With the outbreak of the COVID-19 disease, the research community is producing unprecedented efforts dedicated to better understand and mitigate the effects of the pandemic. In this context, we review the data integration efforts required for accessing and searching genome sequences and metadata of SARS-CoV2, the virus responsible for the COVID-19 disease, which have been deposited into the most important repositories of viral sequences. Organizations that were already present in the virus domain are now dedicating special interest to the emergence of COVID-19 pandemics, by emphasizing specific SARS-CoV2 data and services. At the same time, novel organizations and resources were born in this critical period to serve specifically the purposes of COVID-19 mitigation while setting the research ground for contrasting possible future pandemics. Accessibility and integration of viral sequence data, possibly in conjunction with the human host genotype and clinical data, are paramount to better understand the COVID-19 disease and mitigate its effects. Few examples of host-pathogen integrated datasets exist so far, but we expect them to grow together with the knowledge of COVID-19 disease; once such datasets will be available, useful integrative surveillance mechanisms can be put in place by observing how common variants distribute in time and space, relating them to the phenotypic impact evidenced in the literature.

Food industry led reformulation efforts have attempted to address the prevalence of obesity by modifying nutrient compositions in food products. This study explored progress in nutrient composition alterations in products in Irish supermarkets by comparing the nutrient labels of products sold in 2014 and 2017.

We conducted two supermarket audits in 2014 and 2017 to examine the changes in the nutrient profile of cereals, breads, spreads, unflavoured milks, yogurts and juices. Information on the nutrients of interest to the study (energy, protein, fat, carbohydrate, saturated fat, salt, sugar and some micronutrients) were extracted and stored in Microsoft Excel. The nutrient profile of each product was compared across the two timepoints. Our study shows that the mean level of sugars in cereals remains high and that the mean level of salt remains high in cereals, breads, and spreads.

In total, 143 products were directly compared (86 cereals, 26 breads, 17 spreads and 14 milks). Our study shows that the composition of salt and sugar in cereal, bread, spreads and milk has declined by 12 and 7%, respectively. Saturated fat has declined in cereals (7%), but has increased in breads (12%), spreads (1%), and milks (5%). Manufacturers increased the serving sizes in nine cereals and one milk.

From a population health perspective, the results are encouraging but care should be exercised by the food industry not to allow total fat and saturated fat levels to creep upwards. Further research and engagement of public health specialists and the food industry are needed.

From a population health perspective, the results are encouraging but care should be exercised by the food industry not to allow total fat and saturated fat levels to creep upwards. Further research and engagement of public health specialists and the food industry are needed.Drug repositioning has received increased attention since the past decade as several blockbuster drugs have come out of repositioning. Computational approaches are significantly contributing to these efforts, of which, network-based methods play a key role. Various structural (topological) network measures have thereby contributed to uncovering unintuitive functional relationships and repositioning candidates in drug-disease and other networks. This review gives a broad overview of the topic, and offers perspectives on the application of topological measures for network analysis. It also discusses unexplored measures, and draws attention to a wider scope of application efforts, especially in drug repositioning.

Despite increasing multimorbidity across the lifespan, little is known about the co-occurrence of conditions and risk factors among younger adults. This population-based study examines multimorbidity, social determinants and associated mortality among younger and middle-age adults.

Analysis was based on the Northern Ireland population aged 25-64years enumerated in the 2011 Census (n=878345), with all-cause mortality follow-up to 2014 (8659 deaths). Logistic regression was used to examine social determinants and Cox proportional hazards models in the analysis of associated mortality.

Prevalence of multimorbidity was 13.7% in females and 12.7% in males. There was a strong association between multimorbidity that included mental/cognitive illness and deprivation. Among those never married, multimorbid physical conditions were less likely [relative risk ratios (RRR)=0.92 95% confidence interval (CI)=0.88, 0.95 for males; and RRR=0.90 0.87, 0.94 for females]. Rurality was associated with lower physical multimorbidity (RRR=0.92 0.89, 0.95) but higher mental/cognitive multimorbidity (RRR=1.35 1.12, 1.64) among females. All multimorbid categories were associated with elevated risk of mortality.

The health and economic challenges created by multimorbidity should be addressed further 'upstream’. Future multimorbidity research should include younger adults to inform the development of preventative interventions and align health and social care services more closely with patients’ needs.

The health and economic challenges created by multimorbidity should be addressed further 'upstream’. Future multimorbidity research should include younger adults to inform the development of preventative interventions and align health and social care services more closely with patients’ needs.

Most studies estimate hepatitis C virus (HCV) disease prevalence from convenience samples. Consequently, screening policies may not include those at the highest risk for a new diagnosis.

Clalit Health Services members aged 25-74 as of 31 December 2009 were included in the study. Rates of testing and new diagnoses of HCV were calculated, and potential risk groups were examined.

Of the 2029501 included members, those aged 45-54 and immigrants had lower rates of testing (12.5% and 15.6%, respectively), higher rates of testing positive (0.8% and 1.1%, respectively), as well as the highest rates of testing positive among tested (6.1% and 6.9%, respectively).

In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.

