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Achieving robust cross contexts speech emotion recognition (SER) has become a critical next direction of research for wide adoption of SER technology. The core challenge is in the large variability of affective speech that is highly contextualized. Prior works have worked on this as a transfer learning problem that mostly focuses on developing domain adaptation strategy. However, many of the existing speech emotion corpora, even those considered as large scale, are still limited in size resulting in an unsatisfactory transfer result. On the other hand, directly collecting context-specific corpus often results in an even smaller data size leading to an inevitably non-robust accuracy. In order to mitigate this issue, we propose the concept of enhancing the affect-related variability when learning the in-context acoustic latent representation by integrating out-of-context emotion data. Specifically, we utilize adversarial autoencoder network as our backbone with multiple out-of-context emotion labels derived for each in-context samples that serve as an auxiliary constraint in learning the latent representation. We extensively evaluate our framework using three in-context databases with three out-of-context databases. In this work, we demonstrate not only an improved recognition accuracy but also a comprehensive analysis on the effectiveness of this representation learning strategy.

Background Mapping disease rates is an important aspect of epidemiological research because it helps inform public health policy. Disease maps are often drawn according to local administrative areas (LAAs), such as counties, cities, or towns. In LAAs with small populations, disease rates are unstable and are prone to appear extremely high or low. The empirical Bayes methods consider variance differences among different LAAs, thereby stabilizing the disease rates. The methods of kriging break the constraints of geopolitical boundaries and produce a smooth curved surface in the form of contour lines, but the methods lack the stabilizing effect of the empirical Bayes methods. Methods An easy-to-implement stabilized kriging method is proposed to map disease rates, which allows different errors in different LAAs. Results Monte Carlo simulations revealed that the stabilized kriging method had smaller symmetric mean absolute percentage error than three other types of methods (original LAA-based method, empirical Bayes methods, and traditional kriging methods) in nearly all scenarios considered. Real-world data analysis of oral cancer incidence rates in men from Taiwan demonstrated that the age-standardized rates in the central mountainous sparsely-populated region of Taiwan were stabilized using our proposed method, with no more large differences in numerical values, whereas the rates in other populous regions were not over smoothed. Additionally, the stabilized kriging map had improved resolution and helped locate several hot and cold spots in the incidence rates of oral cancer. Conclusions We recommend the use of the stabilized kriging method for mapping disease rates.

Background: Colorectal peritoneal carcinomatosis (CRPC) is a primary cause of death in colorectal cancer (CRC) patients. In the past, computed tomography (CT) has been the primary method used to ev...

The standard 12-lead electrocardiogram (ECG) records the heart’s electrical activity from electrodes on the skin, and is widely used in screening and diagnosis of the cardiac conditions due to its low price and non-invasive characteristics. Manual examination of ECGs requires professional medical skills, and is strenuous and time consuming. Recently, deep learning methodologies have been successfully applied in the analysis of medical images. In this paper, we present an automated system for the identification of normal and abnormal ECG signals. A multi-channel multi-scale deep neural network (DNN) model is proposed, which is an end-to-end structure to classify the ECG signals without any feature extraction. Convolutional layers are used to extract primary features, and long short-term memory (LSTM) and attention are incorporated to improve the performance of the DNN model. The system was developed with a 12-lead ECG dataset provided by the Kaohsiung Medical University Hospital (KMUH). Experimental results show that the proposed system can yield high recognition rates in classifying normal and abnormal ECG signals.

Chen, CH, Chiu, CH, Tseng, WC, Wu, CY, Su, HH, Chang, CK, and Ye, X. Acute effects of combining dynamic stretching and vibration foam rolling warm-up on lower-limb muscle performance and functions in female handball players. J Strength Cond Res XX(X): 000-000, 2021-The purpose of this study was to compare the acute effects of 3 warm-up protocols on knee flexor and extensor muscles performance in elite female collegiate handball players. Ten female handball players with poor hamstring flexibility completed 3 randomly sequenced experimental visits. During each visit, a different warm-up protocol (general running warm-up [GW], dynamic stretching [DS], or DS combined with vibration foam rolling [DS + VR]) was delivered before the subsequent tests: quadriceps and hamstring muscle stiffness, knee extension and flexion range of motion (ROM), knee joint position sense, knee extension and flexion isokinetic strength with hamstring-quadriceps strength ratio, and muscle endurance during fatiguing exercise. Relative to the GW, the DS + VR protocol resulted in significantly greater knee flexion ROM (mean ± SD: DS + VR = 79.4° ± 7.7°; GW = 69.3° ± 9.6°) and lower hamstring muscle stiffness (DS + VR = 253.33 ± 36.20 N·m-1; GW = 292.89 ± 24.28 N·m-1). In addition, the DS + VR protocol also yielded greater hamstring muscle endurance than the other 2 protocols did (fatigue percentage: DS + VR = 30.24% ± 10.84%; GW = 41.40% ± 8.98%; DS = 42.22% ± 9.42%). Therefore, the results of this experiment suggest that it can be more beneficial for the female handball players to warm-up with the DS + VR, rather than the GW and DS protocols.

Background Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. Methods This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015 – December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015 – December 2019), along with those during the post-COVID-19 period (January – December 2020) were analyzed and compared. Results A total of 6,899 throat swab samples were collected during the pre-pandemic period of 2015 to 2019, with 2,681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year. Conclusions Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers.

Acinetobacter baumannii causes healthcare-associated infections worldwide. Capsular polysaccharide (CPS) is shown an important virulence factor of A. baumannii both in vitro and in vivo. Capsule locus 2 (KL2) for CPS is the most common KL type and is associated with carbapenem resistance. It is unclear whether KL2 is related to the clinical outcome of invasive A. baumannii infection. Here we had followed patients with A. baumannii bacteraemia prospectively between 2009 and 2014. One-third of the unduplicated blood isolates were randomly selected each year for microbiological and clinical studies. The KL2 gene cluster was identified using polymerase chain reaction. A total of 148 patients were enrolled randomly. Eighteen isolates (12.2%) carried KL2, and 130 isolates (87.8%) didn't. Compared with non-KL2 isolates, KL2 isolates had significantly higher resistance to imipenem, sulbactam, and tigecycline. Compared with the non-KL group, in the KL2 group, the hospital stay before development of bacteraemia was longer (P

