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In this work, we propose a self-supervised multi-agent system that meets the online learning of clustering tasks for video behavior recognition spatio-temporal tasks. Encoding visual behavioral actions as discrete temporal sequence(DTS). Real-time clustering recognition task in a multi-agent system for continuous model building, training, and correction. Finally, we implemented a fully decentralized multi-agent system and completed its feasibility verification in a surveillance video application scenario on vehicle path clustering.

The use of technologies to enhance human and animal perception has been explored in pioneering research about artificial life and biohybrid systems. These attempts have revealed that augmented sensing abilities can emerge from new interactions between individuals within or across species. Nevertheless, the diverse effects of different augmented capabilities have been less examined and compared. In this work, we built a human–fish biohybrid system that enhanced the vision of the ornamental fish by projecting human participants onto the arena background. In contrast, human participants were equipped with a mixed-reality device, which visualized individual fish trails (representing situation-oriented perceptions) and emotions (representing communication-oriented perceptions). We investigated the impacts of the two enhanced perceptions on the human side and documented the perceived effects from three aspects. First, both augmented perceptions considerably increase participants’ attention toward ornamental fish, and the impact of emotion recognition is more potent than trail sense. Secondly, the frequency of human–fish interactions increases with the equipped perceptions. The mood recognition ability on the human side can indirectly promote the recorded positive mood of fish. Thirdly, most participants mentioned that they felt closer to those fish which had mood recognition ability, even if we added some mistakes in the accuracy of mood recognition. In contrast, the addition of trail sensing ability does not lead to a similar effect on the mental bond. These findings reveal several aspects of different perceived effects between the enhancements of communication-oriented and situation-oriented perceptions.

Po-Ching Huang,1 Ching-Hsia Hung,1,2 Guan-Wei Chen,3 Ciaran Cashin,3 Mark D Griffiths,4 Wen-Chi Yang5,6 *, Hsiao-Wen Wang3 *, Chung-Ying Lin1,7– 9*, Nai-Ying Ko10 1Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 3Department of Hydraulic and Ocean Engineering, College of Engineering, National Cheng Kung University, Tainan, Taiwan; 4International Gaming Research Unit, Psychology Department, Nottingham Trent University, Nottingham, UK; 5Division of Hematology and Medical Oncology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 6Faculty of School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Biostatistics Consulting Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Occupational Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 9Department of Public Health, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 10Department of Nursing, College of Medicine, National Cheng Kung University, Tainan, Taiwan*These authors contributed equally to this workCorrespondence: Chung-Ying Lin, Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, 1 University Rd, Tainan, 701, Taiwan, Tel +886 6-2353535 ext. 5106, Fax +886 6-2367981, Email cylin36933@gmail.comPurpose: The duties related to COVID-19 control and prevention may have caused psychological stress for the individuals in charge (eg, frontline government workers) and have reportedly led to mental health issues, such as insomnia and post-traumatic stress disorder (PTSD). However, the prevalence of these COVID-19-related disorders and their associated factors remain unclear. Therefore, the purpose of the present study was to investigate the prevalence rates of insomnia, PTSD, COVID-19-related self-stigma, and smartphone addiction, along with the identification of risk factors and protective factors for Taiwan frontline government workers with COVID-19 pandemic control duties.Methods: The survey was carried out with 151 participants between September and October 2021. All participants completed the Fear of COVID-19 Scale (assessing fear of COVID-19), Self-Stigma Scale (assessing self-stigma during the COVID-19 pandemic), Smartphone Application-Based Addiction Scale (assessing the risk of smartphone addiction), Insomnia Severity Index (assessing insomnia), Impacts of Event Scale-6 (assessing PTSD), and a self-designed set of questions assessing trait resilience.Results: The results showed that the prevalence rate was 31.1% for insomnia and 33.8% for PTSD. Furthermore, service duration (adjusted odds ratio [AOR] = 0.93; 95% confidence interval [CI] = 0.86, 0.999) and trait resilience (AOR = 0.19; 95% CI = 0.08, 0.46) were protective factors and fear of COVID-19 (AOR = 1.91; 95% CI = 1.02, 3.57) was a risk factor for insomnia. Fear of COVID-19 (AOR = 2.63; 95% CI = 1.35, 5.14), self-stigma (AOR = 3.62; 95% CI = 1.19, 11.02), and smartphone addiction (AOR = 1.09, 95% CI = 1.001, 1.19) were risk factors, and trait resilience was a protective factor (AOR = 0.58; 95% CI = 0.29, 1.17) for PTSD.Conclusion: The findings demonstrated a high prevalence of insomnia and PTSD. Risk-reducing strategies and protective factor promotion strategies are recommended to help reduce the symptoms of insomnia and PTSD among Taiwan frontline government workers.Keywords: mental health, insomnia, post-traumatic stress disorder, smartphone addiction, village officer

