Human activities are breaking down geographic barriers to species dispersal, providing previously isolated taxa with unprecedented new opportunities for hybridization. Empirical studies on the effects of neophytes on hybridization and on the evolutionary consequences of these processes remain, however, scarce. Here we integrated Kew’s Plants of the World Online database with the Global Naturalized Alien Flora database to study the spatial and taxonomic overlap of hybrids and neophytes. Using the largest dated plant phylogeny to date, we compared diversification rates of genera containing hybrids and neophytes to genera containing neither. In addition, we used the well-studied hybrid flora of Britain to ask whether hybrids are adapted to anthropogenic disturbance and occur in habitats with a higher human footprint than their native and neophyte parents. Overall, we document positive ties between contemporary biodiversity redistribution and hybridization. Neophyte incidence was positively related to hybrid incidence both spatially (across countries) and taxonomically (across genera). Diversification rates were nearly three times higher in genera with both hybrids and neophytes than in genera containing neither. Hybrids occurred, on average, in areas with a higher human footprint than their parents, with little evidence that hybrids threaten native species throughout their range in more native habitats. Together, our results suggest species naturalizations and hybridizations need not have only negative evolutionary outcomes. Against a backdrop of rapid global change, anthropogenic hybridization may promote recombination of genetic variation and help conserve genetic diversity in disturbed environments.

Parentage analyses via molecular markers have revealed multiple paternity within the broods of polytocous species, reshaping our understanding of animal behavior, ecology, and evolution. In a meta-analysis of multiple paternity in bird and mammal species, we conducted a literature search and found 138 bird and 64 mammal populations with microsatellite DNA paternity results. Bird populations averaged 19.5% multiple paternity and mammals more than twice that level (46.1%). We used a Bayesian approach to construct a null model for how multiple paternity should behave at random among species, under the assumption that all mated males have equal likelihood of siring success, given mean brood size and mean number of sires. We compared the differences between the null model and actual probabilities of multiple paternity. While a few bird populations fell close to the null model, most did not, averaging 34.0-percentage points below null model predictions; mammals had an average probability of multiple paternity 13.6-percentage points below the null model. Differences between bird and mammal species were also subjected to comparative phylogenetic analyses that generally confirmed our analyses that did not adjust for estimated historical relationships. Birds exhibited extremely low probabilities of multiple paternity, not only compared to mammals, but relative to other major animal taxa. The generally low probability of multiple paternity in birds might be produced by a variety of factors, including behaviors that reflect sexual selection (extreme mate guarding or unifocal female choice) and sperm competition (e.g., precedence effects favoring fertilization by early or late matings).

Coagulation factors used in prophylactic treatment of patients with clotting disorders are associated with significant costs to health care systems. These products have complex pharmacokinetic profiles subject to large inter-individual variation making their efficient use challenging. Prior to this project, pharmacists were not involved as part of the Hemophilia care teams across Canada. The purpose of this pilot project was to determine whether employment of a pharmacist with expertise and a focus on plasma protein and related products including hemophilia treatments, would be an effective strategy to reduce costs associated with clotting factor prophylaxis regimens and identify the pharmacist’s activities associated with this new role. A cost-minimization analysis was conducted to compare the addition of a pharmacist to the care team of the Hemophilia Treatment Centre (HTC) at a pediatric hospital serving 500,000 children and youth. The analysis was performed from the perspective of the formulary manager, Canadian Blood Services, over a 1-year period including 9 months of interventions. The pharmacist performed 18 therapeutic optimizations on 14 patients with moderate to severe hemophilia A or B, and 1 von Willebrand patient, aged 3 to 18 years old. As a result of the pharmacist’s intervention, clotting factor treatment costs extrapolated over one year were reduced by 20.5% for these patients. This represents a net savings of $225K CAD/year, or $12.5K CAD/optimization/year. The addition of a pharmacist to the HTC to manage recombinant and plasma-derived coagulation factors can optimise the treatment plan and significantly reduce the costs of managing patients with hemophilia.

Persistent volcanic activity is thought to be linked to degassing, but volatile transport at depth cannot be observed directly. Instead, we rely on indirect constraints such as CO2-H2O concentrations in melt inclusions trapped at different depth, but this data is rarely straight-forward to interpret. In this study, we develop a multiscale model of conduit flow during passive degassing to identify how flow behavior in the conduit is reflected in melt-inclusion data and surface gas flux. During the approximately steady flow likely characteristic of passive-degassing episodes, variability in degassing arises primarily from two processes, the mixing of volatile-poor and volatile-rich magma and variations in CO2 influx from depth. To quantify how conduit-flow conditions alter mixing efficiency, we first model bidirectional flow in a conduit segment at the scale of tens of meters while fully resolving the ascent dynamics of intermediate-size bubbles at the scale of centimeters. We focus specifically on intermediate-size bubbles, because these are small enough not to generate explosive behavior, but large enough to alter the degree of magma mixing. We then use a system-scale volatile-concentration model to evaluate the joint effect of magma mixing and CO2 influx on volatile concentrations profiles against observations for Stromboli and Mount Erebus. We find that the two processes have distinct observational signatures, suggesting that tracking them jointly could help identify changes in conduit flow and advance our understanding of eruptive regimes.

