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Summary: Background: The cause and symptoms of long COVID are poorly understood. It is challenging to predict whether a given COVID-19 patient will develop long COVID in the future. Methods: We used electronic health record (EHR) data from the National COVID Cohort Collaborative to predict the incidence of long COVID. We trained two machine learning (ML) models — logistic regression (LR) and random forest (RF). Features used to train predictors included symptoms and drugs ordered during acute infection, measures of COVID-19 treatment, pre-COVID comorbidities, and demographic information. We assigned the ‘long COVID’ label to patients diagnosed with the U09.9 ICD10-CM code. The cohorts included patients with (a) EHRs reported from data partners using U09.9 ICD10-CM code and (b) at least one EHR in each feature category. We analysed three cohorts: all patients (n = 2,190,579; diagnosed with long COVID = 17,036), inpatients (149,319; 3,295), and outpatients (2,041,260; 13,741). Findings: LR and RF models yielded median AUROC of 0.76 and 0.75, respectively. Ablation study revealed that drugs had the highest influence on the prediction task. The SHAP method identified age, gender, cough, fatigue, albuterol, obesity, diabetes, and chronic lung disease as explanatory features. Models trained on data from one N3C partner and tested on data from the other partners had average AUROC of 0.75. Interpretation: ML-based classification using EHR information from the acute infection period is effective in predicting long COVID. SHAP methods identified important features for prediction. Cross-site analysis demonstrated the generalizability of the proposed methodology. Funding: NCATS U24 TR002306, NCATS UL1 TR003015, Axle Informatics Subcontract: NCATS-P00438-B, NIH/NIDDK/OD, PSR2015-1720GVALE_01, G43C22001320007, and Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231.

Abstract Traditional carrier screening has been utilized for the detection of carriers of genetic disorders. Since a comprehensive assessment of the carrier frequencies of recessive conditions in the Southern Chinese population is not yet available, we performed a secondary analysis on the spectrum and carrier status for 315 genes causing autosomal recessive disorders in 1543 Southern Chinese individuals with next-generation sequencing data, 1116 with exome sequencing and 427 with genome sequencing data. Our data revealed that 1 in 2 people (47.8% of the population) was a carrier for one or more recessive conditions, and 1 in 12 individuals (8.30% of the population) was a carrier for treatable inherited conditions. In alignment with current American College of Obstetricians and Gynecologists (ACOG) pan-ethnic carrier recommendations, 1 in 26 individuals were identified as carriers of cystic fibrosis, thalassemia, and spinal muscular atrophy in the Southern Chinese population. When the >1% expanded carrier screening rate recommendation by ACOG was used, 11 diseases were found to meet the criteria in the Southern Chinese population. Approximately 1 in 3 individuals (35.5% of the population) were carriers of these 11 conditions. If the 1 in 200 carrier frequency threshold is used, and additional seven genes would meet the criteria, and 2 in 5 individuals (38.7% of the population) would be detected as a carrier. This study provides a comprehensive catalogue of the carrier spectrum and frequency in the Southern Chinese population and can serve as a reference for careful evaluation of the conditions to be included in expanded carrier screening for Southern Chinese people.

Intracranial stenosis is prevalent among Asians and constitutes a common cause of cerebral ischemia. While the best medical therapy carries stroke recurrence rates in excess of 10% per year, trials with intracranial stenting have been associated with unacceptable peri-procedural ischemic events. Cerebral ischemic events are strongly related to the severity of intracranial stenosis, which is high in patients with severe intracranial stenosis with poor vasodilatory reserve. Enhanced External Counter Pulsation (EECP) therapy is known to improve myocardial perfusion by facilitating the development of collateral blood vessels in the heart. In this randomized clinical trial, we evaluate whether EECP therapy may be useful in patients with severe stenosis of intracranial internal carotid (ICA) or middle cerebral artery (MCA). The review of literature, methods of evaluation, status of currently used therapeutic approaches, and trial protocol have been presented.Clinical trial registrationClinicalTrials.gov, Identifier: NCT03921827.

