Objectives: To compare electromechanical ventricular synchrony when pacing from different sites including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His Bundle pacing (HBP), left bundle branch pacing (LBBP) and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSPring ) in each patient. Methods: Twenty patients with complete atrioventricular block (AVB) indicated for dual-chamber pacemaker implantation were included. Unipolar pacing at different sites including RVAP, RVSP，HBP，LBBP and RVSPring were successively performed. Pacing characteristics and echocardiogram parameters were compared among intrinsic rhythm and pacing at different sites. Results: Similar to HBP(114.84 ±18.67ms), narrower paced QRSd was found in LBBP(116.15±11.60ms) versus RVSPring(135.11±13.68ms), RVSP(141.75±14.08ms) and RVAP(158.15±21.41ms)(p＜0.001). LBBP showed comparable pacing parameters to RVAP or RVSP and were significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP(27.00±21.53ms) than RVAP(54.05±34.21ms, p=0.004) and RVSP(47.56±33.26ms, p=0.029) but similar to HBP(37.05±26.24ms, p=0.283) or RVSPring(42.16±26.19ms, p=0.107). Negative values of interventricular mechanical delay(IVMD) were only identified in LBBP(-20.16±18.47ms), significantly different from RVAP(33.68±30.98ms), RVSP (21.68±22.02ms), HBP (4.74±19.04ms) and RVSPring(14.56±26.76ms(all p＜0.001). Using Pearson’s analysis, Sti-LVAT was positively corelated with QRS, IVMD, TS-12-SD, LVEDV and LVESV while a negative relationship was identified for LVEF. Conclusions: Similar to HBP, LBBP achieved better electrical and mechanical left ventricular synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV among these pacing strategies, in consistent with the RBBB pattern of paced QRS during LBBP.

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Genetic syndromes such as Brugada syndrome can lead to lethal ventricular arrhythmias. Cardiac Sympathetic Denervation has been shown to be effective in ameliorating refractory ventricular arrhythmias. We present a 33-year-old black female with a past medical history of Brugada syndrome with an implantable cardiac defibrillator (ICD), who presented with refractory ventricular tachycardia/atrial fibrillation leading to heart failure and cardiogenic shock, requiring Extracorporeal membrane oxygenation (ECMO). The patient subsequently underwent bilateral stellate ganglion sympathetic denervation in the setting of refractory ventricular arrhythmias. We present this case report to showcase that thoracoscopic bilateral sympathetic denervation can be an effective definitive treatment option for ventricular arrhythmias that remain refractory to medical management.

Background. To estimate effect of COVID-19 control measures taken to mitigate community transmission in many regions, we analyzed data based on influenza surveillance system in Beijing from week 27th, 2014 to week 26th, 2020. Methods. We collected weekly number of influenza-like illness (ILI), weekly positive proportion of ILI and weekly ILI proportion in outpatients and the date of COVID-19 measures. We compared influenza activity indicators of influenza season 2019/2020 with preceding five seasons and built two ARIMAX models to estimate the effective of COVID-19 measures. Results. Compared with preceding five influenza seasons, ILIs, positive proportion of ILI, and duration of influenza epidemic period decreased from 13% to 54%, especially, the number of weeks from the peak to the end of influenza epidemic period, decreased from 12 to one. After natural decline considered, weekly ILIs decreased by 48.6% and weekly positive proportion dropped 15% in the second week after emergency response declared, and finally COVID-19 measures reduced 83%. Conclusions. We conclude public health emergency response can interrupt the transmission of influenza and other respiratory infectious diseases markedly. Keyword. COVID-19 control measures; influenza; ARIMAX

The present study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. Main measures: Pro-inflammatory lipid mediators and their precursor AA; SPMs, their precursors. The level of pro-inflammatory parameters was significantly higher in PCOS-affected women.