Self-stigma is prevalent in individuals with psychiatric disorders and can profoundly affect people. A unified assessment with sound psychometric properties is needed for evaluating self-stigma across psychiatric conditions. The aim of this study was to examine the psychometric properties of the Self-Stigma Scale-Short version (SSS-S) using Rasch modeling. Six-hundred and twelve participants with substance use disorders (n = 319), attention-deficit/hyperactivity disorder (n = 100), and schizophrenia (n = 193) completed the SSS-S. Rasch results confirmed the unidimensionality of the nine items of the SSS-S. The four-point Likert scale of the SSS-S reflected monotonical increases along the self-stigma continuum. No ceiling or floor effects were detected. Among the three subdomains of the SSS-S, cognitive items appeared to be the most robustly endorsed, and behavioral items were the least endorsed. Two items in the SSS-S displayed differential item functioning across the three diagnoses. Additionally, SSS-S scores showed weak to moderate correlation with depression, anxiety, and stress scale scores. The SSS-S had overall satisfactory psychometric properties. Healthcare professionals may use this assessment to assess self-stigma in multiple psychiatric groups, and information gained may facilitate improved care.

In parameter learning, a partial interpretation most often contains information about only a subset of the parameters in the program. However, standard EM-based algorithms use all interpretations to learn all parameters, which significantly slows down learning. To tackle this issue, we introduce EMPLiFI, an EM-based parameter learning technique for probabilistic logic programs, that improves the efficiency of EM by exploiting the rule-based structure of logic programs. In addition, EMPLiFI enables parameter learning of multi-head annotated disjunctions in ProbLog programs, which was not yet possible in previous methods. Theoretically, we show that EMPLiFI is correct. Empirically, we compare EMPLiFI to LFI-ProbLog and EMBLEM. The results show that EMPLiFI is the most efficient in learning single-head annotated disjunctions. In learning multi-head annotated disjunctions, EMPLiFI is more accurate than EMBLEM, while LFI-ProbLog cannot handle this task. ispartof: pages:378-391 ispartof: Advances in Intelligent Data Analysis XX vol:13205 pages:378-391 ispartof: Symposium on Intelligent Data Analysis location:Rennes, France date:20 Apr - 22 Feb 2022 status: published

Patients with advanced esophageal squamous cell carcinoma (SCC) have a poor prognosis when treated with standard chemotherapy. Programmed death ligand 1 (PD-L1) expression in esophageal cancer has been associated with poor survival and more advanced stage. Immune checkpoint inhibitors, such as PD-1 inhibitors, showed benefits in advanced esophageal cancer in clinical trials. We analyzed the prognosis of patients with unresectable esophageal SCC who received nivolumab with chemotherapy, dual immunotherapy (nivolumab and ipilimumab), or chemotherapy with or without radiotherapy. Patients who received nivolumab with chemotherapy had a better overall response rate (ORR) (72% vs. 66.67%, p = 0.038) and longer overall survival (OS) (median OS: 609 days vs. 392 days, p = 0.04) than those who received chemotherapy with or without radiotherapy. In patients receiving nivolumab with chemotherapy, the duration of the treatment response was similar regardless of the treatment line they received. According to clinical parameters, liver and distant lymph nodes metastasis showed a trend of negative and positive impacts, respectively, on treatment response in the whole cohort and in the immunotherapy-containing regimen cohort. Nivolumab add-on treatment showed less gastrointestinal and hematological adverse effects, compare with chemotherapy. Here, we showed that nivolumab combined with chemotherapy is a better choice for patients with unresectable esophageal SCC.

To achieve the goal of limiting global warming to 1.5 °C above preindustrial levels, net-zero emissions targets were proposed to assist countries in planning their long-term reduction. Inverse Data Envelopment Analysis (DEA) can be used to determine optimal input and output levels without sacrificing the set environmental efficiency target. However, treating countries as having the same capability to mitigate carbon emissions without considering their different developmental stages is not only unrealistic but also inappropriate. Therefore, this study incorporates a meta-concept into inverse DEA. This study adopts a three-stage approach. In the first stage, a meta-frontier DEA method is adopted to assess and compare the eco-efficiency of developed and developing countries. In the second stage, the specific super-efficiency method is adopted to rank the efficient countries specifically focused on carbon performance. In the third stage, carbon dioxide emissions reduction targets are proposed for the developed and developing countries separately. Then, a new meta-inverse DEA method is used to allocate the emissions reduction target to the inefficient countries in each of the specific groups. In this way, we can find the optimal CO2 reduction amount for the inefficient countries with unchanged eco-efficiency levels. The implications of the new meta-inverse DEA method proposed in this study are twofold. The method can identify how a DMU can reduce undesirable outputs without sacrificing the set eco-efficiency target, which is especially useful in achieving net-zero emissions since this method provides a roadmap for decision-makers to understand how to allocate the emissions reduction targets to different units. In addition, this method can be applied to heterogeneous groups where they are assigned to different emissions reduction targets.

