Search

Organisms that alter body color undergo color change in response to environmental variations and stimuli by combining chromatophores that develop colors by various mechanisms. Inspired by their body color changes, we can develop sensors and optical materials that change colors in response to multiple stimuli, such as mechanical and light stimuli. In this study, we report on bioinspired composite elastomers that exhibit various color changes as the pigment color, structural color, and background color change. These composite elastomers exhibit structural colors due to their fine structures in which fine silica particles form colloidal crystals, and the structural colors reversibly change as the elastomers elongate. Furthermore, photochromic dyes can reversibly change color depending on the wavelength of irradiated light when they are introduced to the composite elastomers. Since the structural color is one of the three primary colors of light and the pigment color is the color that corresponds to the three primary colors of a pigment, each color becomes vivid when the background color is black or white. Thus, we clarify that the composite elastomers exhibit various color changes due to the combination of structural color change in response to the mechanical stimulus, pigment color change in response to light irradiation, and background color change.

Cancer is one of the world's biggest healthcare burdens and despite the current advancements made in treatment plans, the outcomes for oncology patients have yet to reach their full potential. Hence, there is a pressing need to develop novel anti-cancer drugs. A popular drug class for research are natural compounds, due to their multi-targeting potential and enhanced safety profile. One such promising natural bioactive compound derived from a vine, Tripterygium wilfordii is celastrol. Pre-clinical studies revolving around the use of celastrol have revealed positive pharmacological activities in various types of cancers, thus suggesting the chemical's potential anti-cancerous effects. However, despite the numerous preclinical studies carried out over the past few decades, celastrol has not reached human trials for cancer. In this review, we summarize the mechanisms and therapeutic potentials of celastrol in treatment for different types of cancer. Subsequently, we also explore the possible reasons hindering its development for human use as cancer therapy, like its narrow therapeutic window and poor pharmacokinetic properties. Additionally, after critically analysing both in vitro and in vivo evidence, we discuss about the key pathways effected by celastrol and the suitable types of cancer that can be targeted by the natural drug, thus giving insight into future directions that can be taken, such as in-depth analysis and research of the druggability of celastrol derivatives, to aid the clinical translation of this promising anti-cancer lead compound.

A 128-b rapid single-flux-quantum (RSFQ) Advanced Encryption Standard (AES) encryption accelerator based on bit-slice architecture is proposed for the first time. Unlike the traditional methods, the method of looking up only one 256-B table to complete the entire AES round function is proposed. The proposed method can reduce nearly 50% of the hardware cost compared to the traditional method. The simple lookup table, shift, and xor operations are used in the proposed accelerator where one 256-B table needs to be stored for lookup table operations. The RSFQ logic circuits of the proposed accelerator are designed and simulated at the logic level. It consists of 136 558 JJs based on the Open Dataset of CONNECT Cell Library for AIST ADP2. The simulation results show the proposed accelerator works correctly.

As embodied in Malaysia's Vision 2020, Malaysia aims to become a cashless country. Therefore, the existing statistical data indicated that the e-wallet adoption rate remains at a low percentage. It has been a barrier for Malaysia in achieving the aims to become a cashless country. The use of e-wallet was also expected to rise amidst the Covid-19 pandemic; to optimize an intervention for the Covid-19 outbreak. Thus, the current study investigates the factors that correlate with the intention to use e-wallet during the Covid-19 pandemic. This study is designed using a quantitative approach through cross-sectional data. A total of 160 Malaysian youths participated and collected by using an online survey. Further, the Task-Technology Fit (TTF) model and Technology Acceptance Model (TAM) were integrated into this study with an extended variable, namely, perceived credibility. The analysis results showed that Individual-Technology Fit, Task-Technology Fit, Perceived Usefulness, Perceived Ease of Use and Perceived Credibility were significantly correlated to Covid19 intra-period e-wallet adoption. In conclusion, a considerable theoretical contribution was demonstrated by integrating TTF-TAM and Perceived Credibility in a single integrated model. The constructs in the TTF model (i.e., Individual-technology fit and task-technology fit) has positively related to the constructs in the TAM model (i.e., perceived usefulness and perceived ease of use). This study is useful to stakeholders and provides enhanced directions to meet market needs by understanding and predicting e-wallet user's post-pandemic behavior, thereby helping service providers attract new users and retain their existing users.

Individuals with genetic defects show an increased susceptibility to poorly pathogenic mycobacteria including nontuberculous mycobacteria and Bacillus Calmette-Guerin (BCG). In previous studies, defects in multiple genes were identified to be associated with mycobacterium infection including tyrosine kinase 2 (TYK2). The mutations lead to insufficient production of interferon (IFN)-γ or an insufficient response to IFN-α/β, interleukin (IL)-6, IL-10, IL-12 and IL-23. Herein, we describe a case of Mycobacterium intracellulare infection in a male with abdominal pain and diarrhea. Whole exome sequencing of the genomes revealed a compound heterozygous mutation (c.3083A>G/c.2590C>T, p.N1028S/p.R864C) in the TYK2 gene. The patient recovered after two years of anti-mycobacterial treatment and no relapse was observed so far. We also reviewed 24 cases of mycobacterial infection associated with TYK2 deficiency which provides evidence of how personalised genomics can improve outcomes.

Introduction True non-traumatic radial artery aneurysms (RAAs) are extremely rare, and few cases have been described. The majority of RAAs are post-traumatic or iatrogenic pseudo-aneurysms following arterial cannulation. However, RAAs due to other causes have also been described. Here a rare case of true idiopathic distal RAA, which was managed by surgical resection and repair with interposition vein graft, is described. Report A 62 year old female with a known medical history of hypertension and hyperlipidaemia presented with left wrist swelling of one year duration, associated with a pulsatile lump that was increasing in size. Duplex ultrasound and computed tomography angiography revealed a distal RAA. She underwent open surgical resection and repair with interposition vein graft using the distal left cephalic vein. Histopathology of the specimen revealed an aneurysm with atherosclerosis. She recovered well post-operatively with no complications. Discussion True idiopathic RAAs are rare. Surgical treatment is almost always recommended in view of the risk of complications. A case of true idiopathic distal RAA is presented here, which was managed successfully by surgical resection and repair with interposition vein graft., Highlights • True radial artery aneurysms are extremely rare; most are post-traumatic or iatrogenic. • Options include observation, excision with ligation, primary repair or interposition graft. • Surgery is usually recommended due to risk of complications and has minimal morbidity.