In this population-level study, groups more likely to test positive for HCV also had lower rates of testing. Policy makers and clinicians worldwide should consider creating screening policies using on population-based data to maximize the ability to detect and treat incident cases.This is an international multicentre study aimed at evaluating the combined value of dopaminergic neuroimaging and clinical features in predicting future phenoconversion of idiopathic REM sleep behaviour (iRBD) subjects to overt synucleinopathy. Nine centres sent 123I-FP-CIT-SPECT data of 344 iRBD patients and 256 controls for centralized analysis. 123I-FP-CIT-SPECT images were semiquantified using DaTQUANTTM, obtaining putamen and caudate specific to non-displaceable binding ratios (SBRs). The following clinical variables were also analysed (i) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, motor section score; (ii) Mini-Mental State Examination score; (iii) constipation; and (iv) hyposmia. Kaplan-Meier survival analysis was performed to estimate conversion risk. Hazard ratios for each variable were calculated with Cox regression. A generalized logistic regression model was applied to identify the best combination of risk factors. Bayesian classifier was used tothan 70 with constipation and reduced nigro-putaminal dopaminergic function are at high risk of short-term phenoconversion to an overt synucleinopathy, providing an effective stratification approach for future neuroprotective trials. Moreover, we provide cut-off values for the significant predictors of phenoconversion to be used in single subjects.

There is increasing prevalence of diseases associated with ageing such as hypertension, among people living with HIV (PLWHV). This study sought to assess (1) knowledge related to HIV infection and hypertension, (2) adherence to prescribed medications and (3) clinical outcomes among HIV-positive persons with hypertension at a Nigerian hospital.

The Patient’s HIV Knowledge Questionnaire (PHKQ), Hypertension Knowledge-Level Scale (HK-LS) and Adherence to Refills and Medication Scale (ARMS) were administered to 220 eligible patients through the HIV clinic. Demographic and clinical data were also obtained.

Participants were predominantly females (57.3%), with a median (IQR) age of 46 (38-58) years; majority were married (67.8%) and employed (60.8%). Participants reported a higher hypertension-related knowledge compared with HIV-related knowledge (63.6% versus 33.3%, Z=-10.263, P<0.001), but better adherence to antiretroviral medications compared to antihypertensives (100.0% versus 89.3%, Z=-9.118, P<0.001). Of the 98 participants with documented viral load, 55 (56.1%) had undetectable (<40 copies/ml) values; however, only four (2.0%) of the entire sample had controlled (<140/90 mmHg) blood pressure.

Despite having a higher hypertension-related knowledge, adherence to antihypertensive medications and blood pressure control were poor. There is a need for increased attention to HIV education and comorbidities in PLWHV.

Despite having a higher hypertension-related knowledge, adherence to antihypertensive medications and blood pressure control were poor. There is a need for increased attention to HIV education and comorbidities in PLWHV.

Concern about the health impacts of e-cigarette use is growing; however, limited research exists regarding potential long-term health effects of this behavior. This study explored the relationship between e-cigarette use and COPD in a sample of US adults.

A secondary data analysis using data from the 2018 Behavioral Risk Factor Surveillance Survey in the USA was computed to examine associations between e-cigarette use and COPD controlling for conventional cigarette smoking status, past month leisure physical activity and demographic characteristics including age, sex, education, race, marital status and body mass index.

Significant associations between e-cigarette use and COPD among former combustible cigarette smokers and those who reported never using combustible cigarettes were found. Compared with never e-cigarette users, the odds of having COPD were significantly greater for daily e-cigarette users (OR=1.53; 95% CI 1.11-2.03), occasional users (OR=1.43, 95% CI 1.13-1.80) and former users (OR=1.46 95% CI 1.28-1.67).

Findings from this study indicate a potential link between e-cigarette use and COPD. Further research to explore the potential effects of e-cigarette on COPD is recommended.

Findings from this study indicate a potential link between e-cigarette use and COPD. Further research to explore the potential effects of e-cigarette on COPD is recommended.Despite gene expression programs being notoriously complex, RNA abundance is usually assumed as a proxy for transcriptional activity. Recently developed approaches, able to disentangle transcriptional and post-transcriptional regulatory processes, have revealed a more complex scenario. It is now possible to work out how synthesis, processing and degradation kinetic rates collectively determine the abundance of each gene’s RNA. It has become clear that the same transcriptional output can correspond to different combinations of the kinetic rates. This underscores the fact that markedly different modes of gene expression regulation exist, each with profound effects on a gene’s ability to modulate its own expression. This review describes the development of the experimental and computational approaches, including RNA metabolic labeling and mathematical modeling, that have been disclosing the mechanisms underlying complex transcriptional programs. Current limitations and future perspectives in the field are also discussed.Failures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INFγ, MIF, TNFα, and IL10. These factors were positively correlated with Kiss1 and/or Kiss1r, and a positive correlation between Kiss1 and Kiss1r was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kiss1r on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and Il6 mRNA, and an increase in Tnf mRNA. The findings reveal that there is a gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of the domestic cat, which is modulated by the estrous cycle, and that pyometra affects the expression of these mediators. This study suggests, for the first time, a functional relationship between the Kiss/Kiss1r system and angiogenic and immune mediators in the female genital tract.

