Patients were still at a high risk of relapse after achieving complete remission by CAR-T therapy. The mechanisms underlying CD19+ relapse still remain to be further clarified in B-acute lymphoblastic leukemia (B-ALL). We reported a patient with B-ALL who relapsed at nine months after allogeneic stem cell transplantation. After two times of autologous anti-CD19 CAR-T infusion treatment, he recured with CD19 MRD positive the third time. CD19 antigen density was assessed for recurrence after a second CAR- T infusion and was found to be decreasing. The patient obtained MRD-negative (sCR4) on day 7 of treatment with the initial dose of Blinatumomab and remained negative throughout the four courses of maintenance treatment. Our case demonstrates that patients with CD19 + relapsed MRD treated with CD19-targeted CAR-T are still effective with low-dose Blinatumomab. The secondary infusion of CAR-T with 4-1BB domain may reduce the density of CD19 target antigen on the surface of tumor cells, resulting in the short maintenance of PFS. Treatment with Blinatumomab may not depend on CD19 target antigen density. Blinatumomab as a Bispecific T engager may act as an adaptor to improve T cell and CAR-T responses for patients relapsed after CAR-T therapy, which explained one possible cause of relapse after secondary CAR-T infusion and provided reference for salvage treatment strategies after CAR-T relapse.

Objective: This study aimed to evaluate the impact of bronchopulmonary dysplasia (BPD) on adolescents born extremely preterm (<28 weeks of gestation). Methods: This multicenter cross‐sectional study included adolescents who were born extremely preterm between 2003 and 2007. Questionnaires regarding the history of respiratory symptoms, asthma, quality of life (QOL), and physical growth were sent to 423 participants by mail, and responses were received from 243 participants (response rate: 57.4%). The average age of the respondents was 16.5 years. The participants were divided into the BPD (n = 140) and non-BPD (n = 103) groups. Results: One of three patients in both groups had been rehospitalized owing to respiratory symptoms; however, the difference was not significant (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.56–1.65). Respiratory syncytial virus infection was the most common reason for rehospitalization. The prevalence of adolescents with current wheeze were 4.3% and 2.9% in the BPD and non-BPD groups, respectively; however, the difference was not significant (OR, 1.49; 95% CI, 0.36–6.11). QOL scores were similar in both groups (71.9 vs. 71.0, p = 0.61). The z-scores for body weight and height were significantly different (p = 0.01). Conclusion: Adolescents born extremely prematurely with BPD were smaller physically than those without BPD. No significant differences in rehospitalization, asthma, and QOL scores were noted between the two groups. Further studies are needed to determine the impact of BPD on adults.

In this paper, we consider the asymptotic behavior of the Boussinesq equation with nonlocal weak damping when the nonlinear function is arbitrary polynomial growth. We firstly prove the well-posedness of solution by means of the monotone operator theory. At the same time, we obtain the dissipative property of the dynamical system (E ,S( t)) associated with the problem in the space H 0 2 ( Ω ) × L 2 ( Ω ) and D ( A 3 4 ) × H 0 1 ( Ω ) , respectively. After that, the asymptotic smoothness of the dynamical system (E ,S( t)) and the further quasi-stability are demonstrated by the energy reconstruction method. Finally, different from [21] we show not only existence of the finite global attractor but also existence of the generalized exponential attractor.

Background: An effective chemotherapy calendar system between the clinician and the patient/caregiver can improve patient centered outcomes. There is lack of research on how chemotherapy calendars are created and what aspects are important to pediatric oncology providers. Procedure: In an online survey of pediatric oncology providers, we evaluated institutional practices, perceptions of chemotherapy calendar creation, and desires for future tools. 220 survey participants provided data, with a 10.4% response rate. Results: Participants indicated that 72% always or most of the time their institution provides a chemotherapy calendar, most commonly at the start of a new cycle (90%) or with a dosing change (68%). Factors such as the health literacy of the family, prior non-adherence, type of cancer, and desire of the family affected the creation decision. Advanced practice providers (45%) or nurse coordinator/navigators (43%) were most likely to create the calendar. No significant difference was found between the likelihood of creating a calendar and institutional size (p=0.09) or provider years in practice (p=0.26). About 95% of participants indicated chemotherapy calendar creation software that improved ease and efficiency would be moderately to extremely useful. Conclusion: Future efforts should focus on patient and caregiver perspectives of chemotherapy calendar elements and utilization.