Immune thrombocytopenic purpura (ITP) is characterized by thrombocytopenia and bleeding diathesis. Pancreatitis is a very rare complication but may be fatal. We analyzed data of newly diagnosed ITP patients, excluding those with a history of splenectomy, unknown sex or date of birth, or preexisting pancreatitis at the time of ITP diagnosis, and compared these with selected age-, gender-, and index-year-matched controls, using the Taiwan National Health Insurance Research Database from 1996 to 2013. The study enrolled 100,177 ITP patients and 100,177 controls. We found that pancreatitis risk was higher in secondary ITP patients, regardless of age group, gender, baseline Charlson comorbidity index (CCI) score, history of biliary stone, hyperlipidemia, or alcoholism, than in the control population. Primary ITP patients with CCI score 1 and without biliary tract stone history also showed a higher pancreatitis risk than the controls. The incidence rate and cumulative incidence of pancreatitis were increased in primary, secondary, and unspecified ITP cases. These phenomena may be related to the presence of autoantibodies against glycoprotein IIb/IIIa, or to IgG4, microparticle obstruction, or sclerosis. We noted a direct association between ITP and the development of pancreatitis in Taiwan population.

This study estimates the environmental efficiency of 150 economies during the period of 2010–2017 to understand the environmental efficiency trend worldwide. This research adopts the meta-Malmquist approach to compare and capture the dynamic change in environmental efficiency among different income groups. The empirical results indicate that among the four income groups, only the low-income group suffers from regression in terms of environmental efficiency, while the high-income group achieves the greatest progress. For the high-income group, the source of improvement originates from the frontier shift rather than from efficiency change. By contrast, the improvement of the lower-income groups results from the catching-up effect. With regard to the effect of the Paris Agreement, only the lower middle-income group exhibits a statistical difference between the two periods, and environmental efficiency increases after the adoption of the Paris Agreement. The fight against global warming cannot succeed by relying only on specific countries. The whole world must cooperate and improve together, and thus, additional help must be devoted to the low-income group. The statistical results support that differences exist in terms of environmental efficiency among the four income groups. In particular, the low-income group is deteriorating.

Probabilistic model checking has been developed for verifying systems that have stochastic and nondeterministic behavior. Given a probabilistic system, a probabilistic model checker takes a property and checks whether or not the property holds in that system. For this reason, probabilistic model checking provide rigorous guarantees. So far, however, probabilistic model checking has focused on propositional models where a state is represented by a symbol. On the other hand, it is commonly required to make relational abstractions in planning and reinforcement learning. Various frameworks handle relational domains, for instance, STRIPS planning and relational Markov Decision Processes. Using propositional model checking in relational settings requires one to ground the model, which leads to the well known state explosion problem and intractability. We present pCTL-REBEL, a lifted model checking approach for verifying pCTL properties of relational MDPs. It extends REBEL, a relational model-based reinforcement learning technique, toward relational pCTL model checking. PCTL-REBEL is lifted, which means that rather than grounding, the model exploits symmetries to reason about a group of objects as a whole at the relational level. Theoretically, we show that pCTL model checking is decidable for relational MDPs that have a possibly infinite domain, provided that the states have a bounded size. Practically, we contribute algorithms and an implementation of lifted relational model checking, and we show that the lifted approach improves the scalability of the model checking approach.

Background Stereotactic radiosurgery (SRS), a validated treatment for brain tumors, requires accurate tumor contouring. This manual segmentation process is time-consuming and prone to substantial inter-practitioner variability. Artificial intelligence (AI) with deep neural networks have increasingly been proposed for use in lesion detection and segmentation but have seldom been validated in a clinical setting. Methods We conducted a randomized, cross-modal, multi-reader, multispecialty, multi-case study to evaluate the impact of AI assistance on brain tumor SRS. A state-of-the-art auto-contouring algorithm built on multi-modality imaging and ensemble neural networks was integrated into the clinical workflow. Nine medical professionals contoured the same case series in two reader modes (assisted or unassisted) with a memory washout period of 6 weeks between each section. The case series consisted of 10 algorithm-unseen cases, including five cases of brain metastases, three of meningiomas, and two of acoustic neuromas. Among the nine readers, three experienced experts determined the ground truths of tumor contours. Results With the AI assistance, the inter-reader agreement significantly increased (Dice similarity coefficient [DSC] from 0.86 to 0.90, P < 0.001). Algorithm-assisted physicians demonstrated a higher sensitivity for lesion detection than unassisted physicians (91.3% vs 82.6%, P = .030). AI assistance improved contouring accuracy, with an average increase in DSC of 0.028, especially for physicians with less SRS experience (average DSC from 0.847 to 0.865, P = .002). In addition, AI assistance improved efficiency with a median of 30.8% time-saving. Less-experienced clinicians gained prominent improvement on contouring accuracy but less benefit in reduction of working hours. By contrast, SRS specialists had a relatively minor advantage in DSC, but greater time-saving with the aid of AI. Conclusions Deep learning neural networks can be optimally utilized to improve accuracy and efficiency for the clinical workflow in brain tumor SRS.