Background Methicillin-resistant Staphylococcus aureus (MRSA) is the predominant cause of skin and soft tissue infections (SSTIs), which is a problem in prisons and jails. We conducted this study to understand MRSA molecular characteristics among inmates with SSTIs, and we chose MRSA isolates from a community hospital as a comparison. Methods A total of 219 MRSA isolates from three custodial facilities and 134 isolates from a community hospital in Taiwan were collected in the 2017 calendar year. MRSA isolates were investigated molecularly by staphylococcal chromosome cassette mec (SCCmec) type, mupirocin, and chlorhexidine genotypical resistance, and multi-locus sequence typing (ST). Results Of the 219 MRSA isolates from custodial facilities, SCCmec IV was the most prevalent type (65.3%), followed by type VT (32.4%) and type V (1.8%). Regarding sequence types, ST59 (36.4%), 8 (35.3%), and 45 (17.9%) were the leading three predominant types out of 184 selected MRSA isolates, and ST45 MRSA was more prevalent in custodial facilities (p = 0.019). The antimicrobial resistance rates varied for different MRSA strains, with ST45 MRSA having the lowest rates of resistance to most antimicrobials. Overall, 91.5% of isolates carried mupA gene and 25.8% were positive for qacA/B gene, this was independent of the MRSA sequence types. Conclusions ST59, ST8, and ST45 MRSA are the leading three MRSA strains causing SSTIs in Taiwan, 2017, but the molecular distribution varied distinctly between the custodial facilities and hospital settings. The genotypical mupirocin resistance rate is quite high in this study. The frequency of chlorhexidine resistance gene is relatively low, especially in MRSA isolates from custodial facilities.

A strategy to prevent hepatitis B virus (HBV) virologic reactivation (HBVr) and clinical reactivation (CR) during direct acting antiviral (DAA) treatment of hepatitis C virus (HCV)/HBV dual infection remains an unresolved issue.Noncirrhotic patients with dual HCV/HBV infection were enrolled and allocated randomly to 1 of 3 groups as follows: 12 weeks of DAA alone (group 1), 12 weeks of DAA plus 12 weeks of entecavir (group 2), or 12 weeks of DAA plus 24 weeks of entecavir (group 3). The entire study duration was 72 weeks. The primary end point was the occurrence of HBVr (defined by an increase of HBV DNA level10-fold with quantifiable HBV DNA at baseline or the presence of HBV DNA with prior unquantifiable HBV DNA) and CR (defined by serum alanine aminotransferase level2-fold the upper limit of normal in addition to HBVr).Fifty-six patients were allocated randomly as follows: 20 patients in group 1, 16 patients in group 2, and 20 patients in group 3. In group 1, HBV DNA levels increased significantly as early as 4 weeks after initiation of DAA and persisted until the end of the study. During DAA treatment, HBVr occurred in 50% in group 1 vs 0% in group 2 and 0% in group 3 (P.001), whereas the majority of HBVr in groups 2 and 3 occurred 12 weeks after cessation of entecavir (cumulative incidence, 93.8% in group 2 and 94.7% in group 3). Three patients (5.4%; 1 in each group) showed CR at week 48 and did not receive entecavir treatment.Twelve weeks of entecavir is suggested to be co-administered with DAA for HCV/HBV dually infected patients.gov no: NCT04405011.

Background NMDAR hypofunction has been implicated in several psychiatric disorders with an impairment of cognitive flexibility. However, the molecular mechanism of how NMDAR hypofunction with decreased NMDAR tone causes the impairment of cognitive flexibility has been minimally understood. Furthermore, it has been unclear whether hippocampal astrocytes regulate NMDAR tone and cognitive flexibility. Methods We employed cell-type specific genetic manipulations, ex vivo electrophysiological recordings, sniffer patch recordings, cutting-edge biosensor for norepinephrine, and behavioral assays to investigate whether astrocytes can regulate NMDAR tone by releasing D-serine and glutamate. Subsequently, we further investigated the role of NMDAR tone in the heterosynaptic long-term depression, metaplasticity and cognitive flexibility. Results We found that hippocampal astrocytes regulate NMDAR tone via Best1-mediated co-release of D-serine and glutamate. Best1 knockout mice (Best1 KO) exhibited reduced NMDAR tone and impairments of homosynaptic and α1-adrenergic receptor-dependent heterosynaptic long-term depression, which leads to the defects in metaplasticity and cognitive flexibility. These impairments in Best1 KO can be rescued by hippocampal astrocyte-specific Best1 expression or enhanced NMDAR tone through D-serine supplement. Importantly, D-serine injection in Best1 KO during initial learning rescues subsequent reversal learning. Conclusions These findings indicate that NMDAR tone during initial learning is important for subsequent learning, and hippocampal NMDAR tone regulated by astrocytic Best1 is critical for heterosynaptic long-term depression, metaplasticity and cognitive flexibility.

Background Investigation of lymph node micrometastasis (mN) of gastric cancer has been focused on either T1 disease or T1-4N0 disease. Yet, it is unclear whether standard management algorithm toward poorly differentiated gastric cancer (PDGC) is more vulnerable to existence of mN, given its inherently biological aggressiveness, as compared with other histological types. Patients and methods A surgical series (n = 3456) of gastric cancer categorized by histological differentiation was enrolled to analyze survival stratification. Of them, a cohort of T1-T4 N0 PDGC (n = 100) were subjected to cytokeratin immunohistochemistry, a surrogate of mN. Results Cancer-specific survival by AJCC8 staging system could be nicely differentiated in both well-/moderately differentiated and signet ring cell types, while those between stage IA versus IB (p = 0.105), and stage IB versus IIA (p = 0.141) in PDGC could not. Thirteen (13%) out of 100 node-negative PDGC cases exhibited mN, with 5, 2, 5 and 1 cases occurring in T1, T2, T3, and T4 stage, respectively, without identifiable contributing factors. Prognostic performance of AJCC8 working upon PDGC became more discriminative by incorporating mN, as hazard ratio of stage IIIC referenced to stage IA increased from 43 to 78. Conclusion Defective discriminative survival of PDGC by standard staging algorithm prompted us to survey mN occurring in T1-T4N0 PDGC. The prognostic performance of AJCC8 working upon PDGC was enhanced by incorporating mN. As so, we recommend documentation of mN exclusively on node-negative PDGC that helps unveil stage migration phenomenon and switch to appropriate adjuvant therapy in need.