ABSTRACT: The complex and interrelated management components of dairy farming are associated with health, production, and profitability of the herd, yet there is limited objective data on current management practices of the far-off, close-up, and fresh periods across Canadian dairy farms. We aimed to describe management practices of Canadian dairy farms by using a pre-existing risk assessment tool and outline potential management opportunities. Upon veterinarians' or producers' request, a transition management risk assessment (The Vital 90, Elanco) was performed by trained observers (n = 10) during farm visits (n = 78) between August 2014 and March 2018. Most farms were in Ontario (n = 64), whereas the remaining were in Alberta (n = 5), British Columbia (n = 4), Manitoba (n = 1), Prince Edward Island (n = 2), Newfoundland (n = 1), and Saskatchewan (n = 1). The study included 79 questions about nutrition, pen management, and cow comfort of the dry (approximate ranges: far-off, −60 to −20 d in milk; close-up, −20 to 0 d in milk) and fresh (0–30 d in milk) periods. The herds averaged 125 milking cows, and most had 2 defined dry groups (81%). Freestall (FS; 54%) and straw-bedded loose pack (BP; 81%) were the most common housing systems observed in the far-off and close-up periods, respectively. Heifers and cows were housed together in 56, 80, and 59% of the far-off, close-up, and fresh pens, respectively. A large proportion of the far-off (FS: >100% stocking density; BP: 80% stocking density; BP:

Introduction: Biomolecules bind to and transform nanoparticles, mediating their fate in biological systems. Despite over a decade of research into the protein corona, the role of protein modifications in mediating their interaction with nanomaterials remains poorly understood. In this study, we evaluated how glycation of the most abundant blood protein, human serum albumin (HSA), influences the formation of the protein corona on 40 nm silver nanoparticles (AgNPs) and the toxicity of AgNPs to the HepG2 human liver cell line.Methods: The effects of glycation on AgNP-HSA interactions were quantified using circular dichroism spectroscopy to monitor protein structural changes, dynamic light scattering to assess AgNP colloidal stability, zeta potential measurements to measure AgNP surface charge, and UV-vis spectroscopy and capillary electrophoresis (CE) to evaluate protein binding affinity and kinetics. The effect of the protein corona and HSA glycation on the toxicity of AgNPs to HepG2 cells was measured using the WST cell viability assay and AgNP dissolution was measured using linear sweep stripping voltammetry.Results and Discussion: Results from UV-vis and CE analyses suggest that glycation of HSA had little impact on the formation of the AgNP protein corona with protein-AgNP association constants of ≈2x107 M-1 for both HSA and glycated HSA (gHSA). The formation of the protein corona itself (regardless of whether it was formed from HSA or glycated HSA) caused an approximate 2-fold decrease in cell viability compared to the no protein AgNP control. While the toxicity of AgNPs to cells is often attributed to dissolved Ag(I), dissolution studies showed that the protein coated AgNPs underwent less dissolution than the no protein control, suggesting that the protein corona facilitated a nanoparticle-specific mechanism of toxicity. Overall, this study highlights the importance of protein coronas in mediating AgNP interactions with HepG2 cells and the need for future work to discern how protein coronas and protein modifications (like glycation) may alter AgNP reactivity to cellular organisms.

Cd248 has recently been associated with adipose tissue physiology, demonstrated by reduced weight gain in high fat diet-fed mice with genetic deletion of Cd248 relative to controls. Here we set out to determine the metabolic consequences of loss of Cd248. Strikingly, we find these to be sex specific; By subjecting Cd248-/- and Cd248+/+ mice to a high fat diet and indirect calorimetry study, we identified that only male Cd248-/- mice show reduced weight gain compared to littermate control wildtype mice. In addition, male (but not female) mice showed a lower respiratory exchange ratio on both chow and high fat diets, indicating a predisposition to metabolise lipid. Lipidomic studies on specific fat depots found reduced triglyceride and diglyceride deposition in male Cd248-/- mice, and this was supported by reduced expression of lipogenic and adipogenic genes. Finally, metabolomic analysis of isolated, differentiated preadipocytes found alterations in metabolic pathways associated with lipid deposition in cells isolated from male, but not female, Cd248-/- mice. Overall, our results highlight the importance of sex controls in animal studies and point to a role for Cd248 in sex- and depot-specific regulation of lipid metabolism.

