Early Phase Research Articles

Transcriptomics of early responses to purified Piscine orthoreovirus-1 in Atlantic salmon (Salmo salar L.) red blood cells compared to non-susceptible cell lines.

Piscine red blood cells (RBC) are nucleated and have been characterized as mediators of immune responses in addition to their role in gas exchange. Salmonid RBC are major target cells of Piscine orthoreovirus-1 (PRV-1), the etiological agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar). PRV-1 replicates in RBC ex vivo, but no viral amplification has been possible in available A. salmon cell lines. To compare RBC basal transcripts and transcriptional responses to PRV-1 in the early phase of infection with non-susceptible cells, we exposed A. salmon RBC, Atlantic salmon kidney cells (ASK) and Salmon head kidney cells (SHK-1) to PRV-1 for 24 h. The RNA-seq analysis of RBC supported their previous characterization as pluripotent cells, as they expressed a wide repertoire of genes encoding pattern recognition receptors (PRRs), cytokine receptors, and genes implicated in antiviral activities. The comparison of RBC to ASK and SHK-1 revealed immune cell features exclusively expressed in RBC, such as genes involved in chemotactic activity in response to inflammation. Differential expression analysis of RBC exposed to PRV-1 showed 46 significantly induced genes (≥ 2-fold upregulation) linked to the antiviral response pathway, including RNA-specific PRRs and interferon (IFN) response factors. In SHK-1, PRV induced a more potent or faster antiviral response (213 genes induced). ASK cells showed a differential response pattern (12 genes induced, 18 suppressed) less characterized by the dsRNA-induced antiviral pathway. Despite these differences, the RIG-I-like receptor 3 (RLR3) in the family of cytosolic dsRNA receptors was significantly induced in all PRV-1 exposed cells. IFN regulatory factor 1 (IRF1) was significantly induced in RBC only, in contrast to IRF3/IRF7 induced in SHK-1. Differences in IRF expression and activity may potentially affect viral propagation.

Exercise behaviours and motivation after a first psychotic episode: A digital intervention.

Research has demonstrated that participation in aerobic exercise can have significant beneficial effects across both physical and mental health domains for individuals who are in the early phase of schizophrenia. Despite these notable benefits of exercise, deficits in motivation and a lack of methods to increase engagement are significant barriers for exercise participation, limiting these potentially positive effects. Fortunately, digital health tools have the potential to improve adherence to an exercise program. The present study examined the role of motivation for exercise and the effects of an automated digital text messaging program on participation in an aerobic exercise program. A total of 46 first-episode psychosis participants from an ongoing 12-month randomized clinical trial (Enhancing Cognitive Training through Exercise Following a First Schizophrenia Episode (CT&E-RCT)) were included in an analysis to examine the efficacy of motivational text messaging. Personalized motivational text message reminders were sent to participants with the aim of increasing engagement in the exercise program. We found that participants with higher levels of intrinsic motivation to participate in a text messaging program and in an exercise intervention completed a higher proportion of individual, at-home exercise sessions. In a between groups analysis, participants who received motivational text messages, compared to those who did not, completed a higher proportion of at-home exercise sessions. These results indicate the importance of considering a person's level of motivation for exercise and the potential utility of using individualized and interactive mobile text messaging reminders to increase engagement in aerobic exercise in the early phase of psychosis. We emphasize the need for understanding how individualized patient preferences and needs interplay between intrinsic motivation and digital health interventions for young adults.

International Endometrial Tumor Analysis (IETA) descriptors in the diagnosis of chronic endometritis