In 2017, new regulations in England introduced upfront charging for non-urgent care within the National Health Service (NHS). Individuals from outside the European Economic Area who have not paid the immigration surcharge are chargeable for NHS care at 150% of cost.

A freedom of information (FOI) request was sent to 135 acute non-specialist NHS trusts in England to create a database of overseas visitors charges. This was analysed using multiple linear regression to explore the relationship between sex, age, nationality, ethnicity, urgency and the cost of healthcare.

Of 135 acute non-specialist trusts in England 64 replied, providing a data set of 13484 patients. Women were found to be invoiced higher amounts than men (P=0.002). Patients were more likely to be women (63 versus 37% men), and within this group, almost half of patients were of reproductive age, with 47.9% (3165) aged 16-40years old. Only seven trusts supplied data on urgency, and within these trusts the urgency of treatment was significantly related to cost, with the most urgent (immediately necessary) treatment costing the most (P<0.001).

This research reflects that that migrant women, and particularly undocumented women, are disproportionately impacted by the NHS charging policies in England.

This research reflects that that migrant women, and particularly undocumented women, are disproportionately impacted by the NHS charging policies in England.The size and quality of chemical libraries to the drug discovery pipeline are crucial for developing new drugs or repurposing existing drugs. Existing techniques such as combinatorial organic synthesis and high-throughput screening usually make the process extraordinarily tough and complicated since the search space of synthetically feasible drugs is exorbitantly huge. While reinforcement learning has been mostly exploited in the literature for generating novel compounds, the requirement of designing a reward function that succinctly represents the learning objective could prove daunting in certain complex domains. Generative adversarial network-based methods also mostly discard the discriminator after training and could be hard to train. In this study, we propose a framework for training a compound generator and learn a transferable reward function based on the entropy maximization inverse reinforcement learning (IRL) paradigm. We show from our experiments that the IRL route offers a rational alternative for generating chemical compounds in domains where reward function engineering may be less appealing or impossible while data exhibiting the desired objective is readily available.

There are currently no studies synthesizing the screening rate and influential factors of low-dose computed tomography (LDCT)-screened lung cancer in Asian population.

A systematic review was conducted, using both English and Chinese language databases on March, 2019. The pooled screening rate and estimated odds ratios (ORs) of influential factors were analyzed using random effects models. Subgroup and meta-regression analyses were also employed to explore the heterogeneity.

The pooled LDCT lung cancer screening rate was 1.12% (95% confidence interval (CI) 0.94%, 1.32%), and increased with age. Adenocarcinoma and stage I lung cancer had higher screening rates. Analysis of influential factors in the general population showed that female and elder age (≥50years) were significantly influencing LDCT lung cancer screening rate (for female, OR = 1.32, 95% CI 1.15-1.52; for adults ≥ 50years, OR = 1.94, 95% CI 1.52-2.49). Meta-regression analysis indicated that the heterogeneity maybe significantly correlated with the sample size, risk population and source of population.

Unlike European and American populations, female and adults > 50years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

 50 years rather than smoking adults were positively associated with screening rate in Asian populations. It is important to further study the benefits of lung cancer screening with LDCT in Asian populations.

Preventative interventions may be effective in reducing and preventing symptoms of mental ill health in children and young people. However, there is a paucity of research in this area that explores the views of young people. This paper reports on a qualitative study to inform the future development of attractive and appropriate early and preventative school-based mental health interventions.

Semi-structured interviews were conducted with a purposive sample of 12 young people aged 14-17 in North East England. Interviews were audio-recorded, transcribed, anonymised and analysed following a thematic approach.

Four key themes were identified, relevant to those providing, designing and commissioning early and preventative mental health interventions in schools 'mental health literacy’, 'risk factors for wellbeing decline’, 'experience of school-based support’ and 'recommendations for future support’.

Young people have varying levels of mental health literacy, but are able to identify academic stress, bullying and the transition from primary to secondary school as leading causes of worry. Young people want more regular and in-depth mental health education, tailored levels of support in school and improved training for teachers.

Young people have varying levels of mental health literacy, but are able to identify academic stress, bullying and the transition from primary to secondary school as leading causes of worry. Young people want more regular and in-depth mental health education, tailored levels of support in school and improved training for teachers.In recent correspondences and articles published, the role of religious and spiritual interventions has been discussed for the attention of the medical community in the time of COVID-19 pandemic and part of these interventions is to provide spiritual care. Attention has been given to provide spiritual care among COVID-19 patients. However, there is also a dire need to offer spiritual care towards healthcare professionals because they, too, are 'wounded healers’. This paper discusses the urgent call for the medical and spiritual communities to come up with comprehensive spiritual care programme for healthcare professionals so that they may attain spiritual well-being as they serve in the frontlines, risking their lives and providing spiritual care to patients especially in this trying times of the pandemic as a public health crisis.

In response to the outbreak of Ebola Virus Disease (EVD) in West Africa in 2014 and evidence of spread to other countries, pre-entry screening was introduced by PHE at five major ports of entry in the England.

All passengers that entered the England via the five ports returning from Liberia, Guinea and Sierra Leonne were required to complete a Health Assessment Form and have their temperature taken. The numbers, characteristics and outcomes of these passengers were analysed.