This paper is concerned with sufficient conditions for existence solutions of noninstantaneous impulsive Hilfer-Katugampola fractional differential equations of order 1/2 < α < 1 and parameter 0 ≤ β ≤ 1 with fractional Brownian motion (fBm) and poisson jumps, by using M¨onch fixed point theorem, fractional calculus and stochastic analysis. At last, as an application, an example is presented to illustrate the abstract results.

The main objective of this research article is to summarize the study of the application of Lie symmetry reduction to the fractional-order coupled nonlinear complex Hirota system of partial differential equations. By the efficient use of symmetries and explicit solutions, this system reducing to nonlinear fractional ordinary differential equations (FODEs) with the application of Erdyli-Kober (E-K) operators for fractional derivatives and integrals depending on real order. Investigating the convergent series solution along with adjoint system and providing the conservation laws by Noether’s theorem.

To explore the impacts of regional evolution and impulses on the persistence or extinction of species, a generalized logistic model with impulses in an evolving domain is proposed and researched. Firstly, the ecological reproduction index, which is regarded as a threshold value, is introduced and characterized. Secondly, in the case of monotone or non-monotone impulsive function, the asymptotic behavior of population is fully investigated and the sufficient conditions for the solution to persist, be extinct or blow up are given. Finally, numerical simulations results indicate that whatever impulse is, larger periodic evolution rates are more favorable for species. However, impulsive harvesting has a negative impact on persistence of species, while birth pulse admits a positive impact and even results in blowup.

This paper aims to investigate the Caputo fractional differential equation involving ρ(τ) Laplacian operator and nonlocal multi-point of Riemann-Lioville’s fractional integral. We also prove the uniqueness of positive solutions for Boyd and Wong’s non-linear contraction via the Guo-Krasnoselskii fixed point theorems in Banach spaces. Finally, we illustrate the theoretical results and show that by solving the nonlocal problems is possible to obtain accurate approximations of the solutions.

Runs of homozygosity (ROH) are continuous homozygous segments that arise through the transmission of haplotypes that are identical by descent (IBD). The length and distribution of ROH segments provide insight into the genetic diversity of populations and are useful to detect selection signatures. Here, we analysed pooled whole-genome sequencing data from 265 Western honey bee colonies from the two subspecies Apis mellifera mellifera and Apis mellifera carnica. Integrating individual ROH patterns and admixture levels in a high-resolution population network visualization allowed us to ascertain major differences between the two subspecies. Within A. m. mellifera, we identified well-defined substructures according to the genetic origin of the colonies and a fair amount of admixed colonies, despite the current applied conservation efforts. In contrast, A. m. carnica colonies were more inbred and could not be differentiated according to the geographical origin. We identified 29 coding genes in overlapping ROH segments within the two subspecies. Genes embedded in A. m. carnica specific homozygosity islands suggested a strong selection for production and behavioural traits, whilst the identified cuticula protein-coding genes (CPR3 and CPR4) were associated with their breed-specific stripe pattern. Local adaption of the two subspecies could be confirmed by the identification of two genes involved in the response to ultraviolet (UV) light. We demonstrated that colony genotypes derived from pooled honey bee workers are reliable to unravel the population dynamics in A. mellifera and provide fundamental information to conserve native honey bees.

Background: The COVID-19 pandemic and the accompanying new generation vaccines have entered our lives with many unknown effects. Method and result: This is a case report of myopericarditis diagnosed with fever and chest pain 3 days after the 2nd dose of Pfizer-BioNTech COVID-19 mRNA Vaccine in an 18-year-old man. The diagnosis was confirmed by cardiac MRI(CMR), but we presented that this diagnosis and follow-up could be made accurately with strain echocardiography(SE). Conclusion: It would be beneficial for the cardiologists who perform the primary follow-up of these patients to know that it is possible with SE to support the diagnosis and follow-up of these patients, even if CMR is not accesible.