Objective: to compare the terms, definitions and measurement methods developed by the IETA group with the ultrasound criteria of chronic endometritis (CE) used in Russia.Material and methods. A retrospective cohort study of 158 reproductive age women with clinical and laboratory diagnosis of CE was carried out. Sonographic examination was performed in the early or middle proliferative phase (cycle day 4–10 days) with the use of Affiniti70 ultrasound system (Philips, the Netherlands) with a multifrequency 3D endocavitary probe. Uterine corpus volume, endometrial thickness and volume were measured, followed by percentage endometrial/uterine volume ratio calculation, the so-called adjusted endometrial volume. Qualitative analysis of grayscale imaging included assessment of endometrial structure and echogenicity; closure or separation of the endometrial layers; contour of endometrial midline; the presence of acoustic artifacts, such as reverberation in the presence of gas or liquid in the uterine cavity, described by a number of authors. Relevant IETA descriptions were searched when assessing all qualitative CE features. In parallel, a qualitative score analysis proposed by the IETA group was carried out.Timely preoperative diagnosis of endometrioic cyst (endometrioma), as well as deep endometriosis remains relevant. The aim of the study was to assess the diagnostic value of ultrasound in patients with endometriomas and assess the combination of them with other foci of external genital endometriosis. The study based on retrospective analysis of a date of 95 patients with ultrasound signs of ovarian endometriomas, who underwent examination in MedicoProfi LLC – Borisov Medical and Diagnostic Clinic (Krasnoyarsk) during the period from January 2019 to October 2023. All of patients underwent surgery , followed by morphological evaluation. In the vast majority of cases, it was possible to detect a combination of endometriomas with one or more foci of deep endometriosis. Superficial peritoneal endometriosis and adhesions were found on surgery in all cases when endometriomas appeared isolated on ultrasound. The results of the study showed: endometriomas combined with deep endometriosis in 96.8% of cases. Thus, ultrasound detection of endometrioma is a very reliable sign of deep endometriosis presence. The “kissing ovaries” symptom in bilateral endometriomas can be considered as an absolutely reliable sign of the uterosacral ligaments endometriosis with specificity of 100% and positive predictive value of 100%. The presence of the “kissing ovaries” sign should be depicted in the conclusion of the ultrasound protocol, since it highly suggestive to obliteration of the pouch of Douglas and involvement of adjacent organs (fallopian tubes, intestines, ureters, etc.) in the endometrioid infiltrates, which is extremely important for the surgery planning, as well as in patients with infertility. There is an obvious need to introduce the extended pelvic ultrasound protocol to the diagnostic algorithm for patients with suspected endometriosis, which will more accurately describe the disease extension.Results. The comparative analysis of endometrium description in CE indicates a similar measurement technique for endometrial and intrauterine lesions thickness, both proposed by the IETA group and used in our country. Most of the IETA descriptors for qualitative ultrasound findings may be used in CE diagnosis. However, there are no some significant ultrasound features for identifying the inflammation, such as marked and partially or completely thickened midline, as well as gas focuses within the endometrium or in the uterine cavity, in IETA description.Conclusion. Terminology standardization allows compare the results and perform multicenter studies followed by meta-analysis for the diagnosis of chronic endometritis, if researchers use the similar descriptors.

Early versus late follicular phase ovarian stimulation: a randomized controlled trial

Research questionIs late follicular phase stimulation equally efficient as early follicular phase stimulation in a GnRH antagonist protocol in oocyte donors in terms of number of oocytes? DesignIn this open label, phase 3, non-inferiority, RCT using a two-arm design with 1:1 allocation ratio, 84 oocyte donors were allocated to early follicular start (control group, n=41), or late follicular start (study group, n=43). In the control group, patients followed a fixed GnRH antagonist protocol with r-FSH 225IU. In the study group, r-FSH 225IU was initiated in the late follicular phase. Primary outcome was number of oocytes. Secondary endpoints included number of mature oocytes, consumption of gonadotropins and GnRH antagonist, and stimulation cost. ResultsNumber of oocytes did not differ between control group and study group (intention-to-treat analysis 15.5±11.0 vs 14.0±10.7, p=0.52, per-protocol analysis 18.2±9.7 vs 18.8±7.8, p=0.62). Number of mature oocytes did not differ (14.1±8.1 vs 12.7±8.5, p=0.48). Duration of stimulation was shorter in the control group (10.0±1.6 vs 10.9±1.5 days, p=0.01). Total amount of r-FSH used was lower in the control group (2240.7±313.9 IU vs 2453.9±330.1 IU p=0.008). A GnRH antagonist was used for approximately 6 days in the control group, while in the study group, only in one patient a GnRH antagonist was prescribed (6.0±1.4 days vs 0.13±0.7 days p<0.001). There was a significant difference in medication cost per cycle (1147.9±182.8€ in control group, vs 979.9±129.0€ in study group, p<0.001). ConclusionsLate follicular phase stimulation is as efficient as early follicular phase stimulation in terms of number of oocytes.