Purpose Tuberculosis remains a major public health problem globally, especially in undeveloped countries. This study aimed to evaluate and review the long-term epidemic trends of tuberculosis in China. Methods Data were extracted from the Global Health Data Exchange. Metrics (prevalence, incidence and mortality) and Joinpoint regression were used to identify the epidemic trends. Results From 1990 to 2017, decreasing trends in prevalence (average annual percent change, AAPC: -0.5%, 95% CI: -0.6% to -0.5%), incidence (-3.2%, 95% CI: -3.5% to -2.9%), and mortality (-5.7%, 95% CI: -6.2% to -5.3%) of tuberculosis were observed. The incidence and mortality of multidrug-resistant tuberculosis (MDR-TB) decreased with AAPC of -2.3% (-3.1% to -1.4%) and -4.9% (-5.4% to -4.5%), respectively, while the prevalence increased with an AAPC of 1.2% (0.3% to 2.0%). The burden of extensively drug-resistant tuberculosis (XDR-TB) increased with an AAPC of 12.5% (11.9% to 13.2%) in prevalence, 7.6% (6.5% to 8.7%) in incidence, and 4.5% (3.6% to 5.4%) in mortality. The disease burden of tuberculosis increased with age and peaked among those aged over 70. Conclusion The epidemic of tuberculosis decreased in China, while the disease burden was still challenging to control. MDR-TB and XDR-TB should be emphasized along with the epidemic. It will certainly be a difficult task to achieve the post-2015 global targets by 2025 and 2035.

Background: Nonalcoholic fatty liver disease (NAFLD) is commonly occurred in the non-obese individuals. The serum uric acid (UA) to high-density lipoprotein cholesterol (HDL-c) ratio (UHR) is considered as a predictive factor of NAFLD. However, it is still difficult to confirm the correlation in lean Chinese people with normal blood lipid levels. It is aimed to analyze the correlation of UHR with NAFLD among lean Chinese population without dyslipidemia and compared UHR with other predictors in this study.Methods: 9838 lean people without NAFLD were included in a retrospective cohort study. NAFLD was diagnosed by liver ultrasound.Results: A total of 9,838 lean patients with normal blood lipid levels were included in the final study. During the five-year follow-up period, the overall prevalence of NAFLD was 8.7%. across the quintile 1, 2, 3, 4 and 5 of UHR, the prevalence of NAFLD among lean patients was increased from 2.4%, 5%, 7.9%, 10.3% to 17.8%. After adjustment for age, markers of liver and kidney function, gender and metabolic indicators, multivariate cox proportional hazard regression analysis demonstrated that the hazard ratio(HR) was 1.99(1.43-2.73) in highest UHR (quintile 5) compared with lowest UHR(quintile 1). The area under the curve(AUC) of UHR (0.690) was higher than in UA (0.666) and HDL-c (0.636), which showed that the predictive ability of the UHR to new-onset NAFLD was better than serum uric acid and HDL-c. Even within the normal range of UA and HDL-c levels, UHR was independently associated with NAFLD, and HR (95% confidence interva, 95%CI) for NAFLD in Quintile 5 of UHR was 6.74(4.32-10.53). Compared with other significant predictors, the AUC value of UHR(0.67) was similar to that of low-density lipoprotein cholesterol(LDL-c)/HDL-c ratio(0.68), non-high-density lipoprotein cholesterol (NHDL-c)/HDL-c ratio(0.68) and alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) ratio(0.7), and superior to that of LDL-c (0.63), remnant cholesterol (RC,0.59), albumin(ALB)/alkaline phosphatase(ALP) ratio(0.61). The sensitivity of UHR (70.5%) was the highest among all indicators. In the subgroup of ALT, the AUC of UHR was 0.70, which was the highest among all predictors in subjects with ALT< 40. For subjects with elevated ALT levels (ALT > 40 U/L), there was no statistical significance among RC (P=0.441), ALB/ALP (P=0.419) and ALT/AST(P=0.159). In contrast, UHR's performance in predicting NAFLD was meaningful and reliable (AUC=0.61, pConclusions: UHR serve as an inexpensive and reliable predictor of NAFLD in lean Chinese people with normal blood lipid levels. It can be used to identify people at high risk of NAFLD.

Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed. Methods This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors. Conclusion This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.

Alternative antimicrobial therapies are urgently needed for a variety of multidrug-resistant bacterial pathogens. Faropenem is an orally available β-lactam in the class of carbapenem antibiotics. Thus far, little information is available on faropenem susceptibility of multidrug-resistant clinical isolates from China. Therefore, in the current study 141 contemporary clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA: n = 18), coagulase-negative staphylococci (CNS: n = 16), Enterococcus faecalis (n = 14), Enterococcus faecium (n = 7), Pseudomonas aeruginosa (n = 25), Klebsiella pneumoniae (n = 21), Escherichia coli (n = 20), and Acinetobacter baumannii (n = 20), were collected between March 2018 and March 2019 and tested for susceptibility to faropenem and other antimicrobials using the broth microdilution method. All E. faecium, P. aeruginosa, and A. baumannii isolates were fully resistant to faropenem. However, most of the MRSA, CNS, E. faecalis, K. pneumonia, and E. coli isolates appeared to be susceptible to faropenem, with minimal inhibitory concentration90 values of 4 mg/L, 2 mg/L, 2 mg/L, 4 mg/L, and 2 mg/L, respectively. Therefore, faropenem could be considered as alternative therapy for future treatment of multidrug-resistant MRSA, CNS, E. faecalis, K. pneumonia, and E. coli infections in China.