The large meander of the Kuroshio western boundary current is well known to influence the local climate, fisheries, and aquaculture by greatly modulating regional heat transport, but its impacts on biogeochemical processes remain unclear. Using high-resolution numerical ocean modelling and long-term observational datasets, we show that the path of the Kuroshio determines the extent of the shallow nutricline region, where winter convective mixing replenishes nutrient availability for subsequent blooms of phytoplankton during spring. During the large meander phase, this mechanism triggers offshore phytoplankton blooms that are otherwise absent during the non-large meander phase. The large meander also modulates the spatial distributions of primary production, air-sea carbon flux, and export production. These biogeochemical impacts of the Kuroshio large meander exert bottom-up control on regional marine ecosystems that is disproportionate to the thermal effect, and therefore need to be assessed to understand the large meander's overall impacts on fisheries and aquaculture.

Pericardial calcification (PC) typically appears following pericarditis or trauma. The aetiologies of other conditions, such as chronic idiopathic pericarditis, post-cardiac surgery, and mediastinal irradiation, can result in the development of calcified pericardium. This case reports an encounter treating constrictive pericardium which is a belt ring resulting in cardiac champer malformation.

Fibrodysplasia ossificans progressiva is a rare condition with an estimated prevalence of one in two million individuals. The condition is characterised by widespread heterotrophic ossification of skeletal muscles and ligaments. We report the case of an eight-year-old female patient and show the radiological progression of the condition.

