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p-Coumaric acid (p-CA), an invaluable phytochemical, has novel bioactivities, including antiproliferative, anxiolytic, and neuroprotective effects, and is the main precursor of various flavonoids, such as caffeic acid, naringenin, and resveratrol. Herein, we report the engineering of Escherichia coli for de novo production of p-CA via the PAL-C4H pathway. As the base strain, we used the E. coli H-02 strain, which was previously engineered for sufficient supplementation of L-phenylalanine, the main precursor of p-CA. For the bioconversion of L-Phe to p-CA, we constructed and optimized an expression system for phenylalanine ammonia lyase (SmPAL), codon-optimized cinnamate 4-hydroxylase (AtC4H), and its redox partner, cytochrome P450 reductase (AtCPR1). We confirmed that the engineered cell showed higher production of p-CA at 30 °C and the addition of 0.5 mM 5-aminolevulinic acid could increase the production titer further. Subsequently, the main pathways of acetic acid (poxB and pta-ackA) were eliminated to reduce its accumulation and restore cell growth. Next, to increase the available pool of cofactor (NADPH), the co-expression system of the zwf gene in the pentose phosphate pathway (PPP) was integrated into genome and the expression level was optimized with synthetic promoters. Finally, by optimizing fed-batch culture in a 5 L-scale bioreactor, the engineered strain achieved 1.5 g/L p-CA with a productivity of 31.8 mg/L/h., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. The authors declare that they have no competing financial interests or personal relationships that could have appeared to impact the work reported in this paper. Ethical approval: This paper does not contain any studies with human participants or animals performed by any of the authors., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Diet affects the development of chronic diseases such as type 2 diabetes, but the underlying biological mechanisms are only partly understood., Objectives: This study aimed to identify proteomic markers of the Alternative Healthy Eating Index (AHEI) and the Dietary Approaches to Stop Hypertension (DASH) diet and their association with type 2 diabetes risk., Methods: We examined the associations between the AHEI and DASH diet quality scores and 1317 plasma proteins in African American participants of the Jackson Heart Study (JHS, n = 1878). These findings were validated in a Singapore Multi-Ethnic Cohort (n = 2395) and examined in relation to type 2 diabetes incidence (n = 539 cases). We adjusted for multiple testing by using false discovery rate-adjusted q values., Results: We identified 13 proteins consistently associated with the AHEI or DASH scores with the strongest associations for the AHEI score and epidermal growth factor receptor (β:0.089; SE: 0.017; q < 0.001) and for the DASH score and tissue factor (β: -0.114; SE: 0.022; q < 0.001). Most of these proteins were related to inflammation, thrombosis, adipogenesis, and glucose metabolism. Concentrations of myeloperoxidase, epidermal growth factor receptor, hepatocyte growth factor receptor, coagulation factor Xa, contactin 4, kynureninase, neurogenic locus notch homolog protein 1, and vesicular integral-membrane protein VIP36 were associated with the risk of type 2 diabetes in the Asian cohort. The diabetes odds ratio for a 2-fold higher protein abundance concentration ranged from 0.03 (95% CI: 0.01, 0.08) for neurogenic locus notch homolog protein 1 to 3.04 (95% CI: 2.13, 4.33) for kynureninase. Furthermore, genetic markers for myeloperoxidase and hepatocyte growth factor receptor were significantly associated with diabetes risk., Conclusions: Our study across geographically and ethnically diverse populations identified robust protein biomarkers for healthy dietary patterns. Furthermore, our findings suggest novel biological mechanisms linking dietary patterns with type 2 diabetes development., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Lymphatic vessels grow through active sprouting and mature into a vascular complex that includes lymphatic capillaries and collecting vessels that ensure fluid transport. However, the signaling cues that direct lymphatic sprouting and patterning remain unclear. In this study, we demonstrate that chemokine signaling, specifically through CXCL12 and CXCR4, plays crucial roles in regulating lymphatic development. We show that LEC-specific Cxcr4-deficient mouse embryos and CXCL12 mutant embryos exhibit severe defects in lymphatic sprouting, migration and lymphatic valve formation. We also discovered that CXCL12, originating from peripheral nerves, directs the migration of dermal lymphatic vessels to align with nerves in developing skin. Deletion of Cxcr4 or blockage of CXCL12 and CXCR4 activity results in reduced VEGFR3 levels on the LEC surface. This, in turn, impairs VEGFC-mediated VEGFR3 signaling and downstream PI3K and AKT activities. Taken together, these data identify previously unknown chemokine signaling originating from peripheral nerves that guides dermal lymphatic sprouting and patterning. Our work identifies for the first time a neuro-lymphatics communication during mouse development and reveals a previously unreported mechanism by which CXCR4 modulates VEGFC, VEGFR3 and AKT signaling., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Introduction: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental condition characterised by inattention and/or hyperactivity-impulsivity. The ADHD symptoms are often evaluated and quantified using various assessment tools, such as the Conners' Continuous Performance Test II (CCPT-II), ADHD Rating Scale (ADHD-RS), Child Behaviour Checklist (CBCL), Clinical Global Assessment Scale (CGAS) and Clinical Global Impression Scale (CGIS). This study sought to compare CCPT-II with parent- and clinician-rated rating scales (ADHD-RS, CBCL, CGAS and CGIS) in measuring the core ADHD symptoms within the paediatric ADHD population., Methods: The data, gathered from a large-scale randomised controlled trial involving 172 children aged 6-12 years with ADHD, was pooled, and a Pearson correlation analysis was conducted., Results: No significant correlations were observed between CCPT-II and ADHD-RS, as well as the various subscales of CBCL, CGAS and CGIS., Conclusion: While CCPT-II may offer insights into ADHD symptomatology, its relationship with parent- and clinician-rated rating scales such as ADHD-RS, CBCL, CGAS and CGIS appears limited. Further research is warranted to elucidate the nuances of these assessment tools and their roles in evaluating ADHD., (Copyright © 2024 Copyright: © 2024 Singapore Medical Journal.)