Water quality monitoring using Wireless Sensor Networks (WSNs) is essential in aquaculture water quality management. In the field of water quality monitoring, dissolved oxygen (DO) is a key parameter, and its prediction can provide decision support for aquaculture production, thereby reducing farming risk. However, it is difficult to build a precise prediction model, and existing methods of DO prediction neglect the importance of analyzing DO content. To address this problem, this study proposes a hybrid DO prediction model, named KIG-ELM, which is composed of K-means, improved genetic algorithm (IGA), and extreme learning machine (ELM). This model is based on edge computing architecture, in which data acquisition, processing and dissolved oxygen prediction are distributed in sensing nodes, routing nodes and server respectively. Sensing technique and clustering operation are applied in the process of data acquisition and processing. Meanwhile, an optimized extreme learning machine is implemented for DO prediction. We evaluate the efficiency and accuracy of proposed prediction approach in a practical aquaculture on massive water quality data. Experimental results show that the hybrid model achieves significant prediction results and can meet the needs of practical production and management.

Objective: Arteriovenous fistulas are a principal mainstay of long-term dialysis access for patients with end stage renal failure. However, the patency of arteriovenous fistulas is limited, often requiring percutaneous transluminal angioplasty as a salvage procedure. We report a case of percutaneous method of arteriovenous fistula salvage. Methods: A gentleman with brachiocephalic arteriovenous fistula created in 2015 was admitted under us for dialysis access issue. His fistula history was notable for recurrent and refractory venous outflow stenosis of the cephalic vein and the cephalic arch with multiple previous interventions. Ultrasound showed cephalic arch occlusion with high venous pressures. He underwent left brachicephalic fistula percutaneous bypass. We describe the percutaneous creation of a brachial–subclavian arteriovenous fistula via a bypass graft from a worsening brachial-cephalic fistula with cephalic arch occlusion that is not amendable to angioplasty. Results: Final angiogram showed smooth flow to central vein. He is 2 years post procedure, and his fistula remained patent with no interventions required. Conclusion: Percutaneously created jump bypass grafts can reliably produce sustained long-term patency.

Exercise rhabdomyolysis is a potentially life-threatening medical condition if not adequately managed early. With the increase in the popularity of indoor cycling, known as Spinning®, over recent years, there has been an increased occurrence of spin-related rhabdomyolysis observed among previously fit adults after undertaking their first spin bike class session. They present with the triad of myalgia, muscle weakness, and dark tea-colored urine within a week of their first spin session. This case series highlights several admissions to the hospital with spin-related rhabdomyolysis and their clinical management.

Background Cognitive training can improve cognition in healthy older adults. Objective The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. Methods A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). Results A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased (b=2.32, P=.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated (b=–0.57, P=.01, 95% CI [–1.00 to –0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 (b=–13.5, P=.01, 95% CI [–23.95 to –3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group (b=5.38, P=.06, 95% CI [–0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest (b=–0.36, P=.08, 95% CI [–0.75 to 0.04]) and visuospatial domain (b=0.46, P=.08, 95% CI [–0.05 to 0.96]) that were not statistically significant. Conclusions CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. Trial Registration ClinicalTrials.gov NCT04439591; https://clinicaltrials.gov/ct2/show/NCT04439591

Resveratrol (3,4',5-trihydroxy-trans-stilbene) has been expected to ameliorate cancer and foster breakthroughs in cancer therapy. Despite thousands of preclinical studies on the anticancer activity of resveratrol, little progress has been made in translational research and clinical trials. Most studies have focused on its anticancer effects, cellular mechanisms, and signal transduction pathways in vitro and in vivo. In this review, we aimed to discern the causes that prevent resveratrol from being used in cancer treatment. Among the various limitations, poor pharmacokinetics and low potency seem to be the two main bottlenecks of resveratrol. In addition, resveratrol-induced nephrotoxicity in multiple myeloma patients hinders its further development as an anticancer drug. New insights and strategies have been proposed to accelerate the conversion of resveratrol from bench to bedside. In the interim, the most promising approach is to enhance the bioavailability of resveratrol with new formulations. Alternatively, more potent analogues of resveratrol could be developed to augment its anticancer potency. Given all the gaps mentioned, much work remains to be done. However, if remarkable progress can be made, resveratrol may finally be used for cancer therapy.

Microdevices, since their inception in the last decade of 20th century, have changed our outlook toward science and technology due to their potential applications in fields ranging from optics, semiconductors, and microelectronics industry to drug discovery and development, point-of-care clinical diagnostics, sensitive bioanalytical systems, and other areas of the biological sphere. Microfluidics comprise constraining liquids on a micrometer or submicrometer scale. The fast growth and widespread research pertaining to microfluidic systems have been sustained by their appositeness for abovementioned biological applications that can be carried out using smaller sample volumes and at a fraction of the cost and time as compared to conventional macroscale systems. In this chapter, we review the potential applications of microfluidic platforms for drug discovery applications comprising high throughput screening in target selection, lead identification/optimization, and preclinical testing. We also discuss the potential applications of microfluidics in chemical analysis as well as analysis of metabolites in blood for studying pathology, which can potentially replace conventional benchtop equipment by miniaturized chips that are portable and can be easily handled.

Light weight and excellent mechanical flexibility are the most important advantages of organic solar cells (OSCs), compared with their inorganic counterparts. However, the development of flexible OSCs lags behind the cells fabricated on rigid glass. Herein, we report efficient flexible nonfullerene OSCs with a novel device structure: AgNWs@PI/ZnO/active layer/MoO3/Ag, where AgNWs@PI (silver nanowires embedded in polyimide substrates) is used as the substrate and the bottom electrode. Optimized ZnO processed from isopropyl alcohol (IPA) solutions physically does not destroy/dissolve the PI substrates, and is chemically compatible with the nonfullerene active layer. With PBDB-T-2F:IT-4F as the nonfullerene active layer, the fabricated flexible solar cell displays a power conversion efficiency of 11.6% (VOC = 0.82 V, JSC = 19.6 mA cm−2, and FF = 0.72).

