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Esophageal cancer has a poor prognosis due to its aggressiveness and low survival rate. In Ease Asia, esophageal squamous cell carcinoma (ESCC) outnumbers esophageal adenocarcinoma (EAC). The ESCC patients still have high mortality despite modern surgical resection and neoadjuvant treatment. Determining patient and outcome prognostic factors is critical in ESCC treatment. In esophageal cancer, early growth response-1 (Egr-1) is a tumor suppressor gene, but the mechanism and associated genes are unknown. The study utilizes RNA interference method, the platform of Next Generation Sequencing (NGS) and bioinformatics analysis to investigate the influences after the Egr-1 gene slicing on the ESCC cells. The heat maps of differentially expressed mRNA and microRNAs were analyzed using the algorithm, Burrows-Wheller Aligner. The study showed that the expression of 51 mRNA and 26 microRNAs have significant changes in ESCC cells after Egr-1 knockdown. The KEGG enrichment analysis linked Egr-1-regulated genes and microRNAs. Egr-1 interactions with these genes and microRNAs may be important in tumor progression. In conclusions, this study provided the transcriptome patterns and relating pathway analysis for Egr-1 knockdown in ESCC cells. The mRNA and microRNAs altered by Egr-1 gene silencing might provide key information in the treatment of ESCC.

Background and Hypothesis Antipsychotics remain the main treatment for schizophrenia, but their effectiveness is challenging to compare. We aimed to assess the comparative real-world effectiveness of antipsychotics in preventing readmission among patients in Asia with early-stage schizophrenia to inform clinical decision making. Study Design We did a retrospective cohort study of first-admission schizophrenia patients (ICD-9-CM: 295; ICD-10-CM: F20 and F25) from January 1, 2001, to December 31, 2017. The cohort was identified from the National Health Insurance Research Database NHIRD for Psychiatric Inpatients. The exposure was any antipsychotics prescribed post-discharge. The primary outcome was the readmission risk due to psychotic disorders, which was measured by adjusted hazard ratios (aHRs). Within-individual extended Cox models were applied for analyses, where the periods of oral risperidone use served as his or her own control. Study Results We selected 75 986 patients (men, 53.4%; mean [SD] age, 37.6 [12.0] years; mean [SD] duration of follow-up, 8.9 [5.0]) who were first admitted to psychiatric wards with schizophrenia in Taiwan. Among them, 47 150 patients (62.05%) had at least one readmission within 4 years. Compared to the period under treatment with oral risperidone, that under monotherapy with long-acting injectable antipsychotics (LAIs) had the lowest risk for psychotic readmission, with a risk reduction of 15–20%. However, the prevalence of person-prescription prevalence of LAIs remained low (< 10%) during the follow-up period. Conclusions The use of LAIs after the first admission for schizophrenia has notable advantages in preventing readmission. Such formulations should be offered earlier in the course of illness.

The assembly of functional biomolecular condensates often involves liquid-liquid phase separation (LLPS) of proteins with multiple modular domains, which can be folded or conformationally disordered to various degrees. To understand the LLPS-driving domain-domain interactions, a fundamental question is how readily the interactions in the condensed phase can be inferred from inter-domain interactions in dilute solutions. In particular, are the interactions leading to LLPS exclusively those underlying the formation of discrete inter-domain complexes in homogeneous solutions? We address this question by developing a mean-field LLPS theory of two stoichiometrically constrained solute species. The theory is applied to the neuronal proteins SynGAP and PSD-95, whose complex coacervate serves as a rudimentary model for neuronal postsynaptic densities (PSDs). The predicted phase behaviors are compared with experiments. Previously, a three-SynGAP, two-PSD-95 ratio was determined for SynGAP/PSD-95 complexes in dilute solutions. However, when this 3:2 stoichiometry is uniformly imposed in our theory encompassing both dilute and condensed phases, the tie-line pattern of the predicted SynGAP/PSD-95 phase diagram differs drastically from that obtained experimentally. In contrast, theories embodying alternate scenarios postulating auxiliary SynGAP-PSD-95 as well as SynGAP-SynGAP and PSD-95-PSD-95 interactions in addition to those responsible for stoichiometric SynGAP/PSD-95 complexes produce tie-line patterns consistent with experiment. Hence, our combined theoretical-experimental analysis indicates that weaker interactions or higher-order complexes beyond the 3:2 stoichiometry, but not yet documented, are involved in the formation of SynGAP/PSD-95 condensates, imploring future efforts to ascertain the nature of these auxiliary interactions in PSD-like LLPS., Comment: 38 pages, 5 figures. Accepted for publication in Biophysical Journal