Purpose: To study the natural course of hydroxychloroquine (HCQ) retinopathy, and to discuss the relationship between HCQ and its toxicity in retina in terms of ATP-binding cassette transporter gene, ABCR (also known as ABCA4) and HCQ blood level. Methods: Here we reported two cases of retinopathy associated with HCQ from a tertiary referral center. We then performed a literature review of studies on HCQ cessation in patients with HCQ retinopathy. Results: One of them stopped the HCQ therapy in her early stage of HCQ retinopathy and gained some regression on visual field testing. The other patient continued to use HCQ without screening till a severe toxicity in macula was found. Although she ceased HCQ, aggravation was found. Their HCQ blood level was 20557.4ng/ml and 402.8ng/ml respectively when they were advised to stop the treatment. Patient 1 was carrier of transition 6764G > T and patient 2 was heterozygous for the transition 5844A > G and 5814A > G . Conclusion : The study suggests that the integrity of outer retinal layers on OCT as a remarkable sign of possibility of recovery. But severe damage to macular structure can hardly regress which emphasizes the importance of HCQ cessation at an early stage of this disease. To the future, more studies are needed to better understand the relationship between HCQ retinopathy and ABCA4 genotypes and blood concentration.

Background Co-prescribing a proton pump inhibitor (PPI) with an anticoagulant, in patients with atrial fibrillation (AF) at high risk of bleeding, decreases the risk of gastrointestinal bleeding. This study aimed to identify Australian prescribing trends for this topic to inform practice in this area. Methods This was a retrospective cohort study in which a cross-sectional analysis of general practice data obtained from MedicineInsight was performed, to evaluate current Australian prescribing trends of PPIs in patients with AF. Patients aged 18 years or more initiated on an oral anticoagulant between January 1st, 2011 and April 25th, 2019 were included. Results A total of 28,863 participants were included; of these, 5,092 (17.6%) received PPI co-therapy. There were 4,211 (14.6%) participants at high risk of bleeding, with 878 (20.9%) of these receiving PPI co-therapy. Participants were significantly more likely to be prescribed a PPI if prescribed dabigatran (adjusted odds ratio (AOR) 1.42 [1.28-1.57], 95% confidence interval (CI)), apixaban (AOR 1.36 [1.26-1.46], 95%CI) or rivaroxaban (AOR 1.28 [1.18-1.38], 95%CI) compared to warfarin. Factors associated with PPI prescribing included, antiplatelet co-therapy (AOR 2.09 [1.82-2.39], 95% CI), high CHA2DS2-VASc score (≥2 male or ≥3 female) (AOR 1.50 [1.28-1.77], 95% CI) and a low ORBIT score (<3) (AOR 1.42 [1.23-1.64], 95% CI). Conclusion In this large nationally representative cohort, only 20.9% of participants who were at high risk of bleeding were co-prescribed a PPI. Further research is required to investigate whether increased prescribing of PPIs could improve patient outcomes. Key words: Atrial fibrillation, proton pump inhibitors

Background and Purpose: Excellent drug therapy is usually characterized by longer duration with sufficiently high occupancy on desired target. Except for classical pharmacokinetics (PK) contribution, binding kinetics (BK) and target kinetics (TK) are emerging as key role. This study aims to establish mathematical simulation model of kinase target engagement by integrating three intrinsic kinetic processes (i.e., PK, BK and kinase target kinetics, KTK) of interaction between kinase inhibitors (KIs) and kinase protein. Experimental Approach: Five half-life ratios, innovative pharmacokinetics-inhibition-kinase kinetics (PIKK) and diagnostic line plots (DLPs) were generated to assess which parameters were playing crucial role in the kinases target occupancy (KTO) decline. PK-BK-TKT model was first developed by a series of differential equations, and using this model simulated time courses of protein kinase occupancy. And the temporal kinase selectivity (TKS) method was firstly developed to judge inhibitor selectivity. Key Results: By three visualization approaches, key rate-limiting factors were first identified in kinase occupancy. We first simulated time course profiles of interaction between 55 approved inhibitors with 55 clinically validated protein kinases. Subsequently, the TKS between 30 inhibitors and 55 protein kinases were generated, and 6 inhibitors were identified as a highly selective chemical probe for their respective primary target. Conclusion and Implications: The mathematic model can describe the entire process of inhibitor-kinase interaction in-depth and shows extensive applications in many aspects.