Between 14 October 2014 and 13 October 2015, a total of 12648 passengers from affected countries had been screened. The majority of passengers were assessed as having no direct contact with EVD cases or high-risk events (12069, 95.4%), although 535 (4.2%) passengers were assessed as requiring public health follow-up. In total, 39 passengers were referred directly to secondary care, although none were diagnosed with EVD. One high-risk passenger was later referred to secondary care and diagnosed with EVD.

Collection of these screening data enabled timely monitoring of the numbers and characteristics of passengers screened for EVD, facilitated resourcing decisions and acted as a mechanism to inform passengers of the necessary public health actions.

Collection of these screening data enabled timely monitoring of the numbers and characteristics of passengers screened for EVD, facilitated resourcing decisions and acted as a mechanism to inform passengers of the necessary public health actions.YES. MONTHLY EXTENDED-RELEASE INJECTABLE NALTREXONE (XR-NTX) TREATS OPIOID USE DISORDER AS EFFECTIVELY AS DAILY SUBLINGUAL BUPRENORPHINE-NALOXONE (BUP-NX) WITHOUT CAUSING ANY INCREASE IN SERIOUS ADVERSE EVENTS OR FATAL OVERDOSES. (STRENGTH OF RECOMMENDATION A, 2 GOOD-QUALITY RCTS).A diagnosis was arrived at by doing something that the patient’s other doctors hadn’t perform a biopsy.A thorough history and physical are key to proper diagnosis and treatment following a patient’s encounter with an insect, arachnid, or other arthropod.The patient had a history of treatment for head lice, but a dermatoscopic exam revealed that lice weren’t to blame for his itchy scalp.► Abdominal pain ► Lower-leg itching ► Dark urine & yellow eyes.The new draft recommendations from the US Preventive Services Task Force make a significant change to the previous colorectal cancer screening recommendations. This month, Dr. Campos-Outcalt describes that change and provides a look at the financial implications (as stipulated by the Affordable Care Act) of the screening method chosen.A daily dose of this prescription fish oil may be worth a trial in light of the cardiovascular benefits it affords statin-treated patients with high triglycerides.This service, which significantly improves outcomes for many patients, is beneficial in this time of COVID-19.Family medicine’s leadership in primary care is slipping as it loses its vision of whole-person care. This model of care can help us better manage and combat chronic disease.This pictorial review can help you advise patients on how to reduce pain and increase ROM, strength, and balance following acute injury or in chronic impairment.Early recognition, management of comorbid conditions, and appropriate treatment of peripheral arterial disease can help you improve your patient’s outcome.As countries in Europe gradually relaxed lockdown restrictions after the first wave, test-trace-isolate strategies became critical to maintain the incidence of coronavirus disease 2019 (COVID-19) at low levels1,2. Reviewing their shortcomings can provide elements to consider in light of the second wave that is currently underway in Europe. Here we estimate the rate of detection of symptomatic cases of COVID-19 in France after lockdown through the use of virological3 and participatory syndromic4 surveillance data coupled with mathematical transmission models calibrated to regional hospitalizations2. Our findings indicate that around 90,000 symptomatic infections, corresponding to 9 out 10 cases, were not ascertained by the surveillance system in the first 7 weeks after lockdown from 11 May to 28 June 2020, although the test positivity rate did not exceed the 5% recommendation of the World Health Organization (WHO)5. The median detection rate increased from 7% (95% confidence interval, 6-8%) to 38% (35-44%) overd wave.This commentary will focus on the role of thrombectomy for the treatment of embolic stroke during the 2019 novel coronavirus disease (COVID-19). We will begin with review of recently promulgated guidelines for use of thrombectomy in COVID-19-associated stroke. We will then survey the reported experience of thrombectomy applied to treatment of large-vessel occlusion (LVO) stroke in COVID-19. We will conclude by discussing unusual challenges confronted by neuro-interventionalists seeking to perform thrombectomy in COVID-19 patients with acute LVO stroke.

The aim of this study was to correlate plasma levels of the synaptic proteins α-synuclein and γ-synuclein in autism spectrum disorder (ASD) children in order to elucidate their possible contribution to the pathogenesis of ASD and to study their association with the severity of the disorder.

Plasma levels of α-synuclein and γ-synuclein were measured in 38 male children diagnosed with ASD and 40 healthy age-matched male children by ELISA.

Our results showed that plasma levels of α-synuclein (18.02 ± 5.3 pg/mL) were significantly higher in ASD children than in control children (14.39 ± 2 pg/mL), and plasma levels of γ-synuclein were decreased in the ASD group (23.74 ± 7.7 pg/mL) compared to the control group (32.40 ± 6.8 pg/mL) (p < 0.0001). Our data also indicate that plasma levels of both α-synuclein and γ-synuclein are significantly associated with the severity of ASD.

Our study showed that alteration in α-synuclein and γ-synuclein might be associated with ASD pathogenesis and could be an indicator of the severity of the disorder.

Our study showed that alteration in α-synuclein and γ-synuclein might be associated with ASD pathogenesis and could be an indicator of the severity of the disorder.