This study aims to find the relationship between CEOs and CFOs’ Big Five personality traits and the cumulative abnormal return with the announcement of M&A activities by using machine-learning algorithm. We use Personality Insights with IBM Watson AI in google play store to conduct our analysis through examining CEOs and CFOs’ personal characteristics. Our research includes firms listed from 2010 to 2016 and announced M&A activities in the next three-years. The empirical results show that personality traits, agreeableness and neuroticism impact significantly. Keywords: Executive personality, Machine-learning Algorithm, Big-five, M&A JEL Classification Numbers: G34, G14, G41

Background Thymoma is a type of rare mediastinal tumor whose clinical characteristics and indicators of prognosis are poorly understood. This single‐institution retrospective study aimed to assess the predictive value of tumor, node, metastasis (TNM) staging incorporating tumor size in predicting the risk of thymoma recurrence after resection. Methods Four binary logistic regression models were developed. Models I and II included median tumor size and TNM stage, respectively. Model III included the above two variables. Model IV was model III containing these two variables and their interaction terms. All models were adjusted for WHO histological type, operational time, and adjuvant therapy. Results A total of 276 patients with a median age of 51.0, including 21 patients with thymoma recurrence, were included in this study. Models II or III showed a lower ‐2LogL and higher AUC (0.735 and 0.738 vs. 0.576) with significantly better discrimination than model I, and model III and model II shared similar discrimination. In model III, TNM stage was positively correlated with thymoma recurrence. The recurrence risk of patients with TNM stage IV was significantly higher than those with TNM stage I (OR of 11.03, p = 0.022). No significant correlation between the tumor size and recurrence risk (p = 0.779) and no interaction was found between medium tumor size and TNM stage in model IV. Conclusions This study suggests that the prediction contribution of the TNM stage combined with tumor size is similar to the TNM stage alone for tumor recurrence in patients with thymoma after surgical resection., A multiple logistic regression model was used to measure the associations of tumor, node, metastasis (TNM) stage and tumor size with recurrence of thymoma and thymic carcinoma. Models I and II included medium tumor size and TNM stage, respectively. Model III included the two variables. Model IV was model III containing interaction terms (TNM stage x medium tumor size). The tesults show that medium tumor size, TNM stage III, or TNM stage IV were significantly associated with thymoma recurrence risk, respectively. The additive effect is absent between tumor size and TNM staging.

Metabolic syndrome (MetS) is associated with cardiovascular diseases, type 2 diabetes, chronic renal diseases, and all-cause mortality. Furthermore, MetS is associated with poor health-related quality of life (HRQOL). However, the impact of dynamic changes in MetS on changes in the HRQOL was not previously explored. This was an eight-year, prospective cohort study in which 906 middle-aged adults from Shipai, Taipei in northern Taiwan were enrolled during 2009–2010 (baseline). Of those sampled, 427 participants completed the follow-up investigation after 8 years. The HRQOL was measured using the Short Form Health Survey (SF-36). Other variables including age, sex, marital status, level of education, smoking, alcohol consumption, baseline body mass index, and changes in physical activity were adjusted. Compared with adults who never experienced MetS, adults with persistent MetS had a negative change in mental HRQOL (β − 4.20, 95% CI − 7.54 to − 0.86, p = 0.01). The negative changes of persistent MetS on the HRQOL were in the domains of vitality and mental health (β − 4.42, 95% CI − 8.10 to − 0.73 and β − 3.47, 95% CI − 6.90 to − 0.04, respectively). Women and overweight adults were vulnerable to the detrimental effects of persistent MetS. For better HRQOL, more resources should be devoted to reversing MetS in public health.

Biomolecular condensates, physically underpinned to a significant extent by liquid-liquid phase separation (LLPS), are now widely recognized by numerous experimental studies to be of fundamental biological, biomedical, and biophysical importance. In the face of experimental discoveries, analytical formulations emerged as a powerful yet tractable tool in recent theoretical investigations of the role of LLPS in the assembly and dissociation of these condensates. The pertinent LLPS often involves, though not exclusively, intrinsically disordered proteins engaging in multivalent interactions that are governed by their amino acid sequences. For researchers interested in applying these theoretical methods, here we provide a practical guide to a set of computational techniques devised for extracting sequence-dependent LLPS properties from analytical formulations. The numerical procedures covered include those for the determination of spinodal and binodal phase boundaries from a general free energy function with examples based on the random phase approximation in polymer theory, construction of tie lines for multiple-component LLPS, and field-theoretic simulation of multiple-chain heteropolymeric systems using complex Langevin dynamics. Since a more accurate physical picture often requires comparing analytical theory against explicit-chain model predictions, a commonly utilized methodology for coarse-grained molecular dynamics simulations of sequence-specific LLPS is also briefly outlined.