Androgen deprivation therapy (ADT) includes bilateral orchiectomy or long-acting gonadotropin-releasing hormone (GnRH) agonists/antagonists. It remains controversial with respect to ADT associated cardiovascular outcomes. Hereby, we compared the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with prostate cancer receiving either surgical castration or GnRH therapies.Using the Taiwan Cancer Registry and Taiwan's National Health Insurance Research Database, we identified 8,413 patients receiving GnRH therapies compared with 694 receiving surgical castration from 2008 to 2017. The median followup duration was 3 years.The crude incidences of 3-year mortality and MACCEs were 19.90% vs 26.51% and 8.23% vs 8.65% in patients receiving GnRH therapies or surgical castration, respectively. After adjusting for age, cancer stage and comorbidities, despite no significant differences in MACCEs between groups there was a slight increase in the incidence of acute myocardial infarction (AMI) in patients receiving surgical castration compared with those receiving GnRH therapies. The mortality adjusted hazard ratios of MACCEs and AMI among patients receiving surgical castration were 1.11- and 1.8-fold higher than those receiving GnRH therapies. Notably, in subgroup analysis regarding cancer stage, patients with cancer stage IV showed the most significantly increasing risk of AMI in those receiving surgical castration compared with GnRH therapies.Collectively, we indicated an increased risk of AMI in patients with prostate cancer, especially in patients receiving surgical castration rather than those receiving GnRH therapies. Our findings highlight concerns regarding the cardiac safety of surgical castration compared with GnRH therapies.

The incidence of opioid use disorder (OUD) is increasing worldwide, and the opioid-related overdose crisis is currently a major global challenge. This study investigated the effects of adjuvant laser meridian massage (LMM) in men with OUD undergoing methadone maintenance treatment (MMT).A case-controlled study was conducted from February 2019 to April 2020. Fourteen men with OUD on MMT were enrolled from an addiction treatment center as an experimental group. An age-matched control group comprising 13 men was also enrolled. The experimental group received LMM on the back, including over the Bladder meridian and Governor Vessel, three times weekly for 4 weeks. The control group received only MMT. Urinary morphine levels, patients' self-reports of the number of episodes or days of heroin use, and visual analog scale scores for heroin craving/refusal to use heroin during the previous week were evaluated. Quality of life was reported using the Short Form (SF)-12v2.The experimental group showed a significant decrease in heroin use (p 0.05), whereas the control group showed a significant increase in heroin craving (p 0.05). The SF-12v2 Health Survey revealed a significant improvement in physical health in the experimental group (P 0.05).The results of this study suggest that laser meridian massage can be considered a safe, well-tolerated, and potentially useful adjuvant intervention for opioid use disorder.

Background/purpose Streptococcus pneumoniae causes pneumonia and other invasive diseases, and is a leading cause of mortality in the elderly population. The present study aimed to provide current antimicrobial resistance and epidemiological profiles of S. pneumoniae infections in Taiwan. Methods A total of 252 nonduplicate S. pneumoniae isolates were collected from patients admitted to 16 hospitals in Taiwan between January 2017 and December 2019, and were analyzed. The minimum inhibitory concentration of antibiotics was determined using the Vitek 2 automated system for antimicrobial susceptibility testing. Furthermore, epidemiological profiles of S. pneumoniae infections were analyzed. Results Among the strains analyzed, 88% were recognized as invasive pneumococcal strains. According to the Clinical and Laboratory Standards Institute criteria for non-meningitis, the prevalence of penicillin-non-susceptible S. pneumoniae demonstrated a declining trend from 43.6% in 2017 to 17.2% in 2019. However, the rate of penicillin-non-susceptible S. pneumoniae was 85.7% based on the criteria for meningitis. Furthermore, the prevalence of ceftriaxone-non-susceptible S. pneumoniae was 62.7% based on the criteria for meningitis. Isolates demonstrated higher susceptibility toward doripenem and ertapenem than toward meropenem and imipenem. An increased rate of non-susceptibility toward levofloxacin was observed in southern Taiwan (15.1%) and elderly patients (≥65 years; 11.4%). Most isolates were susceptible to vancomycin and linezolid. Conclusion Empirical treatment with ceftriaxone monotherapy for pneumococcal meningitis should be carefully monitored owing to its high non-susceptibility rate. The susceptibility rates of most isolates to penicillin (used for treating non-meningitis pneumococcal diseases), carbapenems (ertapenem and doripenem), respiratory quinolones (moxifloxacin and levofloxacin), vancomycin, and linezolid suggested the potential of these antibiotics in treating pneumococcal diseases in Taiwan.

Machine learning has been widely used for solving challenging problems in diverse areas. However, to the best of our knowledge, seldom literature has discussed in-depth how machine learning approaches can be used effectively to “hunt” (identify) threats, especially advanced persistent threats (APTs) , in a monitored environment. In this study, we share our past experiences in building machine learning-based threat-hunting models. Several challenges must be considered when a security team attempts to build such models. These challenges include (1) weak signal, (2) imbalanced data sets, (3) lack of high-quality labels, and (4) no storyline. In this study, we propose Fuchikoma and APTEmu to demonstrate how we tackle the above-mentioned challenges. The former is a proof of concept system for demonstrating the ideas behind autonomous threat-hunting. It is a machine learning-based anomaly detection and threat hunting system which leverages natural language processing (NLP) and graph algorithms. The latter is an APT emulator, which emulates the behavior of a well-known APT called APT3, which is the target used in the first round of MITRE ATT&CK Evaluations. APTEmu generates attacks on Windows machines in a virtualized environment, and the captured system events can be further used to train and enhance Fuchikoma’s capabilities. We illustrate the steps and experiments we used to build the models, discuss each model’s effectiveness and limitations of each model, and propose countermeasures and solutions to improve the models. Our evaluation results show that machine learning algorithms can effectively assist threat hunting processes and significantly reduce security analysts’ efforts. Fuchikoma correctly identifies malicious commands and achieves high performance in terms of over 80% True Positive Rate and True Negative Rate and over 60% F3. We believe our proposed approaches provide valuable experiences in the area and shed light on automated threat-hunting research.