Although adequately detailed kerosene chemical-combustion Arrhenius reaction-rate suites were not readily available for combustion modeling until ca. the 1990’s (e.g., Marinov [1998]), it was already known from mass-spectrometer measurements during the early Apollo era that fuel-rich liquid oxygen + kerosene (RP-1) gas generators yield large quantities (e.g., several percent of total fuel flows) of complex hydrocarbons such as benzene, butadiene, toluene, anthracene, fluoranthene, etc. (Thompson [1966]), which are formed concomitantly with soot (Pugmire [2001]). By the 1960’s, virtually every fuel-oxidizer combination for liquid-fueled rocket engines had been tested, and the impact of gas phase combustion-efficiency governing the rocket-nozzle efficiency factor had been empirically well-determined (Clark [1972]). Up until relatively recently, spacelaunch and orbital-transfer engines were increasingly designed for high efficiency, to maximize orbital parameters while minimizing fuels and structural masses: Preburners and high-energy atomization have been used to pre-gasify fuels to increase (gas-phase) combustion efficiency, decreasing the yield of complex/aromatic hydrocarbons (which limit rocket-nozzle efficiency and overall engine efficiency) in hydrocarbon-fueled engine exhausts, thereby maximizing system launch and orbital-maneuver capability (Clark; Sutton; Sutton/Yang). The combustion community has been aware that the choice of Arrhenius reaction-rate suite is critical to computer engine-model outputs. Specific combustion suites are required to estimate the yield of high-molecular-weight/reactive/toxic hydrocarbons in the rocket engine combustion chamber, nonetheless such GIGO errors can be seen in recent documents. Low-efficiency launch vehicles also need larger fuels loads to achieve the same launched mass, further increasing the yield of complex hydrocarbons and radicals deposited by low-efficiency rocket engines along launch trajectories and into the stratospheric ozone layer, the mesosphere, and above. With increasing launch rates from low-efficiency systems, these persistent (Ross/Sheaffer [2014]; Sheaffer [2016]), reactive chemical species must have a growing impact on critical, poorly-understood upper-atmosphere chemistry systems.

Static features of the executive control network (ECN), dorsal attention network (DAN), default mode network (DMN), and salience network (SN) have displayed dysfunction in people with autism spectrum disorder (ASD). However, research on the dynamic brain function of these networks in ASD is rare. In this study, co-activation pattern (CAP) analysis was performed on the whole cortex to study dynamic dysfunction in ASD using a large multisite resting-state fMRI dataset (295 ASDs, 446 healthy controls). Eight transient network states (TNSs) were defined, the dwell time, persistence, and transitions of each TNS were calculated to evaluate dynamic brain function. Using hierarchical clustering, the eight TNSs were divided into three clusters: ‘DMN activating’, ‘SN activating’, and ‘ECN and DAN activating’. We found ‘ASD-biased’ DMN and SN TNSs, which showed larger dwell time and longer persistence in ASD group than healthy control (CON) group. More transition within ‘ASD-biased’ TNSs were found in ASD group. Dwell time of the ‘ASD-biased’ ‘SN activating’ TNS was significantly correlated with social deficits only in the ASD group. Our results imply the dynamic dysfunction of ASD does not come from the occurrence of DMN, ECN, or SN, but comes from the atypical co-activation patterns within them. Our results also indicate people with ASD have stronger negative connectivity between DMN and ECN in childhood. This connection dosen’t change significantly with age in ASD group, but is supposed to increase with age until adulthood as the growth trajectory in healthy inviduals, which implies the early overgrowth of ASD children.