Consider an agent who faces choice problems and learns information about an objective state of the world through a technology of sequential experiments. We consider two cases of learning costs. In the first, the agent discounts future payoffs geometrically. In the second, she incurs a constant flow cost of time. If the observable data consist only of the joint distributions over chosen actions and decision times, an analyst can uniquely identify the discount factor in the first case and the flow cost of time in the second case. Moreover, we show how an analyst can recover the agent’s ex ante welfare in both cases, besides identifying her prior belief. Our approach does not rely on any knowledge about the underlying sequential experiment.

Antigen-specific lung-resident memory T cells (TRMs) constitute the first line of defense that mediates rapid protection against respiratory pathogens and inspires novel vaccine designs against infectious pandemic threats, yet effective means of inducing TRMs, particularly via non-viral vectors, remain challenging. Here, we demonstrate safe and potent induction of lung-resident TRMs using a biodegradable polymeric nanoshell that co-encapsulates antigenic peptides and TLR9 agonist CpG-oligodeoxynucleotide (CpG-ODN) in a virus-mimicking structure. Through subcutaneous priming and intranasal boosting, the combinatorial nanoshell vaccine elicits prominent lung-resident CD4+ and CD8+ T cells that surprisingly show better durability than live viral infections. In particular, nanoshells containing CpG-ODN and a pair of conserved class I and II major histocompatibility complex-restricted influenza nucleoprotein-derived antigenic peptides are demonstrated to induce near-sterilizing immunity against lethal infections with influenza A viruses of different strains and subtypes in mice, resulting in rapid elimination of replicating viruses. We further examine the pulmonary transport dynamic and optimal composition of the nanoshell vaccine conducive for robust TRM induction as well as the benefit of subcutaneous priming on TRM replenishment. The study presents a practical vaccination strategy for inducing protective TRM-mediated immunity, offering a compelling platform and critical insights in the ongoing quest toward a broadly protective vaccine against universal influenza as well as other respiratory pathogens.

The SNO+ experiment is a multi-purpose neutrino detector located 2 km underground at SNOLAB in Vale’s Creighton Mine in Sudbury, Ontario. The centerpiece of SNO+ is a 12-m diameter acrylic vessel (AV), containing the target medium. The AV is surrounded by 7 kilotonnes of external ultrapure water shielding and about 9400 photomultiplier tubes. SNO+ is operating in three phases, defined by the target medium: water, scintillator, and scintillator loaded with tellurium. The physics program at SNO+ includes solar neutrino measurements, antineutrino detection, supernova neutrino monitoring, and the main physics goal: neutrinoless double beta decay search. All of these physics analyses require precise measurements of the detector’s optical and timing responses using known sources to establish constraints on the energy and position reconstruction within the detector. In its water phase, SNO+ calibrated using optical and radioactive sources developed for its predecessor, the SNO experiment, and these calibrations provide external background measurements and baseline calibration constants for the detector. The radioactive sources include the 16N and AmBe sources. The tagged 6.13 MeV γs of the 16N source provided a clean calibration sample in the energy region of interest for both the 8B solar neutrinos measurement and the invisible nucleon decay search during the water phase. Currently in the scintillator phase, some of these sources have been leveraged to provide calibration information of the scintillator from outside of the AV. These calibrations allow for measurement of the internal background and validation of the external background measured in the water phase. These calibration results will be presented. New calibration deployment systems and sources are in development to allow for calibration in the scintillator inside the AV. The status of these developments will be described. The findings from both internal and external calibrations will inform the SNO+ physics analyses.