Background and Purpose: Parkinson’s disease (PD) patients often complain of pain, but this problem has been neglected and is poorly understood. High mobility group box-1 (HMGB1), an alarmin/damage-associated molecular patterns protein, is increased in the cerebrospinal fluid in PD patients. However, little is known of the relationship between HMGB1 and pain associated with PD. Here, we investigated the role of central HMGB1 in the regulation of nociceptive hypersensitivity in a mouse model of PD. Experimental Approach: Male ddY mice were microinjected unilaterally with 6-hydroxydopamine (6OHDA) into the striatum. These hemi-PD mice were treated with anti-HMGB1 neutralizing antibody (nAb; 10 µg in 10 µL) by intranasal (i.n.) administration. The mechanical hypersensitivity of the hind paws was evaluated with the von Frey test. Spinal microglial activity was analyzed by immunostaining for ionized calcium-binding adapter molecule 1. Key Results: The 6OHDA-administered mice displayed unilateral loss of dopamine neurons in the substantia nigra and mechanical hypersensitivity in both hind paws. Moreover, spinal microglia were activated in these hemi-PD mice. Twenty-eight days after the 6OHDA injections, repeated i.n., but not systemic, treatment with anti-HMGB1 nAb inhibited the bilateral mechanical hypersensitivity and spinal microglial activation. However, the anti-HMGB1 nAb did not ameliorate the dopamine neuron loss. Moreover, intracerebroventricular injection with recombinant HMGB1 induced mechanical hypersensitivity. Conclusions and Implications: These findings indicate that HMGB1 is involved in the maintenance of nociceptive symptoms in hemi-PD mice via spinal microglial activation. Therefore, central HMGB1 may have potential as a therapeutic target for pain associated with PD.

Drug resistance, a major challenge in cancer therapy, is typically attributed to mutations and genetic heterogeneity. On the other hand, emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance. However, the underlying mechanisms remain poorly understood. Here, we present a new mathematical approach with game theoretical underpinnings that we developed to model real-time growth data of non-small cell lung cancer (NSCLC) cells and discern patterns in response to treatment 68 with cisplatin. We show that the cisplatin-sensitive and cisplatin-tolerant NSCLC cells when co69 cultured in the absence or presence of the drug, display dynamic group behavior strategies. Tolerant cells exhibit a ‘persister-like’ behavior and are attenuated by sensitive cells; they also appear to ‘educate’ sensitive cells to evade chemotherapy. Further, tolerant cells can switch phenotypes to become sensitive, especially at low cisplatin concentrations. Finally, switching treatment from continuous to an intermittent regimen can attenuate the emergence of tolerant cells, suggesting that intermittent chemotherapy may improve outcomes in lung cancer.

Myeloid sarcoma (MS) occurs when immature myeloid cells settle in the extra medullary area. It may be associated with acute myeloblastic leukemia (AML) or it may be alone and then develop AML. The orbit is one of the places where myeloid sarcoma is common in childhood. In this case report, we present a case of orbital myeloid sarcoma living in Africa, presenting with advanced proptosis and vision loss, whose proptosis improved dramatically with chemotherapy and vision returned.

Biomass is a common, universal indicator of ecosystem productivity for exploring biodiversity–ecosystem functioning (BEF) relationships in all types of ecosystems. However, positive BEF is often missing in aquatic consumer communities with multitrophic interactions. Here, we apply a new indicator, integrated trophic position (iTP), which is defined as the summed TPs of all consumers weighed by the relative biomass of each taxon, for multitrophic systems to test the vertical diversity hypothesis (VDH) that functional diversity can enhance trophic energy flows within a food web. Using a meta-community of coastal benthic macroinvertebrates, we demonstrate that iTP increases in more diverse communities, supporting the VDH. Comparing our results with previous findings that stream benthic macroinvertebrates exhibit a negative BEF in contrast to the VDH, we discuss a possible mechanism to explain this contrasting pattern. Finally, we use a size-based food web approach to deepen our mechanistic understanding of the observed BEF.