Energy consumption is a critical issue in resource-constrained wireless neural recording applications with limited data bandwidth. Compressed sensing (CS) has emerged as a powerful framework in addressing this issue owing to its highly efficient data compression procedure. In this paper, a CS-based approach termed Simultaneous Analysis Non-Convex Optimization (SANCO) is proposed for large-scale, multi-channel local field potentials (LFPs) recording.

The SANCO method consists of three parts (1) the analysis model is adopted to reinforce sparsity of the multi-channel LFPs, therefore overcoming the drawbacks of conventional synthesis models. (2) An optimal continuous order difference matrix is constructed as the analysis operator, enhancing the recovery performance while saving both computational resources and data storage space. (3) A non-convex optimizer that can by efficiently solved with alternating direction method of multipliers (ADMM) is developed for multi-channel LFPs reconstruction.

Experimental results on real datasets reveal that the proposed approach outperforms state-of-the-art CS methods in terms of both recovery quality and computational efficiency.

Energy efficiency of the SANCO make it an ideal candidate for resource-constrained, large scale wireless neural recording. Particularly, the proposed method ensures that the key features of LFPs had little degradation even when data are compressed by 16x, making it very suitable for long term wireless neural recording applications.

Energy efficiency of the SANCO make it an ideal candidate for resource-constrained, large scale wireless neural recording. Particularly, the proposed method ensures that the key features of LFPs had little degradation even when data are compressed by 16x, making it very suitable for long term wireless neural recording applications.Graphite/silicon (G/Si) composites are considered as possible alternative anode materials to commercial graphite anodes. However, the unstable solid electrolyte interphase (SEI) on G/Si particles results in rapid capacity decay, impeding practical applications. Herein, a facile and low-cost Al2O3 coating was developed to fabricate stable artificial SEI layers on G/Si composites. The amorphous Al2O3 coating with a thickness of 10-15 nm was synthesized by a simple sol-gel method followed by high-temperature annealing. The Al2O3 coated G/Si anode delivers an initial discharge capacity of 540 mAh g-1 at 25 °C and has improved Coulombic efficiency and cycling stability. After 100 cycles, the capacity retention is 76.4%, much higher than the 56.4% of the uncoated anode. Furthermore, the Al2O3 coating was found to be more effective at improving the stability of G/Si at a higher temperature (55 °C). This was explained by the Al2O3 coating suppressing the growth of SEI on Si/G and thus reducing the charge transfer resistance at the G/Si-electrolyte interface. It is expected that the Al2O3 coating prepared by the sol-gel process can be applied to other Si-based anodes in the manufacture of practical high-performance lithium-ion batteries.

Computational models of neural activity at the meso-scale suggest the involvement of discrete oscillatory bursts as constructs of cognitive processing during behavioral tasks. Classical signal processing techniques that attempt to infer neural correlates of behavior from meso-scale activity employ spectral representations of the signal, exploiting power spectral density techniques and time – frequency energy distributions to capture band power features. However, such analyses demand more specialized methods that incorporate explicitly the concepts of neurophysiological signal generation and time resolution in the tens of milliseconds. This paper focuses on working memory (WM), a complex cognitive process involved in encoding, storing and retrieving sensory information, which has been shown to be characterized by oscillatory bursts in the beta and gamma band. Employing a generative model for oscillatory dynamics, we present a Marked Point Process (MPP) representation of bursts during memory creation and reademployed time – frequency methods. Finally, our results underscore the novelty in interpreting oscillatory dynamics encompassed by the marked features of the point process.

An MPP representation of meso-scale activity not just enables a rich, high – resolution parameter space for analysis but also presents a novel tool for diverse neural applications.

An MPP representation of meso-scale activity not just enables a rich, high – resolution parameter space for analysis but also presents a novel tool for diverse neural applications.T-cell immunotherapy holds promise for the treatment of cancer, infection, and autoimmune diseases. Nevertheless, T-cell therapy is limited by low cell expansion efficiency ex vivo and functional deficits. Here we describe two 3D bioprinting systems made by different biomaterials that mimic the in vivo formation of natural lymph vessels and lymph nodes which modulate T-cell with distinct fates and functions. We observe that coaxial alginate fibers promote T-cell expansion, less exhausted and enable CD4+ T-cell differentiation into central memory-like phenotype (Tcm), CD8+ T-cells differentiation into effector memory subsets (Tem), while alginate-gelatin scaffolds bring T-cells into a relatively resting state. Both of the two bioprinting methods are strikingly different from a standard suspension system. The former bioprinting method yields a new system for T-cell therapy and the latter method can be useful for making an immune-chip to elucidate links between immune response and disease.We describe a radiation therapy treatment plan optimization method that explicitly considers the effects of interfraction organ motion through optimization on the clinical target volume (CTV), and investigate how it compares to conventional planning using a planning target volume (PTV). The method uses simulated treatment courses generated using patient images created by a deformable registration algorithm to replicate the effects of interfraction organ motion, and performs robust optimization aiming to achieve CTV coverage under all simulated treatment courses. The method was applied to photon-mediated treatments of three prostate cases and compared to conventional, PTV-based planning with margins selected to achieve similar CTV coverage as the robustly optimized plans. Clinical goals for the CTV and healthy tissue were used in comparison between the two types of plans. Out of the two clinical goals for overdosage of the CTV, the three robustly optimized plans violated respectively 2, 2, and 0 goals in the mean over the scenarios, whereas none of the PTV plans violated these goals. Of the ten clinical goals for rectum, bladder, anal canal, and bulbus, the robustly optimized plans violated respectively 0, 1, and 1 goals in the mean, whereas the PTV plans violated 5, 7, and 4 goals. Compared to PTV-based planning, the inclusion of treatment course scenarios in the optimization has the potential to reduce the dose to healthy tissues while retaining a high probability of target coverage. This may reduce the need for adaptive replanning.