Objectives Prescribing drugs outside regulatory recommendation is known as off-label use. Studies have reported widespread off-label drug use in oncology practice. But the clinical, economic and humanistic outcomes for such practice are often uncertain. Hence, it is important to gather oncology practitioners’ perspective for the creation of clinical practice framework and policies. The aim of the study was to evaluate perception of oncology practitioners on off-label use in cancer therapy. Methods This study employed a cross-sectional design implemented in the form of the self-administered questionnaire at National Cancer Centre Singapore where more than 50% cancer patients of the country are treated. Key findings Eighty-one practitioners involving nurses (38%), medical oncologist (37%) and pharmacists (25%) were surveyed. The majority of practitioners (57%) agreed off-label use as indispensable practice in cancer therapy. Main reasons cited include advanced cancers where standard lines of treatment are exhausted (58%), lack of alternative approved drug (43%) and rare tumours (47%). Compared with other practitioners, medical oncologists viewed Phase 2 (73% versus 31%, P = 0.001) and conference abstracts (56% versus 23%, P = 0.003) as reasonable evidence for off-label use. Major concerns included lack of efficacy (58%), patient understanding (47%), uncertain safety (43%) and out-of-pocket cost (41%) associated with off-label use. Most viewed need for obtaining informed consent (86%) and institutional guidance (75%) as important elements in practice framework. Conclusion The study provides insights about off-label drug use practice and establishes the need for robust clinical guidance and educational strategies for oncology practitioners.

SummaryWhat is known and objective The off-label use of medicines is widespread in several diseases. This type of prescribing practice is particularly more acute in oncology. However, the suitability of anticancer medications for off-label use remains an issue of controversy, due to uncertainty around the clinical benefits and potential toxicities, limited evidence to support clinical decision-making, increased out-of-pocket costs for patients and ethical concerns around the lack of informed consent. Currently, data pertaining to the global prevalence of off-label use in cancer therapy are lacking. The aim of this review was to provide an overview of off-label drug use prevalence in oncology. Methods A systematic literature search was performed in PubMed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from 1975 to 2016. Studies assessing the prevalence of off-label use of anticancer drugs were included. Data synthesis Of the 199 eligible papers retrieved, 23 studies were included in this systematic literature review. Off-label drug use in inpatients ranged from 18% to 41%. Among adult patients with cancer, 13%–71% received a minimum of one off-label chemotherapy. The main reasons for off-label drug use were ‘drug unapproved for specific tumour’ and ‘modified drug applications’. Among adults, metastatic cancers and palliative care patients received the most off-label drugs. The off-label drug use unsupported by standard treatment guidelines or drug compendia was in the range of 7%–31%. Conclusion Off-label drug use in cancer therapy is commonly practised but outcomes could vary significantly. Hence, greater scrutiny and robust clinical guidance is needed to establish the favourable benefit–risk ratio for patients at the time of prescribing at each level of oncology care to facilitate rational off-label prescribing.

The ultimate goal of therapeutics is to ensure that the appropriate treatment is administered to the individual patient at the most appropriate dose for optimal effects. In drug development, clinical trials are conducted in 3 broad phases (Phase I, II and III) before registration for a new drug is granted. In Phase I clinical trials, the primary objectives are to define safety and tolerability of a new treatment and to establish the recommended dose/s for efficacy studies. Clinical pharmacokinetics (PK) is an invaluable tool that can help with achieving this goal, when applied early and throughout the clinical drug development phases. In this chapter, the following topics will be covered: 1. Selected PK concepts specific to clinical drug development of oncology drugs. 2. Practical issues in designing PK studies in Phase I trials. 3. Application of PK in specific situations and drug interactions.

Background Few empirical studies support a bio-psycho-social conceptualization of frailty. In addition to physical frailty (PF), we explored mental (MF) and social (SF) frailty and studied the associations between multidimensional frailty and various adverse health outcomes. Methods Cross-sectional and longitudinal analyses were conducted using data from a population-based cohort (SLAS-1) of 2387 community-dwelling Singaporean Chinese older adults. Outcomes examined were functional and severe disability, nursing home referral and mortality. PF was defined by shrinking, weakness, slowness, exhaustion and physical inactivity, 1–2 = pre-frail, 3–5 = frail; MF was defined by ≥1 of cognitive impairment, low mood and poor self-reported health; SF was defined by ≥2 of living alone, no education, no confidant, infrequent social contact or help, infrequent social activities, financial difficulty and living in low-end public housing. Results The prevalence of any frailty dimension was 63.0%, dominated by PF (26.2%) and multidimensional frailty (24.2%); 7.0% had all three frailty dimensions. With a few exceptions, frailty dimensions share similar associations with many socio-demographic, lifestyle, health and behavioral factors. Each frailty dimension varied in showing independent associations with functional (Odds Ratios [ORs] = 1.3–1.8) and severe disability prevalence at baseline (ORs = 2.2–7.3), incident functional disability (ORs = 1.1–1.5), nursing home referral (ORs = 1.5–3.4) and mortality (Hazard Ratios = 1.3–1.5) after adjusting for age, gender, medical comorbidity and the two other frailty dimensions. The addition of MF and SF to PF incrementally increased risk estimates by more than 2 folds. Conclusions This study highlights the relevance and utility of PF, MF and SF individually and together. Multidimensional frailty can better inform policies and promote the use of targeted multi-domain interventions tailored to older adults’ frailty statuses.

Introduction: The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis. Methodology: We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis. Results: Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result. Conclusions: Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

An 8-bit bit-slice TEA-cryptographic accelerator for 64-bit RSFQ secure coprocessors is proposed. The accelerator is based on Tiny Encryption Algorithm (TEA) and mainly consists of bit-slice adders and bit-slice shifters. Synchronous concurrent-flow clocking is used to design a fully pipelined RSFQ logic design. For verifying the algorithm and the logic design, the RSFQ logic circuits of the proposed accelerator have been simulated with a target operating frequency of 50 GHz. It consists of 21 stages. The throughput is 7.672 × 107 64-bit TEA encryptions per second.

