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Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.

Densities, speeds of sound, and viscosity values have been experimentally measured at temperature ranges from (298.15 to 308.15 K) and a pressure of 0.1 MPa for the whole compositions for the binary mixtures of tetrahydrofuran with methyl acetate, propyl acetate, and pentyl acetate. Excess molar volume (VmE), excess molar isentropic compressibility (ΔKS,mE), viscosity deviation (Δη), excess Gibb’s free energy of activation for viscous flow (ΔG*E), and partial molar volume (V̅m,i) have been derived with the help of experimental results and fitted to an extended Redlich–Kister equation by the least-squares approach that simultaneously considers the dependency on composition and temperature. For the calculated and experimental data, the standard deviations are estimated. The magnitude and sign of these excess properties have been utilized to explain the results in terms of structural and intermolecular interactions. Various semiempirical viscosity relations were tested using the data of viscosity of binary mixtures.

Free space optical (FSO) communication system is a promising candidate for today's era of intelligent networks for the reason that it has potential advantages such as, high data rates, large bandwidth, non-licensed spectrum, line-of-sight communication and many more. Relay-assisted communication provides an additional boost to system's performance by expanding its capacity, coverage range, enhancing data rates and mitigating the effect of turbulence. In this manuscript, three dual-hop systems are considered i.e., FSO-FSO, radio frequency (RF)-FSO and FSO-RF systems employing decode and forward (DF) relaying protocol. Furthermore, chaotic signals are incorporated in these systems to enhance their confidentiality using differential chaos shift keying (DCSK). This is demonstrated by performing secrecy analysis on the system. Here, it is assumed that RF link experiences Nakagami-m fading while the affect of fading in FSO channel is caused by Gamma-Gamma turbulence along with pointing errors. The average bit error rate (BER) of three proposed systems is analyzed, and the results indicated that the FSO-RF-DCSK system outperformed the other three in terms of performance. Finally, secrecy performance is accomplished using secrecy outage probability (SOP) as a metric for the proposed systems. The findings are noteworthy as FSO-FSO-DCSK system demonstrates superior performance as compared to FSO-RF-DCSK and RF-FSO-DCSK systems in terms of secrecy. As compared to other counterparts, FSO-FSO-DCSK system shows an improvement of more than 10 order of magnitude in terms of signal-to-noise (SNR) ratio.

Lignocellulosic biomass is one of the biggest renewable reservoirs for organic carbon that can be exploited as feed for various value-added products like fuel, nutraceuticals enzymes, and proteins. Biofuel is not only valuable but also a top priority target to address the energy crisis. Hence the current work was planned to valorize the cellulose-rich residual biomass (CRB), left after xylitol production for ethanol fermentation by yeast. Xylose-rich hydrolysate was prepared with dilute acid pretreatment (0.1 M H2SO4, 145 ℃, and 90 min) for xylitol production and CRB was further processed for enzymatic hydrolysis (crude cellulase). Acid hydrolysis offered maximum reducing sugars of 0.33±0.01 g⋅g−1biomasscomprised of xylose 0.31±0.01 g⋅g−1biomass. Besides sugar, biomass hydrolysis also produced 0.21 ±0.01 g.L−1furans and 0.34±0.11 g.L−1acetic acid. Pichia guilliermondiiRLV-04 (MH588234.1) have shown 0.90±0.02 gxylitol.g−1xyloseconversion of xylose to xylitol. The primary process has left more than 50–55 % biomass that was rich in cellulose. Enzymatic hydrolysis of the CRB using crude cellulase showed maximum glucose recovery of 0.56±0.02 g⋅g−1available celluloseat 15 FPU at 50 ℃, after 12 h. In addition, yeast biomass recovered from xylitol production was hydrolysed and used as a nitrogen source. Under an anaerobic environment, a maximum ethanol yield of 0.36±0.01 g.g−1glucosewas achieved with commercial baker’s yeast while the addition of yeast biomass hydrolysate improved the alcohol yield to 0.48±0.02 g.g−1glucose. Reutilization of biocatalysts as nitrogen source not only upgraded fermentation processes but also lowered process waste and improved process economics.