Safety and Effect on Length of Stay of Intravenous Sotalol Initiation for Arrhythmia ManagementDiane H. Rizkallah, BS; Marwan M. Refaat, MDDivision of Cardiology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, LebanonRunning Title: Safety and Effect on LOS of IV SotalolWords: 598 (excluding the title page and references)Keywords: Heart Diseases, Cardiovascular Diseases, Cardiac Arrhythmias, Safety, Length of StayFunding: NoneDisclosures: NoneCorresponding Author:Marwan M. Refaat, MD, FACC, FAHA, FHRS, FRCPTenured Professor of MedicineTenured Professor of Biochemistry and Molecular GeneticsVan Dyck Medical Educator and Director of the Cardiovascular Fellowship ProgramDepartment of Internal Medicine, Cardiovascular Medicine/Cardiac ElectrophysiologyAmerican University of Beirut Faculty of Medicine and Medical CenterPO Box 11-0236, Riad El-Solh 1107 2020- Beirut, LebanonUS Address: 3 Dag Hammarskjold Plaza, 8th Floor, New York, NY 10017, USAOffice: +961-1-350000/+961-1-374374 Extension 5353 or Extension 5366 (Direct)Email: mr48@aub.edu.lbSotalol is a class III antiarrhythmic drug with beta-adrenergic blocking activity, used to manage both supraventricular and ventricular arrhythmias. It is available in both oral and intravenous formulations[1]. The FDA approved intravenous Sotalol in March 2020. Sotalol is known to cause QTc prolongation with serum sotalol concentration linearly correlating with QTc length regardless of the route of administration [2,3], with women being at higher risk than men[4]. QTc interval prolongation is one of many parameters that is associated with cardiovascular mortality [5]. QTc prolongation may lead to polymorphic ventricular tachycardia/Torsade de Pointes which is a potentially lethal condition that is acquired from medications or due to an underlying channelopathy predisposing to sudden cardiac arrest[6]. Additional adverse effects of sotalol may include hypotension, bradycardia and AV block[7,8]. Nevertheless, since its approval, IV sotalol has been successfully and safely used in both adult and pediatric patient populations for the management of arrhythmias in acute and chronic settings [9,10,11,12]. Initiation of sotalol therapy with PO loading requires 5 successive oral doses over a 3-day hospital stay for monitoring, at an estimated cost of $2931.55 per day [13]. In 2020, a protocol for IV loading of sotalol was developed using data modeling. This protocol was hypothesized to allow a significant reduction in the length of hospitalization, and thus in the incurred costs[14]. However, there has not been any large-scale implementation of this protocol, nor any comparison of its safety profile and efficacy to that of the traditional oral loading protocol.This study by Liu et al. is a nonrandomized clinical trial in which 29 patients underwent IV sotalol loading. They were compared by chart review to 20 patients who underwent PO sotalol loading in the same timeframe. The indication for sotalol initiation in both cases was for primary atrial or ventricular arrhythmias. The study’s main aim was to assess the safety profile of IV sotalol loading while comparing the length of hospitalization to that required for PO sotalol loading. The same exclusion and inclusion criteria were applied to both groups. Notably, patients with significantly depressed LVEF and creatinine clearance were excluded. The study revealed that safety outcomes were similar in both groups but that IV sotalol loading led to significantly shorter hospital stays. It also found that QT or QTc in patients receiving IV sotalol was similar at the conclusion of the one-hour infusion to that at discharge.These findings support the use of IV loading for sotalol initiation, as they suggest it requires shorter hospital stays than PO loading with similar safety profiles. As shorter hospital stays translate into lower patient days, lower costs, and these results suggest IV sotalol loading is more cost-efficient than its oral counterpart. They also suggest that the maximal increase in QT or QTc length following sotalol initiation is attained by the end of IV loading, thus indicating that patients may be discharged within less than 24 hours of drug initiation.While this study offered valuable insight, its design had significant limitations. Firstly, this was not a randomized clinical trial. A comparison of baseline characteristics between the two populations studied revealed a significantly higher proportion of females in the oral group, which may have inherently skewed outcomes related to QT and QTc length.Secondly, the sample size was small, with no long-term follow-up. Lastly, patients with significantly depressed GFR or LVEF, particularly prone to developing adverse effects with sotalol use, were excluded from the study. Randomized clinical trials examining the short-term and long-term safety of IV sotalol loading and the optimal length of hospitalization are needed, and such efforts are already underway.References:Batul, S. A., & Gopinathannair, R. (2017). Intravenous Sotalol - Reintroducing a Forgotten Agent to the Electrophysiology Therapeutic Arsenal. Journal of atrial fibrillation , 9 (5), 1499. https://doi.org/10.4022/jafib.1499Somberg, J. C., Preston, R. A., Ranade, V., & Molnar, J. (2010). QT prolongation and serum sotalol concentration are highly correlated following intravenous and oral sotalol. Cardiology , 116 (3), 219–225. https://doi.org/10.1159/000316050Barbey, J. T., Sale, M. E., Woosley, R. L., Shi, J., Melikian, A. P., & Hinderling, P. H. (1999). Pharmacokinetic, pharmacodynamic, and safety evaluation of an accelerated dose titration regimen of sotalol in healthy middle-aged subjects. Clinical pharmacology and therapeutics , 66 (1), 91–99. https://doi.org/10.1016/S0009-9236(99)70058-5Somberg, J. C., Preston, R. A., Ranade, V., Cvetanovic, I., & Molnar, J. (2012). Gender differences in cardiac repolarization following intravenous sotalol administration. Journal of cardiovascular pharmacology and therapeutics , 17 (1), 86–92. https://doi.org/10.1177/1074248411406505Al-Kindi SG, Refaat M, Jayyousi A, Asaad N, Al Suwaidi J, Abi Khalil C. Red Cell Distribution Width is Associated with All-Cause and Cardiovascular Mortality in Patients with Diabetes. Biomed Res Int 2017; 2017: 5843702Refaat MM, Hotait M, Tseng ZH: Utility of the Exercise Electrocardiogram Testing in Sudden Cardiac Death Risk Stratification.Ann Noninvasive Electrocardiol 2014; 19(4): 311-318.Marill, K. A., & Runge, T. (2001). Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol. Academic emergency medicine,  8 (2), 117–124. https://doi.org/10.1111/j.1553-2712.2001.tb01275.xMacNeil, D. J., Davies, R. O., & Deitchman, D. (1993). Clinical safety profile of sotalol in the treatment of arrhythmias. The American journal of cardiology , 72 (4), 44A–50A. https://doi.org/10.1016/0002-9149(93)90024-7Malloy-Walton, L. E., Von Bergen, N. H., Balaji, S., Fischbach, P. S., Garnreiter, J. M., Asaki, S. Y., Moak, J. P., Ochoa, L. A., Chang, P. M., Nguyen, H. H., Patel, A. R., Kirk, C., Sherman, A. K., Avari Silva, J. N., & Saul, J. P. (2022). IV Sotalol Use in Pediatric and Congenital Heart Patients: A Multicenter Registry Study. Journal of the American Heart Association , 11 (9), e024375. https://doi.org/10.1161/JAHA.121.024375Borquez, A. A., Aljohani, O. A., Williams, M. R., & Perry, J. C. (2020). Intravenous Sotalol in the Young: Safe and Effective Treatment With Standardized Protocols. JACC. Clinical electrophysiology , 6 (4), 425–432. https://doi.org/10.1016/j.jacep.2019.11.019Kerin, N. Z., & Jacob, S. (2011). The efficacy of sotalol in preventing postoperative atrial fibrillation: a meta-analysis. The American journal of medicine , 124 (9), 875.e1–875.e8759. https://doi.org/10.1016/j.amjmed.2011.04.025Milan, D. J., Saul, J. P., Somberg, J. C., & Molnar, J. (2017). Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis. Cardiology , 136 (1), 52–60. https://doi.org/10.1159/000447237Varela, D. L., Burnham, T. S., T May, H., L Bair, T., Steinberg, B. A., B Muhlestein, J., L Anderson, J., U Knowlton, K., & Jared Bunch, T. (2022). Economics and outcomes of sotalol in-patient dosing approaches in patients with atrial fibrillation. Journal of cardiovascular electrophysiology , 33 (3), 333–342. https://doi.org/10.1111/jce.15342Somberg, J. C., Vinks, A. A., Dong, M., & Molnar, J. (2020). Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion. Cardiology research , 11 (5), 294–304. https://doi.org/10.14740/cr1143