Presence of a patent ductus arteriosus (PDA) in neonates is assessed by echocardiography. Echocardiographic assessment has disadvantages, primarily its discontinuous nature. We hypothesize that the continuously measured ratio of arterial blood pressures (ABP) at the borders of a window surrounding the systolic peak ratio discriminates non-PDA from PDA patients.

Preterm infants (gestational age <32 weeks) with and without PDA were included. Patients were divided into controls (n=8) and PDA patients (n=22), the latter with a subset of patients with closed PDA after three doses Ibuprofen (n=10). For each patient, a six-hour ABP segment from 12 AM to 6 AM on the day of echocardiographic assessment patency or closure of the DA was selected. The mean ratio of the ABP values a samples before and p samples after the systolic peak (R

) was calculated for each segment. If R

<1, the patient was predicted to have a PDA. The a and p with the least misclassifications were selected (-64 and +104 ms).

R

was significantly lower in PDA patients (median 0.95, IQR 0.06) compared to controls (median 1.05, IQR 0.10; p=0.0024). R

correctly predicted 19 out of 22 patients (86.4%) and six out of eight controls (75%). R

increased after closure in nine out of 10 patients (median 1.01, IQR 0.04; p=0. 0182).

R

may discriminate preterm PDA patients from non-PDA patients and can be calculated continuously from clinical data measured during standard of care.