Background: This paper deals with the investigation of the newly obtained solitary solutions of perturbed optical metamaterial with Kerr law nonlinearity. Methods: Two novel analytical techniques namely, the extended Riccati equation rational expansion (ERERE) method and the extended rational exp(-(φ’/φ)(ξ))-expansion (EREE) method are applied two develop new solitary solutions. Results: The resultant wave profiles are periodic wave solution, singular kink, anti-peakon, dark, singular anti-kink, anti-kink, grey and singular soliton solutions. Conclusion: The detailed dynamics of the retrieved solutions are the most potent influence of the proposed methods which shows the efficacy and fruitfulness of the methods.

We report exotic hybrid rogue wave and breather solutions for a complex mKdV equation describing soliton dynamics in shallow water wave and optics. Starting from the Lax pair, the higher-order Darboux transformations for the equation are constructed. Further, we obtain a series of theorems to compute the hybrid rogue wave and breather solutions. We also demonstrate the interaction features between rogue waves and breathers by controlling parameters. These results are of importance to understand nonlinear wave dynamics in water wave systems.

Seaweed farming in the Western Indian Ocean (WIO) is among the income-generating activities; apart from seaweeds being primary producers, they are foundation species important for marine ecosystem capable of modifying their surrounding abiotic and biotic environments. The WIO coast provides natural and necessary environments for seaweeds farming. In this review article seaweed farming in WIO was investigated; its contribution to provision of ecosystem services; medicinal and nutritional value; role of women; challenges and the wellbeing of farmers and the whole ecosystem. It was observed that among the challenges facing seaweed farmers include lack of modernized farming tools hence farmers use low depth areas leading to attack by diseases, death of seaweed, low yields, and income. Farmers has been reported to be affected by diseases which may be contributed by inadequate of use of protective gears, indicating the need for knowledge on personal protection. This may be contributed by lack of knowledge which leads to farmers participation without using protective equipment leading to contamination from toxic chemical compounds from seaweed, epiphytic bacteria or harmful algal bloom and absorbed heavy metals from seawater as a result of long-term exposure. Farming practices such as uprooting of seaweeds during farm preparation have been observed to cause degradation and decrease fish population. Therefore, there is the need for use of modern technologies; supervision of these activities by professionals in the field, and provision of knowledge to farmers for the sustainability of WIO marine ecosystem.

In this paper, we have obtained new Hermite Hadamard Fejer type inequality different from the classical fejer inequality. With the help of this inequality, we have achieved Hermite Hadamard inequality for all of the Riemann Liouville and Conformable fractional integral that are both available and can be obtained.

A numerical algorithm to generate a set of optimal 3D rotations is presented. A list is created, with each new rotation found in a way to minimise the gap in angular coverage for a global angular search or a local angular refinement problem. Efficiency can be gained by combining rotations in groups when fitting molecular density representations to an experimental electron density map in cryo electron microscopy, and this algorithm also works for those combined rotations. Lists of optimal rotations written as quaternions and code to generate those lists are provided. The maximum gap in the angular coverage decays as a reciprocal-cubic function of the number of rotations.

Mesothelioma is rare in children and more common in adults for whom outcome is dismal. We diagnosed and treated two patients. Both had peritoneal tumors which harbor ALK gene mutations. Clinical presentations included cervical adenopathies with thromboses of neck veins and extensive peritoneal tumors encasing the different organs in the abdomen. Both had surgery and chemotherapy. Patient one has residual disease that has been stable for ten years. Both patients received oral Crizotinib. We describe the clinical course and outcome and give a brief summary of ALK inhibitors for mesothelioma in children.