As we approach the three-year anniversary of the pandemic, we are now facing a seasonal influenza epidemic after two years without one. In light of growing concerns over the potential risk of a “twindemic,” the Republic of Korea is currently experiencing the first peak of seasonal flu and the overall pattern is quite similar to that observed before the COVID-19 pandemic. Notably, no sudden or early increase in cases has been detected, which is unique compared to other countries.

Influenza is an infectious disease caused by a type of Arani virus that enters the lungs and causes an acute infection of the respiratory tract. The Spanish flu pandemic in 1918 killed about 40 to 50 million people worldwide. In Iran, influenza is an endemic disease and cases of infection and death of this disease are registered in the country every year. Antibiotics are unnecessary costs in the initial treatment of influenza, because they can have potential side effects and spread resistant bacteria. Antibiotics help. From an economic point of view, the cost of antibiotic treatment in the hospital in 2000 was estimated at about 40 billion dollars, of which the share of developing countries was about one third. In 1990, the percentage of antibiotic sales of all medicines worldwide was 12%, of which the share of developing countries was 19%, while in 2000, this figure reached 34%. Therefore, the growth of the cost of antibiotics, especially in developing countries, has continued despite the efforts made to limit the unnecessary use of antibiotics. It is important to identify the cause of the disease in the first stage and choose the right and scientific method of treatment in the next stage; And if it is necessary to use antibiotics, first identify the type of bacteria, because the selection of antibiotics based on its results plays a very important role in the successful treatment of infections, proper sampling before starting the use of the first antibiotic is also important. .

A 7-year-old American short-haired cat was presented with blepharospasm in the right eye. The case was finally performed with orbital exenteration, leading to the diagnosis of feline restrictive orbital myofibroblastic sarcoma. Adjuvant chemotherapy with toceranib was given for one month after surgery. However, the case died four months after surgery.