VISUAL AND REFRACTIVE OUTCOME OF NEW GENERATION SMALL INCISION LENTICULE EXTRACTION (SMILE) IN MYOPIA AND MYOPIC ASTIGMATISM

Introduction: Two main options for the surgical correction of high myopia and myopic astigmatism are corneal refractive surgery and implantation of phakic intraocular lens (IOL). Small Incision Lenticule Extraction (SMILE) is becoming more popular technique which includes a minimally invasive flap-free procedure. The aim of this study is to evaluate the visual and refractive outcome of New Generation SMILE in myopia and myopic astigmatism. Methods: This is an observational retrospective study in patients who underwent SMILE using Visumax 800 Femtosecond laser procedure at Undaan Eye Hospital in period December 2022 to February 2023. Pre and post operative uncorrected visual acuity (UCVA), spherical equivalent (SE), astigmatism value, keratometry and intra ocular pressure (IOP) were evaluated at 1 day, 1 week and 1 month follow-up. Results: The study comprised 30 eyes of 15 patients age from 18 to 32 years old. The mean post operative UCVA was significantly improved to 0.03 ± 0.06 logMAR at 1-day, 0.02 ± 0.04 logMAR at 1-week and -0.01 ± 0.02 logMAR at 1-month follow-up compared to preoperative UCVA 1.35 ± 0.23 logMAR (p&lt;0.001). The mean refractive spherical equivalent was significantly changed from -4.60 ± 1.47 D preoperatively to -0.57 ± 0.38 D at 1-month follow up (p &lt; 0.001). The mean refractive astigmatism decreased from -1.02 ± 0.66 D preoperatively to -0.34 ± 0.25 D at 1- month follow up (p&lt;0.001). Conclusion: New Generation of SMILE has shown good visual and refractive outcome for the correction of myopia and myopic astigmatic eyes since the early phase after surgery.

Human induced pluripotent stem cells are resistant to human cytomegalovirus infection primarily at the attachment level due to the reduced expression of cell-surface heparan sulfate.

Numerous factors such as attachment, virus particle entry, transcription, and virus particle egress can affect viral susceptibility. Since 1984, pluripotent cells are known to be CMV resistant; however, the exact mechanism underlying this resistance remains elusive. Some researchers suggest inhibition in the initial phase of HCMV binding, while others have suggested the possibility of a sufficient amount of HCMV entering the cells to establish latency. This study demonstrates that HCMV particles rarely attach to the surfaces of hiPSCs. This is not due to limitations in the electrostatic interactions between the surface of hiPSCs and HCMV particles, but due to HS expression. Therefore, HS expression should be recognized as a key factor in determining the susceptibility of HCMV in congenital infection in vitro and in vivo. In the future, drugs targeting HS may become crucial for the treatment of congenital CMV infections. Thus, further research in this area is warranted.

Evaluation of the Usefulness of Contrast-Enhanced Computed Tomography for the Early Detection of Anastomotic Leakage After Esophagectomy.

Anastomotic leakage is one of the most severe complications after esophagectomy. However, a diagnostic gold standard for anastomotic leakage has not been established yet. This retrospective cohort study aimed to evaluate the potential use of routine postoperative contrast-enhanced computed tomography findings as an early predictor of anastomotic leakage in patients who underwent esophagectomy for esophageal cancer. This study included 75 patients who underwent Mckeown esophagectomy, of whom 22 developed anastomotic leakage after surgery. The computed tomography findings for this patient cohort were categorized into 3 grades based on mural enhancement patterns observed at the anastomotic site. Both semiquantitative and quantitative analyses were performed, and the interobserver agreement between the 2 experienced radiologists was assessed. It was found that poor enhancement in both the early and portal venous phases (grade 2) had a robust association with the occurrence of anastomotic leakage. The computed tomography enhancement ratio that is used to estimate wall degeneration and ischemia was significantly higher in patients with anastomotic leakage. Routine postoperative contrast-enhanced computed tomography could be beneficial for the early detection of anastomotic leakage, even in asymptomatic patients, after esophagectomy.