Systemic-Onset Juvenile Idiopathic Arthritis with unusual Cutaneous Manifestation and peripheral eosinophilia: Case ReportAuthor details:Albraa Babiker Mohammed Alameen, MBBS, Omdurman Islamic University, Faculty of Medicine. (Author) Anas Babiker Mohammed Elamin, MBBS, University of Khartoum, Faculty of Medicine. (Co-Author) AbstractIntroduction: Systemic-onset juvenile idiopathic arthritis (SoJIA) is unique subtype of juvenile idiopathic arthritis (JIA) with very special clinical manifestations, complications and management options. The simultaneous presentation of tinea capitis has not been reported in the context of Systemic-Onset Juvenile Idiopathic Arthritis before.The case: in march 2021 a 5-years old Sudanese male presented to Ahmed Gasim Hospital with fever and bilateral ankle arthritis in a background of extensive scalp lesions which were scaly, itchy and associated with hair loss. On examination: his weight was 15 kg (on the 5thcentile). There was cervical lymphadenopathy, hepatomegaly and swelling and tenderness in both ankle joints with restriction of movements. Complete blood counts revealed leucocytosis, thrombocytosis, mild eosinophilia and microcytic hypochromic anaemia. Anti-dsDNA antibody was 45 IU/ml (positive), ANA profile was 0,8 Ratio (Equivocal), CRP was 34.4 mg/l, HDL was very high, these results support the diagnosis of SoJIA in a background of a kerion. Patient received: antibiotic, systemic antifungal, Corticosteroids, Hydroxychloroquine, Calcium and Vitamin D to which he achieved good results.Consent:Witten informed consent was obtained from patient’s parent to publish this report in accordance with the journal’s patient consent policy.Keywords: Systemic-onset juvenile idiopathic arthritis; Systemic juvenile idiopathic arthritis; Tinea capitis; eosinophilia; case report.IntroductionJuvenile idiopathic arthritis is a group of arthritis that occur before 16 years and last more than 6 weeks after exclusion of other aetiologies which is classified according to the International league of Associations for Rheumatology (ILAR) into 3 subtypes according to the clinical manifestations, complications and therapeutic options.(1–3) Systemic-onset juvenile idiopathic arthritis (SoJIA) is a very special subtype of juvenile idiopathic arthritis (JIA) that is characterized by fever which has a characteristic one or two spikes (>39°C) per day.(4) Also more than 80% of patients of this disease has a transient salmon-coloured macular or maculopapular rash that that accompanies the fever. They may have also myalgias and tenosynovitis and arthritis which may be oligoarticular to polyarticular.(3) The widely affected joints include wrists, knee, and ankles; but any joint can be affected, even the temporomandibular joints(5), cervical spine(6), hips(7), and the small joints of the hand and feet. SoJIA may present as painless lymphadenopathy (25%) hepatomegaly, splenomegaly or pericarditis which may be complicated by cardiac tamponade (3,4) There is no specific laboratory features that distinguishes SoJIA from other conditions, but the pattern of laboratory abnormalities may support the diagnosis, for examples; microcytic hypochromic anaemia, neutrophilic leucocytosis, thrombocytosis, high ESR, high CRP, high serum ferritin, low serum albumin, mildly elevated AST, high D-dimer and negative autoantibodies.(3) The treatment of JIA as whole focuses on suppressing inflammation, preserving functions, and preventing deformity and blindness.(8) the currently available drugs include nonsteroidal anti-inflammatory drugs (NSAID), Systemic corticosteroids and Disease-modifying anti-rheumatic drugs (DMARDs).(3,9,10) Eosinophil cells were associated with allergic bronchopulmonary aspergillosis and asthma exacerbation due to fungal antigens.(11) Moreover, a case report of kerion associated eosinophilia was described in which a dermatophytid reaction was thought to be the cause which responded to corticosteroid and antifungal.(12) 2 Case reports of 2 patients with systemic lupus erythromatosis in which tinea capitis was disseminated, one of them was using steroid the other was not.(13,14) and this is the first report related to juvenile idiopathic arthritis.Case reportHistory In March 2021; a 5-years old Sudanese male from Algazira, center of Sudan presented with bilateral ankle swelling, bilateral knee and hip pain and fever which started 1 month prior to presentation. His mother was also concerned about scales and hair loss all over the scalp which started 2 months prior to presentation. His symptoms started insidiously with the fever mainly at night and relieved by antipyretics. He had anorexia and weight loss but neither abdominal pain, vomiting, diarrhea, cough, upper respiratory tract symptoms, headache nor history of trauma. He had a past history of right knee swelling which was resolved spontaneously. He had no family history of autoimmune disease or malignancy and not exposed to any medications.ExaminationOn examination the patient was ill but not pale, jaundiced or cyanosed. His weight was 15 Kg (along the 5th centile) (fig. 1). The scalp had white-yellow scales with some swelling, hair loss and dried pus over some areas of the scalp (Fig. 2). There were Bilateral cervical lymphadenopathy which were non-tender, discrete and maximum diameter was 1×1 cm. Both ankle joints were Swollen (fig. 3),and tender to palpation and there was restriction of movements. Other joint examinations were normal. Abdominal examination revealed palpable liver which was 4 cm below the costal margin and palpable paraaortic lymph nodes.InvestigationsComplete blood count and peripheral blood picture revealed leucocytosis (WBCS=13.4*\(10^{3}\) which is high), neutrophil% = 49%, lymphocyte% = 38%, monocyte% = 5% and eosinophil% = 8% (mild eosinophilia) Thrombocytosis (614*\(10^{3}\)) and mild hypochromia (Hb=10.3 g/dl, MCV=71.8 fl, MCH=22.3 pg, MCHC=31.1 g/dl) were also present. Anti-dsDNA antibody was 45 IU/ml (positive). ANA profile was 0.8 Ratio (Equivocal). CRP was 34.4 mg/l (high) and ESR = 49 mm/hr. LDH was very high. Patient was treated with: Methylprednisolone 30mg/kg/day for 3 days. Followed by oral prednisone 1mg/kg/day. Hydroxychloroquine tabs 5mg/kg/day. Griseofulvin syrup 7.3mg/kg/day. Antibiotic Calcium and vitamin D. After 1 month of treatment follow-up the patient was improved and we refer him to the ophthalmologist for slit lamp examination.Discussion In this case the full detailed history and proper clinical examination in addition to laboratory findings are in favour of the diagnosis of systemic-onset juvenile idiopathic arthritis. This case may show that, musculoskeletal manifestations may be present earlier than any other symptoms. Also, we noticed that in the lipid profile the HDL was very high but serum ferritin and ESR was normal, a complicating macrophage activation syndrome was putted in mind and then excluded.(15,16) Does tinea capitis occur more extensively in this patient due to the disease itself we don’t know fully but in a previous case report to a patient with systemic lupus erythromatosis in which disseminated infection occurred simultaneously at the time of the diagnosis before even the use of corticosteroid.(13) in that case the causative agent was Microsporum gypseum but unfortunately in our case the diagnosis was made clinically only and microbiological consultation was not ordered due to financial problems but what make our case unique is its association with systemic-onset juvenile idiopathic arthritis and not Systemic lupus erythromatosis even before the start of immunosuppressive therapy.(13,14) Mild peripheral eosinophilia explanation in our case was challenging; whether it is related to a dermatophytid reaction with no obvious morbilliform or lichenoid lesions or due to other causes that are not typical with the present history such as drug tubulointerstitial nephritis or any other occult helminthic infection. But according to the other laboratory and history points the later causes were excluded and we left with the occult dermatophytid reaction which was consistent with the same observation from another case report of kerion due to T. tonsurans with 21% eosinophil in the complete which was reduced to 6% one month later after oral griseofulvin and corticosteroid were used.(12) but unlike that case in which the patient was 45 year old female with a clear medical background unlike our case. But this may point to the fact that complete blood count is not routinely ordered in tinea capitis and eosinophilia may be underreported if we associate this to the fact that eosinophil recognizes ß-glucan of the fungal cell wall and react to it by releasing its granules and this area is an area of investigation in the future.(11)Conclusion:Physicians should be alert to the presentation of systemic-onset JIA in our country in order to make prompt diagnosis and treatment decisions as early as possible. Careful follow-up of prolonged febrile patients with arthritis of unknown origin is important to reaching the diagnosis early and initiating treatment.Conflict of interest:NO conflict of interest.Recommendations:Further studies about the eosinophil count and its role in tinea capitis and systemic-onset juvenile idiopathic arthritis.Further studies about the immune response against fungi in the setting of juvenile idiopathic arthritis.Multidisciplinary team consultation (rheumatologist, ophthalmologist, orthopaedics and paediatrician) in case of SoJIA.Educate the patients about the disease and its complications, which are important to monitor the disease and long-term morbidity and mortality.References:1. Ravelli A MA. Juvenile idiopathic arthritis. Lancet. 2007;369:767–78.2. Petty RE, Southwood TR MP. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis second revision, Edmonton, 2001. J Rheumatol. 2004;31((2)):390–2.3. Lee, Jennifer JY and RS. “Systemic juvenile idiopathic arthritis.” Pediatr Clin. 2018;(65.4):691–709.4. Calabro JJ, Holgerson WB SG. Juvenile rheumatoid arthritis: a general review and report of 100 patients observed for 15 years. Semin Arthritis Rheum. 1976;5(3):257–98.5. Ringold S CR. The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic. Pediatr Rheumatol Online J. 2009;7(1):11.6. Ornilla E, Ansell BM SA. Cervical spine involvement in patients with chronic arthritis undergoing orthopaedic surgery. Ann Rheum Dis. 1972;31:364–8.7. Modesto C, Woo P, García-Consuegra J, Merino R, García-Granero M, Arnal C, et al. Systemic onset juvenile chronic arthritis, polyarticular pattern and hip involvement as markers for a bad prognosis. Clin Exp Rheumatol. 2001;19(2):211–7.8. Nelson essentials of pediatrics, 7th edition.9. Guzman J, Oen K, Tucker LB, Huber AM, Shiff N, Boire G, et al. The outcomes of juvenile idiopathic arthritis in children managed with contemporary treatments: results from the ReACCh-Out cohort. Ann Rheum Dis. 2015 Oct;74(10):1854–60.10. Horneff G, Schulz AC, Klotsche J, Hospach A, Minden K, Foeldvari I, et al. Experience with etanercept, tocilizumab and interleukin-1 inhibitors in systemic onset juvenile idiopathic arthritis patients from the BIKER registry. Arthritis Res Ther. 2017 Nov;19(1):256.11. Manuscript A. NIH Public Access. 2009;181(4):2907–15.12. Martin ES, Elewski BE. bacterial pyoderma. 2003;177–9.13. Sanusi T, Gong J, Wang X, Zhao M, Zhao Y, An X, et al. Disseminated Favus Caused by Microsporum gypseum in a Patient with Systemic Lupus Erythematosus. 2016;(c):270–1.14. Feng J, Liu F, Wu F, Deng Q De. Tinea Infection with Scutula-like Lesions Caused by Microsporum Gypseum in a SLE Patient : Case Report and Literature Review. 2013;255–8.15. Cortis E, Insalaco A. Macrophage activation syndrome in juvenile idiopathic arthritis. Acta Paediatr Suppl. 2006 Jul;95(452):38–41.16. Ravelli, A., Magni-Manzoni, S., Pistorio, A. et al. Preliminary diagnostic guidelines for macrophage acti- vation syndrome complicating systemic juvenile idiopathic arthritis. J Pediatr. 2004;12.016(146):598–604.17. Colella, M. , Buttaro, G. , Masi, L. , Palma, E. , Amelio, R. and Vallone A. The difficult management of systemic-onset juvenile rheumatoid arthritis. Level of serum ferritin as aspecific diagnostic finding. Open J Pediatr. 2012;2:53–5.18. Jandus, P., Wang, W., Seitz, M. et al. High serum ferritin in adult-onset still’s disease. International Journal of Clinical Medicine. 2010;1:81–3.19. Meijvis, H., Endeman, A.B.M., Geers, E.J. and Borg EJ. Extremely high serum ferritin levels as diagnostic tool in adult-onset still’s disease. Netherl J Med. 2007;65:212–4.