This study investigates the growth characteristics of Salmonella enteritidis ( S. enteritidis ) in liquid whole egg under both isothermal and non-isothermal storage conditions to understand the risks associated with inadequate temperature management in the egg industry. Using controlled laboratory simulations, liquid whole egg samples inoculated with S. enteritidis were stored under various isothermal (5, 15, 25, 35, and 45 °C) and non-isothermal conditions (5-10, 15-20, 25-30, 35-40, and 45-50 °C). The growth behavior of the S. enteritidis was analyzed using a two-step predictive modeling approach. First, growth kinetic parameters were estimated using a primary model, and then the effects of temperature on the estimated specific growth rate and lag time were described using a secondary model. Independent growth data under both isothermal and non-isothermal conditions were used to evaluate the models. The results showed that S. enteritidis exhibits different growth characteristics depending on temperature conditions, emphasizing the need for strict temperature control to prevent foodborne illnesses. To address this, a predictive growth model tailored for non-isothermal conditions was developed and validated using experimental data, demonstrating its reliability in predicting S. enteritidis behavior under dynamic temperature scenarios. Additionally, temperature management technologies were proposed and tested to improve food safety during refrigerated storage. This study provides a scientific basis for improving food safety protocols in the egg industry, thereby protecting public health and maintaining consumer confidence amid temperature fluctuations.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Metabolic abnormalities in hepatic encephalopathy (HE) cause brain edema or demyelinating disease, resulting in symmetric regional cerebral edema (SRCE) on MRI. This study aimed to investigate the usefulness of the clustering analysis of SRCE in predicting the development of brain failure., Materials and Methods: MR findings and clinical data of 98 consecutive patients with HE were retrospectively analyzed. The correlation between the 12 regions of SRCE was calculated using the phi (Φ) coefficient, and the pattern was classified using hierarchical clustering using the φ 2 distance measure and Ward's method. The classified patterns of SRCE were correlated with clinical parameters such as the model for end-stage liver disease (MELD) score and HE grade., Results: Significant associations were found between 22 pairs of regions of interest, including the red nucleus and corpus callosum (Φ = 0.81, p < 0.001), crus cerebri and red nucleus (Φ = 0.72, p < 0.001), and red nucleus and dentate nucleus (Φ = 0.66, p < 0.001). After hierarchical clustering, 24 cases were classified into Group I, 35 into Group II, and 39 into Group III. Group III had a higher MELD score ( p = 0.04) and HE grade ( p = 0.002) than Group I., Conclusion: Our study demonstrates that the SRCE patterns can be useful in predicting hepatic preservation and the occurrence of cerebral failure in HE., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2024 The Korean Society of Radiology.)

Immunoglobulin G4 (IgG4)-related lung disease can have various clinical courses. To our knowledge, reports of IgG4-related lung disease with waxing and waning pulmonary infiltrates only are very rare. A few lung nodules and ground glass opacities were incidentally found in a pre-operative evaluation in a 36-year-old female. The lung lesions showed waxing and waning in the follow-up chest CT. She underwent a surgical biopsy, and IgG4-related lung disease was confirmed., Competing Interests: Conflicts of Interest: The authors have no potential conflicts of interest to disclose., (Copyrights © 2023 The Korean Society of Radiology.)

Recent advances in the RNA delivery system have facilitated the development of a separate field of RNA therapeutics, with modalities including mRNA, microRNA (miRNA), antisense oligonucleotide (ASO), small interfering RNA, and circular (circRNA) that have been incorporated into oncology research. The main advantages of the RNA-based modalities are high flexibility in designing RNA and rapid production for clinical screening. It is challenging to eliminate tumors by tackling a single target in cancer. In the era of precision medicine, RNA-based therapeutic approaches potentially constitute suitable platforms for targeting heterogeneous tumors that possess multiple sub-clonal cancer cell populations. In this review, we discussed how synthetic coding and non-coding RNAs, such as mRNA, miRNA, ASO, and circRNA, can be applied in the development of therapeutics. SIGNIFICANCE STATEMENT: With development of vaccines against coronavirus, RNA-based therapeutics have received attention. Here, the authors discuss different types of RNA-based therapeutics potentially effective against tumor that are highly heterogeneous giving rise to resistance and relapses to the conventional therapeutics. Moreover, this study summarized recent findings suggesting combination approaches of RNA therapeutics and cancer immunotherapy., (Copyright © 2023 by The American Society for Pharmacology and Experimental Therapeutics.)

Various studies have been conducted on multi-task learning techniques in natural language understanding (NLU), which build a model capable of processing multiple tasks and providing generalized performance. Most documents written in natural languages contain time-related information. It is essential to recognize such information accurately and utilize it to understand the context and overall content of a document while performing NLU tasks. In this study, we propose a multi-task learning technique that includes a temporal relation extraction task in the training process of NLU tasks such that the trained model can utilize temporal context information from the input sentences. To utilize the characteristics of multi-task learning, an additional task that extracts temporal relations from given sentences was designed, and the multi-task model was configured to learn in combination with the existing NLU tasks on Korean and English datasets. Performance differences were analyzed by combining NLU tasks to extract temporal relations. The accuracy of the single task for temporal relation extraction is 57.8 and 45.1 for Korean and English, respectively, and improves up to 64.2 and 48.7 when combined with other NLU tasks. The experimental results confirm that extracting temporal relations can improve its performance when combined with other NLU tasks in multi-task learning, compared to dealing with it individually. Also, because of the differences in linguistic characteristics between Korean and English, there are different task combinations that positively affect extracting the temporal relations., (© 2023. The Author(s).)

Hepatic encephalopathy (HE) is a severe neuropsychiatric abnormality in patients with either acute or chronic liver failure. Typical brain magnetic resonance imaging findings of HE are bilateral basal ganglia high signal intensities due to manganese deposition in chronic liver disease and hyperintensity in T2, fluid-attenuated inversion recovery, or diffusion-weighted imaging (DWI) with hemispheric white matter changes including the corticospinal tract. Low values on apparent diffusion coefficient mapping of the affected area on DWI, indicating cytotoxic edema, can be observed in acute HE. However, neuropsychological impairment in HE ranges from mild deficits in psychomotor abilities affecting quality of life to stupor or coma with higher grades of hepatic dysfunction. In particular, the long-lasting compensatory mechanisms for the altered metabolism in chronic liver disease make HE imaging results variable. Therefore, the clinical relevance of imaging findings is uncertain and differentiating HE from other metabolic diseases can be difficult. The recent introduction of concepts such as "acute-on-chronic liver failure (ACLF)," a new clinical entity, has led to a change in the clinical view of HE. Accordingly, there is a need to establish a corresponding concept in the field of neuroimaging diagnosis. Herein, we review HE from a historical and etiological perspective to increase understanding of brain imaging and help establish an imaging approach for advanced new concepts such as ACLF. The purpose of this manuscript is to provide an understanding of HE by reviewing neuroimaging findings based on pathological and clinical concepts of HE, thereby assisting in neuroimaging interpretation.

