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In this research, we conduct a computational investigation into the mixed convection flow of copper/water nanofluids (NFs) within a rectangular cavity, utilizing the Lattice Boltzmann Method (LBM). The cavity is uniquely configured with five high-temperature obstructions (HOBs), and we vary their dimensions and positions to evaluate Nusselt numbers (Nu) across a range of Richardson numbers (Ri). The three walls of the cavity, excluding the moveable top wall, are thermally insulated, while the latter is maintained at a lower temperature. A constant magnetic field (MCF) exerts influence within the cavity, with Ri spanning from 0.01 to 100, HOBs ranging from 0.1 to 0.5, and HOBs at the bottom wall spanning from 0.25 to 0.4. This numerical investigation is executed using a customized in-house code, focusing on examining heat transfer (HTR) dynamics within the cavity. Our findings reveal that augmenting the height of the HOBs and positioning them closer to the cold wall significantly enhances the average Nusselt number (Nuav). Conversely, an increase in Ri leads to a reduction in Nuav on the cold wall. Specifically, the most notable enhancement, with a 66.7 % increase in Nuav, occurs at Ri = 0.01 when HOBs are elevated from 0.1 to 0.5. On the other hand, an increment in Ri from 0.01 to 100 results in a 79.4 % reduction in Nuav. Furthermore, elevating the HOBs from 0.25 to 0.4 produces a substantial 44.3 % increase in Nuav.

Abstract Background: Post-transplant infections remain a leading cause of morbidity and mortality in solid organ transplant recipients (SOTRs) and local standardized antimicrobial treatment guidelines may contribute to improved clinical outcomes. Our study assessed the rate of therapeutic compliance with local standard guidelines in the treatment of common infections in SOTR, and their associated outcomes. Methods: Consecutive adult SOTRs admitted to the transplant floor from January–September 2020 and were treated for an infectious syndrome were followed until discharge or for 30 days following the date of diagnosis, whichever was shorter. Data was extracted from electronic medical records. Guideline compliance was characterized as either appropriate, effective but unnecessary, undertreatment, or inappropriate. Results: Nine hundred and thirty-six SOTR were admitted to the transplant ward, of which 328 patients (35%) received treatment for infectious syndromes. Guidelines were applicable to 252 patients, constituting 275 syndromes: 86 pneumonias; 82 urinary tract infections; 40 intra-abdominal infections; 38 bloodstream infections; and 29 C. difficile infections. 200/246 (81%) of infectious syndromes received appropriate or effective but unnecessary empiric treatment. In addition, appropriate tailoring of antimicrobials resulted in a significant difference in 30-day all-cause mortality (adjusted OR of 0.07, 95% CI 0.01–0.38; P = .002). Lastly, we found that guideline-compliant empiric therapy was found to prevent the development of multi-drug resistance in a time-dependent analysis (adjusted HR of 0.21, 95% CI 0.08–0.52; P = .001). Conclusion: Our data show that adherence to locally developed guidelines was associated with reduced mortality and resistant-organism development in our cohort of SOTR.

Solid organ transplant (SOT) recipients have a higher risk of developing invasive mould diseases (IMD). Isavuconazole is a novel broad-spectrum azole active against Aspergillus spp. and Mucor, well tolerated, with an excellent bioavailability and predictable pharmacokinetics, that penetrates in most tissues rapidly, and has few serious adverse effects, including hepatic toxicity. Contrary to other broad-spectrum azoles, such as voriconazole and posaconazole, isavuconazole appears to show significant smaller drug-drug interactions with anticalcineurin drugs. We have performed an extensive literature review of the experience with the use of isavuconazole in SOT, which included the SOTIS and the ISASOT studies, and published case reports. More than 140 SOT recipients treated with isavuconazole for IMD were included. Most patients were lung and kidney recipients treated for an Aspergillus infection. Isavuconazole was well tolerated (less than 10% of patients required treatment discontinuation). The clinical responses appeared comparable to that found in other high-risk patient populations. Drug-drug interactions with immunosuppressive agents were manageable after the reduction of tacrolimus and the adjustment of mTOR inhibitors at the beginning of treatment. In conclusion, isavuconazole appears to be a reasonable option for the treatment of IMD in SOT. More clinical studies are warranted.