Background: Insomnia and suicidal thoughts are two of negative impacts that have been caused by the COVID-19 pandemic. Identifying the factors that contribute to these psychological problems may help develop strategies to sustain mental health of the public.Aims: The present study examined the psychosocial impacts caused by the COVID-19 pandemic among different populations in Taiwan, and investigated the relationships between these psychosocial factors, insomnia, and suicidal thoughts.Method: Between September 2020 and May 2021, online questionnaires including psychometrically validated scales were distributed to outpatients (n = 205), healthcare workers (HCWs) (n = 500), and individuals in the general population (n = 1200) in Taiwan to collect the data. Multiple linear regression and multivariate logistic regression methods were used to identify potential factors predicting suicidal thoughts and insomnia.Results: Trust in information sources was a significant predictor of suicidal thoughts among outpatients (β = -0.176) and the general population (β = -0.082), and fear of COVID-19 was a significant predictor of suicidal thoughts among HCWs (β = 0.136) and general population (β = 0.142). Resilience was a significant predictor of insomnia among all three populations (outpatients: OR = 0.819, 95% CI = 0.725-0.926; HCWs: OR = 0.803, 95% CI = 0.728-0.887; general population: OR = 0.829, 95% CI = 0.785-0.875).Conclusions: Trust in information sources, fear, and resilience were important factors for suppressing suicide and insomnia among the three study populations. Health policies that monitor psychological status and build resiliency of the public are recommended to help develop tailored strategies for different populations affected by the COVID-19 pandemic.

We consider an agent who decides whether to employ an information structure to learn about a payoff-relevant state of the world before making a decision. Information is costly either because (1) the agent has to wait for the availability of the information structure and is impatient or because (2) she has to pay a fixed and menu-independent cost to use the information structure. For each menu of options we assume the analyst observes random choice from the menu and whether the agent acquires the information. We give a full characterization of when this random choice is consistent with either of the cases (1) or (2) and show how the analyst can distinguish between the two cases using random choice data. We show in either case how random choice data allows identification of the information structure the agent can employ and respectively discount factor or additive costs.

BACKGROUND This study aimed to evaluate the differences in nurses' willingness to discuss palliative care with terminally ill patients and their family members. METHODS The participants were randomly recruited from registered staff nurses ≥20 years of age who were responsible for clinical inpatient care in a tertiary hospital in northern Taiwan. A semi-structured questionnaire was administered to evaluate nurses' experiences of discussing do-not-resuscitate (DNR) decisions and their willingness to discuss palliative care with terminal patients and their family members. The differences in nurses' experiences regarding DNR and willingness to discuss palliative care with terminally ill patients and their family members were compared using the Chi-square test. Logistic regressions were used to analyze factors associated with nurses' willingness to discuss palliative care with patients and their families. RESULTS More participants had experienced initiating discussions about DNR with patients' families than with patients (72.2% vs 61.9%, p < 0.001). Unadjusted logistic regression analysis showed that the experiences of actively initiating DNR discussions with patients were a significant factor associated with palliative care discussion with patients (odds ratio [OR] = 2.91, 95% confidence interval [CI]: 1.09-7.79). On the other hand, the experiences of actively initiating DNR discussions with patients and with patients' families were significant factors associated with palliative care discussion with patients' families (OR = 3.84, 95% CI: 1.22-12.06 and OR = 3.60, 95% CI: 1.19-10.90, respectively). After adjusting for covariates, no significant factors were found to be independently associated with nurses' willingness to discuss palliative care with patients and their family members. CONCLUSION There are significant differences in nurses' willingness to discuss palliative care with patients and their family members. Further research is needed to evaluate factors associated with nurses' willingness to discuss palliative care with patients and their families to facilitate these discussions and protect patients' autonomy.

Remote rainfall related to tropical cyclones (TCs) can be attributed to interaction between the northeasterly monsoon and TC circulation (hereafter monsoon mode), and topographic blocking and lifting effects (hereafter topographic mode). Typhoon Khanun (2017) is a case in point affected by both modes. The objective of this study is to understand the key factors leading to uncertainty in the TC-induced remote rainfall. Ensemble simulations are conducted, with the ensemble members related to the monsoon mode classified into subtypes based on the geographic location of the precipitation maxima. The results demonstrate that frontogenesis and terrain-induced uplifting are the main mechanisms leading to the heavy precipitation in northeastern Taiwan, while the orographic lifting and the interaction between the TC circulation and the topographically blocked northeasterlies result in the heavy rainfall in southeastern Taiwan. For the topographic mode, at a larger rainfall threshold, strong relation is found between the inflow angle of the TC circulation and the cumulative frequency of the rainfall, while at a smaller rainfall threshold, rainfall cumulative frequency is related to the ensemble track directions. Sensitivity experiments with TC-related moisture reduced (MR) and the terrain of Taiwan removed (TR) show that the average of the 3-day accumulated rainfall is reduced by 40% and more than 90% over the mountainous area in MR and TR, respectively. Overall, this study highlights the fact that multiple mechanisms contribute to remote rainfall processes in Khanun, particularly the orographic forcing, thus providing better insights into the predictability of TC remote rainfall.