BACKGROUND Vanishing white matter disease (VWMD) - also known as childhood ataxia with central nervous system hypomyelination - is one of the most commonly inherited white matter diseases in children. Notably, a course of chronic progressive disease with episodes of rapid and major stress-induced neurological deterioration, such as fever and minor head trauma, is a typical clinical feature of VWMD. The combination of clinical features with specific magnetic resonance imaging findings, including diffuse and extensive white matter lesions with rarefaction or cystic destruction, could recommend a genetic diagnosis. However, VWMD is phenotypically diverse and can affect individuals of all ages. CASE REPORT A 29-year-old female patient presented with recent aggravation in gait disturbance. She had progressive movement disorder, with symptoms ranging from hand tremors to upper- and lower-extremity weakness, for 5 years. Whole-exome sequencing was performed to confirm the diagnosis of VWMD, and it revealed a mutation in homozygous eIF2B2 gene. The temporal evolution of VWMD observed in the patient for 17 years (from the age of 12 to 29 years) indicated an increased extent of T2 white matter hyperintensity in the cerebrum into the cerebellum and an increased amount of dark signal intensities in the globus pallidus and dentate nucleus. Moreover, a T2*-weighted imaging (WI) scan revealed diffuse, linear, and symmetrical hypointensity along the juxtacortical white matter on the magnification view. CONCLUSIONS This is the case report about rare and unusual finding of diffuse linear juxtacortical white matter hypointensity on T2*-WI scan as a potential radiographic marker for adult-onset VWMD.

Background: Attention deficit hyperactivity disorder (ADHD) is a prevalent child neurodevelopmental disorder that is treated in clinics and in schools. Previous trials suggested that our brain-computer interface (BCI)-based attention training program could improve ADHD symptoms. We have since developed a tablet version of the training program which can be paired with wireless EEG headsets. In this trial, we investigated the feasibility of delivering this tablet-based BCI intervention at home., Methods: Twenty children diagnosed with ADHD, who did not receive any medication for the preceding month, were randomised to receive the 8-week tablet-based BCI intervention either in the clinic or at home. Those in the home intervention group received instructions before commencing the program and got reminders if they were lagging on the training sessions. The ADHD Rating Scale was completed by a blinded clinician at baseline and at week 8. Adverse events were monitored during any contact with the child throughout the trial and at week 8., Results: Children in both groups could complete the tablet-based intervention easily on their own with minimal support from the clinic therapist or their parents (at home). The intervention was safe with few reported adverse effects. Clinician-rated inattentive symptoms on the ADHD-Rating Scale reduced by 3.2 (SD 6.20) and 3.9 (SD 5.08) for the home-based and clinic-based groups respectively, suggesting that home-based intervention was comparable to clinic-based intervention., Conclusions: This trial demonstrated that the tablet version of our BCI-based attention training program can be safely delivered to children in the comfort of their own home. Trial registration This trial is registered at clinicaltrials.gov as NCT01344044., (© 2023. The Author(s).)

Social dysfunction is a key characteristic of autism. Determining and treating autism-related social deficits have been challenging. The medical model views interpersonal difficulties in autism as a localized set of deficits to be managed, whereas the neurodiversity movement calls for the accommodation of differences by the larger community. One common assumption underlying these perspectives is a misalignment in social behaviors between autistic individuals and neurotypicals. This paper reviews and interrogates current perspectives on social functioning in autism to uncover the intricacies of such a notion. Even though extant literature has alluded to a misalignment in social behaviors between autistic and neurotypical individuals, it is uncertain where this disparity lies. Implications for future research and practice are discussed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Lim and Lee.)

Cinnamaldehyde (CAD) has various applications in foods and pharmaceuticals and has gained prominence as a potent nematicide in agricultural research owing to its nematicidal activity. However, conventional methods of CAD production, including extraction from plants or organic chemical synthesis, are environmentally hazardous and limit its utilization for downstream applications. Here, we engineered Corynebacterium glutamicum as a whole-cell biocatalyst for the efficient bioconversion of trans -cinnamic acid ( t -CA) into CAD. An expression module of Mycobacterium phlei carboxylic acid reductase was constructed for the conversion of t -CA to CAD. Additionally, the putative dehydrogenase-related genes ( dkgA , adhC , and cg 1176) responsible for the conversion of CAD to cinnamyl alcohol were deleted from the engineered C. glutamicum strain to prevent the loss of CAD. Furthermore, as the conversion is NADPH-dependent, we investigated the conversion efficiency by exchanging the putative promoter region for the zwf gene, which encodes glucose-6-phosphate dehydrogenase, with a strong promoter to increase the NADPH pool. Finally, a bioconversion platform using C. glutamicum as a whole-cell biocatalyst was developed by deleting the vdh gene, which is involved in the reverse conversion of CAD to t -CA. Taken together, a 100% conversion yield of 1.1 g/L CAD from 1.2 g/L t -CA was obtained within 30 min.

We propose the "Tile-net" method based on dividing an image into smaller tiles. Using the tile as the input to the neural network, the network is simplified substantially. The Tile-net learns at a much faster rate than the networks without tiling. The training and reconstruction times for the Tile-net are reduced by 40% and 33%, respectively compared to the networks without tiling. The Tile-net performance is evaluated through the normalized mean square error (NMSE), peak signal to noise ratio (PSNR), structure similarity index measure (SSIM) and the quality of the reconstructed image for test datasets. The Tile-net does not degrade performance; however, it reduces the NMSE by 0.3% compared to the networks without tiling., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Degenerative spondylolisthesis is a common back pathology in the general adult population. Patients with this condition may present for epidural steroid injection, epidural blood patch, or epidural analgesia. We report five patients with degenerative spondylolisthesis who experienced inadvertent dural puncture during interlaminar epidural steroid injection attempts: four with intrathecal contrast spread or cerebrospinal backflow into the epidural needle and one with subdural contrast spread. Patients with degenerative spondylolisthesis may be at higher risk for dural puncture due to stretching of the dura and contraction of the epidural space at the translated spinal level. In the following report, we summarize the cases and suggest risk mitigation strategies for both chronic and acute pain physicians., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: trans-cinnamic acid (t-CA) is a phenylpropanoid with a broad spectrum of biological activities including antioxidant and antibacterial activities, and it also has high potential in food and cosmetic applications. Although significant progress has been made in the production of t-CA using microorganisms, its relatively low product titers still need to be improved. In this study, we engineered Corynebacterium glutamicum as a whole-cell catalyst for the bioconversion of L-phenylalanine (L-Phe) into t-CA and developed a repeated bioconversion process., Results: An expression module based on a phenylalanine ammonia lyase-encoding gene from Streptomyces maritimus (SmPAL), which mediates the conversion of L-Phe into t-CA, was constructed in C. glutamicum. Using the strong promoter P H36 and ribosome binding site (RBS) (in front of gene 10 of the T7 phage), and a high-copy number plasmid, SmPAL could be expressed to levels as high as 39.1% of the total proteins in C. glutamicum. Next, to improve t-CA production at an industrial scale, reaction conditions including temperature and pH were optimized; t-CA production reached up to 6.7 mM/h in a bioreactor under optimal conditions (50 °C and pH 8.5, using NaOH as base solution). Finally, a recycling system was developed by coupling membrane filtration with the bioreactor, and the engineered C. glutamicum successfully produced 13.7 mM of t-CA (24.3 g) from 18.2 mM of L-Phe (36 g) and thus with a yield of 75% (0.75 mol/mol) through repetitive supplementation., Conclusions: We developed a highly efficient bioconversion process using C. glutamicum as a biocatalyst and a micromembrane-based cell recycling system. To the best of our knowledge, this is the first report on t-CA production in C. glutamicum, and this robust platform will contribute to the development of an industrially relevant platform for the production of t-CA using microorganisms., (© 2021. The Author(s).)