Title : Distinct and mutually exclusive Ca++ flux- and adenyl cyclase-inducing gene expression profiles of G-Protein-Coupled Receptors on human antigen-specific B cellsAuthors : Iris Chang1,2†, Abhinav Kaushik, PhD1,2†, Pattraporn Satitsuksanoa PhD1, Minglin Yang1, Laura Buergi Msc1, Stephan R. Schneider Msc1, Cezmi A. Akdis, MD1, Kari Nadeau MD, PhD2, Willem van de Veen, PhD1, Mübeccel Akdis, MD, PhD1*1 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.2 Sean N. Parker Center for Allergy and Asthma Research, Department of Medicine, Stanford University, Palo Alto, CA, USA.† Contributed equally* Corresponding authorB cells play an essential role in allergies by producing allergen-specific IgE, which is a prerequisite for allergen-induced degranulation of mast cells (MCs) and basophils. MCs, basophils, dendritic cells and bacteria are capable of releasing inflammatory mediators including histamine. Histamine is a bioactive amine that exerts its function through binding to histamine receptors (HRs), which are 7-transmembrane G-protein-coupled receptors (GPCRs). There are four types of HRs (HR1-4), wherein HR1 ligation triggers Ca2+ mobilization, HR2 stimulates and increases cAMP concentrations, and HR3 and HR4 inhibit cAMP accumulation1. In the presence of histamine in the environment, high affinity HR1is triggered causing cellular activation, followed by expression of 10 times lower affinity HR2 to regulate the over-inflammatory events. These HRs trigger different intracellular events upon activation, with HR1 as a Ca2+ flux-inducing activating receptor and HR2 as an adenyl cyclase-stimulating suppressive receptor 1,2. Therefore, to explore the response of B-cells in allergic diseases, we analyzed the expression profile of HRs and other GPCRs in B cell clones. We hypothesized that the expression profile of HRs (HR1+ vs HR2+ B cell clones) is associated with significant changes in the expression profile of other GPCRs that govern the downstream cascade of pathways associated with cAMP signaling or Ca2+ mobilization.A total of 27 IgG1 and IgG4 expressing B cell clones were isolated for gene expression analysis under BCR stimulated and unstimulated conditions (Figure 1A and Online Supplementary Methods) . Interestingly, we observed B-cell clones with mutually exclusive expression profile of HRH1 and HRH2 genes (Figure 1B), with more HRH1+ B-cell clones in BCR-stimulated samples than unstimulated samples. The subsequentHRH1+ vs HRH2+ differential gene expression analysis (Figure 1C ), reveal 27 differentially expressed (DE) GPCRs in unstimulated samples, with up-regulated P2RY13  and C5AR1genes  in HRH2 + B-cell clones (Figure 2A) , which are associated with the cAMP signaling and suppressive pathway3,4. To further prioritize the DE GPCRs specifically associated with Ca2+ and cAMP signaling pathways, we reconstructed the co-expression networks and performed the weighted degree analysis across HRH1+ vs HRH2+ clones. The analysis reveals that the purinergic receptor family of GPCRs (i.e. P2RY1 , P2RY13 )  and complement component 5a receptor family of genes (i.e. C5AR1  and C5AR2 ) share highest degree of interactions. These genes are up-regulated inHRH2+ samples and are well-known to affect cAMP signaling pathway3,4 (Figure S1A ). Intriguingly, we also observed upregulation of GPR35  in HRH2 + B cells, which is associated in maintaining a low baseline Ca2+ level5. Similarly, we also observed up-regulation of GPR68 and GPR171 in HRH1 + B cells; both are known to stimulate Ca2+ flux (Online Supplementary Discussion) .Similarly, 28 GPCRs were differentially expressed in BCR-stimulated samples (Figure 2B ), including higher expression of serotonin receptor type 1A (HTR1A ) and HCAR1  (or GPR81 ) inHRH2+ samples, with a cAMP-linked suppressive function. In addition, we also observed upregulation of complement component 5a receptor family of genes (i.e., C5AR1  and C5AR2 ) and GPR35 , in agreement with the trend observed in unstimulatedHRH2 + B-cell clones. Surprisingly, we observed a higher expression of prostaglandin E2 receptor subtype EP4 (PTGER4)  and adenosine A2A receptor (ADORA2A ) in HRH2+ samples3,6, which are known to be associated with activation of cAMP production and share the highest strength of interactions with the cAMP signaling sub-network (Figure S1B ). Among the up-regulated genes in HRH1 + samples, we found three Ca2+ mobilizing genes, i.e., GPR34 ,P2RY10  and PTAFR .The results reported in this study provides data for a novel hypothesis suggesting investigation of co-expressed genes that may play important synergistic or antagonistic regulatory roles in B-cell function.