PURPOSE/OBJECTIVE(S) Apolipoprotein E (APOE) polymorphism is a well-known risk associated with Alzheimer's disease. Its role in neurocognition decline after whole brain radiotherapy (WBRT) for brain metastases is not well-investigated. The present secondary analysis of a prospective blinded randomized controlled phase II trial aimed to evaluate the impact of APOE genotypes upon neurocognitive outcomes after WBRT with or without hippocampal avoidance. MATERIALS/METHODS Adult patients with brain metastases were stratified by prior radiosurgery and randomized to hippocampal avoidant conformal WBRT versus conformal WBRT without hippocampal avoidance to 30 Gy in 10 fractions from March 2015 to November 2018. Memantine was not used during or after WBRT. Standardized neurocognitive test battery (Hopkins Verbal Learning Test-Revised [HVLT-R], Trail Making Test), was performed at baseline, 1, 2, 4, 6, and every 3 months up to two years by trained independent health professionals. Both clinical trial participants and examiners were blinded to the treatment group assignment. APOE alleles were determined by the genome-wide genotyping. The association between APOE genotypes and neurocognitive outcomes was analyzed by general linear model. The role of APOE genotypes on the effect of hippocampal avoidance during WBRT was also evaluated. Factorial ANOVA was used to assess the independent factors associated with neurocognitive outcomes. RESULTS Among 65 analyzable patients, APOE genotyping was available for 64.6% (n = 42) of patients. The most frequent APOE allele was e3 homozygote (e3/e3, n = 24), followed by e2 carrier (e2/e3, n = 11) and e4 carrier (e4/e3, n = 7). No differences in baseline characteristics and cognitions between patients of different APOE genotypes. At 6-month, patients carrying APOE e2 and e4 allele had the best and worst preservation in HVLT-R total recall (mean difference, e2: +3.18 versus e4: -3.20, P = 0.008), and delayed recall (mean difference, e2 carrier: +0.46 versus e4 carrier: -2.40, P = 0.03), respectively. The effect of preservation in 6-month memory score is the strongest in the APOE e2 carriers followed by the APOE e3 homozygotes, and the least in the APEO e4 carriers in order (P = 0.028). Only patients of APOE e3 homozygotes showed improved preservation in late memory score by hippocampal avoidant WBRT at 6-month (mean difference, hippocampal avoidant: +3.67 versus conformal: -3.18, P = 0.037) and beyond. APOE genotyping was independent of age and hippocampal avoidance to be associated with the preservation of 6-month HVLT-R total recall (P = 0.042), and HVLT-R delayed recall (P = 0.032). CONCLUSION The APOE genotype is associated with the risk of memory decline after WBRT. Specifically, APOE e2 carriers exhibited better while e4 carriers showed worse perpetuation in verbal memory function after WBRT. APOE e3 homozygotes but not APOE e2 or e4 carriers benefit late memory preservation by hippocampal avoidant WBRT for brain metastases.

Taiwan&rsquo, s Financial Supervisory Commission of the Executive Yuan promulgated the fully amended Certified Public Accountant Act in 2007, which directly led to significant changes in accounting law. From the perspective of the economic theory of law, this study investigates the amendment of the Certified Public Accountant Act resulting in an increase or decrease in the overall revenue and different revenue shares of accounting firms, and puts forward measures that should be taken by accounting firms and stakeholders. We focus on large accounting firms and divide the sample period into before and after 2008. This study uses the translog revenue function and revenue share functions of the public accounting industry, and based on the 1989&ndash, 2017 Survey Report of Audit Firms in Taiwan, and we find that the amendment of the Certified Public Accountant Act has had a positive effect on overall revenue, increasing overall revenue and the overall management advisory services shares, and in reducing the overall accounting and auditing shares and tax services shares of large accounting firms. Additional analyses provide regulators with public policy implications and provide accounting firms with managerial information.