Background: Case studies and small series have demonstrated that beverage ethanol may pose a serious poisoning hazard to infants. Intoxicated infants may not present with the classic signs or symptoms of ethanol poisoning. The objective of this study was to describe the epidemiology of beverage ethanol exposures among infants reported to the United States poison control centers., Methods: Data from the National Poison Data System were retrospectively analyzed for infants <12 months of age who were exposed to beverage ethanol from 2009-2018., Results: Over the 10-year study period, 1,818 infant exposures to beverage ethanol were reported. Most exposures were single substance (95.2%), and the most common route of exposure was ingestion ( n  = 1,738). Infants 9-11 months were the most commonly exposed age group subset (45.3%). The annual number and rate of alcoholic beverage exposure increased by 37.5% and 42.9%, respectively, from 2009 to 2018. Of the 563 infants evaluated at a healthcare facility, 38% of exposures were hospitalized. Infants 0-5 months of age had higher odds of being admitted to a non-critical (OR: 2.35, 95% CI: 1.41-3.92) or critical care unit (OR: 2.39; 95% CI: 1.50-3.79) compared to infants 6-11 months of age. Infants 0-5 months of age were more likely to (OR: 4.65; 95% CI: 3.18-6.79) experience a serious outcome compared to infants ages 6-11 months. Five fatalities in infants <6 months old were documented. An in-depth case review identified improper storage and subsequent formula preparation with beverage ethanol as a common exposure mechanism., Conclusions: Beverage ethanol exposures among infants are associated with hospitalization, serious clinical effects, and mortality. Infants may present with atypical signs and symptoms of intoxication, requiring a high index of suspicion. Opportunities exist to reduce exposures by addressing improper storage of beverage alcohols.

This study investigated the effects of a rehabilitation program using a wearable device on upper limb function, the performance of activities of daily living, and rehabilitation participation in acute phase stroke patients. A total of 44 patients were randomly divided into two groups. The experimental group (n = 22) was requested to wear a glove-type device while they were administered a game-based virtual reality (VR) rehabilitation program of 30 mins per session, 5 sessions per week, for 4 weeks. The program was given in addition to conventional physical therapy. The control group (n = 22) was administered only conventional physical therapy. To examine the intervention effects, the Fugl-Meyer assessment scale, hand strength test, and Jebsen-Taylor hand function tests were performed to examine upper limb function. The Korean version of the modified Barthel Index was used to assess the performance of activities of daily living, and the Pittsburgh rehabilitation participation scale was used to estimate rehabilitation participation. Neither the experimental nor the control group showed significant differences in the pre-intervention homogeneity test, while both groups showed significant improvement in all post-intervention dependent variables. Notably, the experimental group showed a significantly greater improvement in the results of the hand strength test, Jebsen-Taylor hand function test, and Modified Barthel Index. The findings suggest that the rehabilitation program using a wearable device, in addition to conventional physical therapy, is more effective than conventional therapy alone for improving upper limb function, the performance of activities of daily living, and rehabilitation participation in acute phase stroke patients. Our findings suggest that the novel rehabilitation program using a wearable device will serve not only as an effective therapy for enhancing the upper limb function, the performance of activities of daily living, and rehabilitation participation in acute phase stroke patients but also as a highly useful intervention in actual clinical practice alongside conventional physical therapy.

Background: Studies on gender differences in attention-deficit/hyperactivity disorder (ADHD) comorbidities in the Asian populations have been limited and previous studies have shown inconclusive findings. Singapore is a city-state country in Southeast Asia with a population of 5.7 million. This study examined gender differences in internalizing and externalizing problems in Singaporean children and adolescents with ADHD. The plausible social factors underlying the gender differences were discussed., Methods: A total of 773 participants (aged 6 to 18, 88% males) newly diagnosed with ADHD were recruited from the largest public child and adolescent psychiatric center in Singapore. Their internalizing and externalizing problems were assessed using the Child Behavioral Checklist and Teacher's Report Form by parents and teachers respectively. Demographics and relevant social factors were collected using parent questionnaires., Results: Females with ADHD were reported to have less delinquent and aggressive behavior but more depressive symptoms than their male counterparts, similar to findings in the Western literature. Gender remained a significant predictor of externalizing problem after controlling for other factors. Lower socioeconomic status and parental use of physical punishment were significant predictors of both internalizing and externalizing problems., Conclusions: Gender differences in ADHD comorbidities do exist in the Asian clinical population. The lack of externalizing symptoms in females with ADHD has made timely referral and diagnosis challenging. More research is needed in understanding the gender differences in ADHD and the biopsychosocial mechanism underlying the differences in order to improve the detection of ADHD in females.

Objective: The purpose of this study was to determine the immediate effects of ankle non-elastic taping on balance and gait ability in patients with chronic stroke., Methods: Thirty patients (inpatients and outpatients) with stroke were randomly assigned to 2 groups: the non-elastic taping group (n = 15) and the placebo-taping group (n = 15). Patients in the non-elastic taping group received Endura sports taping for their ankle joint, and patients in the placebo-taping group received Endura fix tape for their ankle joint. The Balance System SD assessed balance, and the GAITRite system assessed gait ability. We recorded measurements before and after intervention., Results: The non-elastic taping group showed a significant improvement in static and dynamic standing balance (P ≤ .001) after intervention; in addition, this group showed significant increases in the velocity, cadence, step length, and stride length of gait (P ≤ .001) after intervention. However, the placebo-taping group showed no significant improvements in standing balance and gait ability after intervention (P >.05). Furthermore, significant differences in static and dynamic standing balance, cadence, and velocity were observed between the 2 groups after intervention (P ≤ .001)., Conclusions: Our results demonstrate that the application of ankle non-elastic taping is effective at improving balance and gait abilities in patients with stroke. Ankle non-elastic taping appears to be an effective method to facilitate active rehabilitation in patients with hemiplegia., (Copyright © 2020. Published by Elsevier Inc.)