The effect of a strict facial-mask policy on the spread of COVID-19 in Switzerland during the early phase of the pandemic

During several weeks in the second half of the year 2020, the cantons of Switzerland could choose to adopt the government-determined facial-mask policy, corresponding to mandatory facial-mask wearing on public transport, or a strict facial-mask policy, corresponding to mandatory facial-mask wearing on public transport and in all public or shared spaces where social distancing was not possible. We estimate the effect of introducing the strict facial-mask policy on the spread of COVID-19 in Switzerland during this first phase of the pandemic in 2020, using the cantonal heterogeneity in facial-mask policies. We adjust for social distancing behavior, weather, other non-pharmaceutical policies and further variables. We estimate a significant reduction in the expected spread of COVID-19 in the early pandemic if the strict facial-mask policy is adopted.

Construction and validation of a risk-prediction model for anastomotic leakage after radical gastrectomy: A cohort study in China

ObjectivesAnastomotic leakage (AL) stands out as a prevalent and severe complication following gastric cancer surgery. It frequently precipitates additional serious complications, significantly influencing the overall survival time of patients. This study aims to enhance the risk-assessment strategy for AL following gastrectomy for gastric cancer. MethodsThis study included a derivation cohort and validation cohort. The derivation cohort included patients who underwent radical gastrectomy at Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, from January 1, 2015 to December 31, 2020. An evidence-based predictor questionnaire was crafted through extensive literature review and panel discussions. Based on the questionnaire, inpatient data were collected to form a model-derivation cohort. This cohort underwent both univariate and multivariate analyses to identify factors associated with AL events, and a logistic regression model with stepwise regression was developed. A 5-fold cross-validation ensured model reliability. The validation cohort included patients from August 1, 2021 to December 31, 2021 at the same hospital. Using the same imputation method, we organized the validation-queue data. We then employed the risk-prediction model constructed in the earlier phase of the study to predict the risk of AL in the subjects included in the validation queue. We compared the predictions with the actual occurrence, and evaluated the external validation performance of the model using model-evaluation indicators such as the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration curve. ResultsThe derivation cohort included 1377 patients, and the validation cohort included 131 patients. The independent predictors of AL after radical gastrectomy included age ≥65 y, preoperative albumin <35 g/L, resection extent, operative time ≥240 min, and intraoperative blood loss ≥90 mL. The predictive model exhibited a solid AUROC of 0.750 (95% CI: 0.694–0.806; p < 0.001) with a Brier score of 0.049. The 5-fold cross-validation confirmed these findings with a calibrated C-index of 0.749 and an average Brier score of 0.052. External validation showed an AUROC of 0.723 (95% CI: 0.564–0.882; p = 0.006) and a Brier score of 0.055, confirming reliability in different clinical settings. ConclusionsWe successfully developed a risk-prediction model for AL following radical gastrectomy. This tool will aid healthcare professionals in anticipating AL, potentially reducing unnecessary interventions.

Fully Automated Versions of Clinically Validated Nephrometry Scores Demonstrate Superior Predictive Utility versus Human Scores.

To automate the generation of three validated nephrometry scoring systems on preoperative computerised tomography (CT) scans by developing artificial intelligence (AI)-based image processing methods. Subsequently, we aimed to evaluate the ability of these scores to predict meaningful pathological and perioperative outcomes. A total of 300 patients with preoperative CT with early arterial contrast phase were identified from a cohort of 544 consecutive patients undergoing surgical extirpation for suspected renal cancer. A deep neural network approach was used to automatically segment kidneys and tumours, and then geometric algorithms were used to measure the components of the concordance index (C-Index), Preoperative Aspects and Dimensions Used for an Anatomical classification of renal tumours (PADUA), and tumour contact surface area (CSA) nephrometry scores. Human scores were independently calculated by medical personnel blinded to the AI scores. AI and human score agreement was assessed using linear regression and predictive abilities for meaningful outcomes were assessed using logistic regression and receiver operating characteristic curve analyses. The median (interquartile range) age was 60 (51-68) years, and 40% were female. The median tumour size was 4.2 cm and 91.3% had malignant tumours. In all, 27% of the tumours were high stage, 37% high grade, and 63% of the patients underwent partial nephrectomy. There was significant agreement between human and AI scores on linear regression analyses (R ranged from 0.574 to 0.828, all P < 0.001). The AI-generated scores were equivalent or superior to human-generated scores for all examined outcomes including high-grade histology, high-stage tumour, indolent tumour, pathological tumour necrosis, and radical nephrectomy (vs partial nephrectomy) surgical approach. Fully automated AI-generated C-Index, PADUA, and tumour CSA nephrometry scores are similar to human-generated scores and predict a wide variety of meaningful outcomes. Once validated, our results suggest that AI-generated nephrometry scores could be delivered automatically from a preoperative CT scan to a clinician and patient at the point of care to aid in decision making.