Although there has been an effective seasonal influenza vaccine available for more than 60 years, influenza continues to circulate and cause illness. The Eastern Mediterranean Region (EMR) is very diverse in health systems capacities, capabilities, and efficiencies, which affect the performance of services, especially vaccinations, including seasonal influenza vaccination. In this article, we have analyzed data from a regional seasonal influenza survey conducted in 2022, Joint Reporting Form (JRF), and verified their validity by the focal points. We also compared our results with those of the regional seasonal influenza survey conducted in 2016. This analysis provides a comprehensive overview on country-specific influenza vaccination policies, vaccine delivery, and coverage in EMR. Fourteen countries (64%) had reported having a national seasonal influenza vaccine policy. About (44%) countries recommended influenza vaccine for all SAGE recommended target groups. Up to (69%) of countries reported that COVID-19 had an impact on influenza vaccine supply in the country, with most of them (82%) reporting increases in procurement and supply of influenza vaccine, with the other countries reporting decreases in procurement due to COVID-19. We suggest supporting countries to develop a roadmap for influenza vaccine uptake and utilization, assessment of barriers and burden of influenza, including measuring the economic burden to enhance vaccine acceptance.

Gene regulation is the regulation of gene expression behavior by various related substances in cells, which controls almost all cell activities. Therefore, the study of gene regulation can not only explore the internal law of life activities, but also play a great role in the prediction, diagnosis, treatment and drug design of gene-related diseases. Using multi-source biological information such as gene expression profile data, transcription factor information and protein interaction information, a network model can be established to describe the regulatory relationship between genes, so as to facilitate the above studies. In order to solve the problem of low accuracy of traditional gene regulatory network construction methods, a new dynamic model of gene regulatory network was established by combining hybrid genetics and threshold restriction. The model is divided into two parts: solution space reduction and parameter fitting. In the phase of solution space reduction, singular value decomposition method is used to define the mathematically feasible gene regulatory network to reduce unnecessary calculation, and then the control gene of each gene is limited to a certain scale by threshold limitation method, which improves the computational efficiency and accords with the bioinformatics rules. In the parameter fitting part, the parallel genetic algorithm is used to optimize the whole solution space quickly, and then the mountain climbing method is used to solve the problem carefully in a small range to improve the calculation accuracy. In this study, we applied this method to the establishment of genetic regulatory systems for complex skin melanoma and type 2 diabetes. By comparing with the real network, the correctness of the method is proved. Compared with traditional genetic and PSO methods, the effectiveness of the proposed method was verified. In this paper, the deep mechanism of gene regulation is modeled, and the regulation process involving genes, proteins and small biological molecules is described in more detail, so as to be more detailed than other models and more consistent with the intracellular dynamics law.

A document by En Zhou Ye. Click on the document to view its contents.

The spread of COVID-19, namely SARS-CoV-2, has created a disastrous situation around the world causing an unclear future. Machine Learning (ML) and Deep Learning (DL) have a vital role in tracking the disease, predicting the outgrowth of the epidemic, and outlining strategies and policies to control its spread. Despite the inaccuracies of medical forecasts, the numbers of COVID-19 cases forecasts provide us with valuable information for recognizing the present and preparing for the future. This study proposes a time series based deep learning model, specifically the Long Short-Term Memory (LSTM) model. The model will predict the active, confirmed, deaths and recovered cases for 7 days ahead for Egypt and Saudi Arabia based on real-time data. The Egypt prediction model achieves Mean Absolute Percentage Error (MAPE) of 3.26150, a Root Mean Square Error (RMSE) of 0.0144, a Mean Square Error (MSE) of 0.0002, and a Mean Absolute Error (MAE) of 0.0092. While the Saudi prediction model obtains a MAPE of 5.0553, a RMSE of 0.0170, a MSE of 0.0002, and a MAE of 0.0150.