Background Double diapering may help to maintain a baby's hips in flexion and abduction posture, but the efficacy in facilitating hip maturation has never been verified. We investigated whether double diapering results in greater improvement of the alpha angle in newborn babies. Methods This prospective study enrolled newborns with Graf type IIa immature hips and assigned them to the double-diaper or single-diaper group by the day of birth in a week. Parents were instructed on proper hip positioning, except for diapering. Change in the alpha angle from newborn to 1 month after birth, rate of improvement to bilateral Graf type I hips in 1 month, and number of ultrasound examinations and orthopaedic clinic visits in the first year were compared between the two groups. Results Seventy newborns with 102 type IIa hips were included from January to December 2017. They were allocated to the double-diaper group (n = 33) and single-diaper group (n = 37). With a comparable sex ratio, gestational age, and newborn alpha angle, the double-diaper group had a greater increase of alpha angles in 1 month than the single-diaper group (+7.9° vs. +5.2°, t-test, p = 0.011). Twenty-eight babies in the double-diaper group (84.8%) and 20 babies in the single-diaper group (54.1%) improved to having bilateral Graf type I hips (chi-square test, p = 0.006). Under the same clinical management pathway, subsequent clinical visits and hip ultrasounds before 1 year were significantly reduced in the double-diaper group. Conclusion Double diapering enhances hip maturation and reduces clinical costs in newborns with physiological immature hips, but the therapeutic role for hip dysplasia requires further study.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

BACKGROUND Rapid developments in medical care-such as monitoring devices, medications, and working hours restrictions for intensive care personnel-have dramatically increased the demand for intensive care physicians. Therefore, nurse practitioner (NP)-staffed care is becoming increasingly important. This study was aimed to compare the outcomes of daytime NP-staffed and daytime resident-staffed nonsurgical intensive care units (ICU). METHODS We retrospectively assessed patients admitted to a nonsurgical ICU from March 2017 to December 2017. We collected basic patient data, including age, sex, admission diagnosis, transferring unit, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Primary endpoints were ICU mortality, hospital mortality, and 30-day mortality. Secondary endpoints were 48-h readmission, discharge to nonhome locations, and lengths of ICU and hospital stay. RESULTS A total of 838 subjects were analysed: 334 subjects in the NP-staffed group and 504 in the resident-staffed group. The NP-staffed group was more likely to come from inpatient units (38.3% vs 16.5% for resident-staffed group; p

Background Femoral revision surgery in patients with substantial bone loss is challenging. Impaction bone grafting using a cemented stem can be a good solution for reconstruction of the femur with poor bone stock and extensive bone loss. This study aimed to evaluate the mid-to-long-term clinical and radiographic results of impaction bone grafting using a cemented stem for Paprosky IV femoral bone defects. Methods Thirteen patients (13 hips) who underwent revision total hip arthroplasty with impaction bone grafting using a cemented stem and were followed up for at least 5 years were enrolled in this study. In all patients, a sufficient amount of fresh frozen bone of good quality was used. When cortical segmental defects were present, peripheral reinforcement with metal mesh and strut allograft was performed. The average follow-up duration was 11.1 (range, 5.3–15.1) years. The clinical and radiographic outcomes were reviewed at the final follow-up. Results The average Harris hip score was 82.5 (range, 79–94), and the average University of California, Los Angeles activity score was 5.6 (range, 4–8) at the final follow-up. Radiographic assessment revealed an average femoral component subsidence level of 0.67 (range, 0.05–2.81) mm. There were no complications, except one case (7.6%) of periprosthetic fracture. Conclusions Impaction bone grafting using a cemented stem yielded excellent mid-to-long-term outcomes. It is a reliable technique for Paprosky IV femoral bone defects, and even when severe femoral cortical bone defects are present, long-term stability can be obtained using a metal mesh and/or strut allograft.

Background Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesized to depend on deficient noradrenergic signaling in corticostriatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD. Methods We carried out a randomized, double-blind, placebo-controlled, crossover study with 26 participants with CUD and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control. The effects of a single dose of atomoxetine (40 mg) were compared with placebo on stop-signal reaction time performance and functional network connectivity using dynamic causal modeling. Results We found that atomoxetine speeded Go response times in both control participants and those with CUD. Improvements in stopping efficiency on atomoxetine were conditional on baseline (placebo) stopping performance and were directly associated with increased inferior frontal gyrus activation. Further, stopping performance, task-based brain activation, and effective connectivity were similar in the 2 groups. Dynamic causal modeling of effective connectivity of multiple prefrontal and basal ganglia regions replicated and extended previous models of network function underlying inhibitory control to CUD and control volunteers and showed subtle effects of atomoxetine on prefrontal-basal ganglia interactions. Conclusions These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control participants and in those with CUD. Our results emphasize inferior frontal cortex function as a future treatment target owing to its key role in improving response inhibition in CUD.

Background Emergence delirium (ED) is a common phenomenon occurring in the recovery period. The aim of this study was to investigate the incidence, risk factors, and consequences of ED in adults after elective brain tumor resection. Methods We retrospectively analyzed the data of a prospective cohort performed in a tertiary university hospital. Adult patients admitted to the intensive care unit (ICU) immediately after elective brain tumor resection were consecutively enrolled. Level of consciousness was assessed using the Richmond Agitation–Sedation Scale and ED was assessed using the Confusion Assessment Method for the ICU. Risk factors for ED were determined by multivariable logistic regression. Results A total of 659 patients met the inclusion criteria, of which 41 patients with coma were excluded. Among the remaining 618 patients, 131 (21.2%) developed ED. Independent risk factors for ED were: age, education level, use of anticholinergic and mannitol, Glasgow Coma Score and arterial partial pressure of oxygen postoperatively, postoperative pain, malignant tumor, and frontal approach craniotomy. ED was associated with increased postoperative delirium, longer length of hospital stay, and higher hospitalization costs. There was no significant difference in the neurological function deficits (modified Rankin Scale score) between ED and non-ED groups. Conclusions ED has a high incidence and is associated with poor outcomes in adults after elective brain tumor resection. Early screening and prevention for ED should be established in perioperative management of this population.

Failure mode and effects analysis (FMEA) is a systematic and proactive risk prevention and management tool used to improve the reliability and safety of a system, process or service. However, many defects around the traditional FMEA affect the effectiveness of its practical applications. When dealing with the FMEA problems, the first and the most important step is to collect the risk assessment information of experts regarding failure modes. Moreover, clustering failure modes is more adaptable to actual needs, especially under a tight resource constraint. In this article, a new FMEA model using double hierarchy hesitant fuzzy linguistic term sets (DHHFLTSs) and k-means clustering is developed to evaluate and cluster the risk of failure modes. First, the DHHFLTSs are utilized to describe the complex linguistic assessments on failure modes given by FMEA team members. Next, an improved k-means algorithm is proposed and used to cluster failure modes into priority classes. Finally, a case study concerning the risk evaluation over floating offshore wind turbine is provided to illustrate the effectiveness and usefulness of our proposed FMEA. The results show that the new risk classification approach is more reasonable and practical for risk management decision making.

