchatka Peninsula to the central Okhotsk basin. Still during glacial intervals, the initiation (i.e., at ∼900 ka) of the Mid-Pleistocene Transition marks the changes to even lower marine productivity, suggesting that sea-ice coverage became larger during the last 900 ka. During interglacial intervals, the central Okhotsk Sea was either devoid of sea-ice or the ice was at best seasonal; resulting in high marine productivity. The weaker formation of Okhotsk Sea Intermediate Water, lower ventilation, and microbial degradation of organic matter depleted the oxygen concentration in the bottom water and created a reduced environment condition in the sea basin. The freshwater supplied by snow or glacier melting from Siberia and Kamchatka delivered fine grain sediments to the Okhotsk Sea. During the stronger interglacial intervals after the Mid-Brunhes Transition (i.e., Marine Isotope Stages 1, 5e, 9, and 11), strong freshwater discharges from Amur River drainage area are in association with intensified East Asian Summer Monsoon. This process may have enhanced the input of fine-grained terrigenous sediments to the central Okhotsk Sea.

As the technology of Internet of Things (IoT) becomes popular, the number of sensor nodes also increases. The network coverage, extensibility, and reliability are also the key points of technical development. To address the challenge of environmental restriction and deployment cost, most sensor nodes are powered by batteries. Therefore, the low-power consumption becomes an important issue because of the finite value of battery capacity. In addition, significant interference occurs in the environment, thereby complicating reliable wireless communication. This study proposes a fuzzy-based adaptive data rate for the transmission power control in wireless sensor networks to balance the communication quality and power consumption. The error count and error interval perform the inputs of a fuzzy system and the corresponding fuzzy system output is guard that is utilized for limiting the upper bounds of data rate and transmission power. The long-term experimental results are introduced to demonstrate that the control algorithm can overcome environmental interference and obtain low-power performance. The sensor nodes have reliable communication under an ultra-low-power consumption. The experimental results show that the total power consumption of the proposed approach has been improved 73% compared with the system without executing the algorithm and also indicate the Packet Error Rate (PER) is close to 1%. Therefore, the proposed method is suitable for the battery supply IoT system.

Stereotactic radiosurgery (SRS) is generally considered a substitute for cranial cavernous malformations (CCMs). However, prognostic factors for post-radiosurgery CCM rebleeding and adverse radiation effects have not been well evaluated, and the effect of timing and optimal treatment remains controversial. Therefore, this study evaluated prognostic factors for post-radiosurgical rebleeding and focal edematous changes in 30 patients who developed symptomatic intracranial hemorrhage due to solitary non-brainstem CCM and received linear accelerator (LINAC) SRS in a single medical center from October 2002 to June 2018. An overall post-radiosurgical annual hemorrhage rate with 4.5% was determined in this study. In addition, a higher marginal dose of >1600 centigray and earlier LINAC SRS intervention were correlated with a significantly lower post-radiosurgical annual hemorrhage rate. A lesion size larger than 3 cm3 and a coexisting developmental venous anomaly were significant risk factors for post-radiosurgical focal brain edema but mostly resulted in no symptoms and were temporary. This study demonstrated the efficacy of LINAC SRS in preventing CCM rebleeding and suggests that earlier radiosurgery treatment with a higher dose for non-brainstem symptomatic CCMs be considered.

Wind energy is becoming a common source of renewable energy in the world. Wind turbines are increasing in number, both for onshore and offshore applications. One challenge with wind turbines is in detecting anomalies that cause their breakdown. Due to the complex nature of the wind turbine assembly, it is quite an extensive process to detect causes of malfunctions in the system. This study uses the Mahalanobis distance (MD) to detect anomalies in wind turbine operation, using SCADA alarm data as a comparison. Different predictive models were generated as the bases for analyses in MD computations. Using the SCADA alarm data as a reference, trend patterns that deviated from the threshold value were compared. Results showed that the MD could be used to detect anomalies within a group of data sets, with behaviors learned based on the model used. A large portion of those data sets deviated from the threshold level, corresponding to serious alarms in the SCADA data. We concluded that the MD can detect anomalies in different wind turbine components, based on this study. MD analysis of models can be used in conditions monitoring systems of wind turbines.

The disease burden of AF is greater in Asia-Pacific than other areas of the world. Direct oral anticoagulants (DOACs) have emerged as effective alternatives to vitamin K antagonists (VKA) for preventing thromboembolic events in patients with AF. The Asian Pacific Society of Cardiology developed this consensus statement to guide physicians in the management of AF in Asian populations. Statements were developed by an expert consensus panel who reviewed the available data from patients in Asia-Pacific. Consensus statements were developed then put to an online vote. The resulting 17 statements provide guidance on the assessment of stroke risk of AF patients in the region, the appropriate use of DOACs in these patients, as well as the concomitant use of DOACs and antiplatelets, and the transition to DOACs from VKAs and vice versa. The periprocedural management of patients on DOAC therapy and the management of patients with bleeding while on DOACs are also discussed.