Pulmonary Aspergilloma Surgery Analysis and Results of a Series of 69 Cases

Pulmonary aspergilloma is an infectious human disease caused by colonization of a pre-existing cavity in the lung by a fungus of the genus Aspergillus. The spores are transmitted through the air, without contagiousness between people and germinate in a cavity to form a “mycelial” ball. The disease can go unnoticed, especially in the early phases, but is often complicated by hemoptysis of variable abundance which can even be dramatic. Surgery is the treatment to stop the progression of the disease, but this surgery is burdened with significant morbidity and mortality. We report a study of 69 patients operated on for pulmonary aspergilloma. Our results in terms of better quality of life and prevention of complications are acceptable at the cost of reduced morbidity.

A Multidisciplinary Evasion of the Futuristic Goals of Technology and Marketing

New technologies have revolutionized every aspect of human existence including the ways that firms make products and service to consumers. Marketing has a long tradition of studying the adoption of new technologies. New technologies give rise to innovations in marketing techniques, tools and strategies. Technology is defined as scientific knowledge and its application to useful purposes. Technology can relate both to the product or the service that follows from the scientific knowledge and to the knowledge itself. Technology in marketing helps distinguishing between the products or service and the technology it encompasses, which is at times impossible, because technology matters overtime. Thus technology is new when it is in the innovator or early adopter phase. These technological innovations and the resulting applications and solutions, with their unprecedented effects and unfamiliar outcomes, compel marketers to get ahead of the knowledge curve. Furthermore, innovations emerging in technology, data storage, analytics, and solutions highlight opportunities for marketing practitioners to create, communicate, capture, and deliver value for and with their customers. This research paper examines how technological innovations are likely to shape the practice and discipline of marketing for the next several decades,it also analysis a range of new marketing technologies, impact on marketing and technology- marketing framework that helps the marketing field.

Transmission potential of mpox in mainland China, June-July 2023: estimating reproduction number during the initial phase of the epidemic.

Despite reporting very few mpox cases in early 2023, mainland China observed a surge of over 500 cases during the summer. Amid ambiguous prevention strategies and stigma surrounding mpox transmission, the epidemic silently escalated. This study aims to quantify the scale of the mpox epidemic and assess the transmission dynamics of the virus by estimating the effective reproduction number (Re) during its early phase. Publicly available data were aggregated to obtain daily mpox case counts in mainland China, and the Re value was estimated using an exponential growth model. The mean Re value was found to be 1.57 (95% credible interval [1.38-1.78]), suggesting a case doubling time of approximately 2 weeks. This estimate was compared with Re values from 16 other countries' national outbreaks in 2022 that had cumulative case count exceeding 700 symptomatic cases by the end of that year. The Re estimates for these outbreaks ranged from 1.13 for Portugal to 2.31 for Colombia. The pooled mean Re was 1.49 (95% credible interval [1.32-1.67]), which aligns closely with the Re for mainland China. These findings underscore the need for immediate and effective control measures including targeted vaccination campaigns to mitigate the further spread and impact of the epidemic.

Time-course analysis of liver and serum galectin-3 in acute liver injury after alpha-galactosylceramide injection.

Galectin-3 is a beta-galactoside-binding lectin that plays important roles in diverse physiological functions, such as cell proliferation, apoptosis, and mRNA splicing. This protein is expressed on inflammatory cells and acts as a local inflammatory mediator. Recently, galectin-3 has been detected in several diseases, such as chronic liver, heart, and kidney diseases, diabetes, viral infection, autoimmune and neurodegenerative diseases, and tumors, and its role as a biomarker has attracted attention. Alpha-galactosylceramide is an artificially synthesized sphingolipid that can induce acute liver injury via the natural killer T pathway. However, the pathophysiological roles and kinetics of galectin-3 in acute liver injury are not fully understood. This study aimed to elucidate the expression and time course of galectin-3 in liver tissues during acute liver injury following alpha-galactosylceramide injection. Animals were histologically examined on days 1, 2, 4, and 7 after intraperitoneal injection of alpha-galactosylceramide, and the expressions of galectin-3 and ionized calcium-binding adaptor molecule 1 were analyzed. Notably, galectin-3 formed characteristic cluster foci, particularly on day 2 after injection. Cluster formation was not observed in chronic liver disease. Simultaneously, ionized calcium-binding adaptor molecule 1-positive cells were observed in the cluster foci. Serum galectin-3 levels increased on day 2 of treatment and correlated well with the number of galectin-3-positive cell clusters in the liver. Moreover, galectin-3 expression was an important mediator of the early phase of liver injury after alpha-galactosylceramide injection. These results suggest that serum galectin-3 may be a biomarker for the early diagnosis of acute liver injury and that clusters of galectin-3-positive cells may be a specific finding in acute liver injury.