Abstract The adaptive immune system and associated inflammation are vital in surveillance and host protection against internal and external threats, but can secondarily damage host tissues. The central nervous system is immune-privileged and largely protected from the circulating inflammatory pathways. However, T cell involvement and the disruption of the blood–brain barriers have been linked to several neurodegenerative diseases including Parkinson's disease, Alzheimer’s disease, and multiple sclerosis. Under normal physiological conditions, regulatory T cells (Treg cells) dampen the inflammatory response of effector T cells. In the pathological states of many neurodegenerative disorders, the ability of Treg cells to mitigate inflammation is reduced, and a pro-inflammatory environment persists. This perspective review provides current knowledge on the roles of T cell subsets (e.g., effector T cells, Treg cells) in neurodegenerative and ocular diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, and glaucoma. Many neurodegenerative and ocular diseases have been linked to immune dysregulation, but the cellular events and molecular mechanisms involved in such processes remain largely unknown. Moreover, the role of T cells in ocular pathologies remains poorly defined and limited literature is available in this area of research. Adoptive transfer of Treg cells appears to be a vital immunological approach to control ocular pathologies. Similarities in T cell dysfunction seen among non-ocular neurodegenerative diseases suggest that this area of research has a great potential to develop better therapeutic agents for ocular diseases and warrants further studies. Overall, this perspective review article provides significant information on the roles of T cells in numerous ocular and non-ocular neurodegenerative diseases.

Abstract The heterogeneity of clinical responses to antifungals in aspergillosis is partially understood. We hypothesized that besides direct antifungal effects, these discrepancies may be related to different immunomodulatory profiles. Human THP-1 monocytes were coincubated in vitro with Aspergillus fumigatus and variable concentrations of voriconazole (0.5, 1 and 2 mg/l), caspofungin (1 and 2 mg/l), amphotericin B deoxycholate (0.25, 0.5 and 1 mg/l) and liposomal amphotericin B (1, 2 and 3 mg/l). After 6 h of coincubation, total cellular RNA was extracted, converted into cDNA, and transcription of 84 genes involved in antifungal immunity was measured through RT-qPCR. The presence of A. fumigatus was the main driver of the global immune-related transcriptomic response. After Aspergillus infection, thirty genes were upregulated, while 19 genes were downregulated. Discrepancies across antifungals were also evident; voriconazole-containing conditions showed similar reaction to natural infection, while the use of liposomal Amphotericin B significantly decreased the inflammatory response. Chemokines (notably CCL20 and CXCL2) and pro-inflammatory cytokines (IL1A, IL1B, IL23, G-CSF) exhibited the most pronounced differences across antifungals. Pattern recognition receptors and adaptor protein transcription were minimally affected. Protein–protein-interaction network analysis showed that IL23A played a dominant role in upregulated genes. Pathway enrichment analysis indicated that cytokine-cytokine receptor integration, TNF signaling pathways and Toll-like receptor pathways were highly involved. This exploratory study confirms the heterogeneous immunomodulatory role of antifungals. Overall, voriconazole appears to maintain an early pro-inflammatory response seen in natural infection. Assessment of immunomodulatory response with clinical response may provide a better rationale for differences observed across antifungals.

In the data-driven world, data is created in huge volume and then analyzed by several organizations to get benefit from them. Smart city is one of the examples to use big data to offer improved services for its resident and tourist. However, some countries face certain obstacles to analyze the big data integration for sustainability in smart city development. Therefore, the purpose of this research paper is to identify and analyze the significant barriers related to sustainable smart city development. To accomplish this objective, fourteen barriers of big data analytics are selected through the combined approach of literature review and expert input. After that, these barriers are evaluated using the best worst method for obtaining deeper insights. The result of this study reveals that the most significant barrier is ‘lack of technologies for BDA’, ‘lack of BDA framework’, ‘nature of big data’, and ‘low availability of analytics platforms for big data’. These barriers need to address on priority to develop a sustainable smart city. This study is helpful to the urban planner, government, and consultancy agencies to decide on the adoption of BDA for sustainable smart city development. Further, they can also optimize their resources in the best possible manner to achieve the sustainable development of the existing smart cities.