BACKGROUND AND OBJECTIVE Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p

Background Oxidative stress and memory impairment have been implicated, a common functional brain disease. Nuclear factor E2-related factor 2 (Nrf2) is highly induced in oxidative stress, indicating that Nrf2 is an emerging target of memory therapy. This study aimed to investigate the effect of Noni on brain memory impairment induced by hydrocortisone and its protection mechanism in mice. Methods Male Kuming mice were (n = 8/group) given hydrocortisone by gastric gavage for 14 consecutive days to establish the memory impairment model except for those in the control group. At the same day, the corresponding drugs were given by gastric gavage. The changes in ethology were examined. Brains were extracted and subjected to western blot analysis and biochemical analyses to assess the activities of oxidative stress. Results The middle and high-dose Noni groups ameliorated the ethology and the high-dose Noni group increased cerebral protein expressions of Nrf2, kelch-like ECH-associated protein 1 (KEAP1) and heme oxygenase-1 (HO-1), as compared to the model group. The arrangement of CA3 vertebral cells in hippocampus of mice was slightly compact and hyperchromatic and pyknosis were alleviated. Furthermore, the biochemical analyses showed the activities of related enzymes of oxidative stress in high-dose Noni group were increased. Conclusions Noni might be a powerful antioxidant that can protect nerve cell and may possess as a potential benefit for the treatment of memory impairment.

This article presents a programmable multiple frequencies clock generator with a process and temperature compensation circuit design. The proposed clock generator can achieve a stable and wide frequency range output for a single input frequency by using digital control codes as well as process and temperature compensation mechanisms. In our approach, the first step is to adjust the duty-cycle of the input clock by using a digitally controlled pulsewidth modulator (DCPWM) to generate an output clock signal with a duty-cycle of 20% to 80%. Second, the various duty-cycle clock outputs of the DCPWM are integrated by the duty-cycle-to-voltage converter to generate analog voltage signals to control the succeeding voltage-controlled ring oscillator (VCO). Through the use of various control voltages, different VCO output frequencies are generated. Finally, by using the process and temperature compensation circuit, the proposed clock generator can provide a stable and wide frequency range. The proposed chip is fabricated in a 180-nm CMOS process and has an output frequency range of 35–138 MHz at a supply voltage of 0.9 V. At 120 MHz, the power dissipation and rms jitter are 224.3 μW and 7.84 ps, respectively. The active area of the chip is 0.62 mm × 0.76 mm.

Web3.0, often cited to drastically shape our lives, is ubiquitous. However, few literatures have discussed the crucial differentiators that separate Web3.0 from the era we are currently living in. Via a thorough analysis of the recent blockchain infrastructure evolution, we capture a key invariant featuring the evolution, based on which we provide the first academic definition for Web3.0. Our definition is not the only way of understanding Web3.0, yet, it captures the fundamental and defining trait of Web3.0, and meanwhile it is has two desirable properties. Under this definition, we articulate three key infrastructural enablers for Web3.0: individual blockchains, federated or centralized platforms capable of publishing verifiable states, and an interoperability platform to hyperconnect those state publishers. While innovations in all categories are necessary to fully enable Web3.0, in this paper, we present a design for the third enabler, namely HyperService, that delivers interoperability and programmability across heterogeneous blockchains and state publishers. HyperService is powered by two innovative designs: a developer-facing programming framework that allows developers to build cross-chain applications in a unified programming model; and a secure blockchain-facing cryptography protocol that provably realizes those applications on blockchains. We implement a prototype of HyperService in 62,000 lines of code to demonstrate its practicality, usability, and scalability.

Background Herpes zoster presents as clustered blisters on one side of the body, accompanied by nerve pain. This is caused by reactivation of the varicella zoster virus, and it occurs primarily in people with weakened immunity. Tumor and chemotherapy drugs can impair the patient's immune function, induce herpes zoster and prolong the course of disease.In these patients, skin changes can last for months and blisters can recur and cause serious complications such as postherpetic neuralgia.Acupuncture is a common alternative therapy for herpes zoster in East Asia. Case presentation We report a case of an elderly male patient with widespread herpes zoster in the trunk after non-Hodgkin's lymphoma chemotherapy. The patient had received conventional treatment with valaciclovir and mecobalamin within 24 hours of symptom onset. Because neither the clustered blisters nor the nerve pain were improved a week later, acupuncture and related techniques were applied. These included electro-acupuncture, surrounding acupuncture, fire acupuncture, and cupping. The patient recovered 20 days after the herpes zoster attack, and there were no adverse reactions during the treatment process. Conclusions This case suggests that acupuncture and related techniques are effective interventions for this condition.This case report is innovative because it shows that acupuncture as an adjuvant treatment can improve the skin lesions in patients with HZ after tumour chemotherapy, relieve pain, and shorten the course of HZ.

In the last two decades, fall detection (FD) systems have been developed as a popular assistive technology. Such systems automatically detect critical fall events and immediately alert medical professionals or caregivers. To support long-term FD services, various power-saving strategies have been implemented. Among them, a reduced sampling rate is a common approach for an energy-efficient system in the real-world. However, the performance of FD systems is diminished owing to low-resolution (LR) accelerometer signals. To improve the detection accuracy with LR accelerometer signals, several technical challenges must be considered, including misalignment, mismatch of effective features, and the degradation effects. In this work, a deep-learning-based accelerometer signal enhancement (ASE) model is proposed to improve the detection performance of LR-FD systems. This proposed model reconstructs high-resolution (HR) signals from the LR signals by learning the relationship between the LR and HR signals. The results show that the FD system using support vector machine and the proposed ASE model at an extremely low sampling rate (sampling rate < 2 Hz) achieved 97.34% and 90.52% accuracies in the SisFall and FallAllD datasets, respectively, while those without ASE models only achieved 95.92% and 87.47% accuracies in the SisFall and FallAllD datasets, respectively. This study demonstrates that the ASE model helps the FD systems tackle the technical challenges of LR signals and achieve better detection performance.

RationalePulmonary fibrosis is a devastating lung disease with few therapeutic options. Chitinase 1 (CHIT1), an 18 glycosyl hydrolase family member, contributes to the pathogenesis of pulmonary fibrosis through regulation of Transforming Growth Factor (TGF)-β signaling and effector function. Therefore, CHIT1 is a potential therapeutic target of pulmonary fibrosis.ObjectivesThis study aimed to identify and characterize a druggable CHIT1 inhibitor with strong antifibrotic activity and minimal toxicity for therapeutic application to pulmonary fibrosis.MethodsExtensive screening of small molecule libraries identified the aminoglycoside antibiotic Kasugamycin as a potent CHIT1 inhibitor.Measurements and Main ResultsElevated levels of CHIT1 were detected in the lungs of patients with pulmonary fibrosis. In vivo bleomycin- and TGF-β-stimulated murine models of pulmonary fibrosis, Kasugamycin showed impressive anti-fibrotic effects in both preventive and therapeutic conditions. In vitro studies also demonstrated that Kasugamycin inhibits fibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation. Null mutation of transforming growth factor beta associated protein 1 (TGFBRAP1), a recently identified CHIT1 interacting signaling molecule, phenocopied antifibrotic effects of Kasugamycin in in vivo lungs and in vitro fibroblasts responses. Kasugamycin inhibits physical association between CHIT1 and TGFBRAP1, suggesting that antifibrotic effect of Kasugamycin is mediated through regulation of TGFBRAP1, at least in part.ConclusionsThese studies demonstrate that Kasugamycin is a novel CHIT1 inhibitor with strong antifibrotic effect that can be further developed as an effective and safe therapeutic drug for pulmonary fibrosis.