Background and purpose: Myricetin (3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one) is a polyhydroxyfavonol compound widely found in nature has been shown to possess anticancer effects in various cancers. Despite its efficacy, poor water solubility and low oral bioavailability hinders its therapeutic application. To overcome these limitations, Nanoemulsion (NE) emerged as a promising approach that combines the advantages of NE into a single delivery system. The present study aimed to investigate the advantage of myricetin loaded NE over and above native Myricetin. Experimental Approach: The nano-emulsion was formulated using Capryol 90 as oil, Tween 20 as a surfactant, and Transcutol HP as a co-surfactant. Further comparative analysis of Myricetin and nano-emulsified Myricetin (Myr-NE) were carried out in triple negative breast cancer (MDA-MB-231) cells for anticancer activity. Key results: The optimized Myr-NE had a zeta potential of -6.35±0.3, an average particle size of 89.32±2.8 nm, PDI of 0.105±0.02, and a spherical shape as confirmed in transmission electron microscopy. Diffusion-dominant drug release was observed with 95.49±2.84 % Drug release for 24hrs, 2-fold higher than Myr-suspension. When nano-emulsified, Myricetin exhibited efficient inhibition of cell proliferation, clonogenicity, and increased apoptosis with IC50 of 37 µM, a dose ~2.5 fold lower than native Myricetin. Mechanistic insights reveal that Myr-NE induced more ROS generation and considerably inhibited AKT and mTOR activation, leading to enhanced anticancer activity. Conclusions & Implications: In conclusion, these findings suggest that the therapeutic efficacy of Myricetin significantly improved through a novel Myr-NE formulation which may be a promising therapeutic approach for treating TNBC.