Objective: This feasibility study examined the effects of a particular Traditional Chinese Medicine (TCM) herbal formula on attention-deficit/hyperactivity disorder (ADHD) and related problem behaviors. Design: A total of 79 participants aging 6-12 years consumed a granulated TCM herbal formula twice daily over a period of 3 months and underwent assessments at months 0, 3, and 6. Changes in ADHD symptoms and related behaviors were measured using the ADHD rating scale-IV (ADHD-RS-IV), child behavior checklist (CBCL), children's global sssessment scale (CGAS), as well as the clinical global impressions-severity (CGI-S) and improvement (CGI-I) scales. Results: Repeated measures mixed model analyses revealed significant differences in scores across time on all ADHD-RS-IV and CBCL subscales as well as on the CGAS, CGI-S, and CGI-I scales. Pairwise comparisons between months 0 and 3 as well as months 0 and 6 indicated significant improvements in scores. Scores also did not differ significantly between months 3 and 6. The results may suggest that this particular TCM formula possesses potential therapeutic qualities in the treatment of ADHD. Furthermore, changes in ADHD symptoms generally appear to be stable 3 months after discontinuation. However, these findings could also be attributed to placebo effects as well as reporting biases. Conclusion: This particular TCM formula may prove to be a useful adjunctive treatment for children with ADHD, and randomized controlled trials need to be conducted to evaluate its efficacy.

Objectives: To compare the differences in radiologic and pathologic features of surgically resected chronic obstructive pulmonary disease (COPD)-related adenocarcinomas according to the presence of emphysema., Methods: A total of 216 smokers with surgically resected lung adenocarcinoma were included in this retrospective study, and 102 patients were diagnosed with COPD. We classified COPD patients as emphysematous or non-emphysematous group based on the emphysema severity on computed tomography (CT) and evaluated the differences in the CT and pathologic features between the two groups. The relationship between emphysema and disease-free survival was assessed using a Kaplan-Meier curve., Results: Lung adenocarcinomas in emphysema group presented a more aggressive pathologic grade and higher prevalence of solid lesions (vs subsolid lesions) on CT than those in non-emphysematous group (P = 0.006 and <0.001, respectively). After adjustment for age, sex, smoking pack-years and tumor size, emphysema group had a greater risk for higher histologic grade and higher prevalence of solid lesions than non-emphysema group (odds ratio, 3.445; 95% confidence interval, 1.124-10.564; P = 0.030, odds ratio, 6.192; 95% confidence interval, 1.804-21.254; P = 0.004, respectively). Kaplan-Meier survival curves showed that patients with emphysema had significantly impaired disease-free survival compared with those without emphysema (median disease-free survival = 37.0 vs 57.5 months, P = 0.038)., Conclusion: Adenocarcinomas in emphysema-present COPD had more aggressive features of pathology and CT findings, and worse disease-free survival than those without emphysema. These findings might provide an insight into the different pathobiology and prognostic implications of lung adenocarcinomas according to the presence of emphysema in patients with COPD., (© 2020 John Wiley & Sons Ltd.)

Specific phobia is highly prevalent worldwide. Although the body of intervention studies is expanding, there is a lack of reviews that summarise recent progress and discuss the challenges and direction of research in this area. Hence, this rapid review seeks to systematically evaluate the available evidence in the last five years in the treatment of specific phobias in adults. Studies published between January 2014 to December 2019 were identified through searches on the electronic databases of Medline and PsychINFO. In total, 33 studies were included. Evidence indicates that psychotherapy, and in particular cognitive behaviour therapy, when implemented independently or as an adjunctive, is a superior intervention with large effect sizes. Technology-assisted therapies seem to have a beneficial effect on alleviating fears and are described to be more tolerable than in vivo exposure therapy. Pharmacological agents are investigated solely as adjuncts to exposure therapy, but the effects are inconsistent; propranolol and glucocorticoid may be promising. A handful of cognitive-based therapies designed to alter fear arousal and activation pathways of phobias have presented preliminary, positive outcomes. Challenges remain with the inherent heterogeneity of specific phobia as a disorder and the accompanying variability in outcome measures and intervention approaches to warrant a clear conclusion on efficacy., Competing Interests: No competing interests were disclosed.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2020 Thng CEW et al.)

Objective: The purpose of this study was to determine the effects of underwater treadmill gait training with water-jet resistance and underwater treadmill gait training with ankle weights on balance and gait abilities in chronic stroke patients. Methods: Twenty-two inpatients and outpatients with stroke-induced impairments were randomly assigned into two groups: an underwater treadmill gait training with water-jet resistance group ( n = 11) and an underwater treadmill gait training with ankle weights group ( n = 11). Participants received conventional physical therapy for 30 min and underwater treadmill gait training with water-jet resistance or ankle weights for 30 min. Intervention was performed 5 days a week for 4 weeks. The Balance System SD was used to assess static and dynamic balance. The GAITRite system was used to assess gait velocity, cadence, step length, stride length, and swing phase. All measurements were performed at the beginning of the study and 4 weeks after the intervention. Results: The water-jet resistance group and ankle weights group showed significant improvement in static balance ( P < 0.00 vs. P = 0.01), dynamic balance ( P < 0.00 vs. P = 0.57), gait velocity ( P < 0.00 vs. P = 0.037), cadence ( P < 0.00 vs. P = 0.001), step length ( P < 0.00 vs. P = 0.003), stride length ( P < 0.00 vs. P = 0.023), and swing phase ( P < 0.00 vs. P < 0.00). However, the static and dynamic balance ability score ( P < 0.00), gait velocity ( P < 0.00), cadence ( P < 0.00), step length ( P < 0.00), stride length ( P < 0.00), and swing phase ( P = 0.023) in the group that received underwater treadmill gait training with water-jet resistance improved more than in the group that received underwater treadmill gait training with ankle weights. Conclusions: Our results demonstrated that underwater treadmill gait training with water-jet resistance is effective in improving static and dynamic balance as well as gait abilities in chronic stroke patients. Thus, training using underwater treadmill gait training with water-jet resistance may be useful in facilitating active rehabilitation in chronic stroke patients., (Copyright © 2020 Lim.)

Objective: The use of brain-computer interface in neurofeedback therapy for attention deficit hyperactivity disorder (ADHD) is a relatively new approach. We conducted a randomized controlled trial (RCT) to determine whether an 8-week brain computer interface (BCI)-based attention training program improved inattentive symptoms in children with ADHD compared to a waitlist-control group, and the effects of a subsequent 12-week lower-intensity training., Study Design: We randomized 172 children aged 6-12 attending an outpatient child psychiatry clinic diagnosed with inattentive or combined subtypes of ADHD and not receiving concurrent pharmacotherapy or behavioral intervention to either the intervention or waitlist-control group. Intervention involved 3 sessions of BCI-based training for 8 weeks, followed by 3 training sessions per month over the subsequent 12 weeks. The waitlist-control group received similar 20-week intervention after a wait-time of 8 weeks., Results: The participants' mean age was 8.6 years (SD = 1.51), with 147 males (85.5%) and 25 females (14.5%). Modified intention to treat analyzes conducted on 163 participants with at least one follow-up rating showed that at 8 weeks, clinician-rated inattentive symptoms on the ADHD-Rating Scale (ADHD-RS) was reduced by 3.5 (SD 3.97) in the intervention group compared to 1.9 (SD 4.42) in the waitlist-control group (between-group difference of 1.6; 95% CI 0.3 to 2.9 p = 0.0177). At the end of the full 20-week treatment, the mean reduction (pre-post BCI) of the pooled group was 3.2 (95% CI 2.4 to 4.1)., Conclusion: The results suggest that the BCI-based attention training program can improve ADHD symptoms after a minimum of 24 sessions and maintenance training may sustain this improvement. This intervention may be an option for treating milder cases or as an adjunctive treatment., Competing Interests: The authors have declared that no competing interests exist.