Membrane proteins represent a class of proteins that are difficult targets to characterize. Their structural and functional characterization requires that they first be produced at quantities that enable their biophysical and biochemical analysis. Because they are natively produced at levels much lower than their soluble counterparts, extraction from their natural sources is not sufficient to produce enough material for these studies. Recombinant protein expression and production has become a popular method to produce large amounts of proteins for research and industrial purposes. Significant effort has been spent finding new ways to optimize and increase protein expression. As cutting edge techniques in synthetic biology continue to advance they offer a potential well of opportunities to tune expression through better control of the transcription and translation processes. Many techniques being developed are geared toward the production of soluble proteins, but in the following review, a focus on effective strategies to maximize membrane protein production in yeast is presented and includes many of the most innovative approaches to maximize expression using synthetic biology. Synthetic biology utilizes modern techniques in molecular biology and genetic engineering to optimize the production of compounds produced in microbes by altering gene elements required for transcription and translation of critical genes responsible for their synthesis. Compounds include natural products, hydrocarbon-based compounds for biofuels, and therapeutic proteins. Producing membrane proteins recombinantly using similar methods to increase expression yields is described in this review along with cutting edge techniques like cell-free expression, which circumvents many of the common problems that plague overexpression of membrane proteins microbial-based platforms.

Objective: In a population of patients undergoing cardiac surgery for rheumatic mitral valve disease, evaluate the impact of preoperative PH on early surgical mortality.Methods: This is a prospective cohort carried out from January 1, 2017 to December 30, 2020. All patients over 18 years of age who underwent cardiac surgery to correct rheumatic mitral valve disease with functional tricuspid regurgitation in an echocardiogram performed up to 6 months before surgery were included. Systolic pulmonary artery pressure (sPAP) value was also defined by preoperative echocardiogram evaluation. The primary outcome was surgical mortality.Results: 144 patients were included. The mean age was 46.2 (±12.3) years with 107 (74.3%) female individuals, the median left ventricular ejection fraction was 61.0% (55 - 67) and sPAP was 55.0 mmHg (46 - 74), with 45 (31.3%) individuals with right ventricular dysfunction. The predominant valve disease was mitral stenosis (74.3%). The prevalence of severe tricuspid regurgitation was 47.2%. The total in-hospital mortality was 15 (10.4%) individuals. sPAP was independently associated with early surgical death RR 1.04 (1.01 – 1.07), p = 0.003. To determine a sPAP cut-off that indicates higher mortality and help decision making in clinical practice, we performed an analysis through the ROC curve (area 0.70, p=0.012). The estimated value of 73.5mmHg has the highest accuracy in our model for predicting early mortality.Conclusion: In patients with rheumatic heart disease who will undergo mitral valve surgery, pulmonary hypertension is associated with higher early mortality. Values above 73.5 mmHg predict higher risk and, in this part of the population, additional measures to control intraoperative and immediate postoperative pulmonary hypertension should be considered.

State of charge (SOC) estimation of lithium-ion batteries is the most important role of a battery management system. to improve the SOC estimation speed and accuracy in the operational environment, a novel method is proposed by combining a gated recurrent unit (GRU) neural network and a least mean square (LMS) adaptive filter. First a GRU network is used to estimate the SOC based on the battery measurement data. Then the LMS filter is used for online error reduction through unpredicted operation conditions, the LMS is a lite adaptive filter that updates its coefficient based on operation conditions with low computation cost. To verify the method robustness, its performance was checked under constant and varying temperature for standard drive cycles like UDDS and LA92. The proposed method is able to estimate SOC with less than 10-min discharge voltage, current and temperature data as the input with an error of less than 0.6% during working hour. Therefore, compared with conventional methods like LSTM and GRU the proposed GRU-LMS method has better speed and accuracy in the SOC estimation.

In light of climate change, wildfires are concurrently becoming more frequent and devastating worldwide. Though we have a good understanding of fire frequency changes in the past using charcoal analysis, records of the characteristics of these fires, such as fire severity, are lacking. This limits our ability to model how fire severity responds to climate change. Boron isotopes in clay minerals show promise as a novel fire severity proxy, where increased 𝛿11B is correlated with higher fire severity. Through reacting boron leached from experimentally combusted plants with clays, we determine that the observed correlation with fire severity is likely caused by input of isotopically heavier boron from combusted leaves. In contrast, combusted barks lower the 𝛿11B of clays upon reaction. Despite the different results, in both experiments with barks and leaves, similar boron isotope fractionation is observed during boron adsorption onto clays, where the lighter 10B is preferentially adsorbed. Therefore, the different results are likely caused by the different boron isotope composition of leaves and barks, where leaves have a much higher 𝛿11B (~30 ‰) than bark (~9 ‰). Combustion temperature can also affect the 𝛿11B of clays: changes to the 𝛿11B of clays were observed only when reacting with bark combusted at >300 °C, or with leaves combusted at >550 °C. This could be because more boron can be leached into solution from materials combusted at higher temperatures, which in turn results in greater adsorption onto clays during reactions. Clays have higher 𝛿11B in soils affected by high severity fires that consume tree crowns, because these fires combust more leaves that then deposit their isotopically heavier boron content into the soil. This relationship could help complete our fire record and improve our ability to predict future fire characteristics.