Ecological or reproductive barriers can maintain species by preventing introgression in closely related taxa when their distributions overlap. In sympatry, sister-taxa may have greater genetic divergence than comparing the sister-taxa in allopatric parts of their range. When analyzing populations within a species, this may translate to greater genetic divergence between sympatry and allopatry. This genetic differentiation can be caused by either genetic drift or natural selection, depending on the evolutionary history of secondary contact. To identify a selective process, it is critical to find genes responsible for maintaining species barriers in sympatry. Here, we examined the role of natural selection in genetic differentiation within two recently diverged rockfish species, Sebastes diaconus and Sebastes mystinus. These species overlap along over 400 km of coastline in the eastern Pacific, with no evidence of hybridization. We found evidence of geographic genetic differentiation across a large span of the S. diaconus range, but not within S. mystinus. For both species, we identified outlier loci associated with regions of the genome under directional selection in allopatric versus sympatric populations. We also found signals of directional selection in shared genomic regions of both species, suggesting the evolutionary process of reinforcement maintained species boundaries once the two species were in secondary contact.

Nowadays, vehicle industrialization has realized several connectivity protocols to enable in-vehicle network communication. These protocols have been collectively standardized in a de facto standard for the in-vehicle network viz controller area network (CAN). Merely, CAN protocol shortages several security features that make vehicular communications susceptible to diverse message injection attacks that may mislead original electronic control units (ECUs) or cause failures. Therefore, defending the in-vehicle network from cyber-attacks is an essential concern. This paper proposes a fast anomalous traffic detection system for secure vehicular communications. The proposed system differentiates the performance of four different machine-learning approaches: Adaboost trees (ABT), Coarse decision trees (CDT), naïve Bayes classifier (NBC), and support vector machine (SVM). The models were evaluated on a recent dataset from a real-time vehicular communications environment, the car-hacking-2018 dataset. Specifically, the system considers five balanced classes, including one normal traffic class and four classes for message injection attacks over the in-vehicle controller area network: fuzzy attack, DoS attack, RPM attack (spoofing), and gear attack (spoofing). Our best performance outcomes belong to the ABT model, which notched 99.8% classification accuracy and 6.67 µseconds of classification overhead. Such results have outweighed existing in-vehicle intrusion detection systems employing the same/similar dataset.

Background: The characteristics and incidence of patients with tricuspid valve (TV) prolapse after leadless pacemaker implantation are unknown. Methods and Results: We retrospectively identified 35 of 85 patients with sufficient echocardiographic TV imaging before and after Micra transcatheter pacing system (Micra TPS) implantation. The post-procedure incidence of TV prolapse was 8.6%, and the cause of prolapse was chordae tendineae rupture. Patients with TV prolapse had significantly longer procedure times and more deployments than patients without TV prolapse. Conclusions: TV prolapse after Micra TPS implantation is not a rare complication and is accompanied by frequent deployments and prolonged procedure times.