Summary: Background: The pathogenesis of coronavirus disease 2019 (COVID-19) is characterized by enhanced platelet activation and diffuse hemostatic alterations, which may contribute to immunothrombosis/thromboinflammation and subsequent development of target-organ damage.Thrombopoietin (THPO), a growth factor essential to megakariocyte proliferation, is known to prime platelet activation and leukocyte-platelet interaction. In addition, THPO concentrations increase in several critical diseases, such as acute cardiac ischemia and sepsis, thus representing a potential diagnostic and prognostic biomarker. Furthermore, several data suggest that interleukin (IL)-6 is one of the most important inflammatory mediators involved in these phenomena, which led to explore the potential therapeutic role of IL-6 inhibitors.In this prospective cohort study, we aimed to study THPO and IL-6 concentrations in COVID-19 patients at the time of first clinical evaluation in the Emergency Department (ED), and to investigate their potential use as diagnostic and prognostic biomarkers. In addition, we sought to explore the role of THPO contained in plasma samples obtained from COVID-19 patients in priming in vitro platelet activation and leukocyte-platelet interaction. Methods: We enrolled 66 patients presenting to the ED with symptoms suggestive of COVID-19, including 47 with confirmed COVID-19 and 19 in whom COVID-19 was excluded (Non-COVID-19 patients). As controls, we also recruited 18 healthy subjects.In vitro, we reproduced the effects of increased circulating THPO on platelet function by adding plasma from COVID-19 patients or controls to platelet-rich plasma or whole blood obtained by healthy donors, and we indirectly studied the effect of THPO on platelet activation by blocking its biological activity. Findings: THPO levels were higher in COVID-19 patients than in both Non-COVID-19 patients and healthy subjects. Studying THPO as diagnostic marker for the diagnosis of COVID-19 by receiver-operating-characteristic (ROC) statistics, we found an area under the curve (AUC) of 0.73, with an optimal cut-off value of 42.60 pg/mL. IL-6 was higher in COVID-19 patients than in healthy subjects, but did not differ between COVID-19 and Non-COVID-19 patients.THPO concentrations measured at the time of diagnosis in the ED were also higher in COVID-19 patients subsequently developing a severe disease than in those with mild disease. Evaluating THPO as biomarker for severe COVID-19 using ROC analysis, we found an AUC of 0.71, with an optimal cut-off value of 57.11 pg/mL.IL-6 was also higher in severe than in mild COVID-19 patients, with an AUC for severe COVID-19 of 0.83 and an optimal cut-off value of 23 pg/ml.THPO concentrations correlated with those of IL-6 (r=0.2963; p=0.043), and decreased 24 h after the administration of tocilizumab, an IL-6 receptor blocking antibody, showing that the increase of THPO levels depends on IL-6-stimulated hepatic synthesis.In vitro, plasma obtained from COVID-19 patients, but not from healthy subjects, primed platelet aggregation and leukocyte-platelet binding, and these effects were reduced by inhibiting THPO activity. Interpretation: Increased THPO may be proposed as an early biomarker for the diagnosis of COVID-19 and for the identification of patients at risk of developing critical illness. Elevated THPO may contribute to enhance platelet activation and leukocyte-platelet interaction in COVID-19 patients, thus potentially participating in immunothrombosis/thromboinflammation. Funding: This work was supported by Ministero dell'Università e della Ricerca Scientifica e Tecnologica (MURST) ex 60% to GM and EL.

Background: Mother-to-baby transmission of group B Streptococcus (Streptococcus agalactiae) is the main cause of early-onset infection. Objectives: We investigated if intrapartum antibiotic prophylaxis directed by a rapid intrapartum test reduces maternal and neonatal antibiotic use, compared with usual care (i.e. risk factor-directed antibiotics), among women with risk factors for vertical group B Streptococcus transmission, and examined the accuracy and cost-effectiveness of the rapid test. Design: An unblinded cluster randomised controlled trial with a nested test accuracy study, an economic evaluation and a microbiology substudy. Setting: UK maternity units were randomised to either a strategy of rapid test or usual care. Participants: Vaginal and rectal swabs were taken from women with risk factors for vertical group B Streptococcus transmission in established term labour. The accuracy of the GeneXpert® Dx IV GBS rapid testing system (Cepheid, Maurens-Scopont, France) was compared with the standard of selective enrichment culture in diagnosing maternal group B Streptococcus colonisation. Main outcome measures: Primary outcomes were rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection and accuracy estimates of the rapid test. Secondary outcomes were maternal antibiotics for any indication, neonatal antibiotic exposure, maternal antibiotic duration, neonatal group B Streptococcus colonisation, maternal and neonatal antibiotic resistance, neonatal morbidity and mortality, and cost-effectiveness of the strategies. Results: Twenty-two maternity units were randomised and 20 were recruited. A total of 722 mothers (749 babies) participated in rapid test units and 906 mothers (951 babies) participated in usual-care units. There were no differences in the rates of intrapartum antibiotic prophylaxis for preventing early-onset group B Streptococcus infection in the rapid test units (41%, 297/716) compared with the usual-care units (36%, 328/906) (risk ratio 1.16, 95% confidence interval 0.83 to 1.64). There were no differences between the groups in intrapartum antibiotic administration for any indication (risk ratio 0.99, 95% confidence interval 0.81 to 1.21). Babies born in the rapid test units were 29% less likely to receive antibiotics (risk ratio 0.71, 95% confidence interval 0.54 to 0.95) than those born in usual-care units. The sensitivity and specificity of the rapid test were 86% (95% confidence interval 81% to 91%) and 89% (95% confidence interval 85% to 92%), respectively. In 14% of women (99/710), the rapid test was invalid or the machine failed to provide a result. In the economic analysis, the rapid test was shown to be both less effective and more costly and, therefore, dominated by usual care. Sensitivity analysis indicated potential lower costs for the rapid test strategy when neonatal costs were included. No serious adverse events were reported. Conclusions: The Group B Streptococcus 2 (GBS2) trial found no evidence that the rapid test reduces the rates of intrapartum antibiotic prophylaxis administered to prevent early-onset group B Streptococcus infection. The rapid test has the potential to reduce neonatal exposure to antibiotics, but economically is dominated by usual care. The accuracy of the test is within acceptable limits. Future work: The role of routine testing for prevention of neonatal infection requires evaluation in a randomised controlled trial. Trial registration: Current Controlled Trials ISRCTN74746075. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 12. See the NIHR Journals Library website for further project information.