Background Age‐related muscle dysfunctions are common disorders resulting in poor quality of life in the elderly. Probiotic supplementation is a potential strategy for preventing age‐related sarcopenia as evidence suggests that probiotics can enhance muscle function via the gut–muscle axis. However, the effects and mechanisms of probiotics in age‐related sarcopenia are currently unknown. In this study, we examined the effects of Lactobacillus casei Shirota (LcS), a probiotic previously reported to improve muscle function in young adult mice. Methods We administered LcS (1 × 108 or 1 × 109 CFU/mouse/day) by oral gavage to senescence‐accelerated mouse prone‐8 mice for 12 weeks (16‐ to 28‐week‐old). Sixteen‐week‐old and 28‐week‐old SMAP8 mice were included as non‐aged and aged controls, respectively. Muscle condition was evaluated using dual‐energy X‐ray absorptiometry for muscle mass, holding impulse and grip strength tests for muscle strength, and oxygen consumption rate, gene expressions of mitochondrial biogenesis, and mitochondrial number assays for mitochondria function. Inflammatory cytokines were determined using enzyme‐linked immunosorbent assay. Gas chromatography–mass spectrometry was utilized to measure the short‐chain fatty acid levels. The gut microbiota was analysed based on the data of 16S rRNA gene sequencing of mouse stool. Results The LcS supplementation reduced age‐related declines in muscle mass (>94.6%, P 66% in holding impulse and >96.3% in grip strength, P 65.9% in the mice given high dose of LcS, P 89.4%, P 2.0] were positively correlated with healthy muscle and physiological condition (P 2.0) were negatively associated with healthy muscle and physiological condition (P

Predicting customer repurchase propensity/frequency has received broad research interests from marketing, operations research, statistics, and computer science. In the field of marketing, Buy till You Die (BTYD) models are perhaps the most representative techniques for customer repurchase prediction. Those probabilistic models are parsimonious and typically involve only recency and frequency of customer activities. Contrary to BTYD models, a distinctly different class of predictive models for customer repurchase is machine learning. This class of models include a wide variety of computational and statistical learning algorithms. Unlike BTYD models built on low-dimensional inputs and behavioral assumptions, machine learning is more data-driven and excels at fitting predictive models to a large array of features from customer transactions. Using a large online retailing data, we empirically assess the prediction performance of BTYD modeling and machine learning. More importantly, we investigate how the two approaches can complement each other for repurchase prediction. We use the BG/BB model given the discrete and non-contractual problem setting and incorporate BG/BB estimates into high-dimensional Lasso regression. In addition to showing significant improvement over BG/BB and Lasso without BG/BB, the integrated Lasso-BG/BB provides interpretability and identifies BG/BB predictions as the most influential feature among ∼100 predictors. The lately developed CART-artificial neural networks exhibit similar patterns. Robustness checks further show the proposed Lasso-BG/BB outperforms two sophisticated recurrent neural networks, validating the complementarity of machine learning and BTYD modeling. We conclude by articulating how our interdisciplinary integration of the two modeling paradigms contributes to the theory and practice of predictive analytics.

Background/Purpose: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes. Methods: Plasma samples were collected from patients with AIS at

Recent studies support the development of cancer therapeutics to target Globo H-ceramide, the most prevalent tumor-associated carbohydrate antigen in epithelial cancers. Herein, we evaluated the expression of Globo H and its prognostic significance in intrahepatic cholangiocarcinoma (ICC) and conducted preclinical studies to assess the antitumor activity of Globo H-specific antibody in thioacetamide (TAA)-induced ICC in rats. Globo H-ceramide in tumor specimens was detected by immunohistochemistry (IHC) and mass spectrometry. Antitumor efficacy of anti-Globo H mAbVK9 was evaluated in TAA-induced ICC in rat. Natural killer (NK) cells and their related genes were analyzed by IHC and quantitative real-time polymerase chain reaction. Data mining revealed that B3GALT5 and FUT2, the key enzymes for Globo H biosynthesis, were significantly up-regulated in human ICC. In addition, Globo H expression was detected in 41% (63 of 155) of ICC tumor specimens by IHC staining, and validated by mass spectrometric analysis of two IHC-positive tumors. Patients with Globo H positive tumors had significantly shorter relapse-free survival (RFS) and overall survival (P = 0.0003 and P = 0.002, respectively). Multivariable Cox regression analysis identified Globo H expression as an independent unfavorable predictor for RFS (hazard ratio: 1.66, 95% confidence interval: 1.08-2.36, P = 0.02) in ICC. Furthermore, gradual emergence of Globo H in liver tissues over 6 months in TAA-treated rats recapitulated the multistage progression of ICC in vivo. Importantly, administration of anti-Globo H mAbVK9 in rats bearing TAA-induced ICC significantly suppressed tumor growth with increased NK cells in the tumor microenvironment. Conclusion: Globo H is a theranostic marker in ICC.

Background/purpose: Increasing evidence indicates an association of video laryngoscopy with the success rate of airway management in patients with neck immobilization. Nevertheless, clinical practice protocols for tracheal intubation in patients immobilized using various types of cervical orthoses and the outcomes remain unclear. Methods: We retrospectively assessed the tracheal intubation techniques selected for patients immobilized using cervical orthoses from 2015 to 2018. The endpoints were the intubation outcomes of the different techniques and the factors associated with the selection of the technique. Results: We included 218 patients, 118 of whom wore halo vest braces (halo vest group) and 100 wore cervical collars (collar group). GlideScope video laryngoscopy (GVL) and fiberoptic bronchoscopy (FOB) were the initial intubation methods in 98 and 120 patients, respectively. GVL had a higher first-attempt success rate than did FOB in the collar group (p = 0.002) but not in the halo vest group (p = 0.522). GVL was associated with a lower risk of episodes of SaO2< 90% (adjusted relative risk [aRR], 0.11; 95% CI, 0.02–0.67; p = 0.016) and shorter intubation time (aRR, −3.52; 95% CI, −4.79∼−2.25; p