R ABP may discriminate preterm PDA patients from non-PDA patients and can be calculated continuously from clinical data measured during standard of care.Coaxial type piezoelectric energy generator (C-PEG) nanofiber was fabricated by a self-designed continuous electrospinning deposition system. Piezoelectric PVDF-TrFE nanofiber as an electroactive material was electrospun at a discharge voltage of 9-12 kV onto a simultaneously rotating and transverse moving Cu metal wire at an angular velocity of ω g = 60-120 RPM. The piezoelectric coefficient d33 of the PVDF-TrFE nanofiber was approximately -20 pm V-1. The generated output voltage (V G) increased according to the relationship exp(-α P) (α = 0.41- 0.57) as the pressure (P) increased from 30 to 500 kpa. The V G values for ten and twenty pieces of C-PEG were V G = 3.9 V and 9.5 V at P = 100 kpa, respectively, relatively high output voltages compared to previously reported values. The high V G for the C-PEG stems from the fact that it can generate a fairly high V G due to the increased number of voltage collection points compared to a conventional two-dimensional (2-dim) capacitor type of piezoelectric film or fiber device. C-PEG yarn was also fabricated via the dip-coating of a PDMS polymer solution, followed by winding with Ag-coated nylon fiber as an outer electrode. The current and power density of ten pieces of C-PEG yarn were correspondingly 22 nA cm-2 and 8.6 μW cm-3 at V G = 1.97 V, higher than previously reported values of 5.54 and 6 μW cm-3. The C-PEG yarn, which can generate high voltage compared to the conventional film/nanofiber mat type, is expected to be very useful as a wearable energy generator system.We are exploring a scintillator-based PET detector with potential of high sensitivity, DOI capability, and timing resolution, with single-side readout. Our design combines two previous concepts 1) Multiple scintillator arrays stacked with relative offset, yielding inherent DOI information, but good timing performance has not been demonstrated with conventional light sharing readout. 2) Single crystal array with one-to-one coupling to the photodetector, showing superior timing performance compared to its light sharing counterparts, but lacks DOI. The combination, where the first layer of a staggered design is coupled one-to-one to a photodetector array, may provide both DOI and timing resolution and this concept is here evaluated through light transport simulations. Results show that 1) Unpolished crystal pixels in the staggered configuration yield better performance across all metrics compared to polished pixels, regardless of readout scheme. 2) One-to-one readout of the first layer allows for accurate DOI extraction using a single threshold. The number of MPPC pixels with signal amplitudes exceeding the threshold corresponds to the interaction layer. This approach was not possible with conventional light sharing readout. 3) With a threshold of 2 optical photons, the layered approach with one-to-one coupled first layer improves timing close to the MPPC compared to the conventional one-to-one coupling non-DOI detector, due to effectively reduced crystal thickness. Single detector timing resolution values of 91, 127, 151 and 164 ps were observed per layer in the 4-layer design, to be compared to 148 ps for the single array with one-to-one coupling. 4) For the layered design with light sharing, timing improves with increased MPPC pixel size due to higher signal per channel. In conclusion, the combination of straightforward DOI determination, good timing performance, and relatively simple design makes the proposed concept promising for DOI-TOF PET detectors.Stem cell spheroids have been widely investigated to accelerate bone tissue regeneartion. However, the directed differentiation of stem cells into osteoblastic lineage and the prevention of cells from damage by reactive oxygen species (ROS) remain challenge. Here, we developed osteoinductive and ROS scavenging extracellular matrix (ECM)-mimicking synthetic fibers based on epigallocatechin gallate (EGCG) coating. They were then utilized to fabricate engineered spheroids with human adipose-derived stem cells (hADSCs) for bone tissue regeneation. The EGCG-mineral fibers (EMF) effectively conferred osteoinductive and ROS scavenging signals on the hADSCs within spheroids, demonstrating relative upregulation of antioxidant genes (SOD-1 (25.8±2.1) and GPX-1 (3.3±0.1) and greater level of expression of osteogenic markers, RUNX2 (5.8±0.1) and OPN (5.9±0.1), compared to hADSCs in the spheroids without EMF. The in vitro overexpression of osteogenic genes from hADSCs was achieved from absence of osteogenic supplenments. Furthermore, in vivo transplantation of hADSCs spheroids with the EMF significantly promoted calvarial bone regeneration (48.39±9.24%) compared to that from defect only (17.38±6.63%), suggesting that the stem cell spheroid biofabrication system with our novel mineralization method described here is a promising tool for bone tissue regeneration.Elastography provides significant information on staging of fibrosis in patients with liver disease and may be of some value in assessing steatosis. However, there remain questions as to the role of steatosis and fibrosis as cofactors influencing the viscoelastic measurements of liver tissues, particularly shear wave speed (SWS) and shear wave attenuation (SWA). In this study, by employing the theory of composite elastic media as well as two independent experimental measurements on oil-in-gelatin phantoms and also finite element simulations, it is consistently shown that fat and fibrosis jointly influence the SWS and SWA measurements. At a constant level of fat, fibrosis stages can influence the SWA by factors of 2-4. Moreover, the rate of increase in SWA with increasing fat is strongly influenced by the stages of fibrosis; softer background cases (low fibrosis stages) have higher rate of SWA increase with fat than those with stiffer moduli (higher fibrosis stages). Meanwhile, SWS results are influenced by the presence of fat, however the degree of variability is more subtle. The results indicate the importance of jointly considering fat and fibrosis as contributors to SWS and SWA measurements in complex liver tissues and in the design and interpretation of clinical trials.A novel three-dimensional (3D) vertically-few-layer MoS2(V-MoS2) nanosheets- zero-dimensional (0D) PbS quantum dots (QDs) hybrid structure based broadband photodetector was fabricated, and its photoelectric performance was investigated in detail. We synthesized the V-MoS2nanosheets by chemical vapor deposition (CVD), using the TiO2layer as the induced layer, and proposed a possible growth mechanism. The use of the TiO2induction layer successfully changed the growth direction of MoS2from parallel to vertical. The prepared V-MoS2nanosheets have a large specific surface area, abundantly exposed edges and excellent light absorption capacity. The V-MoS2nanosheets detector was then fabricated and investigated, which exhibits a high sensitivity for 635 nm light, a fast response time and an excellent photoelectric response. The V-MoS2 nanosheets with a height of approximately 1 μm successfully broke the light absorption limit caused by the atomic thickness. Finally, we fabricated the PbS QDs/V-MoS2nanosheets hybrid detector and demonstrated their potential for high-performance broadband photodetectors. The response wavelength of the hybrid detector extends from the visible band to the near-infrared band. The responsivity of the hybrid detector reaches 1.46 A/W under 1450 nm illumination. The combination of 3D MoS2nanosheets and QDs further improves the performance of MoS2-based photodetector devices. We believe that the proposed zero-dimensional QDs and three-dimensional vertical nanosheets hybrid structure broadband photodetector provides a promising way for the next-generation optoelectronic devices.Flexible bioinspired mesostructures and electronic devices have recently attracted intense attention because of their widespread application in microelectromechanical