Abstract Purpose To test tough gel adhesives to repair meniscus tears under relevant loading conditions and determine if they have adequate biomechanical properties to repair meniscus tears in a bovine cadaveric study. Methods Cyclic compression tests on 24 dissected bovine knees were performed. The tough gel adhesive was used either as an adhesive patch or as a coating bonded onto commercially available surgical sutures. Forty‐eight menisci were tested in this study; 24 complete radial tears and 24 bucket‐handle tears. After preconditioning, the specimens underwent 100 cycles of compression, (800 N/0.5 Hz) on an Instron© machine and the size of the gaps measured. One third of the menisci were repaired with pristine sutures, one third with adhesive patches, and one third with sutures coated in adhesive gel. The size of the gaps was compared after 100 and 500 cycles of compression. Results The mean gap measured at the tear site without treatment was 6.46 mm (± 1.41 mm) for radial tears and 1.92 mm (± 0.65 mm) for bucket‐handle tears. After treatment and 500 cycles of compression, the mean gap was 1.63 mm (± 1.41 mm) for pristine sutures, 1.50 mm (± 1.16 mm) for adhesive sutures and 2.06 mm (± 1.53 mm) for adhesive gel patches. There was no significant difference between treatments regardless of the type of tear. Also, the gaps for radial tears increased significantly with the number of compression cycles applied (p > 0.001). Conclusion From a biomechanical standpoint, the tough adhesive gel patch is as effective as suturing. In addition, it would allow the repair of non‐suturable tears and thus broaden the indications for meniscus repair. Level of evidence Controlled laboratory study.

The design of controller for nonlinear system in strict feedback form in which the equilibrium point is the origin is the focus of the study. Backstepping is the technique applied. Recursive design is used in the backstepping control technique. Using the backstepping approach, we are given a reasonably simple method to design the control law for a system with these properties. The closed-loop system’s global asymptotic stability is attained by incorporating a Lyapunov function; in this case, a quadratic one was selected for the study. To demonstrate the viability of the technique, we also performed simulations of the system and the designed control with some initial values, and positive results were reported.

Objectives This study aimed to uncover the strategies that junior doctors implement to maintain their mental, physical and social well-being, and the barriers they experience in practising these strategies.Participants Fifteen junior doctors in their postgraduate year 1 or 2 currently practising in Australia were recruited.Outcome measures Semistructured interviews were conducted, and the transcripts underwent thematic analysis.Results Three key themes emerged from thematic analysis, namely: well-being strategies, barriers to well-being and and future interventions. Exercise, a healthy and balanced diet, quality sleep, and workplace organisations were frequently reported well-being strategies. High workload, unpredictable routines, lack of familiarity with the healthcare system and ongoing stigma surrounding mental health were seen as barriers to well-being. Suggested interventions included increased control over rosters, subsidised access to facilities such as gyms and increased internship preparedness programmes organised by the medical schools.Conclusions The findings from this study may assist in developing more personalised and targeted methods to help junior doctors maintain their mental, physical and social well-being. Future studies may address the structural and systemic changes required to develop a workforce that fosters the well-being of junior doctors and reduces the institutional barriers to practising well-being strategies.

Abstract Background The global development and advancement of genomic medicine in the recent decade has accelerated the implementation of personalized medicine (PM) and pharmacogenomics (PGx) into clinical practice, while catalyzing the emergence of genetic testing (GT) with relevant ethical, legal, and social implications (ELSI). Results The perception of university undergraduates with regards to PM and PGx was investigated, and 80% of undergraduates valued PM as a promising healthcare model with 66% indicating awareness of personal genome testing companies. When asked about the curriculum design towards PM and PGx, compared to undergraduates in non-medically related curriculum, those studying in medically related curriculum had an adjusted 7.2 odds of perceiving that their curriculum was well-designed for learning PGx (95% CI 3.6–14.6) and a 3.7 odds of perceiving that PGx was important in their study (95% CI 2.0–6.8). Despite this, only 16% of medically related curriculum undergraduates would consider embarking on future education on PM. When asked about their perceptions on GT, 60% rated their genetic knowledge as “School Biology” level or below while 76% would consider undergoing a genetic test. As for ELSI, 75% of undergraduates perceived that they were aware of ethical issues of GT in general, particularly on “Patient Privacy” (80%) and “Data Confidentiality” (68%). Undergraduates were also asked about their perceived reaction upon receiving an unfavorable result from GT, and over half of the participants perceived that they would feel “helpless or pessimistic” (56%), “inadequate or different” (59%), and “disadvantaged at job seeking” (59%), while older undergraduates had an adjusted 2.0 odds of holding the latter opinion (95% CI 1.1–3.5), compared to younger undergraduates. Conclusion Hong Kong undergraduates showed a high awareness of PM but insufficient genetic knowledge and low interest in pursuing a career towards PM. They were generally aware of ethical issues of GT and especially concerned about patient privacy and data confidentiality. There was a predominance of pessimistic views towards unfavorable testing results. This study calls for the attention to evaluate education and talent development on genomics, and update existing legal frameworks on genetic testing in Hong Kong.