Objective:Hyperfamiliarity is a phenomenon where new stimuli are perceived as familiar. Previous studies have demonstrated familiarity disorder in mild cognitive impairment (MCI), but mostly from the perspective of a neuropsychological approach, and the exact correlation of MCI aetiologies with the phenomenon remains uncertain. Based on current evidence suggesting a frontal-subcortical pathway contributing to familiarity processing, we hypothesize that individuals with a vascular aetiology of MCI will likely suffer more familiarity deficits. This study aims to examine the real-life hyperfamiliarity symptoms in amnestic versus vascular MCI.Methods:Informants of 11 amnestic and 9 vascular cognitive impairment patients were interviewed about the frequency of hyperfamiliarity symptoms in the previous month. MRI brain images of vascular cognitive impairment patients were analysed as well.Results:Patients with vascular cognitive impairment with no dementia (VCIND) showed a significantly higher frequency of hyperfamiliarity for people but not places or objects. Within VCIND patients, overall basal ganglia hyperintensities, particularly in the putamen, were found to significantly correlate to hyperfamiliarity.Conclusions:Patients with VCIND suffer more real-life hyperfamiliarity during people recognition compared to patients with amnestic mild cognitive impairment (aMCI), despite a comparative global decline in cognitive. This is likely due to impaired memory retrieval and matching processes resulting from subcortical ischaemic lesions.

Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models. The main mechanisms of action of nimbolide include anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD) studies have been carried out, nimbolide is still at the infant stage in the drug development pipeline due to the lack of systematic pharmacokinetic (PK) studies and long-term toxicological studies. Preclinical PK and toxicological studies are vital in determining the dosage range to support the safety of nimbolide for first-in-human clinical trials. In this review, we will provide a comprehensive summary for the current status of nimbolide as an anticancer and chemopreventive lead compound, and highlight the importance of systematic preclinical PK and toxicological studies in accelerating the process of application of nimbolide as a therapeutic agent against various malignancies.

215 Background: Esophageal squamous cell carcinoma (ESCC) is a lethal cancer with a high unmet medical need. Camrelizumab, an anti-PD-1 monoclonal antibody, significantly improved overall survival (OS) and objective response rate (ORR) in Chinese patients (pts) with advanced ESCC compared with chemotherapy, with a manageable safety profile in phase III randomized trial (ESCORT). However, the absolute long-term survival benefiting from PD-1 inhibitors is limited, and new effective treatments are needed. Here, our study aimed to assess the efficacy and safety of combination with camrelizumab and apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC. Methods: This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg intravenous camrelizumab every two weeks plus 250 mg oral apatinib daily in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS. Results: At data cutoff (Sept 11, 2020), 36 pts were enrolled, 7 females and 29 males, and 25 pts had lymph node metastases. Twelve pts received radiotherapy and 25 underwent surgery. Twenty-five pts were included in the efficacy analysis with median follow-up time of 5.0 months and 36 pts in the safety analysis with median follow-up time of 4.6 months. The primary endpoint ORR without confirmation was 40 % with complete response in two pts (8%) and partial response in eight pts (32%). Thirteen pts (52%) had stable disease, and the DCR was 92%. The median PFS and OS were not reached. A total of 72.2% of pts had AEs, and 30.6% of pts experienced grade 3 AEs. The most common AEs (all grade, grade≥3) were elevated aspartate aminotransferase (30.6%, 19.4%), elevated alanine aminotransferase (30.6%, 13.9%), hypertension (25%, 2.8%),neutrophil (25%, 5.6%), thrombocytopenia (25%, 0%), leukopenia (22.2%, 2.8%), anemia (11.1%, 0%), proteinuria (11.1%, 0%), hematochezia (8.3%, 0%), reactive cutaneous capillary endothelial proliferation (5.6%, 2.8%), pruritus (5.6%, 0%), esophageal fistula (5.6%, 0%), fatigue (2.8%, 0%) and hypothyroidism (2.8%, 0%). Conclusions: This is the first study to explore the combination of PD-1 inhibitor and anti-angiogenesis inhibitor as a second-line treatment for advanced ESCC. Camrelizumab plus apatinib demonstrated encouraging clinical efficacy and acceptable safety as second-line treatment, and might be a favorable option for pts with advanced ESCC. Further phase III randomized trials are warranted. Clinical trial information: NCT03736863.

Objective To analyze the clinical and laboratory features and determine the predictors of acute liver failure (ALF) among inpatients with anti-tuberculosis (TB) drug-induced liver injury (DILI). Method Patients diagnosed with anti-TB DILI from 2010 to 2016 at The First Affiliated Hospital of Zhejiang University were retrospectively included in this study. Demographic and clinical data were collected by reviewing electronic medical records. Results Among 155 inpatients with anti-TB DILI, 55 (35.48%) developed ALF, with an overall mortality of 9.68%. The median time to DILI onset was significantly longer in the ALF compared with the non-ALF group (51 versus 24 days). Eighty-three patients (53.55%) developed DILI (53.55%) within the first month of anti-TB treatment, and 60% of ALF cases occurred within 2 months. Multivariable models for ALF incorporating aspartate aminotransferase, total bilirubin, platelets, white blood cell count, and pre-existing hepatitis yielded a concordance (C-statistic) of 98.93%. Conclusions The results of this study suggest that approximately half of all cases of DILI occur within the first month, while 60% of ALF cases occur within 2 months. Elevated total bilirubin, aspartate aminotransferase, white blood cell count, pre-existing hepatitis, and low platelet count are independent risk factors for the development of anti-TB drug-induced ALF.

In the last decade, the tremendous improvement in the sensitivity and also affordability of Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) have revolutionized its application in pharmaceutical analysis, resulting in wide-spread of employing LC-MS/MS for determining pharmaceutical compounds including anticancer drugs in pharmaceutical research and also industries. Currently, LC-MS/MS has been widely used to quantify small molecule oncology drugs in various biological matrices to support preclinical and clinical Pharmacokinetic studies in R & D of oncology drugs. This mini-review article will describe the state-of-the art LC-MS/MS and its application in rapid quantification of small molecule anticancer drugs. In addition, efforts have also been made in this review to address several key aspects in the development of rapid LC-MS/MS methods, including sample preparation, chromatographic separation and matrix effect evaluation.