We report the outcome of a 43 year old man who developed fatal ventriculoencephalitis due to cytomegalovirus (CMV) infection 7 months post allogeneic stem cell transplant. He failed multiple lines of treatment, including intravenous ganciclovir, foscarnet, and CMV-specific immunoglobulins, without improvement in CSF CMV copies. Novel intrathecal administration of CMV immunoglobulins was given but did not lead to clearance of CMV from CSF. No adverse effects related to intrathecal CMV immunoglobulins were observed. Notably, throughout this period, CMV in blood remained undetectable. This case highlights the difficulty in treating CMV encephalitis, and that novel therapeutic approaches are needed.

This paper presents the simulations of the cooling system of a battery pack (BTPC) consisting of lithium-ion (LIN) plate batteries. The BTPC includes six battery cells (BTCL) in two rows with three BTCLs, which are placed in a channel with one inlet and two outlets. The laminar and steady airflow flows in the channel. Phase-change material (PCM)-filled rectangular cubic enclosures enclose every BTCL. Transiently adjusting the cavity aspect ratio (AR) every 6000 s is how this investigation is conducted. For four values of AR, the values of the PCM volume percentage surrounding each BTCL in the BTPC, and the temperature of each BTCL are calculated. The simulations are performed using the FEM and COMSOL software. The results demonstrate that the maximum changes in temperature of the battery (TOB) pack by changing the AR occur when the TOB pack is reduced. The maximum temperature reduction at this time is 1.88 °C which occurs between AR2 and AR4 at 720 s. The maximum temperature corresponds to AR3 and AR4 and the minimum one is related to AR1 and AR2. From 1260 to 3500 s, the effect of AR on PCM volume fraction is maximal. The value of solid PCM for AR1 and AR2 is higher than that for AR3 and AR4 at different times. Additionally, an increment in the value of the AR enhances the amount of channel pressure drop by 14%.

In the present work, twelve machine learning (ML) models are developed for assessment of monthly average diffuse solar radiation (DSR) with solitary input forecaster as clearness index. Two categories of ML models were demarcated (i.e. diffusion coefficient and diffuse fraction) with six models for each group. The correctness of models was examined as a function of some frequently used statistical pointers. A comparision was also done between developed ML models and some well-recognised models available from previous works. The results show that ML models perform very well in comparision to models available in the literature. The top-performing models in category 1 are the k-nearest neighbours (KNN) model for both training and testing data. In category 2, for training data random forest (RF) model perform well while for testing data support vector regression (SVR) models perform well. The performance can be slightly improved by using two or more input parameters such as temperature difference, relative humidity and relative sunshine along with clearness index as input. Thus, ML models can be used to estimate DSR in the humid-subtropical climate of India.

Heat transfer enhancement caught the attention of researchers owing to the need for compact size heat exchangers. This is because of the development of micro-devices due to advancements in electronics. The heat transfer through natural convection in vertical annular geometry has many benefits and, if designed efficiently, will result in energy saving due to no/less moving parts. This paper reports the review of techniques used by researchers for heat transfer enhancement during natural convection flow in vertical annular geometry. Several techniques that have a significant impact on the design and performance are discussed here in detail viz. use of nanofluids, use of the magnetic field, use of cylinder wall rotation, use of discrete wall heating, use of porous material, use of boiling, use of rings, etc. The implementation of each technique along with its advantages and drawbacks are also discussed. The authors also suggested their recommendation of techniques to be used for heat transfer enhancement. The study highlights research gaps and weak points that have not received the researchers' attention so far. This article outlines areas that needed the most attention in the future.