Abstract Background Patients suffering from advanced cancer often loose contact with their primary care physician (PCP) during oncologic treatment and palliative care is introduced very late. The aim of this pilot study was to test the feasibility and procedures for a randomized trial of an intervention to teach PCPs a palliative care approach and communication skills to improve advanced cancer patients’ quality of life. Methods Observational pilot study in 5 steps. 1) Recruitment of PCPs. 2) Intervention: training on palliative care competencies and communication skills addressing end-of-life issues. 3) Recruitment of advanced cancer patients by PCPs. 4) Patients follow-up by PCPs, and assessment of their quality of life by a research assistant 5) Feedback from PCPs using a semi-structured focus group and three individual interviews with qualitative deductive theme analysis. Results Eight PCPs were trained. Patient recruitment was a challenge for PCPs who feared to impose additional loads on their patients. PCPs became more conscious of their role and responsibility during oncologic treatments and felt empowered to take a more active role picking up patient’s cues and addressing advance directives. They developed interprofessional collaborations for advance care planning. Overall, they discovered the role to help patients to make decisions for a better end-of-life. Conclusions While the intervention was acceptable to PCPs, recruitment was a challenge and a follow up trial was not deemed feasible using the current design but PCPs reported a change in paradigm about palliative care. They moved from a focus on helping patients to die better, to a new role helping patients to define the conditions for a better end-of-life. Trial registration The ethics committee of the canton of Geneva approved the study (2018–00077 Pilot Study) in accordance with the Declaration of Helsinki.

Abstract Coronary artery disease (CAD), the most common manifestation of cardiovascular disease, remains the most common cause of mortality in the United States. Risk assessment is key for primary prevention of coronary events and coronary artery calcium (CAC) scoring using computed tomography (CT) is one such non-invasive tool. Despite the proven clinical value of CAC, the current clinical practice implementation for CAC has limitations such as the lack of insurance coverage for the test, need for capital-intensive CT machines, specialized imaging protocols, and accredited 3D imaging labs for analysis (including personnel and software). Perhaps the greatest gap is the millions of patients who undergo routine chest CT exams and demonstrate coronary artery calcification, but their presence is not often reported or quantitation is not feasible. We present two deep learning models that automate CAC scoring demonstrating advantages in automated scoring for both dedicated gated coronary CT exams and routine non-gated chest CTs performed for other reasons to allow opportunistic screening. First, we trained a gated coronary CT model for CAC scoring that showed near perfect agreement (mean difference in scores = −2.86; Cohen’s Kappa = 0.89, P

Faba beans (Vicia faba L.) constitute a partially outcrossing species requiring an isolation distance to maintain genetic purity when more than one variety is grown in field conditions. This information is crucial for seed growers and faba bean breeders. A study was conducted at the University of Sydney’s Plant Breeding Institute, Narrabri, over two years to examine the extent of natural outcrossing using a creamy white flower characteristic as a morphological marker, which is controlled by a single recessive gene. The white-flowered genotype (IX225c) was grown in paired rows of 150 m length in four directions from a central 480 m2 plot of the normal flowered genotype PBA Warda. A beehive was placed in the central plot at the flowering time and natural pollination was allowed. At maturity, seed samples were taken from the white-flowered genotype at designated intervals along each axis and 100 seeds from each sample were grown in the glasshouse/birdcage to the 4–5 leaf stage and the proportion of plants displaying a stipule spot pigmentation (normal flower color and spotted stipule are linked) was used to determine the percentage of outcrossing. Maximum outcrossing of 2.28% occurred where both genotypes were grown side by side (0 m) and the degree of outcrossing decreased as the distance along each axis from the central plot increased. At a 6 m distance, the outcrossing was less than 1%; however, on occasion, it increased to 1% beyond a distance of 100 m, indicating the volatile and unpredictable nature of bee flights. Distance had a major effect on outcrossing but the direction and its interaction had no effect. The results suggest that to limit outcrossing to below 0.5%, a distance of more than 150 m between plots of different faba beans cultivars would be required. It also indicated that Australian faba bean genotypes are mostly self-fertile and a relatively narrow isolation distance will ensure self-fertilization in seed production and breeding programs.