The vagus nerve plays an essential role in homeostasis and inflammation. Clinically, peptic ulcer patients without helicobacter pylori (HP) infection may provide a population for studying the effect of vagal hyperactivity. There were interests in the association of gastrointestinal disease and urogenital disorders. Herein, we try to investigate subsequent risk of benign prostatic hyperplasia (BPH) in non-HP infected peptic ulcer patients. We identified 17,672 peptic ulcer admission male patients newly diagnosed in 1998–2007 from Taiwan Health Insurance Database, and 17,672 male comparison without peptic ulcer, frequency matched by age, and index-year. We assessed subsequent incidence of BPH in each cohort by the end of 2013, and then compared the risk of developing BPH between individuals with and without peptic ulcer. In addition, peptic ulcer patients underwent surgery were also examined. There were 2954 peptic ulcer patients and 2291 comparisons noted with the occurrence of BPH (25.35 and 16.70 per 1000 person-years, respectively). Compared to comparisons, peptic ulcer patients had a 1.45- and 1.26-fold BPH risk in multivariable Cox model and Fine and Gray model (95% CI 1.37–1.54 and 1.19–1.34). In age-stratified analysis, the highest risk of BPH was in 45–59 years (interaction p

Whether a strategy of postoperative non-sedation produces better outcomes compared with sedation in patients after head and neck reconstruction remains controversial. Therefore, we retrospectively investigated outcomes in 150 of these patients in our institution. Patients with head and neck cancer that received free anterolateral thigh flap were studied retrospectively, and were categorized in terms of their postoperative care into “sedation” and “non-sedation” groups. The related parameters of each patient were collected for analysis. Overall, 150 patients were included (sedation protocol (N = 56) and non-sedation strategy (N = 94)). No significant differences were observed between groups in patient demographics or postoperative outcomes. Significantly shorter durations of mean and median intensive care unit (ICU) length of stay, mechanical ventilation, hospitalization, and operative time were observed in the non-sedation group than in the sedation group. Among all patients, the sedation and flap reopen were the common variables related to prolonged ICU stay, mechanical ventilator duration, and hospitalization. The current study suggested the strategy of postoperative non-sedation is associated with a significant decrease in the duration of mechanical ventilation, ICU length of stay, hospitalization. Regardless of hospital stay, there were no differences in postoperative outcome between 2 groups.

In end-stage renal disease (ESRD) patients receiving dialysis, anemia is common and related to a higher mortality rate. Erythropoietin (EPO) resistance and iron refractory anemia require red blood cell transfusions. Myelodysplastic syndrome (MDS) is a disease with hematopoietic dysplasia. There are limited reports regarding ESRD patients with MDS. We aim to assess whether, for ESRD patients, undergoing dialysis is a predictive factor of MDS by analyzing data from the Taiwan National Health Insurance Research Database. We enrolled 74,712 patients with chronic renal failure (ESRD) who underwent dialysis and matched 74,712 control patients. In our study, we noticed that compared with the non-ESRD controls, in ESRD patients, undergoing dialysis (subdistribution hazard ratio [sHR] = 1.60, 1.16–2.19) and age (sHR = 1.03, 1.02–1.04) had positive predictive value for MDS occurrence. Moreover, more units of red blood cell transfusion (higher than 4 units per month) was also associated with a higher incidence of MDS. The MDS cumulative incidence increased with the duration of dialysis in ESRD patients. These effects may be related to exposure to certain cytokines, including interleukin-1, tumor necrosis factor-α, and tumor growth factor-β. In conclusion, we report the novel finding that ESRD patients undergoing dialysis have an increased risk of MDS.

Background: MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) participates in the MAPK signal transduction pathway, responding to a number of mitogenic and metabolic stimuli, which may be related to breast cancer susceptibility and progression. In this study, we assessed whether overexpression of MAP3K1 promotes proliferation, migration, and invasion of breast cancer cells, and thus, affects the prognosis of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer. Methods: Two HR-positive, HER2-negative breast cancer cell lines (MCF7 and T-47D), both overexpressing MAP3K1, were transfected with MAP3K1 short hairpin RNA plasmids (shMAP3K1) and their proliferation, migration, and invasion were examined. We assessed whether shMAP3K1 affects the cell cycle and levels of downstream signaling molecules, such as ERK and NF-κB, as well as sensitizes cells in both cell lines to chemotherapeutic and hormonal agents. A total of 161 patients with HR-positive, HER2-negative T1-T2 breast cancer and 0 to 3 nodal metastases were included. The expression of MAP3K1 and phospho (p)-ERK proteins was assessed by immunohistochemistry. Results: In both cell lines (MCF7 and T-47D), shMAP3K1 significantly reduced cell growth, migration, and invasion by downregulating MMP-9 and blocking the G2/M phase of the cell cycle and its regulatory molecule cyclin B1. Besides, shMAP3K1 downregulated ERK- and NF-κB-dependent gene transcription, and enhanced sensitivities of both cell lines to doxorubicin, docetaxel, and tamoxifen. Patients with MAP3K1 overexpression exhibited significantly poor 9-year disease-free survival (DFS; 72.6% vs. 88.5%, p = 0.022) and overall survival (OS; 83.8% vs. 96.2%, p = 0.012) relative to those without MAP3K1 overexpression. Furthermore, the p-ERK expression was significantly associated with MAP3K1 expression (p < 0.001) and correlated with a poor 9-year DFS (p = 0.033) and OS (p = 0.023). Conclusions: Our results indicate that overexpression of MAP3K1 plays a major role in poor prognosis of HR-positive, HER2-negative early-stage breast cancer.

BackgroundHippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT is better for preserving neurocognitive function.MethodsThis single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned to receive HA-WBRT or conformal WBRT. Primary end point is the decline of Hopkins Verbal Learning Test–Revised (HVLT-R) Delayed Recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression free survival (BPFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsPatients were enrolled from March 2015 to December 2018 with a median follow-up of 12.4 months. A total of 70 patients were randomized. No differences in baseline neurocognitive function existed between the two arms. There were no differences in any neurocognitive assessments at four months. At six months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, p = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, p = 0.019) and memory score (mean difference = 4.38, p = 0.020) compared with patients undergoing conformal WBRT. There were no differences in TMT part A, part B, or the COWA test between the two arms at any time point. There were no differences in BPFS or OS between arms as well.ConclusionsPatients receiving HA-WBRT without Memantine showed better preservation in late verbal memory, but not in verbal fluency or executive function.

Pancreatic cancer (PC) is a global health problem that features a very high mortality rate. The UL16 binding protein 2 (ULBP2) is a new biomarker for PC detection. This study develops a simple, reliable, and inexpensive immunosensor for the detection of the ULBP2 antigen while also investigating the effects of an array configuration of connected sensors and zinc oxide (ZnO) nanoparticles on the immunosensor&rsquo, s sensitivity. The ULBP2 antibody was immobilized onto the screen-printed carbon electrode (SPCE) surfaces of three different sensors: a simple SPCE (ULBP2-SPCE), an SPCE array, which is a series of identical SPCE connected to each other at different arrangements of rows and columns (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3), and an SPCE combined with ZnO nanoparticles (ULBP2-ZnO/SPCE). Impedance spectrum measurements for the immunosensors to ULBP2 antigen were conducted and compared. According to the result, the array configurations (ULBP2-SPCE-1x2 and ULBP2-SPCE-1x3) show an improvement of sensitivity compared to the ULBP2-SPCE alone, but the improvement is not as significant as that of the ULBP2-ZnO/SPCE configuration (ULBP2-ZnO/SPCE &gt, ULBP2-SPCE: 18 times larger). The ULBP2-ZnO/SPCE immunosensor has a low limit of detection (1 pg/mL) and a high sensitivity (332.2 &Omega, /Log(pg/mL)), excellent linearity (R2 = 0.98), good repeatability (coefficients of variation = 5.03%), and is stable in long-term storage (retaining 95% activity after 28 days storage). In an array configuration, the immunosensor has an increased signal-to-noise ratio (ULBP2-SPCE-1x3 &gt, ULBP2-SPCE: 1.5-fold) and sensitivity (ULBP2-SPCE-1x3 &gt, ULBP2-SPCE: 2.6-fold). In conclusion, either the modification with ZnO nanoparticles onto the sensor or the use of an array configuration of sensors can enhance the immunosensor&rsquo, s sensitivity. In this study, the best immunosensor for detecting ULBP2 antigens is the ULBP2-ZnO/SPCE immunosensor.

Iron overload is related to leukemia transformation in myelodysplastic syndrome (MDS) patients. Siderophores help to transport iron. Type 2-hydroxybutyrate dehydrogenase (BDH2) is a rate-limiting factor in the biogenesis of siderophores. Using qRT-PCR, we analyze BDH2mRNA expression in the bone marrow (BM) of 187 MDS patients, 119 de novo acute myeloid leukemia (AML) patients, and 43 lymphoma patients with normal BM. Elevated BDH2mRNA expression in BM is observed in MDS patients (n = 187 vs. 43, normal BM, P = 0.009), and this is related to ferritin levels. Patients with higher BDH2 expression show a greater risk of leukemia progression (15.25% vs. 3.77%, lower expression, P = 0.017) and shorter leukemia-free-survival (medium LFS, 9 years vs. 7 years, P = 0.024), as do patients with a ferritin level &ge, 350 ng/mL. Additionally, we investigate the mechanisms related to the prognostic ability of BDH2 by using BDH2-KD THP1. The cell cycle analysis, surface markers, and special stain studies indicate that BDH2-KD induces differentiation and decreases the growth rate of THP1 cells, which is associated with the retardation of the cell cycle. Moreover, many genes, including genes related to mitochondrial catabolism, oncogenes, tumor suppressor genes, and genes related to cell differentiation and proliferation influence BDH2-KD THP1 cells. Herein, we demonstrate that BDH2 is involved in cell cycle arrest and the inhibition of differentiation in malignant cells. Furthermore, the high BDH2 expression in MDS patients could be suggestive of a poor prognostic factor. This study provides a foundation for further research on the roles of BDH2 and iron metabolism in the pathogenesis of MDS.