Introduction: Several therapeutic options are usually discussed for otosclerosis management. Patients seek medical advice from an ENT specialist but are also increasingly using the internet for medical issues. This study intends to assess readability and quality of websites with information on otosclerosis. Materials & Methods: This is a cross-sectionnal study performed in a tertiary care center. The results of the first 2 pages of a Google search with the keyword “otosclerosis” were reviewed by two independent investigators. Readability was assessed with the Flesch–Kincaid Grade Level (FKGL), Flesch Reading Ease Score (FRES) and Gunning Fog Index. For quality and reliability assessment, the 16-items DISCERN instrument was used. Spearman’s coefficient was used for correlations, and multivariate analyses of variance were used to assess differences. Inter-rater agreement was evaluated with concordance correlation coefficient. Results: 18 websites were included. Two websites (11.0%) were authored by academic institutions, 5/18 (28%) by government agencies, 6/18 (33%) by professional organizations and 5/18 (28%) were medical information websites. The mean DISCERN score of the 18 websites was 40.2±8.4/80 (range, 23.5–54), corresponding to “fair” quality. The mean FRES score was 43.27 ± 10.6, and the the mean FKGL was 11.43±2.30, corresponding to “difficult to read”. The mean Gunning Fog index was 12.90±2.19 (range 9.81- 18.20), corresponding to a “college freshman” level. Conclusions: This study shows that internet information on otosclerosis has an overall low readability, while the quality is heterogeneous and varies from “poor” to “good”. Efforts should be made to improve the readability of otosclerosis websites.

Objective: Hybrid cardiovascular mock circuits (HMC), designed for dynamic testing of Ventricular Assist Devices (VAD), offer physiologic accuracy by sequestering model complexity in silico and ease of construction by reducing number of model elements in vitro. Despite superior response time and precision, pneumatic actuation is avoided in HMCs due to nonlinear dynamics and noise. We tested the hypothesis that a HMC consisting of a variable elastance-driven numerical circuit coupled to a pneumo-hydraulic physical circuit can be controlled without linearizing system dynamics. Methods: Reference left ventricular and aortic pressures generated in silico were tracked, respectively, in in vitro preload and afterload reservoirs by controlling non-linear pneumatic dynamics using the Lyapunov stability criterion. A centrifugal pump, the speed (i.e. flow) of which was adjusted using PID control, was interposed between the reservoirs and mimicked the VAD under evaluation. The flow of a recirculating gear pump was controlled by the backstepping method to equalize reservoir fluid volumes by rejecting pressure and flow disturbances. Sensor noise was reduced with discrete-time Kalman filtering. Results: Our results showed that normal, failing and assisted cardiovascular physiologies were numerically simulated and tracked at physical VAD terminals with high accuracy. Reservoir volumes remained stable at various combinations of heart rate, pressure, and VAD flow. Conclusion: The HMC described here offers a stable performance testing platform for VAD prototypes. Significance : This is the first proof that hybrid systems using pneumatic actuation at hydraulic interfaces can optimally be regulated with nonlinear controllers to achieve precise reference tracking and robust disturbance rejection.

Cataracts are considered the underlying cause of blindness globally. When the average age of the earth’s population is on the rise, cataract-induced blindness and visual dysfunction will increase dramatically. (1) Currently, the only viable treatment for cataracts is surgery, including removing the opaque lens and replacing it with an artificial one which has a huge impact on improving the patient’s quality of life. Undoubtedly, cataracts have far-reaching repercussions for countries in terms of social and economic burdens, for example, the increasing rate of automobile accidents due to reduced visual acuity. (2) Nonetheless, due to the lack of facilities, ophthalmologists, and funds, surgery is not a choice in developing countries. (3) It should be noted that posterior capsular opacification is a common complication of cataracts, and sometimes, a second intervention is necessary. (4)This research has thrown up many questions in need of further investigation to find medications that restore full transparency of the lens.

This study is focused on the anisotropic fatigue crack growth (FCG) behaviour of an aluminium AA7050-T7451 plate. L-T and S-T orientations were studied in M(T) samples with W=50 mm, in mode I loading, with R-ratio of +0.05. A numerical approach was used, assuming that crack tip plastic strain is the crack driving force. A purely kinematic elastic-plastic model was calibrated using experimental data from low cycle fatigue tests of smooth specimens in L and S orientations. The predicted FCG rates agree well with experimental trends in the Paris’ regime, suggesting that cyclic plastic deformation is the main damage mechanism. The numerical model was used to estimate the stress ratio effect for both orientations, which was found to be linked with crack closure variations. However, the closure free predicted trends for both microstructural orientations at R=0.05 are not overlapped, suggesting an effect of microstructure not linked to crack closure.

The paper addresses the non-cooperative game leader-synchronization problem with time-delays and gain perturbations. In the non-cooperative game, a stochastic communication protocol (SCP) is implemented to prevent the data collisions among agents. Coping with time-delays, SCP and gain perturbation simultaneously makes it extremely hard to get the accurate payoff value. Then, we resort to an explicit upper bound of payoff value as an alternative optimization objective. By using the linear matrix inequality (LMI)-constrained method, the leader-synchronization strategies form the J ̵̄ -Nash Equilibrium ( J ̵̄ -NE) solution of non-cooperative game. Sufficient conditions are established in the infinite-horizon with hope to guarantee the stability behavior. Finally, a simulation example is used to illustrate the validity of the proposed methodology.