For the various climatic zones of India, machine learning (ML) models are created in the current work to forecast monthly-average diffuse solar radiation (DSR). The long-term solar radiation data are taken from Indian Meteorological Department (IMD), Pune, provided for 21 cities that span all of India’s climatic zones. The diffusion coefficient and diffuse fraction are the two groups of ML models with dual input parameters (sunshine ratio and clearness index) that are built and compared (each category has seven models). To create ML models, two well-known ML techniques, random forest (RF) and k-nearest neighbours (KNN), are used. The proposed ML models are compared with well-known models that are found in the literature. The ML models are ranked according to their overall and within predictive power using the Global Performance Indicator (GPI). It is discovered that KNN models generally outperform RF models. The results reveal that in diffusion coefficient models perform well than diffuse fraction models. Moreover, functional form 2 is the best followed by form 6. The ML models created here can be effectively used to accurately forecast DSR in various climates.

The main challenge of the health risk assessment of the aerosol transport and deposition to the lower airways is the high computational cost. A standard large-scale airway model needs a week to a month of computational time in a high-performance computing system. Therefore, developing an innovative tool that accurately predicts transport behaviour and reduces computational time is essential. This study aims to develop a novel and innovative machine learning (ML) model to predict particle deposition to the lower airways. The first-ever study uses ML techniques to explore the pulmonary aerosol TD in a digital 17-generation airway model. The ML model uses the computational data for a 17-generation airway model and four standard ML regression models are used to save the computational cost. Random forest (RF), k-nearest neighbour (k-NN), multi-layer perceptron (MLP) and Gaussian process regression (GPR) techniques are used to develop the ML models. The MLP regression model displays more accurate estimates than other ML models. Finally, a prediction model is developed, and the results are significantly closer to the measured values. The prediction model predicts the deposition efficiency (DE) for different particle sizes and flow rates. A comprehensive lobe-specific DE is also predicted for various flow rates. This first-ever aerosol transport prediction model can accurately predict the DE in different regions of the airways in a couple of minutes. This innovative approach and accurate prediction will improve the literature and knowledge of the field.

Pneumocystis jirovecii is an important etiological agent of pneumonia that is underdiagnosed due to the inability to culture the organism. The 2019 PERCH study identified Pneumocystis as the top fungal cause of pneumonia in HIV-negative children using a PCR cutoff of 104 copies of Pneumocystis per mL of sample in nasopharyngeal/oropharyngeal (NP/OP) specimens. Given that Pneumocystis consists of an environmental ascus form and a trophic from (the latter is the form that attaches to the lung epithelium), it is possible that life-form-specific molecular assays may be useful for diagnosis. However, to accomplish this goal, these assays require genotypic information, as the current fungal genomic data are largely from the US and Europe. To genotype Pneumocystis across the globe, we developed an NGS-based genotyping assay focused on genes expressed in asci as well as trophs using PERCH throat swabs from Africa, Bangladesh, and Thailand, as well as North American samples. The NGS panel reliably detected 21 fungal targets in these samples and revealed unique genotypes in genes expressed in trophs, including Meu10, an ascospore assembly gene; two in mitochondrial gene ATP8, and the intergenic region between COX1 and ATP8. This assay can be used for enhanced Pneumocystis epidemiology to study outbreaks but also permits more accurate RT-CPR- or CRISPR-based assays to be performed to improve the non-bronchoscopic diagnosis of this under-reported fungal pathogen.

The substantial disruption caused by the COVID-19 epidemic to the world's education system is only one of the many setbacks the world has recently experienced. The transition of the students from their offline learning mode to a fully digital approach was not easy from the beginning for them. The online teaching readiness heavily relied on their competencies and skills to adapt the pedagogy, training, technical skills, a proper mindset and new roles. This research endeavors to evaluate the readiness of the teachers belonging to higher education institutions (HEIs) to handle online education based on the online teaching readiness model. A systematic questionnaire with 30 statements was used by the researcher to collect and analyse data from 296 HEI lecturers in Saudi Arabia. Smart PLS3 was used to attain reliability, convergent, discriminate validity and model fitness. These programs will help equip the teachers with the necessary technical skills, pedagogy, competency and readiness to comprehend the requisite techniques of online teaching and the vital strategies for keeping their students engaged. Technical proficiency, pedagogy, competency and teaching readiness show a direct relationship with online education. On the other hand, attitude and training do not show any relationship with online education.