Harnessing the immune system to combat disease has revolutionized medical treatment. Monoclonal antibodies (mAbs), in particular, have emerged as important immunotherapeutic agents with clinical relevance in treating a wide range of diseases, including allergies, autoimmune diseases, neurodegenerative disorders, cancer, and infectious diseases. These mAbs are developed from naturally occurring antibodies and target specific epitopes of single molecules, minimizing off-target effects. Antibodies can also be designed to target particular pathogens or modulate immune function by activating or suppressing certain pathways. Despite their benefit for patients, the production and administration of monoclonal antibody therapeutics are laborious, costly, and time-consuming. Administration often requires inpatient stays and repeated dosing to maintain therapeutic levels, limiting their use in underserved populations and developing countries. Researchers are developing alternate methods to deliver monoclonal antibodies, including synthetic nucleic acid-based delivery, to overcome these limitations. These methods allow for in vivo production of monoclonal antibodies, which would significantly reduce costs and simplify administration logistics. This review explores new methods for monoclonal antibody delivery, including synthetic nucleic acids, and their potential to increase the accessibility and utility of life-saving treatments for several diseases.

Low weight and high strength requirements are prime target design objectives in strength demanding applications. Skillful design of low density, low weight and eco-friendly natural fiber composites could provide an alternative material route to the actualization of lighter structures. The present study proposed ANN-FEM computational framework for the macro-mechanical analysis of multi-oriented Plantain Empty Fruit Bunch Fiber Laminate (PEFBFL) and Plantain Pseudo Stem Fiber Laminate (PPSFL). Control factors were numerically varied using Finite Element Method (FEM) and the resultant FEM models which encapsulated material properties of the laminate was streamlined into Artificial Neural Network (ANN) training scheme. A standard feed-forward backpropagation network was adopted and the ANN model consists of stacking sequence, laminate aspect ratio and fiber orientation as input variables while the selected network outputs variables include average stress and displacement. The laminate constitutive equation was developed which enabled the establishment of laminate load deformation affiliation and equivalent elastic constants. The damage onset for individual lamina was detected by the maximum principal stress theory and the overall laminate strength of 40.12 N/mm^2 was obtained for PEFBFL and 32.16N/mm^2 for PPSFL. On the whole, there was steady reduction in laminates elastic modulus which points to compromised stiffness in material principal axis arising from gradual failure of the plies, this trend continued until the last ply failure occurred in ply 3 and 4 at 90 degrees in tensile mode of transverse direction. Stresses and displacements observed using CLT agree very closely with predictions of ANN.

Beige and brown fat may influence systemic metabolism through secreted signals. Here the authors identify a panel of metabolites secreted from beige and brown fat cells, which signal to influence fat tissue and skeletal muscle metabolism and have anti-obesity effects in mouse models of obesity and diabetes.