Background and Purpose: The Bazhen decoction is one of the most extensively used Traditional Chinese medicine (TCM) prescriptions for anti-aging. However, due to the complicity of the components, the pharmacological mechanism of Bazhen decoction is still limited. Experimental approach: We applied RNA sequencing and transcriptome analysis to get the full view of the signaling pathways regulated by Bazhen decoction in the wild type cell background. By using the progeroid cells derived from Werner syndrome mice, we applied Western blot, Immunofluorescence, flow cytometry and telomere FISH to verify the transcriptome data. Key Results: The transcriptome profile revealed that Bazhen decoction might systematically regulate multiple anti-aging pathways, including stem cell regulation, protein homeostasis, cardiovascular function, neuronal function, anti-inflammation, anti-DNA damage induced stress, DNA helicase activity and telomere lengthening. We found that multiple DNA helicases and telomere regulating proteins were up-regulated by Bazhen decoction, which promoted the resolving of G-quadruplex (G4) structure, and facilitated DNA replication and telomere elongation. These improvements also endowed the cellular resistance to DNA damages induced by replication stress. Together these data suggest that Bazhen decoction facilitate G4 resolving and telomere maintenance, which might contribute to the longevity sustaining properties revealed by transcriptome profile. Conclusions & Implications: Our data revealed a new strategy for recovering the pharmacological signature pathways for TCM, which could help the clinical precision medicine of TCM. By applying transcriptome in TCM-treated normal cell, we tried out a systematic analysis for dissecting the molecular mechanism of complicated TCM prescription in the normal genetic background.

The increasing growth of agro-industrial activity resulting in excessive amounts of agri-waste has led to the accumulation of a large quantity of lignocellulosic residues all over the world, in particular, deforestation initiatives for the removal of invasive trees in South Africa. These lignocellulosic residues are rich in energy resources consisting of a mixture of natural polymers based on lignin, cellulose and hemicellulose. The use of lignolytic fungi such as mushrooms in solid-state fermentation could sufficiently degrade the indigestible lignocellulosic components and add medicinal and nutritional value to otherwise unusable, high-energy waste material. The digestive type of animal for which the potential feed is developed must be identified and considered before deciding on the bioconversion method and process, since the outcomes for obtaining potentially high-quality feeds for non-ruminant and ruminant animals are different. The current study presents the data of the bioconversion of lignocellulosic substrate using solid-state fermentation with the edible and medicinal mushrooms, Ganoderma lucidum, Pleurotus ostreatus, and a possible new species, to increase digestibility and nutritional value to be applied as ruminant animal feed. The solid-state fermentation process was optimised and the resulting product analysed for the degradation of the lignocellulosic components. Results indicated that the solid-state fermentation duration and mushroom species were key components in achieving significant degradation. Data obtained after 18 weeks of degradation indicated a significant (p < 0.05) reduction in the acid detergent fibre, acid detergent lignin and neutral detergent fibre fractions of the biomass, with up to 20% reduction in indigestible components. This increase in digestibility could contribute to to increased energy availability for ruminant animals.

Water resources management is fundamental for rural communities in drylands. Water Harvesting Technologies (WHT) intercept and store the excess rainfall (surface runoff) in soils for increased plant available water and agricultural productivity. The so-called ‘Marab’ WHT was initially developed by Middle Eastern agro-pastoralists that reside or commute in semi-arid and arid rangelands. The Marab WHT is a macro-catchment measure consisting of earth dams and stone spillways along the contours of a lowland depression or floodplain. Dependent on the local context (i.e. climate, soil, management, etc.) the established Marabs show highly-variable effectiveness. This study aims at filling the knowledge gap on the WHT’s performance in changing environments by simulating its hydro-agrological effects for different soils and climatic conditions using the AquaCrop model. A case study performed for a Jordanian Marab over three seasons (2019-2022) confirms its huge improvement potential for barley production. Through Marab-farming, barley production reached 8.37 t ha -1 on average, versus highly variable 0.34 t ha -1 without the WHT. The simulation-based assessment of soil textures identified that silty soils have the largest potential for producing up to 9.25 t ha -1 barley, compared to 6.60 t ha -1 produced in clay soils. Assessing different climate scenarios, a slight increase in daily average temperatures (+ 0.5°C) led to a considerable production decline of 4-8%, while a significant reduction of precipitation (-20%) decreased biomass production by a similar rate (4-10%). This underlines the robustness of the ‘Marab’ WHT to rainfall amount variation. However, simulations also highlight the sensitivity of timing and frequency of flood events: removing the last and the first flood event reduced biomass production by approximately 50% and 80% respectively, while the barley fails to develop if both events were suppressed.

Owing to the emergence of energy storage and electric vehicles, the desire for safe high-energy-density energy storage devices has increased research interest in anode-free lithium metal batteries (AFLMBs). Unlike general LMBs, in which excess Li exists to compensate for the irreversible loss of Li, only the current collector is employed as an anode and paired with a lithiated cathode in the fabrication of AFLMBs. Owing to their unique cell configuration, AFLMBs have attractive characteristics, including the highest energy density, safety, and cost-effectiveness. However, developing AFLMBs with extended cyclability remains an issue for practical applications because the high reactivity of Li with limited inventory causes severely low Coulombic efficiency, poor cyclability, and dendrite growth. To address these issues, tremendous effort has been devoted to stabilize Li-metal anodes for AFLMBs. In this review, we highlight the importance and challenges of AFLMBs. Then, we thoroughly review diverse strategies, such as modifying current collectors, the formation of robust interfaces by engineering advanced electrolytes, and operation protocols. Finally, a future perspective on the strategy is provided to insight into the basis of future research. We hope that this review provides a comprehensive understanding by reviewing previous research and arousing more interest in this field.