Purpose To identify predictive factors associated with US adolescents’ transition through the stages of change for potentially quitting e-cigarettes using the Trans-theoretical model of behavior change.Design Prospective cohort study.Setting United States.Subjects We utilized data from adolescents (12-17 years) in Wave 3 of the Population Assessment of Tobacco and Health study who used e-cigarettes exclusively over the past 30 days (n = 177) and were followed up with in Wave 4.Measures Outcome variables were 3 transition categories: those who remained stagnant, those who progressed, and those who regressed in their stage of quitting e-cigarettes. Predictor variables were socio-demographics, e-cigarette harm perception, e-cigarette use at home or by important people, social norms, e-cigarette and anti-tobacco advertisements, and e-cigarette health warnings.Analysis Weighted-adjusted multinomial regression analysis was performed to determine the association between predictor and outcome variables.Results From Wave 3 to Wave 4, 19% of adolescents remained stagnant; 73.3% progressed; and 7.7% regressed. Adolescents were less likely to progress in their stage of change if they perceived nicotine in e-cigarettes to be “not at all/slightly harmful” (AOR = .26 [95% CI: .25, .27], P< .001); reported important people’s use of e-cigarettes (AOR = .18 [95% CI: .05, .65, P= .009); and “rarely” noticed e-cigarette health warnings (AOR = .28 [95% CI: .08, .98, P= .054).Conclusion Intervention efforts must target specific predictive factors that may help adolescents quit e-cigarettes.

Herein, we report the application of a benzyloxy-functionalized malonic acid half thioester as an activated ester equivalent in a highly enantioselective decarboxylative glycolate aldol reaction. This robust method operates at ambient temperature, tolerates air and moisture, and generates CO2as the only byproduct. The synthetic applicability of the method is demonstrated by the large-scale enantiodivergent synthesis of α-benzyloxy-β-hydroxybutyric acid thioester and its subsequent conversion to diverse polyoxygenated building blocks, deoxy-sugars, and (−)-angiopterlactone B.

Secondary metabolites are generally produced by enzymes encoded by genes within a biosynthetic gene cluster. Transcription factor genes are frequently located within these gene clusters. These transcription factors often drive expression of the other genes of the biosynthetic gene cluster, and overexpression of the transcription factor provides a facile approach to express all genes within a gene cluster, resulting in production of downstream metabolite(s). Unfortunately this approach is not always successful, leading us to engineer more effective hybrid transcription factors. Herein, we attempted to activate a putative cryptic biosynthetic gene cluster in Aspergillus nidulansusing a combination of transcription factor engineering and overexpression approaches. This resulted in the discovery of a novel secondary metabolite we term triorsellinaldehyde. Surprisingly, deletion of the polyketide synthase gene within the gene cluster did not prevent triorsellinaldehyde production. However, targeted deletion of a polyketide synthase gene elsewhere in the genome revealed its role in triorsellinaldehyde biosynthesis.

We examined the differences in neurocognitive functions in individuals dependent on heroin (n= 120), pharmaceutical (n= 52), and natural opioids (n= 66) and compared with healthy controls (HC, n= 94). We estimated independent effects of the opioid groups on cognitive tests, adjusted for effect modifiers. Pharmaceutical opioid dependent group performed worse than HC in Wisconsin Card Sorting Test in conceptual level response and trials to complete first category. Pharmaceutical and heroin groups had higher error scores than HC in verbal and visual N-Back Tests (NBTs). There was no significant difference between pharmaceutical and heroin groups, but both had higher error scores than the natural opioid users in NBTs. Time to complete Trail Making- A test was higher in pharmaceutical than in natural opioid group. The natural opioid group required more trials than HC to complete the first category. Pharmaceutical opioid group had worst cognitive impairment. Cognitive functions are relatively spared in natural opioid-dependent group.

Castleman disease, a rare lymphoproliferative disorder characterized by non-neoplastic lymph node enlargement, typically presents as nodal involvement, while extranodal manifestations are uncommon. We present a unique case of unicentric Castleman disease localized to the gluteal region in a 27-year-old female. Initially mistaken for a neurogenic or vascular tumour, fine needle aspiration cytology (FNAC) revealed a polymorphous population of lymphoid cells with numerous traversing capillaries suggestive of reactive hyperplasia, possibly Castleman disease, which was later confirmed by histopathology. This case highlights the diagnostic challenges posed by rare extranodal presentations of Castleman disease and underscores the importance of interdisciplinary collaboration in accurate diagnosis and management.

Objective: In this study on patients with Cushing disease, post-transsphenoidal surgery (TSS), we attempt to predict the probability of remaining in remission, at least for a year and relapse after that, using Bayes’ theorem and the equation of conditional probability. The number of parameters, as well as the weightage of each, is incorporated in this equation. Design and methods: The study design was a single-centre ambispective study. Ten clinical, biochemical, radiological and histopathological parameters capable of predicting Cushing disease remission were identified. The presence or absence of each parameter was entered as binary numbers. Bayes’ theorem was applied, and each patient’s probability of remission and relapse was calculated. Results: A total of 145 patients were included in the study. ROC plot showed a cut-off value of the probability of 0.68, with a sensitivity of 82% (range 73–89%) and a specificity of 94% (range 83–99%) to predict the probability of remission. Eighty-one patients who were in remission at 1 year were followed up for relapse and 23 patients developed relapse of the disease. The Bayes’ equation was able to predict relapse in only 3 out of 23 patients. Conclusions: Using various parameters, remission of Cushing disease can be predicted by applying Bayes’ theorem of conditional probability with a sensitivity and a specificity of 82% and 94%, respectively. This study provided an objective way of predicting remission after TSS and relapse in patients with Cushing disease giving a weightage advantage to every parameter.