Complex colouration facilitates evolutionary investigations in nature because the interaction between genotype, phenotype and environment is relatively accessible. In a landmark set of studies, Endler addressed this complexity by demonstrating that the evolution male Trinidadian guppy coloration is shaped by the local balance between selection for mate attractiveness versus crypsis. This became a textbook paradigm for how antagonistic selective pressures shape evolutionary trajectory. However, the paradigm's generality was recently questioned by two studies seeking to use Trinidadian guppy populations to test the concept of parallel evolution. Both applied new and more sophisticated colour pattern analysis but these studies neither adequately address the question of evolutionary parallelism nor actually challenge the paradigm. As a guide to future work we review five main underappreciated factors contributing to colour pattern evolution: (1) inter-population variation in female preference, (2) differences in how predators versus conspecifics view males, (3) biased assessment of pigmentary versus structural colouration, (4) the importance of accounting for multi-species predator communities, and (5) the importance of considering the multivariate genetic architecture and multivariate context of selection. We elaborate upon these points and emphasize the depth of consideration necessary for testing evolutionary hypotheses using complex multi-trait phenotypes such as guppy colour patterns. 2

Objective: This study aims to explore the prevalence of anosmia and dysgeusia and their impact on COVID-19 patients. Design: This is a cross-sectional study. Patients diagnosed with COVID-19 between 1st October 2020 and 30th June 2021 were randomly selected from a national COVID-19 registry. The Anosmia Reporting Tool and a brief version of the questionnaire on olfactory disorders were used to measure the outcomes via telephone interviews. Data were analyzed using SPSS 27 statistics software. Results: A total of 405 COVID-19 adults were included in this study, 220 (54.3%) were males and 185 (45.8%) were females. The mean±SD age of participants was 38.2 ± 11.3 years. Alterations in the sense of smell and taste were reported by 206 (50.9%), and 195 (48.1%) of the patients respectively. Sex and nationality of participants were significantly associated with anosmia and dysgeusia (p<0.001) and (p-value=0.001) respectively. Among patients who experienced anosmia and dysgeusia, alterations in eating habits (64.2%), impact on mental wellbeing (38.9%), concerns that the alterations were permanent (35.4%), and physical implications and difficulty performing activities of daily living (34% ) were reported. Conclusion: Anosmia and dysgeusia are prevalent symptoms of COVID-19 disease, especially among females. Neuropsychological implications of COVID-19 in the acute infection phase and prognosis of anosmia and dysgeusia in COVID-19 are areas for further exploration.

Every metropolitan trip is punctuated by traffic signals, which have an immediate effect on drivers, the environment, and the economy whether the route is crowded or not. Traffic signal automation to reduce traffic delay is a major issue all over the world. Nevertheless, the current solutions to reduce exponentially rising traffic issues are not completely dealing with the problem. Companies, traffic engineers and researchers have suggested several Traffic Signal control systems. The main function of the traffic signal management system is to coordinate individual traffic signals to accomplish operational goals for the entire network. The single junction-based systems are unable to reduce the waiting time of exponentially increasing traffic load on the roads. To deal with this, we propose collaborative signal automation on a traffic simulator based on reinforcement learning techniques. The model utilized a q-learning technique that depicts composing units of addressed issues: agents, surrounding and response. The collaborative network takes advantage of traffic flow prediction with signal automation. Multi-junction road environments and vehicles are fed to the network as input. The proposed system suggests optimal signal automation to alleviate delay time and sequence length of traffic. Q-learning-based model decreases the wait time and leads to a steady flow of vehicles with several significances in composite traffic areas.

Figure 6