In this study, the protective effects of β-glucan against Ehrlich ascites carcinoma (EAC) induced liver injury, toxicity, and changes in AFP, ANA, and anti-dsDNA are explored. 40 mice were allocated evenly and randomly into 4 groups: Group1, the control group; Group2, the β-glucan group; Group3, the EAC group; and Group4, the EAC+β-glucan group. The most recent findings showed that EAC caused liver damage and elevated levels of serum ALT, AST, ALP, AFP, and anti-dsDNA. The levels of serum total proteins and albumin, however, significantly decreased as compared to the control. β-glucan treatment of EAC improved liver function and structure against EAC. This suggests that β-glucan may be useful in the prevention and management of liver toxicity.

Background: To investigate the distribution of bacterial pathogens of lower respiratory tract infection (LRTI) in hospitalized elderly patients during the COVID-19 epidemic and to explore the influence of COVID-19 on the distribution of bacterial pathogens, in order to provide guidance for clinical diagnosis. Methods: Specimens of sputum from elderly LRTIs patients at Fuding Hospital of China were collected from October 2022 to January 2023. Cultures and identification were done, and RT-PCR was employed to detect SARS-Cov-2 nucleic acid. Results: A total of 195 isolates were characterized in 163 sputum samples of consecutive hospitalized elderly patients, of which 11.3% were Gram-positive bacteria and 88.7% Gram-negative. The top of frequently isolated pathogens were Klebsiella pneumonia (30.3%), Pseudomonas aeruginosa (19.0%), Acinetobacter baumannii (12.8%), Stenotrophomonas maltophili, (7.7%), Escherichia coli (7.2%). According to the results of novel coronavirus nucleic acid detection, the 163 patients were divided into COVID-19 group and non-COVID control (CNT) group. The comparison of bacterial distribution between the groups revealed that Stenotrophomonas maltophilia was lower in the COVID-19 than in the CNT group, while Acinetobacter baumannii was higher in the COVID-19 group, and the difference was statistically significant (P < 0.05). Conclusion: The major bacteria identified in sputum culture of hospitalized elderly patients were Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia, and Escherichia coli. Furthermore, the distribution of Stenotrophomonas maltophilia and Acinetobacter baumannii between the COVID-19 and CNT groups was found to be significantly different (P< 0.05), while there were no significant differences in the distribution of other bacteria.

Introduction Influenza viruses, due to rapid evolution, lead to great variability. There are 18 highly variable hemagglutinins (H1 to H18) and 11 distinct NAs (N1 to N11) for type A.Influenza type B has no subtypes due to fixed on small antigenic variabilities.Due to rapid evolution and diversification, it is essential to understand genomic epidemiology to detect emerging strains and track their transmission. Methods Samples of the strain were cultivated in the MDCK cell lines for the preparation of neat virus. viral genome after extraction from the neat virus was sent to the National Institute of Infectious Disease, Japan for whole genome sequencing in 2016. The sequences were submitted to GISAID. The H1N1 virus genomes(n=18), from this study, were investigated against the reference genome A/California/07/2009 (GenBank: CY121680). Similarly, the Influenza type B virus genomes(n=27) were investigated against reference genome B/Brisbane/60/2008 (GenBank: KX058884) and B/Wisconsin/01/2010 (GenBank: JN993010). The mutational analyses were performed using Nextclade. The mutations present in the sequences were,subsequently, investigated. Finally, the phylogenetic analysis was done using the Nextclade and CLUSTAL Omega. Out of the 18 HA genome segments, of H1N1, all (n=12) except 6 isolates were of clade 6B, while the rest were of clade 6B.1.For Influenza Type B, out of the 27 HA genome segments, all of the genomes were of clade V1A when compared to B/Brisbane/60/2008. Similarly, when compared to reference genome B/Wisconsin/01/2010 (GenBank: JN993010), all (n=22) except 5 isolates were of clade Y3, while the rest were of clade Y2

Analytical tools are needed to identify and quantify artificial short- and long-term discharge fluctuations, which can disrupt the natural processes of a river. To measure the properties of discharge magnitude, frequency, duration, timing and flow change, such tools typically use a subset of metrics selected from over 170 descriptive statistical indices. Many metrics are based on multi-day mean or median discharges with associated variance or use a single value to describe the entire dataset. However, these source indices do not quantify the temporal configuration of streamflow, an additional hydrologic property that is often overlooked. To address this situation, a non-index approach to quantify all streamflow properties has now been developed using analysis methods based on the lag (1) temporal autocorrelation signature of the streamflow. The discharge (Q), discharge change (dQ/dt), and rate of discharge change (d 2Q/dt 2), along with sequential summations, are presented in novel infographics. A dam release river impact case study for the Colorado River at Lees Ferry, Arizona, is included to demonstrate this innovative way of analyzing streamflow datasets. The result is a set of new tools which yield detailed information about the hydrologic regime, are highly customizable, and can either be used as a stand-alone analysis or be integrated into other existing data analysis techniques. The end result is a better understanding of the hydrologic regime, more focused research, and more effective management planning.