Number processing disorder is an acquired deficit in mathematical skills commonly observed in Alzheimer's disease (AD), usually as a consequence of neurological dysfunction. Common impairments include syntactic errors (800012 instead of 8012) and intrusion errors (8 thousand and 12 instead of eight thousand and twelve) in number transcoding tasks. This study aimed to understand the characterization of AD-related number processing disorder within an alphabetic language (English) and ideographical language (Chinese), and to investigate the differences between alphabetic and ideographic language processing. Chinese-speaking AD patients were hypothesized to make significantly more intrusion errors than English-speaking ones, due to the ideographical nature of both Chinese characters and Arabic numbers. A simplified number transcoding test derived from EC301 battery was administered to AD patients. Chinese-speaking AD patients made significantly more intrusion errors (p = 0.001) than English speakers. This demonstrates that number processing in an alphabetic language such as English does not function in the same manner as in Chinese. The impaired inhibition capability likely contributes to such observations due to its competitive lexical representation in brain for Chinese speakers.

Joel Jun Kai Koh,1,* Rui Xiang Cheng,2,* Yicheng Yap,2,* Victoria Haldane,1 Yao Guo Tan,2 Krichelle Wei Qi Teo,2 Aastha Srivastava,1 Pei Shi Ong,2 Pablo Perel,3 Helena Legido-Quigley1,3 1Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 2Department of Pharmacy, National University of Singapore, Singapore; 3London School of Hygiene and Tropical Medicine, London, UK *These authors contributed equally to this work Background: Atherosclerotic cardiovascular disease (ASCVD) is a growing public health threat globally, and many individuals remain undiagnosed, untreated, and their condition remains uncontrolled. The key to effective ASCVD management is adherence to pharmacotherapy, and non-adherence has been associated with an increased risk of cardiovascular events and complications such as stroke, further impacting a patient’s ability to be adherent. Our qualitative study aimed to explore factors influencing medication adherence in the primary and secondary prevention of ASCVD in Singapore. We propose a synthesized framework, which expands on current understandings of the factors of medication adherence, as a frame of analysis in this study. Methods: We conducted in-depth, semi-structured interviews with 20 patients over the age of 40 with ASCVD and/or its risk factors in Singapore. QSR Nvivo 11 was used to conduct thematic analysis using an inductive approach. Results: Using a synthesized framework, we reported that complex medication regimens, the lack of support received during regimen changes, and the perceived seriousness of a condition could impact a patient’s medication adherence. Key findings suggest that the relationship between health care professionals and patients impacted patient acceptability of the medication regimen and consequently medication adherence. Different patient beliefs regarding diagnosis, medication, and adherence had some bearing on the ability to perceive the need to adhere to their medication. Patients also reported that they could afford medication, sometimes with the help of family members. Patients also largely reported not needing help managing their medication, considering it an individual responsibility. Conclusion: We identified key factors which future interventions looking to improve medication adherence ought to consider. These include changing patient perceptions of health systems, diagnosis, medication, and adherence; patient-centeredness in developing interventions that facilitate adherence through building self-efficacy and stronger support networks via patient empowerment and engagement; decreasing patient co-payments on medication; and cultivating a trusting patient–provider relationship. Keywords: atherosclerotic cardiovascular disease, medication adherence, access, qualitative research, Singapore

Accumulating evidence has implicated the aberrant regulation of histone deacetylases (HDACs) as a nexus for multiple cancer hallmarks and in mediating tumor adaptation and resistance to genotoxic chemotherapy, suggesting a rational pairing of HDAC inhibitors with DNA damaging chemotherapeutic agents in the treatment of human malignancies. Here we report that panobinostat (LBH589), a potent pan-HDAC inhibitor, effectively curbed the proliferation of non-small cell lung cancer (NSCLC) cell lines A549, Calu-1, H226, H460, H838 and SKMES-1 at IC50 concentrations between 4 and 31 nmol/L via pleiotropic mechanisms, including crosstalk with EGFR signal transduction cascades. Combination therapy with carboplatin elicited rapid tumor cell kill and effectively restrained anchorage-independent clonogenic survival to a considerably greater extent over either monotherapy. The administration of carboplatin and panobinostat at clinically relevant doses to NOD-SCID xenograft mice drastically stalled disease progression by 92% as compared with negative control (P = .0026), which was greater than the 28% and 54% achieved with either carboplatin (P = .220) or panobinostat (P = .017) alone. These data demonstrate that panobinostat has strong anti-NSCLC activity and chemosensitizes tumors to carboplatin, thus justifying further evaluation of this combination approach in clinical trials.

Rapid developments have been made in synthetic biology within the past two decades, particularly in combination with chemistry, computer science, and other disciplines. Genetic components and internal features have been a main focus of research for synthetic biologists. Logic gates can be applied in various disciplines, but have not yet been used for plasmid design. GenoCAD is a computer-aided design software programme for synthetic biology that can be used to design complex structures. Thus, in this study, the authors analysed a large, commonly used data set containing over 70,000 feature sequences and eventually obtained comprehensive information for a complete data set without redundancy. By analysing the internal feature sequences, the authors input the most representative data in the GenoCAD platform, along with design rules and grammar for constructing high-quality practical parts. Additionally, the orderly logic gate for building biological parts designed in this study may be useful for professionals and non-professionals and may have applications in the design of a new biological computer. Finally, the authors compared the constructed plasmid with other successful examples in BLAST and PlasMapper software to demonstrate the rationality of the orderly logic gate.