Purpose The impact of epidermal growth factor receptor (EGFR) mutations on radiotherapy for brain metastases (BM) is undetermined. We evaluated the effects of EGFR mutation status on responses and outcomes in non-small cell lung cancer (NSCLC) patients with BM, treated with upfront or salvage stereotactic radiosurgery (SRS). Methods and materials From 2008 to 2015, 147 eligible NSCLC patients with 300 lesions were retrospectively analyzed. Patterns of tyrosine kinase inhibitor (TKI) therapy were recorded. Radiographic response was assessed. Brain progression-free survival (BPFS) and overall survival were calculated and outcome prognostic factors were evaluated. Results Median follow-up time was 13.5 months. Of the EGFR-genotyped patients, 79 (65%) were EGFR mutants, and 42 (35%) were wild type. Presence of EGFR mutations was associated with higher radiographic complete response rates (CRR). Median time to develop new BM after SRS was significantly longer for mutant-EGFR patients (17 versus 10.5 months, p = 0.02), predominantly for those with adjuvant TKI therapy (26.3 versus 15 months, p = 0.01). EGFR mutations independently predicted better BPFS (HR = 0.55, p = 0.048) in multivariate analysis. Conclusions In patients with NSCLC treated with SRS for BM, the presence of EGFR mutations is associated with a higher CRR, longer time for distant brain control, and better BPFS. The combination of SRS and TKI in selective patient group can be an effective treatment choice for BM with favorable brain control and little neurotoxicity.

PURPOSE/OBJECTIVE(S) This phase II blinded randomized trial investigated the neurocognitive outcomes of conformal whole brain radiotherapy (WBRT) with or without hippocampal avoidance for patients with brain metastases. Patients received hippocampal-avoidant WBRT had better preservation in late verbal memory measured by the Hopkins Verbal Learning Test-Revised. Here, we presented the patient-reported health-related quality of life (HRQOL) and functional outcomes. MATERIALS/METHODS Adult patients with brain metastases were randomized to receive hippocampal-avoidant conformal WBRT (HA-cWBRT) versus conformal WBRT without hippocampal avoidance (cWBRT) to 30 Gy in 10 fractions. Memantine was not used during or after WBRT. HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, 2, 4, 6, and every 3 months up to two years with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL function scales were considered: global health status; physical, cognitive, role, social, and emotional functioning. A ≥ 10-point difference from baseline is considered of clinical relevance. HRQOL results were compared at baseline and over time with mixed effects models adjusted for treatment arm, time, and interaction. Pearson correlation between function scales was performed. Statistical significance required P < 0.05. RESULTS From March 2015 to November 2018, 70 patients were randomized and 65 patients (HA-cWBRT group, n = 33; cWBRT group, n = 32) completed protocol treatment. Compliance was 100% at baseline, 56.9% at 6 months, and dropped to 29.2% at 12 months. Thus, only the first year was analyzed. There were no differences in the six primary HRQOL function scales between the two arms at baseline. Patients in the cWBRT arm reported better HRQOL scores in cognitive functioning (P = 0.02), emotional functioning (P = 0.01), and social functioning (P = 0.04), as well as a favorable score in global health status (P = 0.07) than did patients who received HA-cWBRT. There were no differences in physical and role function scales between the two arms over time. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for cognitive functioning at 2 & 4 months, emotional functioning at 2, 9 & 12 months, social functioning at 2 & 4 months, and global health status at 4 months). Correlation analysis showed that cognitive and emotional function scales were highly related (r value = 0.67 at 2 months, 0.85 at 4 months, and 0.68 at 6 months, respectively, all P < 0.001) CONCLUSION: In contract to the objective standardized neurocognitive test, patients received hippocampal-avoidant WBRT for brain metastases reported worse HRQOL in cognitive, emotional and social functioning over time. There as a strong correlation between cognitive and emotional functioning. Further investigation on the emotional outcomes after WBRT is warrant.

Highlights • The role of thoracic control for lung cancer has become increasingly important with improvements in lung cancer treatment and patient survival. Thoracic re-irradiation became feasible with the advance and adaptation of radiation technology. • Our study retrospectively collected data related to clinicopathological features and treatment outcomes of 50 patients who had two courses of thoracic RT in at least 50% overlapping fields. A promissing local control with median time to local progression of 18 months and a median overall survival of 25.1 months were found. • We also found that subsequent chemotherapy with taxanes- or gemcitabine-based regimen following thoracic re-irradiation was significantly related to lethal lung events. • These results helped prove the feasibility of re-irradiation with conventionally fractionated RT and increase awareness regarding underestimated lung toxicity resulting from subsequent chemotherapy following thoracic re-irradiation., Background and purpose Thoracic re-irradiation may be an alternative treatment for lung cancer patients who develop intrathoracic locoregional recurrence without systemic progression. This study aimed to retrospectively assess locoregional control, clinical outcomes, and toxicities in lung cancer patients who received thoracic re-irradiation. Materials and methods We retrospectively reviewed 50 lung cancer patients who received thoracic re-irradiation using conventional photon radiotherapy (RT) and stereotactic body radiotherapy (SBRT) between 2009 and 2017. The correlations of clinicopathologic factors, treatment factors, and dosimetric factors of RT with time to local progression (TTLP), progression-free survival (PFS), and overall survival (OS) after starting thoracic re-irradiation were calculated using log-rank tests and Cox regression models. Results The median re-irradiation dose in equivalent dose in 2-Gy fractions was 51.1 Gy, and the mean re-irradiation planning target volume was 201.58 ml. The median mean lung dose (MLD) was 4.18 Gy, and the total lung volumes receiving a dose of 5 Gy (lung V5) and of 20 Gy (V20) were 19.8% and 5.85%, respectively. The TTLP, PFS, and OS were 18.0, 5.9, and 25.1 months, respectively. Lung V5 (p