The presence of lignocellulose-derived microbial inhibitory compounds (LDMICs) in lignocellulosic biomass (LB) hydrolysates is a barrier to efficient conversion of LB hydrolysates to fuels and chemicals by fermenting microorganisms. Results from this study provide convincing evidence regarding the effectiveness of metabolically engineered C. beijerinckii NCIMB 8052 for the fermentation of LB-derived hydrolysates to acetone–butanol–ethanol (ABE). The engineered microbial strain (C. beijerinckii_SDR) was produced by the integration of an additional copy of a short-chain dehydrogenase/reductase (SDR) gene (Cbei_3904) into the chromosome of C. beijerinckii NCIMB 8052 wildtype, where it is controlled by the constitutive thiolase promoter. The C. beijerinckii_SDR and C. beijerinckii NCIMB 8052 wildtype were used for comparative fermentation of non-detoxified and detoxified hydrothermolysis-pretreated switchgrass hydrolysates (SHs) with and without (NH4)2CO3 supplementation. In the absence of (NH4)2CO3, fermentation of non-detoxified SH with C. beijerinckii_SDR resulted in the production of 3.13- and 2.25-fold greater quantities of butanol (11.21 g/L) and total ABE (20.24 g/L), respectively, than the 3.58 g/L butanol and 8.98 g/L ABE produced by C. beijerinckii_wildtype. When the non-detoxified SH was supplemented with (NH4)2CO3, concentrations were similar for butanol (9.5 compared with 9.2 g/L) and ABE (14.2 compared with 13.5 g/L) produced by C. beijerinckii_SDR and C. beijerinckii_wildtype, respectively. Furthermore, when C. beijerinckii_SDR and C. beijerinckii_wildtype were cultured in detoxified SH medium, C. beijerinckii_SDR produced 1.11- and 1.18-fold greater quantities of butanol and ABE, respectively, than when there was culturing with C. beijerinckii_wildtype. When the combined results of the present study are considered, conclusions are that the microbial strain and medium modifications of the fermentation milieu resulted in greater production of fuels and chemicals from non-detoxified LB hydrolysates.

IntroductionSpinal cord injury (SCI) causes significant and permanent disability affecting motor, sensory and autonomic functions. We conducted a survey on the priorities of functional recovery and preferences for community rehabilitation services in a cohort of Chinese individuals with SCI as well as the primary caregivers. The study also investigated their views on advanced technology and research.MethodsAn online platform with a self-administered questionnaire was used to collect the opinions of clients that received services from an SCI follow-up clinic, a self-help association, or a non-government organization from 1 September−31 December 2021.ResultsEighty-seven subjects (74 individuals with SCI−48 tetraplegic, 26 paraplegic, and 13 caregivers) responded to the survey. Recovery of arm/hand function was given the highest priority among tetraplegics, followed by upper trunk/body strength and balance, and bladder/bowel function. Sexual function had a significant lower ranking than all priority areas except normal sensation (p < 0.05). Paraplegics viewed bladder/bowel function as the most important area of functional recovery, followed by walking movement, upper trunk/body strength and balance, elimination of chronic pain, and regaining normal sensation. There was no statistically significant difference among the top priority areas (p > 0.05). In contrast to previous studies done in Western populations, the study revealed that sexual function was ranked as the lowest by all 3 groups of respondents (tetraplegics, paraplegics, and caregivers). The majority of participants thought community rehabilitation services were inadequate. Most of the respondents were interested to try advanced technology which would facilitate their daily life and rehabilitation. About half of the individuals with SCI thought advance in technology and research could bring significant improvement in their quality of life in the coming 10 years.ConclusionThis survey is the first study specifically looking into the recovery and rehabilitation priorities of a Chinese population of individuals with SCI. This is also the first study to investigate the priorities of the primary caregivers of SCI individuals. The findings are useful as a reference for planning of future research and provision of rehabilitation services for the SCI community locally and in other parts of China.

Bronchiectasis is the abnormal dilation of the airway which may be caused by various etiologies in children. Beyond the more recognized cause of bacterial and viral infections and primary immunodeficiencies, other genetic conditions such as cystic fibrosis and primary ciliary dyskinesia (PCD) can also contribute to the disease. Currently, there is still debate on whether genome sequencing (GS) or exome sequencing reanalysis (rES) would be beneficial if the initial targeted testing results returned negative. This study aims to provide a back-to-back comparison between rES and GS to explore the best integrated approach for the functional and genetics evaluation for patients referred for assessment of bronchiectasis. In phase 1, an initial 60 patients were analyzed by exome sequencing (ES) with one additional individual recruited later as an affected sibling for ES. Functional evaluation of the nasal nitric oxide test, transmission electron microscopy, and high-speed video microscopy were also conducted when possible. In phase 2, GS was performed on 30 selected cases with trio samples available. To provide a back-to-back comparison, two teams of genome analysts were alternatively allocated to GS or rES and were blinded to each other’s analysis. The time for bioinformatics, analysis, and diagnostic utility was recorded for evaluation. ES revealed five positive diagnoses (5/60, 8.3%) in phase 1, and four additional diagnoses were made by rES and GS (4/30, 13%) during phase 2. Subsequently, one additional positive diagnosis was identified in a sibling by ES and an overall diagnostic yield of 10/61 (16.4%) was reached. Among those patients with a clinical suspicion of PCD (n = 31/61), the diagnostic yield was 26% (n = 8/31). While GS did not increase the diagnostic yield, we showed that a variant of uncertain significance could only be detected by GS due to improved coverage over ES and hence is a potential benefit for GS in the future. We show that genetic testing is an essential component for the diagnosis of early-onset bronchiectasis and is most effective when used in combination with functional tools such as TEM or HSVM. Our comparison of rES vs. GS suggests that rES and GS are comparable in clinical diagnosis.