Current literature suggests that right hemisphere lesions produce predominant spatial-related dyslexic error in English speakers. However, little is known regarding such lesions in Chinese speakers. In this paper, we describe the dyslexic characteristics of a Chinese-English bilingual patient with a right posterior cortical lesion. He was found to have profound spatial-related errors during his English word reading, in both real and non-words. During Chinese word reading, there was significantly less error compared to English, probably due to the ideographic nature of the Chinese language. He was also found to commit phonological-like visual errors in English, characterized by error responses that were visually similar to the actual word. There was no significant difference in visual errors during English word reading compared with Chinese. In general, our patient's performance in both languages appears to be consistent with the current literature on right posterior hemisphere lesions. Additionally, his performance also likely suggests that the right posterior cortical region participates in the visual analysis of orthographical word representation, both in ideographical and alphabetic languages, at least from a bilingual perspective. Future studies should further examine the role of the right posterior region in initial visual analysis of both languages.

Background: The use of mobile health (mHealth) has gained popularity globally, including for its use in a variety of health interventions, particularly through short message service (SMS) text messaging. However, there are challenges to the use of mHealth, particularly among older users who have a large heterogeneity in usability and accessibility barriers when using technology. Objective: In order to better understand and conceptualize the diversity of users and give insight into their particular needs, we turned to persona creation. Personas are user archetypes created through data generated from multi-method inquiry with actual target users. Personas are an appropriate yet largely underutilized component of current mHealth research. Methods: Leveraging data from a multi-method study conducted in Singapore with an ethnically diverse population including Chinese, Malay, and Indian participants, we used a proforma to analyze data from the qualitative component (ie, 20 in-depth interviews) and quantitative component (ie, 100 interviewer-guided surveys). We then identified key characteristics, including technology use and preferences as well as adherence factors, to synthesize five personas reflective of persons over the age of 40 years in Singapore with atherosclerotic cardiovascular disease (ASCVD) or ASCVD risk factors, such as hypertension. Results: We present five personas typologized as (1) The Quiet Analog, (2) The Busy Grandparent, (3) The Socializer, (4) The Newly Diagnosed, and (5) The Hard-to-Reach. We report on four key characteristics: health care access, medication adherence, mobile phone technology usage (ie, ownership, access, and utilization), and interest in mHealth. Finally, we provide insights into how these personas may be used in the design and implementation of an mHealth intervention. Our work demonstrates how multi-method data can create biopsychosocial personas that can be used to explore and address the diversity in behaviors, preferences, and needs in user groups. Conclusions: With wider adoption of mHealth, it is important that we consider user-centered design techniques and design thinking in order to create meaningful, patient-centered interventions for adherence to medications. Future research in this area should include greater exploration of how these five personas can be used to better understand how and when is best to deliver mHealth interventions in Singapore and beyond. This research was supported by the Humanities and Social Sciences Seed Fund (R-608-000-137-646) and the National University Health System (NUHS) Singapore Population Health Improvement Centre (SPHERiC).

Objective: This study investigates user performance and user perceptions of dynamic Chinese text displays (Leading display and RSVP display) when users search for target information. Background: Today, information searching with dynamic displays is widely used in TV programs, on Internet advertisements, for traffic information systems, and more. Method: A human factors experiment was conducted to compare both displays. Eighteen subjects participated in evaluating two simulated interfaces for the leading display and the RSVP display. Results: The results show that the leading display was better in terms of search time and certain subjective measurements (Easiness, frustration, anxiety). The latter results are consistent with the conclusions of other research efforts showing that dynamic displays are more effective and efficient when reading information. Conclusion: The leading display is more useful for Chinese users in terms of both information searching and information reading. Application: This study helps design dynamic displays written in Chinese texts.

Objective: In this study, in order to establish a more effective therapeutic model for the patients with chronic rotator cuff tendinosis, the authors attempted to compare the therapeutic effects of general physical therapy, eccentric contraction exercise, extracorporeal shock wave therapy (ESWT) and their combination for patients with noncalcific subscapular tendinosis. Methods: 120 patients with subscapular tendinosis Grade II tendinopathy were divided randomly into four groups: I-IV, with 30 patients in each group. In group I (GI): the patients received conventional rehabilitation program, which included 20 minute of local hot packs, 15 min interferential electrotherapy and 10 min of passive range motion exercise three times weekly for 8 weeks; in Group II: the patients received eccentric contraction exercise three times per day and a rehabilitation program as in GI; in GIII: the patients received ESWT therapy weekly except for a rehabilitation program as in GI; in GIV: they received three combination therapies including a conventional rehabilitation program, three rounds of eccentric contraction exercises per day and weekly ESWT for 8 weeks. The outcome measurements include visual analogue pain scale (VAS), range of shoulder motion, subscapular muscle peak torques, and proprioception of the affected shoulder. Results: The results showed that the combination therapy group GII-IV all had more improvement than the conventional rehabilitation program group I. However, the integrated therapy group IV had the best improvement over GII and GIII in pain reduction and improvement of range of motion, proprioception and muscle peak torques. Additionally, group III and IV had better improvement of range of motion and muscle peak torques than did GII. Conclusion: Eccentric exercise and ESWT had benefit in rehabilitation of patients with noncalcific subscapular tendinosis, and conventional rehabilitation combined with these two therapies will result in more therapeutic effects.

Despite decades of clinical success, tamoxifen therapy is complicated by inter-individual variability due to CYP450 polymorphism and resistance attributed to ERα/HER2 crosstalk. Direct administration of endoxifen shows promise in circumventing obligatory CYP450 bioactivation while maintaining efficacy. Separately, disruption of the crosstalk using probe antagonists against ERα (tamoxifen) and HER2 (e.g., lapatinib) has been explored clinically. However, the efficacy of this combination may be confounded by lapatinib, a potent inactivator of CYP3A4/5 which could negate the bioactivation of tamoxifen to the active metabolite endoxifen. Additionally, in a manner analogous to tamoxifen, endoxifen is similarly not immune to the development of ERα/HER2 crosstalk that could result in resistance. Simultaneous antagonism of ERα and HER2 using endoxifen and lapatinib could overcome these problems. Metabolism studies were performed in human liver microsomes to determine the extent of inhibition of tamoxifen bioactivation by lapatinib. Synergism of endoxifen and lapatinib was assessed using the combination index design in a panel of cell models exhibiting either a priori ERα/HER2 crosstalk (BT474) or acquired ERα/HER2 crosstalk (TAM-R and MCF-7/HER2). Lapatinib inhibited tamoxifen bioactivation by up to 1.8-fold. Synergistic activity was uncovered for lapatinib and endoxifen against BT474, TAM-R and MCF-7/HER2 models of ERα/HER2 crosstalk. Western blot confirmed that endoxifen and lapatinib disrupted this crosstalk. This forward-looking study extends the success of tamoxifen by exploring the effectiveness of combining the next-generation tamoxifen derivative, endoxifen with an anti-HER2 agent to combat ERα/HER2 crosstalk, and at the same time provides a solution to the predicted pharmacokinetic antagonism between lapatinib and tamoxifen.