Accumulating evidence suggests brain network dysfunction in attention-deficit/hyperactivity disorder (ADHD). Whether large-scale brain network connectivity patterns reflect clinical heterogeneity in ADHD remains to be fully understood. This study aimed to characterize the differential within- and between-network functional connectivity (FC) changes in children with ADHD combined (ADHD-C) or inattentive (ADHD-I) subtypes and their associations with ADHD symptoms. We studied the task-free functional magnetic resonance imaging (fMRI) data of 58 boys with ADHD and 28 demographically matched healthy controls. We measured within- and between-network connectivity of both low-level (sensorimotor) and high-level (cognitive) large-scale intrinsic connectivity networks and network modularity. We found that children with ADHD-C but not those with ADHD-I exhibited hyper-connectivity within the anterior default mode network (DMN) compared with controls. Additionally, children with ADHD-C had higher inter-network FC between the left executive control (ECN) and the salience (SN) networks, between subcortical and visual networks, and between the DMN and left auditory networks than controls, while children with ADHD-I did not show differences compared with controls. Similarly, children with ADHD-C but not ADHD-I showed lower network modularity compared with controls. Importantly, these observed abnormal inter-network connectivity and network modularity metrics were associated with Child Behavioral Checklist (CBCL) attention-deficit/hyperactivity problems and internalizing problems in children with ADHD. This study revealed relatively greater loss of brain functional network segregation in childhood ADHD combined subtype compared to the inattentive subtype, suggesting differential large-scale functional brain network topology phenotype underlying childhood ADHD heterogeneity., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: While studies suggest that nutritional supplementation may reduce aggressive behavior in children, few have examined their effects on specific forms of aggression. This study tests the primary hypothesis that omega-3 (ω-3), both alone and in conjunction with social skills training, will have particular post-treatment efficacy for reducing childhood reactive aggression relative to baseline., Methods: In this randomized, double-blind, stratified, placebo-controlled, factorial trial, a clinical sample of 282 children with externalizing behavior aged 7-16 years was randomized into ω-3 only, social skills only, ω-3 + social skills, and placebo control groups. Treatment duration was 6 months. The primary outcome measure was reactive aggression collected at 0, 3, 6, 9, and 12 months, with antisocial behavior as a secondary outcome., Results: Children in the ω-3-only group showed a short-term reduction (at 3 and 6 months) in self-report reactive aggression, and also a short-term reduction in overall antisocial behavior. Sensitivity analyses and a robustness check replicated significant interaction effects. Effect sizes (d) were small, ranging from 0.17 to 0.31., Conclusions: Findings provide some initial support for the efficacy of ω-3 in reducing reactive aggression over and above standard care (medication and parent training), but yield only preliminary and limited support for the efficacy of ω-3 in reducing overall externalizing behavior in children. Future studies could test further whether ω-3 shows promise in reducing more reactive, impulsive forms of aggression.

For mechanical force to induce changes in cellular behaviors, two main processes are inevitable; perception of the force and response to it. Perception of mechanical force by cells, or mechanosensing, requires mechanical force-induced conformational changes in mechanosensors. For this, at least one end of the mechanosensors should be anchored to relatively fixed structures, such as extracellular matrices or the cytoskeletons, while the other end should be pulled along the direction of the mechanical force. Alternatively, mechanosensors may be positioned in lipid bilayers, so that conformational changes in the embedded sensors can be induced by mechanical force-driven tension in the lipid bilayer. Responses to mechanical force by cells, or mechanotransduction, require translation of such mechanical force-induced conformational changes into biochemical signaling. For this, protein-protein interactions or enzymatic activities of mechanosensors should be modulated in response to force-induced structural changes. In the last decade, several molecules that met the required criteria of mechanosensors have been identified and proven to directly sense mechanical force. The present review introduces examples of such mechanosensors and summarizes their mechanisms of action. [BMB Reports 2018; 51(12): 623-629].

A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations of large-scale brain functional networks induced by the 8-week BCI-based attention intervention in ADHD boys using resting-state functional magnetic resonance imaging method. Compared to the non-intervention (ADHD-NI) group, the intervention group (ADHD-I) showed greater reduction of inattention symptoms accompanied with differential brain network reorganizations after training. Specifically, the ADHD-NI group had increased functional connectivity (FC) within the salience/ventral attention network (SVN) and increased FC between task-positive networks (including the SVN, dorsal attention (DAN), somatomotor, and executive control network) and subcortical regions; in contrast ADHD-I group did not have this pattern. In parallel, ADHD-I group had reduced degree centrality and clustering coefficient as well as increased closeness in task-positive and the default mode networks (prefrontal regions) after the training. More importantly, these reduced local functional processing mainly in the SVN were associated with less inattentive/internalizing problems after 8-week BCI-based intervention across ADHD patients. Our findings suggest that the BCI-based attention training facilitates behavioral improvement in ADHD children by reorganizing brain functional network from more regular to more random configurations, particularly renormalizing salience network processing. Future long-term longitudinal neuroimaging studies are needed to develop the BCI-based intervention approach to promote brain maturation in ADHD.

Proper cell-material interactions are critical to remain cell function and thus successful tissue regeneration. Many fabrication processes have been developed to create microenvironments to control cell attachment and organization on a three-dimensional (3D) scaffold. However, these approaches often involve heavy engineering and only the surface layer can be patterned. We found that 3D extrusion based printing at high temperature and pressure will result an aligned effect on the polymer molecules, and this molecular arrangement will further induce the cell alignment and different differentiation capacities. In particular, articular cartilage tissue is known to have zonal collagen fiber and cell orientation to support different functions, where collagen fibers and chondrocytes align parallel, randomly, and perpendicular, respectively, to the surface of the joint. Therefore, cell alignment was evaluated in a cartilage model in this study. We used small angle X-ray scattering analysis to substantiate the polymer molecule alignment phenomenon. The cellular response was evaluated both in vitro and in vivo. Seeded mesenchymal stem cells (MSCs) showed different morphology and orientation on scaffolds, as a combined result of polymer molecule alignment and printed scaffold patterns. Gene expression results showed improved superficial zonal chondrogenic marker expression in parallel-aligned group. The cell alignment was successfully maintained in the animal model after 7 days with distinct MSC morphology between the casted and parallel printed scaffolds. This 3D printing induced polymer and cell alignment will have a significant impact on developing scaffold with controlled cell-material interactions for complex tissue engineering while avoiding complicated surface treatment, and therefore provides new concept for effective tissue repairing in future clinical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2190-2199, 2018., (© 2018 Wiley Periodicals, Inc.)