The objective of this study was to analyse bio-fibre comminution energy and particle size classification as the first step towards converting cellulose based agricultural residues into environment-friendly composite products. Bio-fibres used in the study were water retted, chemically modified and oven dried to remove any trace of moisture. The bio-fibres comminution was performed in a laboratory-scale knife mill at varying mill speed, and chemical treatment concentrations. The particle size classification was aided by mechanical sieving process. Nonlinear Least Square method using the cftool based on Gauss-Newton method of iteration available in MATLAB 2007b was used to fit the experimental data to Rosin-Rammler-Bennett’s (RRB) and Gaudin-Schuhmann’s (GS) size distribution models. Energy consumption was estimated via Kick’s, Rittinger’s and Bond’s models. The result showed that energy requirement for bio-fibre comminution increases with decreasing particle size, with coir fibres requiring the highest energy when compared with banana fibres. As the mill speed increases from 1400 rpm to 2100 rpm the energy consumed in comminution banana fibre increases from 357.46 J/g to 369.38 J/g for 2% NaOH treatment with the kick’s constant increasing from 52.97 J/g to 57.86 J/g for untreated banana fibres. Whereas for coir fibre, the energy consumed in comminution increases from 382.14 J/g to 411.07 J/g for 2% NaOH treatment with the Kick’s constant increasing from 57.25 J/g to 61.83 J/g for untreated coir fibres. Bio-fibre energy consumption was best described by Kick’s model with R2 > 0.910 and RRB model captured the bio-fibres size distribution better than GS model with higher R2 and lower value of SSE and RMSE. Scanning electron microscopy revealed that the surface of the fibres had changed, becoming rougher as a result of chemical modification. Findings also indicated that comminution of bio-fibres with high chemical concentration results in less fine sizes with median size (S50) ranging from 524 μm–1476 μm for banana fibres and 644 μm–660 μm for coir fibres. The data obtained at different speeds of comminution and from various bio-fibre treatment conditions might guide the selection of initial fibre size and other processing parameters to better exploit bio-fibres potential in particulate fibre reinforced composites products design.

Abstract Background Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusions A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

Abstract In any ‘omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewise, protein communities revealed from protein networks can vary widely in sizes depending on the method. Here, we use the concept of persistent homology, drawn from mathematical topology, to identify robust structures in data at all scales simultaneously. Application to mouse single-cell transcriptomes significantly expands the catalog of identified cell types, while analysis of SARS-COV-2 protein interactions suggests hijacking of WNT. The method, HiDeF, is available via Python and Cytoscape.

The second quantum revolution is underway and the deployment of Quantum Technologies (QT) keeps pace with it. This technological paradigm-switch creates opportunities and challenges for industry, innovation and society. Several large companies, as well as start-ups, have started to develop and engineer quantum devices or begun to integrate them into their products: the commercial success of QT, together with progress in research and development, relies on certification and reliability built upon internationally agreed standards and metrological traceability.A group of European National Metrology Institutes (NMIs) and Delegated Institutes (DIs) have recently created a European Metrology Network for Quantum Technologies (EMN-Q) under the auspices of EURAMET.The objective of the EMN-Q is to co-ordinate the activities of the European NMIs and Dis to ensure their efficient support for European competitiveness in quantum technologies. A special focus of the EMN-Q will be to develop new measurement capabilities and dedicated services to serve the rapidly-growing needs of industry and research institutions in this field.Industry, governmental agencies, academic sectors or any other type of stakeholder are welcome to contact the EMN-Q and discuss their metrology needs. These can relate not only to quantum characteristics of quantum devices, but also to metrology of key enabling technologies, metrology that can improve the supply chain of industrial quantum devices or other industrial needs connected with quantum technologies.EMN-Q aims to become is to become the central contact point to stakeholders interested in metrology for quantum technologies by:• contributing to standardisation & certification of quantum technologies;• promoting the take-up of metrology in the development of these technologies;• supporting industrial needs in synergy with the technological objectives of the EC Quantum Flagship and national quantum technology programs; and• promoting the use of quantum measurement techniques where advantageous for “classical” technical areas.We are in process of structuring and developing the communication services of the EMN-Q. One of the key aspect in this EMN-Q development is the establishment the EMN-Q Strategic Research Agenda (SRA). The SRA will contain the technological roadmaps that are created by the EMN-Q members in consultation with the EMN-Q Stakeholder Community.In this paper, we will provide a short overview of the EMN-Q organization, and of the SRA and the relative Technological Roadmaps.