A Novel Serum Exosomal miRNA Signature in the Early Prediction of Persistent Organ Failure in Patients with Acute Pancreatitis.

Current study aims to investigate whether serum exosomal microRNAs (miRNAs) could be potential biomarkers in predicting APs with POF at early phase. Novel biomarkers are sorely needed for early prediction of persistent organ failure (POF) in acute pancreatitis (AP) patients. In the discovery stage, exosomal miRNAs were profiled in sera from APs with or without POF (5 vs. 5) using microarrays. POF-associated miRNA signatures then were assessed in training cohort (n=227) and further validated in three independent cohorts (n=516), including one nested case-control cohort. A total of 743 APs were recruited in this large-scale biomarker identification study with a nested case-control study. Data from the discovery cohort demonstrated that 90 exosomal miRNAs were significantly dysregulated in APs with POF compared with controls. One miRNA classifier (Cmi) comprising 3 miRNAs (miR-4265, 1208, 3127-5p) was identified in the training cohort, and was further evaluated in two validation cohorts for their predictive value for POF. AUCs for Cmi ranged from 0.88 to 0.90, which was statistically superior to AUCs of APACHE-II and BISAP, and outperformed BUN and creatinine in POF prediction across all cohorts (P<.05). Higher levels of Cmi indicated increased need for ICU admission, prolonged hospitalization, and elevated mortality rate, thus poor prognosis. In the nested case-control study, Cmi could help identify prediagnostic POF in post-ERCP pancreatitis cases within "golden hours" after ERCP with high efficacy. Serum exosomal Cmi may be an early predictor for POF in AP, even within "golden hours" after AP onset. ClinicalTrials.gov (NCT02602808).

Evaluating tixagevimab/cilgavimab prophylaxis in allogeneic haematopoietic cell transplantation recipients for COVID-19 prevention.

Allogeneic haematopoietic cell transplantation (allo-HCT) recipients exhibit an increased risk of COVID-19, particularly in the early post-transplant phase, due to insufficient vaccine responses. This retrospective study investigated the incidence of SARS-CoV-2 infection in allo-HCT recipients who received tixagevimab/cilgavimab pre-exposure prophylaxis (T/C PrEP) compared to those who did not. Logistic regression, adjusted for sex, age, SARS-CoV-2 vaccination status and immunosuppressive treatment, revealed a significant reduction in the likelihood of SARS-CoV-2 infection risk with T/C PrEP (adjusted odds ratio aOR = 0.26 [0.07, 0.91]). These findings suggest the potential efficacy of monoclonal antibody PrEP in protecting this vulnerable patient population from COVID-19.

Stochastic model of vesicular stomatitis virus replication reveals mutational effects on virion production.

We present the first complete stochastic model of vesicular stomatitis virus (VSV) intracellular replication. Previous models developed to capture VSV's intracellular replication have either been ODE-based or have not represented the complete replicative cycle, limiting our ability to understand the impact of the stochastic nature of early cellular infections on virion production between cells and how these dynamics change in response to mutations. Our model accurately predicts changes in mean virion production in gene-shuffled VSV variants and can capture the distribution of the number of viruses produced. This model has allowed us to enhance our understanding of intercellular variability in virion production, which appears to be influenced by the duration of the early phase of infection, and variation between variants, arising from balancing the time the genome spends in the active state, the speed of incorporating new genomes into virions, and the production of viral components. Being a stochastic model, we can also assess other effects of mutations beyond just the mean number of virions produced, including the probability of aborted infections and the standard deviation of the number of virions produced. Our model provides a biologically interpretable framework for studying the stochastic nature of VSV replication, shedding light on the mechanisms underlying variation in virion production. In the future, this model could enable the design of more complex viral phenotypes when attenuating VSV, moving beyond solely considering the mean number of virions produced.