Background: For patients with nonmetastatic renal cell carcinoma (nmRCC) treated with nephrectomy, prediction of cancer-specific mortality (CSM) by T stage and substage has not been validated for the separate histological subtypes. Objective: To investigate the ability of pathological T stage and substage to predict CSM for patients with clear-cell, papillary, or chromophobe nmRCC treated with nephrectomy. Design, setting, and participants: Using the SEER database for 2004–2016, we identified 87 149 patients with T1–4 N0/X M0 nmRCC treated with nephrectomy for the clear-cell (65 715; 75.4%), papillary (14 587; 16.7%), or chromophobe (6847; 7.9%) histological subtype. Outcome measurements and statistical analysis: Kaplan-Meier plots and Cox regression models were used to estimate CSM. Results and limitations: For all three histological subtypes, patients with T1a–T3a disease exhibited more favorable CSM than patients with T3b–T4 RCC. For clear-cell RCC, there were clinically meaningful and statistically significant differences for virtually all intergroup comparisons among T1a–T3a stages. For papillary T1a–T3a RCC, clinically meaningful differences disappeared, although the statistical significance remained. For chromophobe T1a–T3a RCC, no clinically meaningful or statistically significant differences were observed. For all three histological subtypes, patients with T3b–T4 RCC exhibited virtually uniformly unfavorable CSM, with no clinically meaningful intergroup CSM differences. Conclusion: The use of T stage and substage for stratification of patients with nmRCC treated with nephrectomy revealed differences in CSM among T1a–T3a cases, but not T3b–T4. The magnitude of the CSM difference was greatest for clear-cell, intermediate for papillary, and marginal for chromophobe RCC. Patient summary: For patients with kidney cancer, the stage of their disease assessed after surgery on the affected kidney can predict how likely they are to die from their cancer. This prediction varies for different subtypes of kidney cancer. Stratification of surgically treated patients with nonmetastatic renal cell carcinoma (RCC) by T stage revealed mortality differences among T1a–T3a cases, but not T3b–T4 cases. The magnitude of the differences was greatest for the clear-cell subtype, intermediate for papillary histology, and marginal for chromophobe RCC.

Imatinib is a crucial therapeutic strategy against chronic myeloid leukemia. Though superficial edema is a common adverse effect of imatinib, massive fluid retention is rarely reported. Here, we report the case of an adolescent who had tolerated imatinib for a long time, and then presented with massive pleural/pericardial effusion during an episode of Campylobacter jejuni bacteremia. A stepwise and comprehensive survey excluded all other plausible causes of disease. The Naranjo scale was used to assess the probability of an adverse effect of medication, and the score turned out to be 9, indicating severe fluid retention to be a definite reaction to imatinib. Drug discontinuation, antibiotic administration, and invasive procedures improved this condition. After this episode, the patient could tolerate imatinib again, illustrating the transient and reversible nature of this reaction. Since prolonged imatinib usage is crucial for chronic myeloid leukemia control, alertness to drug-related adverse effects is recommended, even if the subject has previously shown a good tolerance to the drug due to various physical conditions, especially physiological stressors, like infection or inflammation.

Background Life expectancy (LE) is an important consideration in the clinical decision-making for T1aN0M0 renal cell cancer (RCC) patients. Objective To test the effect of race/ethnicity (Caucasian, African American, Hispanic/Latino, and Asian) on LE predictions from Social Security Administration (SSA) life tables in male and female T1aN0M0 RCC patients. Design, setting, and participants We relied on the Surveillance, Epidemiology, and End Results database. Intervention Radical nephrectomy (RN) and partial nephrectomy (PN). Outcome measurements and statistical analysis Five-year and 10-yr observed overall survival (OS) of pT1aN0M0 RCC patients treated between 2004 and 2006 were compared with the LE predicted from SSA life tables. We repeated the comparison in a more contemporary cohort (2009–2011), with 5-yr follow-up and higher PN rates. Results and limitations In the 2004–2006 cohort, PN rate was 40.7%. OS followed the predicted LE in Caucasians, Hispanics/Latinos, and Asians, but not in African Americans, in whom 5-yr OS rates were 5.0% (male) and 8.7% (female) and 10-yr rates were 4.2% (male) and 11.1% (female) lower than predicted. In the 2009–2011 cohort, PN rate was 59.4%. Same observations were made for OS versus predicted LE in Caucasians, Hispanics/Latinos, and Asians. In African Americans, 5-yr OS rates were 1.5% (male) and 4.9% (female) lower than predicted. Conclusions In RN- or PN-treated pT1aN0M0 RCC patients, LE predictions closely approximated OS of Caucasians, Hispanics/Latinos, and Asians. In African-American patients, SSA life tables overestimated LE, more in females than in males. The limitations of our study are its retrospective nature, its validity for US patients only, and the under-representation of racial/ethnic minorities. Patient summary Social Security Administration life tables can be used to estimate long-term life expectancy in patients who are surgically treated for renal cancer (≤4 cm). However, while for Caucasians, Hispanics/Latinos, and Asians, the prediction performs well, life expectancy of African Americans is generally overestimated by life table predictions. Take Home Message In the clinical decision-making process for T1aN0M0 renal cell cancer patients eligible for radical or partial nephrectomy, the important influence of patient sex and race/ethnicity on life expectancy should be taken into account, when using Social Security Administration life tables.

Objective To assess the predictive value of swab cultures of cryopreserved skull flaps during cranioplasties for surgical site infections (SSIs). Methods A retrospective review was conducted of consecutive patients who underwent delayed cranioplasties with cryopreserved autografts between 2009 and 2017. The results of cultures obtained from swabs and infected surgical sites were assessed. The accuracy, sensitivity, and specificity of swab cultures for SSIs were evaluated. Results The study included 422 patients categorized into two groups, swab and nonswab, depending on whether swab cultures were implemented during cranioplasties. The overall infection rate was 7.58%. No difference was seen in infection rates between groups. There were 18 false-positive and no true-positive swab culture results. All bacteria between swab cultures and SSI cultures were discordant. Meanwhile, there were 19 false-negative swab cultures. The results showed high specificity but low sensitivity for swab cultures to predict SSI occurrence and the pathogens. Conclusions Owing to low accuracy and sensitivity, swab cultures of cryopreserved autografts should not be routinely performed during delayed cranioplasties.