The goal of this study was to improve resource use efficiency in agricultural systems and agro-based industries, reduce wastes that go to landfills and incinerators, and consequently, improve the economics of 2,3-butanediol (2,3-BD) production. This study evaluated the feasibility of 2,3-BD production by replacing the mineral nutrients, and buffers with anaerobic digestate (ADE), poultry-litter (PLBC)- and forage-sorghum (FSBC)-derived biochars. Fermentation media formulations with ADE and 5–20 g/L PLBC or FSBC were evaluated for 2,3-BD production using Paenibacillus polymyxa as a biocatalyst. An optimized medium containing nutrients and buffers served as control. While 2,3-BD production in the ADE cultures was 0.5-fold of the maximum generated in the control cultures, 2,3-BD produced in the PLBC and FSBC cultures were ~1.3-fold more than the control (33.6 g/L). Cost analysis showed that ADE and biochar can replace mineral nutrients and buffers in the medium with the potential to make bio-based 2,3-BD production profitably feasible.

Introduction: The radiation dose absorbed during Computed Tomography (CT) investigation of the head, which could be reduced by altering the scan parameters, is of great concern considering the radiosensitive organs around this region. Aim: To investigate the relationship between variations in scan parameters and image quality in brain CT scanning. Materials and Methods: This was an experimental crosssectional study conducted at a private diagnostic clinic in Enugu State, Nigeria, from September 2018 to February 2019 with a total sample size of 150. All adult patients who reported at the centre for non contrast CT of brain during the study period {but not limited to participants with Anteroposterior Circumference Diameter (APCD) 170-180 cm of brain} were selected using consecutive sampling method. The samples was divided into three groups, a control group and two experimental groups. Scan parameters such as kilovolts (kV), milliamperes (mA) and Gantry Rotation Time (GRT) varied across the three groups studied and the corresponding image parameters such as image noise, Contrast to Noise Ratio (CNR) and Signal to Noise Ratio (SNR) were obtained and statistically analysed using both descriptive and inferential statistics. Results: There were statistically significant correlations of image parameters with scan parameters Group I (control): (CNR: r=0.857, p-value

Abstract In situ detoxification of lignocellulose-derived microbial inhibitory compounds is an economical strategy for the fermentation of lignocellulose-derived sugars to fuels and chemicals. In this study, we investigated homologous integration and constitutive expression of Cbei_3974 and Cbei_3904, which encode aldo-keto reductase and previously annotated short chain dehydrogenase/reductase, respectively, in Clostridium beijerinckii NCIMB 8052 (Cb), resulting in two strains: Cb_3974 and Cb_3904. Expression of Cbei_3974 led to 2-fold increase in furfural detoxification relative to Cb_3904 and Cb_wild type. Correspondingly, butanol production was up to 1.2-fold greater in furfural-challenged cultures of Cb_3974 relative to Cb_3904 and Cb_wild type. With 4-hydroxybezaldehyde and syringaldehyde supplementation, Cb_3974 showed up to 2.4-fold increase in butanol concentration when compared to Cb_3904 and Cb_wild type. Syringic and vanillic acids were considerably less deleterious to all three strains of Cb tested. Overall, Cb_3974 showed greater tolerance to furfural, 4-hydroxybezaldehyde, and syringaldehyde with improved capacity for butanol production. Hence, development of Cb_3974 represents a significant progress towards engineering solventogenic Clostridium species that are tolerant to lignocellulosic biomass hydrolysates as substrates for ABE fermentation.