In recent decades, there have been concerted efforts to improve mental health services for youths alongside the challenges of rising healthcare costs and increasing demand for mental health needs. One important phenomenon is the shift from traditional clinic-based care to community-based mental health services to improve accessibility to services and provide patient-centred care. In this article, we discuss the child and adolescent community mental health efforts within the Asia-Pacific region. We also discuss Singapore's community and school-based mental health service, known as the Response, Early Intervention and Assessment in Community Mental Health (REACH). This article discusses how REACH has evolved over the years in response to the changing needs of youths in Singapore. Finally, we discuss the current challenges and future directions for youth mental health care., Competing Interests: The authors declare no conflict of interest.

Background: To evaluate the added clinical value of 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scans to chest CT imaging in predicting the conversion to thoracotomy during video-assisted thoracoscopic surgery (VATS) lobectomy in patients with lung cancer., Methods: This is a retrospective study of 235 consecutive patients who underwent planned VATS lobectomy for primary lung cancer between 2011 and 2015. CT images were interpreted in terms of the presence and the attenuation of peribronchial lymph nodes (PLN) and peribronchial cuffs of soft (PCS) tissue, pleural calcification, and parenchymal calcified nodule. On FDG PET/CT images, anthracofibrotic lymph node was considered present when high FDG uptake (SUVmax >3.5) was observed on PET/CT images corresponded to PLN or PCS on chest CT., Results: Among the 235 patients undergoing attempted VATS lobectomy, 55 (23.4%) underwent conversion to thoracotomy. Multivariate logistic regression analysis revealed that the attenuation of PLN or PCS on chest CT (OR, 2.57; 95% CI, 1.328-4.380, 0.005) was an only independent predictor of conversion. The ROC curve showed that combined FDG PET/CT and chest CT reading [areas under curve (AUC), 0.847 (95% CI, 0.795-0.891)] was significantly better than that of chest CT scans alone [AUC, 0.655 (95% CI, 0.50-0.751)] in predicting conversion (P=0.024)., Conclusions: The addition of FDG PET/CT scanning to chest CT imaging provides better performance for predicting conversion to thoracotomy during VATS lobectomy in lung cancer patients. Therefore, in lung cancer patients undergoing surgical resection, FDG PET/CT can provide additional reliable information in selecting the appropriate surgical approach for a lobectomy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

[Purpose] This study was designed to investigate the effects of lactose-free milk intake and whole-body vibration exercises on bone density in elderly female nursing home residents who had difficulty exercising outdoors and had not consumed milk. [Subjects and Methods] Twenty seven elderly women aged 70 or older from 3 nursing homes located in Incheon, Korea participated in the study. The experimental group (n=13) carried out whole-body vibration exercises and drank lactose-free milk, while the control group (n=14) continued to live their ordinary nursing home lives. Weight, BMI, T-scores, and Z-scores were compared between the experimental and control groups after 12 weeks. [Results] The comparison of changes in weight and BMI in the control group before and after the 12-week experiment found no statistically significant differences. However, bone mineral density was significantly different, with the T-score significantly decreasing from -2.99 to -3.48 and the Z-score decreasing from -1.87 to -2.58. The other comparisons of physical changes in the control group before and after the 12-week experiment found no statistical significance. [Conclusion] The results indicate that regular consumption of lactose-free milk and performing whole-body vibration exercises can delay the progression of bone density loss in older adults in nursing homes; adequate exercise and calcium intake could eventually help prevent fractures.

[Purpose] This study sought to examine the effects of Pedalo ® training on balance and fall risk in stroke patients. [Subjects and Methods] Thirty-one subjects with stroke were recruited and randomly allocated into two groups: the Pedalo ® group (n=15) and the Treadmill group (n=16). The Pedalo ® group performed conventional physical therapy program with Pedalo ® training for 30 minutes, five times a week, for 8 weeks, while the Treadmill group conducted conventional physical therapy programs and treadmill gait training for 30 minutes, five times a week, for 8 weeks. [Results] After intervention, both groups showed a significant improvement in balance. A significant greater balance improvement was found in the Pedalo ® group compared to the Treadmill group. Also, a significant reduction in risk of fall was seen in both group but this reduction was not significantly different between the two groups. [Conclusion] Pedalo ® training may be used to improve balance and reduce fall risk in stroke patients.

[Purpose] This study was designed to investigate the effects of spiral taping (ST) on the pain and walking performance of individual with chronic ankle instability (CAI). [Subjects and Methods] 12 men and 13 women (mean: 21.52 years; range: 20-31 years) with unilateral CAI (Cumberland ankle instability score: ≤24) were included. All the participants received 3 mm-wide ST. The latter was applied in a 3 × 4 cross shape onto the medial malleolus, the lateral malleolus, and the anterior talotibial joint of the unstable ankle. The pain and walking performance were measured on the visual analogue scale (VAS) and with a timed up and go test (TUGT) at the baseline and 30 minutes after the intervention. [Results] VAS and TUGT scores were significantly improved after application of the ST. [Conclusion] The results indicated that ST can improve the pain and walking performance of CAI individuals.

Background: With the invention of fitness trackers, it has been possible to continuously monitor a user's biometric data such as heart rates, number of footsteps taken, and amount of calories burned. This paper names the time series of these three types of biometric data, the user's "activeness", and investigates the feasibility in modeling and predicting the long-term activeness of the user., Methods: The dataset used in this study consisted of several months of biometric time-series data gathered by seven users independently. Four recurrent neural network (RNN) architectures-as well as a deep neural network and a simple regression model-were proposed to investigate the performance on predicting the activeness of the user under various length-related hyper-parameter settings. In addition, the learned model was tested to predict the time period when the user's activeness falls below a certain threshold., Results: A preliminary experimental result shows that each type of activeness data exhibited a short-term autocorrelation; and among the three types of data, the consumed calories and the number of footsteps were positively correlated, while the heart rate data showed almost no correlation with neither of them. It is probably due to this characteristic of the dataset that although the RNN models produced the best results on modeling the user's activeness, the difference was marginal; and other baseline models, especially the linear regression model, performed quite admirably as well. Further experimental results show that it is feasible to predict a user's future activeness with precision, for example, a trained RNN model could predict-with the precision of 84%-when the user would be less active within the next hour given the latest 15 min of his activeness data., Conclusions: This paper defines and investigates the notion of a user's "activeness", and shows that forecasting the long-term activeness of the user is indeed possible. Such information can be utilized by a health-related application to proactively recommend suitable events or services to the user.