The sonographic appearance of benign and malignant breast nodules overlaps to some extent, and we aimed to assess the performance of the Gail model as an adjunctive tool to ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) for predicting the malignancy of nodules.From 2018 to 2019, 2607 patients were prospectively enrolled by 35 health care facilities. An individual breast cancer risk was assessed by the Gail model. Based on B-mode US, color Doppler, and elastography, all nodules were evaluated according to the fifth edition of BI-RADS, and these nodules were all confirmed later by pathology.We demonstrated that the Gail model, age, tumor size, tumor shape, growth orientation, margin, contour, acoustic shadowing, microcalcification, presence of duct ectasia, presence of architectural distortion, color Doppler flow, BI-RADS, and elastography score were significantly related to breast cancer (all p0.001). The sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the curve (AUC) for combining the Gail model with the BI-RADS category were 95.6%, 91.3%, 85.0%, 97.6%, 92.8%, and 0.98, respectively. Combining the Gail model with the BI-RADS showed better diagnostic efficiency than the BI-RADS and Gail model alone (AUC 0.98 vs 0.80, p0.001; AUC 0.98 vs 0.55, p0.001) and demonstrated a higher specificity than the BI-RADS (91.3% vs 59.4%, p0.001).The Gail model could be used to differentiate malignant and benign breast lesions. Combined with the BI-RADS category, the Gail model was adjunctive to US for predicting breast lesions for malignancy. For the diagnosis of malignancy, more attention should be paid to high-risk patients with breast lesions.

Background Although epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs) have been the standard treatment for advanced EGFR‐mutant adenocarcinoma, the effects of upfront EGFR‐TKI use in unresectable stage III EGFR‐mutant adenocarcinoma remain unexplored. Here, we conducted a retrospective study to compare different treatment strategies in these patients. Methods From October 2010 to June 2019, patients with unresectable stage III adenocarcinoma who received treatment at a tertiary referral center were enrolled. Patients were classified into three groups: EGFR‐mutant adenocarcinoma treated with concurrent chemoradiotherapy (group 1) or EGFR‐TKI (group 2) and EGFR wild‐type adenocarcinoma treated with concurrent chemoradiotherapy (group 3). Progression‐free survival, progression‐free survival‐2, and overall survival were estimated and compared using Kaplan–Meier and log‐rank tests. Results A total of 92 patients were enrolled; 10, 40, and 42 patients were assigned to groups 1, 2, and 3, respectively. Patients with EGFR mutations who received upfront EGFR‐TKIs had significantly longer progression‐free and overall survival than those who received upfront concurrent chemoradiotherapy (hazard ratio 0.33 vs. 0.34, p = 0.006 vs. 0.031) according to a Cox model adjusted for possible confounders. Moreover, upfront concurrent chemoradiotherapy did not lead to higher survival rates in patients with EGFR mutations than in those with EGFR wild‐type adenocarcinoma (progression‐free survival; hazard ratio 0.37, p = 0.036; overall survival; hazard ratio 0.35, p = 0.080) by Cox regression analysis. Conclusion This current study suggests that EGFR‐TKIs is a better choice for patients with unresectable stage III EGFR‐mutant adenocarcinoma. However, further randomized studies are required to validate the results., The study regarding comparison of upfront EGFR‐TKI and upfront CCRT in unresectable stage III EGFR‐mutant adenocarcinoma remain limited. Our real‐world data suggest that upfront EGFR‐TKI monotherapy is a better treatment strategy than upfront CCRT in unresectable stage III EGFR‐mutant adenocarcinoma.

Objective To determine the risk and time trends of hospitalized heart failure (HF) in individuals with newly diagnosed polymyositis (PM) and dermatomyositis (DM) at the general population level. Methods We conducted a retrospective cohort study using a nationwide insurance database in Taiwan. Patients with incident PM/DM and without previous histories of HF were selected between 2000 and 2013. Unmatched and propensity score-matched cohorts were established separately. Multivariable Cox proportional hazard regression model was used to estimate adjusted hazard ratios (HRs) in the unmatched population. In the propensity-matched cohort, controls were selected and matched to the PM/DM group at a 1:1 ratio based on propensity scores, which accounted for confounding factors: sex, age, year of index date, comorbidities, and medication exposure. The cumulative HF incidence was estimated with Kaplan-Meier method. A stratified Cox model was used to calculate HR for HF events in the matched cohort. Results There were 2025 PM/DM patients and 196,109 controls in the unmatched cohort. Multivariable Cox regression model adjusted for age, sex, comorbidities, and medication use revealed a greater risk of hospitalized HF in the PM/DM than in the control groups (adjusted HR: 3.29, 95% confidence interval [CI]: 2.60-4.18). After propensity score matching, a total of 1997 pairs of PM/DM patients and controls were identified. The cumulative HF incidence at 3, 5, and 10 years in patients with PM/DM were 3.3%, 4.4%, and 7.4%, respectively. The absolute risk difference in the PM/DM group versus controls were 1.8% at 3 years, 2.1% at 5 years and 3.0% at 10 years. Compared with non-PM/DM individuals, PM/DM patients exhibited an augmented HF risk (HR: 2.06, 95% CI: 1.36-3.12]. The stratified analysis according to follow-up period revealed that the increased risk of HF persisted for up to 10 years after the PM/DM diagnosis. Conclusions Our results indicated an increased risk of hospitalized HF in patients with PM/DM throughout the study period, supporting the need for increased vigilance and monitoring patients with PM/DM for this potential lethal complication.

The fabrication process and light extraction efficiency of AlGaInP-based flip-chip micro- light-emitting diode ( $\mu $ -LED) array chips are improved by employing a wafer-bonding process, patterned metal contact, and sidewall passivation layers. The epilayers with indium tin oxide (ITO) can be successfully transferred from the GaAs substrate to the sapphire substrate and bound. Three types of patterned n-metal are employed in the $\mu $ -LED as a self-aligning mask and light reflection layer, where the n-GaAs layer can be partially removed by the wet etching process. The dry etching process of MESA has been optimized by applying the BCl3 gas in the inductively coupled plasma (ICP) system, which can suppress the etching rate of the sidewall and improve the etching depth uniformity. Consequently, the leakage current of the $\mu $ -LED array chip is decreased from 85 to 7 nA under the bias of −5 V. Moreover, three configurations of the metal contact/n-GaAs structures with Omnidirectional reflector (ODR) have been designed to reduce the emission light absorption, passivating the sidewall of MESA, and enhance the output power. Finally, the 0.52-in red $\mu $ -LED array with a chip size of $100\,\,\mu \text{m}\,\,\times 100\,\,\mu \text{m}$ and resolution of 138 pixels/in is realized when bonded with the drive IC. Consequently, the $\mu $ -LED array chips with ODR and patterned contact show the highest external quantum efficiency of 51.1% and relative output power enhancement of 441% compared to the chip with SiO2 passivation layer and nonpatterned n-metal contact.