ABSTRACTStates view protests as disruptive and police them. Scholarship points to selective policing of protests that endanger law and order as well as those organized by minority groups. A common form of protest policing in cities is requiring protestors to obtain permits in advance. We use interviews with protestors and the police in New Delhi to examine their perception of protest policing. We test these perceptions empirically using an original dataset of 4,921 protest applications submitted to the Delhi police between 2016 and 2019. We find that the rejection of protest applications is driven by the disruptive threat that they pose rather than the identity of the protesting group. However, the police disproportionately flag protest applications by religious minorities for threat assessment. A postcolonial police force, which privileges preservation of order over its other functions, regularly curtails the democratic freedom to protest.

Determine if a new teaching bundle targeting developmental dysplasia of the hip screening improved interns’ examination skills across multiple pediatric residency programs.This multicenter prospective cohort study included interns across 6 pediatric residency sites within the Academic Pediatric Association’s Better Outcomes through Research for Newborns Network in 2022. Participants underwent a baseline hip examination assessment on models using a checklist derived from textbook descriptions of Galeazzi, Ortolani, and Barlow maneuvers before receiving a teaching bundle. Repeat testing occurred after instruction. Data were analyzed using t-test for continuous and χ2 test for categorical variables. Semistructured focus groups provided qualitative feedback regarding the teaching bundle.We enrolled 117 of 155 interns across 6 sites (76%) for participation in the teaching bundle. Only 2% of participants (n = 2) identified a positive Galeazzi sign at baseline, whereas 88% (n = 103, P < .001) did so on the postinstructional assessment. Although 27% of participants (n = 32) correctly identified a positive Barlow sign at baseline, 69% (n = 81, P < .001) did so on the postinstructional assessment. The ability to correctly detect a positive Ortolani sign increased from 22% (n = 26) to 92% (n = 108, P < .001). Fifteen interns participated in the semistructured focus groups, with resultant themes reinforcing the limited experience of the infant hip examination before this intervention and the positive impact of the teaching bundle.Most participants in this study did not have strong infant hip examination skills at entry into residency. A standardized teaching bundle significantly improved skills in examination technique and identifying abnormalities.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosisinfection status while considering tuberculosis burden of the settings.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

Forecasting COVID-19 waves helps with public health planning and resource allocation. Cycle threshold (Ct) values obtained from positive SARS-CoV-2 nucleic acid amplification test (NAAT) results offer limited value for individual patient management, but real-time analysis of temporal trends of aggregated Ct values may provide helpful information to predict the trajectories of COVID-19 waves in the community. Ct value trends on 59,609 SARS-CoV-2 NAAT-positive results from 574,403 tests using a single testing assay system, between September 2021 and January 2023, were examined to monitor the trend of the proportion of positive NAAT with lower Ct values (≤28) in relation to changing COVID-19 case numbers over time. We applied regression with autoregressive integrated moving average errors modelling approach to study the relation between Ct values and case counts. We also developed an insight product to monitor the temporal trends with Ct values obtained from SARS-CoV-2 NAAT-positive results. In this study, the proportion of lower Ct values preceded by a range of 7–32 days the rising population COVID-19 testing rate reflecting onset of a COVID-19 wave. Monitoring population Ct values may assist in predicting increased disease activity.

Elastic optical networks (EONs) offer tremendous benefits to deal with the exponential increase of the data center traffic. The granularity offered in spectrum allocation supports efficient management of available bandwidth and accommodates multiple traffic to be routed through common links. However, this brings the inherent challenges of routing and spectrum allocation (RSA) constraints. This becomes more complex for elastic optical data center networks (EODCNs), wherein multiple requests arrive at the same time, requiring identical or different bandwidths and each request may have the same or different destination and paths. Also, data requested by different users could be of varying importance levels. Under such a scenario, maintaining the quality of service (QoS) by minimizing the probability of traffic failure and bandwidth blocking is a major task for service providers. To address these problems, we propose an enhanced methodology using path prediction and link-state analysis for efficient allocation of frequency slots and reuse of bandwidth for data centers connected through EONs. Our proposed strategy intents to minimize the number of blocked requests due to non-availability of resources and reduce the failure probability. We introduce here the concept of connectivity degree and Kuhn-Munkres multi-objective optimization for spectrum allocation. We also evaluate the call request blocking probability varying the number of data centers and traffic load. The obtained results show that the proposed algorithm is highly effective in reducing the traffic failure and blocking probability for EODCNs.