In the past few decades, 3D printing has played a significant role in fabricating scaffolds with consistent, complex structure that meet patient-specific needs in future clinical applications. Although many studies have contributed to this emerging field of additive manufacturing, which includes material development and computer-aided scaffold design, current quantitative analyses do not correlate material properties, printing parameters, and printing outcomes to a great extent. A model that correlates these properties has tremendous potential to standardize 3D printing for tissue engineering and biomaterial science. In this study, we printed poly(lactic-co-glycolic acid) (PLGA) utilizing a direct melt extrusion technique without additional ingredients. We investigated PLGA with various lactic acid:glycolic acid (LA:GA) molecular weight ratios and end caps to demonstrate the dependence of the extrusion process on the polymer composition. Micro-computed tomography was then used to evaluate printed scaffolds containing different LA:GA ratios, composed of different fiber patterns, and processed under different printing conditions. We built a statistical model to reveal the correlation and predominant factors that determine printing precision. Our model showed a strong linear relationship between the actual and predicted precision under different combinations of printing conditions and material compositions. This quantitative examination establishes a significant foreground to 3D print biomaterials following a systematic fabrication procedure. Additionally, our proposed statistical models can be applied to couple specific biomaterials and 3D printing applications for patient implants with particular requirements.

It is important to protect health and improve quality of life for people, without causing them inconvenience in today's world. Since most people are living a busy life dealing with various activities at work, school, or home, there is a need for systematic analysis of their life patterns. However, since person's life patterns could change depending on ambient environmental factors, an effective management scheme to specify one's state is required. We propose a method, in this paper, to support and enhance the personal healthy life patterns by analyzing the daily life data that has been continuously recorded by wearable sensors, such as activity trackers. We implement a mobile wellness management system by learning RNN-based user's lifestyle model, and developing behavior recommendation using greedy policy. We also consider user context and feedback to personalize each user's lifestyle.

We have recently developed a bioreactor that can apply both shear and compressive forces to engineered tissues in dynamic culture. In our system, alginate hydrogel beads with encapsulated human mesenchymal stem cells (hMSCs) were cultured under different dynamic conditions while subjected to periodic, compressive force. A customized pressure sensor was developed to track the pressure fluctuations when shear forces and compressive forces were applied. Compared to static culture, dynamic culture can maintain a higher cell population throughout the study. With the application of only shear stress, qRT-PCR and immunohistochemistry revealed that hMSCs experienced less chondrogenic differentiation than the static group. The second study showed that chondrogenic differentiation was enhanced by additional mechanical compression. After 14 days, alcian blue staining showed more extracellular matrix formed in the compression group. The upregulation of the positive chondrogenic markers such as Sox 9, aggrecan, and type II collagen were demonstrated by qPCR. Our bioreactor provides a novel approach to apply mechanical forces to engineered cartilage. Results suggest that a combination of dynamic culture with proper mechanical stimulation may promote efficient progenitor cell expansion in vitro, thereby allowing the culture of clinically relevant articular chondrocytes for the treatment of articular cartilage defects.

For the past few decades, action recognition has been attracting many researchers due to its wide use in a variety of applications. Especially with the increasing number of smartphone users, many studies have been conducted using sensors within a smartphone. However, a lot of these studies assume that the users carry the device in specific ways such as by hand, in a pocket, in a bag, etc. This paper investigates the impact of providing an action recognition system with the information of the possession-way of a smartphone, and vice versa. The experimental dataset consists of five possession-ways (hand, backpack, upper-pocket, lower-pocket, and shoulder-bag) and two actions (walking and running) gathered by seven users separately. Various machine learning models including recurrent neural network architectures are employed to explore the relationship between the action recognition and the possession-way recognition. The experimental results show that the assumption of possession-ways of smartphones do affect the performance of action recognition, and vice versa. The results also reveal that a good performance is achieved when both actions and possession-ways are recognized simultaneously.

Natural product metabolic engineering potentially offers sustainable and affordable access to numerous valuable molecules. However, challenges in characterizing and assembling complex biosynthetic pathways have prevented more rapid progress in this field. The anticancer agent Taxol represents an excellent case study. Assembly of a biosynthetic pathway for Taxol has long been stalled at its first functionalization, putatively an oxygenation performed by the cytochrome P450 CYP725A4, due to confounding characterizations. Here, through combined in vivo (Escherichia coli), in vitro (lipid nanodisc), and metabolite stability assays, we verify the presence and likely cause of this enzyme's inherent promiscuity. Thereby, we remove the possibility that promiscuity simply existed as an artifact of previous metabolic engineering approaches. Further, spontaneous rearrangement and the stabilizing effect of a hydrophobic overlay suggest a potential role for nonenzymatic chemistry in Taxol's biosynthesis. Taken together, this work confirms taxadiene-5α-ol as a primary enzymatic product of CYP725A4 and provides direction for future Taxol metabolic and protein engineering efforts.

Recent advances in metabolic engineering have demonstrated the potential to exploit biological chemistry for the synthesis of complex molecules. Much of the progress to date has leveraged increasingly precise genetic tools to control the transcription and translation of enzymes for superior biosynthetic pathway performance. However, applying these approaches and principles to the synthesis of more complex natural products will require a new set of tools for enabling various classes of metabolic chemistries (i.e., cyclization, oxygenation, glycosylation, and halogenation) in vivo. Of these diverse chemistries, oxygenation is one of the most challenging and pivotal for the synthesis of complex natural products. Here, using Taxol as a model system, we use nature's favored oxygenase, the cytochrome P450, to perform high-level oxygenation chemistry in Escherichia coli. An unexpected coupling of P450 expression and the expression of upstream pathway enzymes was discovered and identified as a key obstacle for functional oxidative chemistry. By optimizing P450 expression, reductase partner interactions, and N-terminal modifications, we achieved the highest reported titer of oxygenated taxanes (∼570 ± 45 mg/L) in E. coli. Altogether, this study establishes E. coli as a tractable host for P450 chemistry, highlights the potential magnitude of protein interdependency in the context of synthetic biology and metabolic engineering, and points to a promising future for the microbial synthesis of complex chemical entities.

The development of lignocellulose as a sustainable resource for the production of fuels and chemicals will rely on technology capable of converting the raw materials into useful compounds; some such transformations can be achieved by biological processes employing engineered microorganisms. Towards the goal of valorizing the hemicellulose fraction of lignocellulose, we designed and validated a set of pathways that enable efficient utilization of pentoses for the biosynthesis of notable two-carbon products. These pathways were incorporated into Escherichia coli, and engineered strains produced ethylene glycol from various pentoses, including simultaneously from D-xylose and L-arabinose; one strain achieved the greatest reported titer of ethylene glycol, 40 g/L, from D-xylose at a yield of 0.35 g/g. The strategy was then extended to another compound, glycolate. Using D-xylose as the substrate, an engineered strain produced 40 g/L glycolate at a yield of 0.63 g/g, which is the greatest reported yield to date., (Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)