Rationale: Lymphoma with an initial manifestation of ascites and peritoneal invasion is rare. Patient concerns: A 65-year-old woman presented to the emergency department with a 3-week history of abdominal distention, anorexia, and night sweating, and a 2-week history of melena. She was a silent hepatitis B virus carrier. Abdominal ultrasound showed massive ascites without cirrhosis. Abdominal computed tomography revealed ascites, infiltrative peritoneal lesions with omental cake appearance, and lymphadenopathies. Diagnosis: We performed paracentesis and the ascites cytology was obtained. The patient also underwent esophagogastroduodenoscopy, which showed ulcerative tumors in the stomach. Both ascites cytology and pathology of the gastric tumors confirmed the diagnosis of B-cell lymphoma. Interventions: This patient received 7 cycles of chemotherapy. Outcomes: Follow-up imaging studies revealed partial remission of lymphoma, but an enlargement of residual tumors in omentum and mesentery, which resulted in intractable ascites and rapid deterioration of performance status. Despite a change of regimen of chemotherapy, this patient expired 10 months after diagnosis. Lessons: Lymphoma should be one of the differential diagnoses in patients with intractable ascites not attributable to other comorbidities.

Background: Most Aristolochiaceae plants are prohibited due to aristolochic acid nephropathy (AAN), except Xixin ( Asarum spp. ). Xixin contains trace amounts of aristolochic acid (AA) and is widely used in Traditional Chinese Medicine. Methylglyoxal and D-lactate are regarded as biomarkers for nephrotoxicity. Thus, this study aimed to evaluate tubulointerstitial injury and interstitial renal fibrosis by determining urinary methylglyoxal and D-lactate after withdrawal of low-dose AA in a chronic mouse model. Methods: C3H/He mice in the AA group ( n =24/group) were given ad libitum access to distilled water containing 3 µg/mL AA (0.5 mg/kg/day) for 56 days and drinking water from days 57 to 84. The severity of tubulointerstitial injury and fibrosis were evaluated using the tubulointerstitial histological score (TIHS) and Masson’s trichrome staining. Urinary and serum methylglyoxal were determined by high-performance liquid chromatography (HPLC); urinary D-lactate were determined by column-switching HPLC. Results: After AA withdrawal, serum methylglyoxal in the AA group increased from day 56 (429.4±48.3 μg/L) to 84 (600.2±99.9 μg/L), and peaked on day 70 (878.3±171.8 μg/L; p Conclusions: Methylglyoxal is induced after AA-induced tubulointerstitial injury, thus methylglyoxal excretion and metabolism may be a detoxification and repair strategy. A low cumulative AA dose is the key factor that limits tubulointerstitial injury and repair. Thus, AA-containing herbs, especially Xixin, should be used at low doses for short durations (less than one month).

Treatment strategies for nasal extranodal NK/T-cell lymphoma (ENKTL), including sequential chemotherapy followed by radiotherapy (SCRT), concurrent chemoradiotherapy (CCRT), or radiotherapy alone (RT), remain varied. The purpose of this study was to assess the treatment outcome, the toxicity, and the potential prognostic factors for patients with early-stage nasal ENKTL treated using definitive RT (minimum of 50 Gy) with or without chemotherapy. From 1998 to 2014, 37 patients were included in the study. Eight patients were treated with RT alone, 1 with CCRT, and 28 with SCRT. Local regional control (LRC), progression-free survival (PFS), and overall survival (OS) were calculated using the Kaplan–Meier method. RT resulted in an overall response rate of 91.2%, with a complete response rate of 78.4%. After a median follow-up time of 36.8 months, the 3-year LRC, PFS and OS were 87.4%, 64.0% and 76.3%, respectively. Acute severe toxicity (Grade 3) of mucositis was observed in 6 (16.2%) of the 37 patients. In univariate analyses, extensive disease (Stage I/II with local invasiveness) and the presence of B symptoms were significantly associated with a poor PFS, whereas extensive disease was significantly associated with a poor OS. Multivariate analysis identified the presence of extensive disease as an independent predictor of PFS (P