Impact of the COVID-19 pandemic on the prevalence of respiratory viral pathogens in patients with acute respiratory infection in Shanghai, China.

This study aimed to evaluate the impact of nonpharmaceutical interventions (NPIs) taken to combat COVID-19 on the prevalence of respiratory viruses (RVs) of acute respiratory infections (ARIs) in Shanghai. Samples from ARI patients were collected and screened for 17 respiratory viral pathogens using TagMan low density microfluidic chip technology in Shanghai from January 2019 to December 2020. Pathogen data were analyzed to assess changes in acute respiratory infections between 2019 and 2020. A total of 2,744 patients were enrolled, including 1,710 and 1,034 in 2019 and 2020, respectively. The total detection rate of RVs decreased by 149.74% in 2020. However, detection rates for human respiratory syncytial virus B (RSVB), human coronavirus 229E (HCoV229E), human coronavirus NL63 (HCoVNL63), and human parainfluenza virus 3 (HPIV3) increased by 91.89, 58.33, 44.68 and 24.29%, in 2020. The increased positive rates of RSVB, HPIV3, resulted in more outpatients in 2020 than in 2019. IFV detection rates declined dramatically across gender, age groups, and seasons in 2020. NPIs taken to eliminate COVID-19 had an impact on the prevalence of respiratory viral pathogens, especially the IFVs in the early phases of the pandemic. Partial respiratory viruses resurged with the lifting of NPIs, leading to an increase in ARIs infection.

Tracking the Impact of Koch-Carbonylated Organics During the Zeolite ZSM-5 Catalyzed Methanol-to-Hydrocarbons Process.

A methanol-based economy offers an efficient solution to current energy transition challenges, where the zeolite-catalyzed methanol-to-hydrocarbons (MTH) process would be a key enabler in yielding synthetic fuels/chemicals from renewable sources. Despite its original discovery over half a century ago over the zeolite ZSM-5, the practical application of this process in a CO2 -neutral scenario has faced several obstacles. One prominent challenge has been the intricate mechanistic complexities inherent in the MTH process over the zeolite ZSM-5, impeding its widespread adoption. This work takes a significant step forward by providing critical insights that bridge the gap in our understanding of the MTH process. It accomplishes this by connecting the (Koch-carbonylation-led) direct and dual cycle mechanisms, which operate during the early and steady-state phases of MTH catalysis, respectively. To unravel these mechanistic intricacies, we have performed catalytic and operando (i.e., UV/Vis coupled with an online mass spectrometer) and solid-state NMR spectroscopic-based investigations on the MTH process, involving co-feeding methanol and acetone (cf. a key Koch-carbonylated species), including selective isotope-labeling studies. Our iterative research approach revealed that (Koch-)carbonyl group selectively promotes the side-chain mechanism within the arene cycle of the dual cycle mechanism, impacting the preferential formation of BTX fraction (i.e., benzene-toluene-xylene) primarily.

BIM-based multi-objective optimization framework for volumetric analysis of building projects

Purpose The purpose of this paper is to develop a building information modelling (BIM)-based multi-objective optimization (MOO) framework for volumetric analysis of buildings during early design stages. The objective is to optimize volumetric spaces (3D) instead of 2D spaces to enhance space utilization, thermal comfort, constructability and rental value of buildings Design/methodology/approach The integration of two fundamental concepts – BIM and MOO, forms the basis of proposed framework. In the early design phases of a project, BIM is used to generate precise building volume data. The non-sorting genetic algorithm-II, a MOO algorithm, is then used to optimize extracted volume data from 3D BIM models, considering four objectives: space utilization, thermal comfort, rental value and construction cost. The framework is implemented in context of a school of architecture building project. Findings The findings of case study demonstrate significant improvements resulting from MOO of building volumes. Space utilization increased by 30%, while thermal comfort improved by 20%, and construction costs were reduced by 10%. Furthermore, rental value of the case study building increased by 33%. Practical implications The proposed framework offers practical implications by enabling project teams to generate optimal building floor layouts during early design stages, thereby avoiding late costly changes during construction phase of project. Originality/value The integration of BIM and MOO in this study provides a unique approach to optimize building volumes considering multiple factors during early design stages of a project