In this paper, we study a dual hop hybrid radio frequency-visible light communication (RF-VLC) system with wireless energy harvesting technique. In the proposed model the RF channel and the VLC channel are modelled by generalized-K distribution and lambertian emission model, respectively. A decode and forward relay is used as an intermediate node where power splitting relaying (PSR) protocol is employed to harvest energy from the received RF information signal. The source transmits the information signal towards the relay via RF channel. The relay then decodes the received signal and convert it into corresponding light signal. Simultaneously the energy harvesting circuit at relay harvests the energy from the received RF signal. The relay utilizes the harvested energy to aid the transmission of the light signal towards the user situated inside the building’s room at the destination. Further, the statistics of the instantaneous SNR of the hybrid RF-VLC system at the destination are derived by employing the PSR protocol to obtain an accurate closed form analytical expression for the system’s end-to-end ergodic capacity and achievable throughput in terms of Meijer’s G function. Further, with the help of numerical simulations, we analysed the end-to-end ergodic throughput performance of the hybrid system under the influence of varying channel parameters such as signal to noise ratio, power splitting factor, shadowing parameters, distance between source & relay and source transmitted power.

•EPO is crucial for maintaining RBC balance, and its dysregulation can cause conditions such as anemia and polycythemia.•This study reveals a new discovery that 2 NRs, Rev-erbα and RORα, act oppositely, suggesting a potential therapy for EPO-related disorders.

Type 2 diabetes mellitus is a long-lasting endocrine disorder characterized by persistent hyperglycaemia, which is often triggered by an entire or relative inadequacy of insulin production or insulin resistance. As a result of resistance to insulin (IR) and an overall lack of insulin in the body, type 2 diabetes mellitus (T2DM) is a metabolic illness that is characterized by hyperglycaemia. Notably, the occurrence of vascular complications of diabetes and the advancement of IR in T2DM are accompanied by dysbiosis of the gut microbiota. Due to the difficulties in managing the disease and the dangers of multiple accompanying complications, diabetes is a chronic, progressive immune-mediated condition that plays a significant clinical and health burden on patients. The frequency and incidence of diabetes among young people have been rising worldwide. The relationship between the gut microbiota composition and the physio-pathological characteristics of T2DM proposes a novel way to monitor the condition and enhance the effectiveness of therapies. Our knowledge of the microbiota of the gut and how it affects health and illness has changed over the last 20 years. Species of the genus Eubacterium, which make up a significant portion of the core animal gut microbiome, are some of the recently discovered ‘generation’ of possibly helpful bacteria. In this article, we have focused on pathogenesis and therapeutic approaches towards T2DM, with a special reference to gut bacteria from ancient times to the present day.

ABSTRACTIn the context of most small businesses, innovativeness is critical for survival. However, small businesses often lack resources and are limited in their ability to influence external constraints. Consequently, they need to innovate in unique and often limited ways. While constraints-based innovativeness is discussed in emerging economies, we know little about how it occurs in advanced economies like Canada. This study uses a case study method in the craft brewery industry to examine different paths to constraints-based innovativeness through two capabilities, namely organizational agility and organizational improvisation capability. Results indicate an important but limited role for these capabilities for constraints-based innovativeness in the context of craft brewing, but also uncover different paths for development and evolution of innovativeness. This opens future research opportunities to study innovativeness, agility and organizational improvisation capability in small businesses facing resource constraints.

A sustainable society requires high-energy storage devices characterized by lightness, compactness, a long life and superior safety, surpassing current battery and supercapacitor technologies. Single-walled carbon nanotubes (SWCNTs), which typically exhibit great toughness, have emerged as promising candidates for innovative energy storage solutions. Here we produced SWCNT ropes wrapped in thermoplastic polyurethane elastomers, and demonstrated experimentally that a twisted rope composed of these SWCNTs possesses the remarkable ability to reversibly store nanomechanical energy. Notably, the gravimetric energy density of these twisted ropes reaches up to 2.1 MJ kg−1, exceeding the energy storage capacity of mechanical steel springs by over four orders of magnitude and surpassing advanced lithium-ion batteries by a factor of three. In contrast to chemical and electrochemical energy carriers, the nanomechanical energy stored in a twisted SWCNT rope is safe even in hostile environments. This energy does not deplete over time and is accessible at temperatures ranging from −60 to +100 °C.