systems (MEMS), reconfigurable electronics, health-monitoring systems, etc. Among various geometric constructions, 3D flexible bioinspired architectures are of particular interest, since they can provide new functions and capabilities, compared to their 2D counterparts. However, 3D electronic device systems usually undergo complicated mechanical loading in practical operation, resulting in complex deformation modes and elusive failure mechanisms. The development of mechanically robust flexible 3D electronics that can undergo extreme compression without irreversible collapse or fracture remains a challenge. Here, inspired by the multilayer mesostructure of Enhydra lutris fur, we introduce the design and assembly of multilayer cage architectures capable of multistage load bearing and collapse prevention under large out-of-plane compression. Combined in situ experiments and mechanical modeling show that the multistage mechanical responses of the developed bionic architectures can be fine-tuned by tailoring the microstructural geometries. The integration of functional layers of gold and piezoelectric polymer allows the development of a flexible multifunctional sensor that can simultaneously achieve the dynamic sensing of compressive forces and temperatures. The demonstrated capabilities and performances of fast response speed, tunable measurement range, excellent flexibility, and reliability suggest potential uses in MEMS, robotics and biointegrated electronics.Recent investigations on spinel CoMn2O4have shown its potential for applications in water splitting and fuel cell technologies as it exhibits strong catalytic behavior through oxygen reduction reactivity. To further understand this material, we report for the first time the synthesis of single-crystalline Co1+xMn2-xO4thin films using molecular beam epitaxy. By varying sample composition, we establish links between cation stoichiometry and material properties using in-situ x-ray photoelectron spectroscopy, x-ray diffraction, scanning transmission electron microscopy, x-ray absorption spectroscopy, and spectroscopic ellipsometry. Our results indicate that excess Co ions occupy tetrahedral interstitial sites at lower excess Co stoichiometries, and become substitutional for octahedrally-coordinated Mn at higher Co levels. We compare these results with density functional theory models of stoichiometric CoMn2O4to understand how the Jahn-Teller distortion and hybridization in Mn-O bonds impact the ability to hole dope the material with excess Co. The findings provide important insights into CoMn2O4and related spinel oxides that are promising candidates for inexpensive oxygen reduction reaction catalysts.Shear wave elastography imaging of the ulnar collateral ligament (UCL) is used to help understand changes in material properties of the ligament. Ensuring that the wrist flexors are relaxed is essential as muscle contractions can alter the alignment of the medial elbow. The purpose of this study was to determine how the structural and material properties of the medial elbow respond to various elbow torques. The medial elbows of 20 healthy adults, free from upper extremity disorders, were imaged in 3 of the following torque conditions (1) neutral relaxed, (2) passive valgus, and (3) active varus. Structural properties (ulnohumeral gap and UCL length) using B-mode and material properties (UCL and flexor muscle stiffness) using shear wave were measured. Passive valgus torque opened the ulnohumeral gap (P less then .001), and increased UCL (P less then .001) and wrist flexor stiffness (P = .001), compared with the neutral condition. Under an active varus contraction, the gap returned back to the neutral position, but UCL (P less then .008) and wrist flexor stiffness (P less then .004) remained elevated compared with neutral, meaning low-intensity torques can influence structural and material properties of the medial elbow. Therefore, effort should be taken to minimize muscle activation during imaging in order to accurately measure medial elbow properties.Social relationships are central to the health and well-being of older adults. Evidence exploring the association of physical activity (PA) with social isolation and loneliness is limited. This study uses a path analysis to investigate the longitudinal association between loneliness and social isolation with PA using the Irish Longitudinal Study on Ageing. Higher levels of social isolation measured using the Berkman-Syme Social Network Index were directly and indirectly associated with lower levels of walking, moderate PA, and vigorous PA over 6 years. Additionally, higher levels of walking were associated with lower levels of loneliness measured using a modified version of the University of California, Los Angeles loneliness scale over a 3-year period. Future interventions should target individuals who are more socially isolated and explore the effects of different types of PA on loneliness over time.This proof-of-concept study examined feasibility of assessing longitudinal changes in body mass index, strength, mobility, and cardiovascular health outcomes in older, racial/ethnic minority adults participating in a park-based physical activity program. Study feasibility was based on follow-through data collection procedures and ability to manage and implement data collection, enrollment, and repeated measures data collection in older adults (≥50 years; n = 380; 45% Hispanic, 41% non-Hispanic Black) over a 28-month period. Mixed models were developed to estimate the effects of program participation over time on participant cardiovascular and fitness outcomes and across poverty and age subgroups. Model estimates adjusted for individual-level sociodemographics showed improvements across each 4 month time point in arm strength (0.55 arm curl; 95% confidence interval [0.33, 0.77]) and systolic (-0.68 mmHg; 95% confidence interval [-1.22, -0.13]) and diastolic (-0.47 mmHg; 95% confidence interval [-0.79, -0.16]) blood pressure. An Age × Poverty interaction found greater improvements in systolic and diastolic blood pressure among younger participants living in low poverty (vs. older in higher poverty). Study of the longitudinal association between fitness class participation and health outcomes was feasible in park-based settings.This study examined the effect of different coaching conditions on the magnitude and reliability of drop jump height in men and women. Nineteen collegiate sport sciences students (10 men) performed two sets of 10 drop jumps under four different coaching conditions neutral, augmented feedback, external focus of attention, and a combination of augmented feedback and external focus of attention. The augmented feedback condition revealed a significantly higher jump height than the neutral condition (p = .002), while no significant differences were observed for the remaining conditions (p ≥ .38). The external focus of attention condition was more reliable than the neutral and augmented feedback conditions (coefficient of variationratio ≥ 1.15), while no differences were observed between the remaining conditions. These results suggest that both the magnitude and reliability of the drop jump height performance are influenced by the coaching condition.This study aimed to determine the instruction that maximizes fencing attack performance and to explore the sensitivity of a novel efficiency index (EI) that considers reaction time, attack velocity, and absolute error to discriminate between beginners and experienced fencers. Instructions that directed attentional focus internally (react as fast as possible and perform the attack movement as fast as possible) or externally (be as accurate as possible) were provided prior to stimulus presentation. The EI did not differ between the instructions in any group (p > .05), the instructions „react as fast as possible” and „be as accurate as possible” promoted in beginners the highest and the lowest EI, and the EI was higher for fencers. Our findings suggest that the EI could be recommended as a general index of fencing attack efficiency.