Psychosis is common in Alzheimer’s disease (AD). However, studies on neuropathology in vascular etiology contributing to psychosis in AD is lacking to date. The aim of this study was to investigate neuropathological vascular related changes in Alzheimer’s disease with psychosis. Data of patients with AD from the National Alzheimer’s Coordinating Center between 2005 to September 2013 was accessed and reviewed. Presence of psychosis was determined based on Neuropsychiatric Inventory Questionnaire taken from the last visit within one year prior to death and patients were divided into psychosis positive and negative group. Comparison of clinical details and neuropathological vascular changes between the groups was performed using Wilcoxon rank sum test and Chi-square/ Fisher’s exact test. Significant variables were further included in a multivariate logistic model. Overall, 145 patients was included. Of these, 50 patients were psychosis positive. Presence of one or more cortical microinfarcts and moderate to severe arteriosclerosis was found to be positively associated with psychosis. Our results suggest vascular changes correlate with psychosis in Alzheimer’s disease.

The basic research of collision and float behavior of inclusions in steel metallurgical production process is of great significance. Only when we grasp the mechanism of the collision and agglomeration of the inclusion, can we propose the improvement program of inclusion removal. This paper mainly summarized how to remove the inclusions by floating, studied it through the hydraulics simulation experiment, verified the correctness of the Stokes formula, revised the Stokes formula according to the experimental data, determined a value range of the correction coefficient, and then obtained a more applicable Stokes correction formula.

A new public key encryption scheme is proposed in this paper, which is based on a hard problem over ergodic matrices. The security of this scheme is equal to the MQ-problem: multivariate quadratic equations over finite fields. This problem has been shown to be NP-complete and can't be solved with polynomial time algorithm.

In this Letter, we studied the optical-induced Freedericksz transition of 5CB doped with 1% volume fraction of bio-molecule, porphyrinozinc(II) (ZnTPP). Excited by Ti:sappire laser with the 82 MHz repetition rate and 100 fs pulse duration, the optical Freedericksz threshold of a 23.6 μm-thickness planar alignment sample occurred at an intensity level of 0.35 mW/mm2 in contrast to the normally observed 83 mW/mm2 value for pure 5CB.

We report a case of a primary parahiatal hernia that was repaired laparoscopically with a composite mesh. A 51-year-old woman presented with vomiting and epigastric pain. CT scan showed a giant paraesophageal hernia with intrathoracic gastric volvulus. Intraoperatively, a diaphragmatic muscular defect was found lateral to an attenuated left crus of the diaphragm, distinct from the normal esophageal hiatus. The defect ring was fibrotic, making a tension-free primary repair difficult. A laparoscopic mesh repair was performed with a composite mesh, which was covered with the hernia sac to prevent potential erosion into the esophagus or stomach. Recovery was uneventful and the patient was discharged on the 5 days postoperatively. She remained asymptomatic at subsequent follow-up. Laparoscopic repair of parahiatal hernia can be safely performed. In circumstances where a large or fibrotic defect prevents a tension-free primary repair, the use of a composite mesh can provide effective repair of the hernia.

We observed an azo-isomerization-induced Freedericksz transition of the 5CB liquid crystal doped with 1% double-azo. In experiment, we found that the Freedericksz transition threshold occurred at optical intensity level of 0.3 mW/mm2 for the 12.5 μm-thickness planar alignment doped 5CB, which is four orders of magnitude lower as that for the pure 5CB. Using optical phase retardation, we measured the relations between the Freedericksz transition threshold and the pump beam polarization. The maximum twist angle of liquid crystal molecules under different pump beam intensity is given. The experiment indicated that trans–cis isomerization plays an important role in the decrease of the Freedericksz transition threshold.

A comparison of experiment and modeling in high-speed recording heads is given from study of the dependence of flux rise times on yoke lengths. A brief overview is given of optical methods for characterizing the response of devices and materials for high data rate recording. Several abilities of the technique and, in particular, measurements of current and flux rise times on high-speed writers are presented. A micromagnetic model that takes into account gyromagnetic effects and eddy currents gives calculations that agree well with experimental data. Flux rise times are found to decrease with shorter yoke lengths for both unlaminated and laminated heads for a current rise time of 0.8 ns.

In order to solve travelling salesman problem (TSP), a hybrid artificial bee colony algorithm combined with simulated annealing algorithm (HABC-SA) is presented for TSP. This algorithm gives a discrete coding method for food source position. Crossover and mutation operators in genetic algorithm are introduced into the new algorithm to do local search, Simulated annealing idea is applied in this hybrid artificial bee colony algorithm to increase the diversity of food sources. The proposed algorithm is tested on benchmark problems, and results show that this algorithm can avoid pre-maturity and advance constringency for TSP.

Two known cleistriosides and six known cleistetrosides were synthesized and evaluated for anticancer and antibacterial activities. This study, for the first time, reports anticancer activity and comprehensively the antibacterial activity for these oligosaccharide natural products. In addition, two new unnatural cleistetroside analogues were synthesized and tested. Biological activities for the 10 oligosaccharides against B. subtilis were found to range between 4 and >64 μM and for NCI-H460 human lung cancer epithelial cells between 7.5 and 90.9 μM. Similar activities were found for seven of the oligosaccharides against the NCI panel of 60 cell lines. The degree of acylation and location of the specific acetate groups had significant effects on the anticancer and antibacterial activity of both the cleistriosides and the cleistetrosides.