The orbitofrontal cortex (OFC) is a key node in the cortico-limbic-striatal circuitry that influences decision-making guided by the relative value of outcomes. Midbrain dopamine from either the ventral tegmental area (VTA) or the dorsal raphe nucleus (DRN) has the potential to modulate OFC neurons, however it is unknown at what concentrations these terminals release dopamine. Male and female adult DATIRES-CRE-tdTomato mice were injected with AAV2/8-EF1a-DIO-eYFP into either the DRN or VTA or the retrograde label CTB 488 in the medial or lateral OFC. We quantified co-expression of CTB 488 or eYFP with tdTomato fluorescence in VTA or DRN as well as eYFP fiber density in the medial or lateral OFC. Both VTA and DRN dopamine neurons project to either the medial or lateral OFC, with greater expression of fibers in the medial OFC. Using fast-scan cyclic voltammetry, we detected optogenetically evoked dopamine from channelrhodopsin2 (ChR2)-expressing VTA or DRN dopamine terminals in either the medial or lateral OFC. Consistent with increased fiber expression in the medial OFC, dopamine was more reliably detected in this region from optical stimulation of VTA or DRN dopamine terminals. We assessed if optical stimulation of dopamine from the VTA or DRN onto the medial OFC could alter layer V pyramidal neuronal firing; however, we did not observe a change in firing at stimulation parameters which evoked dopamine release from either projection. In summary, dopaminergic neurons from the VTA or DRN project to the OFC and release submicromolar dopamine in the medial and lateral OFC.

Parkinson’s disease is a neurodegenerative disorder characterized by the progressive dysfunction and loss of dopamine (DA) neurons of the substantia nigra pars compacta (SNc). Several pathways of programmed cell death are likely to play a role in DA neuron death, such as apoptosis, necrosis, pyroptosis, ferroptosis as well as cell death associated with proteasomal and mitochondrial dysfunction. A better understanding of the molecular mechanisms underlying DA neuron death could inform the design of drugs that promote neuron survival. Necroptosis is a recently characterized regulated cell death mechanism that exhibits morphological features common to both apoptosis and necrosis. It requires activation of an intracellular pathway involving receptor-interacting protein 1 (RIP1) and its kinase (RIP1 kinase, RIPK1), receptor-interacting protein 3 (RIP3) and its kinase (RIP3 kinase, RIPK3), and mixed lineage kinase domain like pseudokinase (MLKL). The potential involvement of this programmed cell death pathway in the pathogenesis of PD has been studied by analyzing the biomarkers for necroptosis, such as the levels and oligomerization of pRIPK3 and pMLKL, in several PD preclinical models and in PD human tissue. While there is evidence that other types of cell death also have a role in DA neuron death, most studies support the hypothesis that this cell death mechanism is activated in PD tissues. Thus drugs that prevent or reduce necroptosis may provide neuroprotection for PD. In this review, we summarize the findings from these studies. We also discuss how manipulating necroptosis might open a novel therapeutic approach to reduce neuronal degeneration in PD.

Autism was previously seen as involving impairment in social communication, theory of mind, and ability to read social cues. Recently, more neurodiversity-affirming frameworks have been introduced that characterize barriers to communication and lack of social understanding between autistics and their neurotypical peers as being a two-way street: the double-empathy problem. Misunderstandings do not exist purely due to a deficit in autistic communication, but due to two different communication styles that are not interpreted by each other as easily. While this has proved an interesting area of research, attempts to mechanistically model this are lacking, despite the wealth of game theory examples that already exist to model cooperation, competition, and coordination between agents with interdependent strategies. This paper models real-world examples of social situations using Lewis signaling games. Within each pairing, pooling by the sender of different states into the same signals and pooling by the receiver of different signals into the same action represent the type of indirect communication, and responsiveness to indirectness, that are often employed by neurotypical people. In contrast, separating strategies, in which each state is assigned its own distinct signal and each signal triggers its own specific response, represent more direct, specific, and straightforward communication. This work is not meant to make direct conclusions about autistic-neurotypical or autistic-autistic communication, as actual human interactions are far too complex to be governed by the simple strategies outlined in the paper, but rather to serve as an example of the basic principles that could govern or influence such interactions.

Continued advancements in environmental DNA (eDNA) research have made it possible to access intraspecific variation from eDNA samples, opening new opportunities to expand non-invasive genetic studies of wild animal populations. However, the use of eDNA samples for individual genotyping, as typically performed in non-invasive genetics, still remained unachieved. We present the first successful individual genotyping of eDNA obtained from snow tracks of three large carnivores: brown bear (Ursus arctos), European lynx (Lynx lynx) and wolf (Canis lupus). DNA was extracted using a protocol for isolating water eDNA and genotyped using amplicon sequencing of short tandem repeats (STR) and, for brown bear, a sex marker, on a high-throughput sequencing platform. Individual genotypes were obtained for all species, but genotyping performance differed among samples and species. Multilocus genotyping success for individual identification was higher for brown bear samples (6 over 7), than for wolf (7 over 10) and lynx (4 over 9) samples. The sex marker was genotyped in 5 out of 7 brown bear samples. Results for three species show that reliable individual genotyping, including sex identification, is now possible from eDNA in snow tracks, underlining its vast potential to complement the non-invasive genetic methods used for wildlife. To fully leverage the application of snow track eDNA, improved understanding of the ideal species- and site-specific sampling conditions, as well as laboratory methods promoting genotyping success are needed. This will also inform efforts to retrieve and type nuclear DNA from other eDNA samples, thereby advancing eDNA–based individual and population level studies.

Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death, using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65–79 and ≥80-years in six European countries. Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome (hospitalisation and death), VE was estimated monthly over eight-week follow-up periods, allowing one month-lag for data consolidation. Cox proportional-hazards regression models were used to estimate adjusted hazard ratios (aHR) and VE=(1 – aHR) x100. Site-specific estimates were pooled using random-effects meta-analysis. Results: For ≥80-years, VE against COVID-19 hospitalisation decreased from 66.9% (95%CI: 60.1; 72.6) to 36.1% (95%CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95%CI: 88.0; 98.4) to 67.7% (95%CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79-years. The second booster VE against hospitalisation ranged between 82.0% (95%CI: 75.9; 87.0) and 83.9% (95%CI: 77.7; 88.4) for the ≥80-years and between 39.3% (95%CI: -3.9; 64.5) and 80.6% (95%CI: 67.2; 88.5) for 65-79-years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80-years. Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multi-country data from EHR facilitate robust near-real-time monitoring of VE in the EU/EEA and supports public health decision-making.

Abstract Introduction Somalia faced significant COVID-19 exposure due to limited lab capacity for pathogen detection. The country’s healthcare system is strained by poverty, conflict, malnutrition, and outbreaks. Urgent action was required to enhance COVID-19 detection, save lives, and support nationwide vaccination and healthcare efforts. Methods With WHO and other partners, the Ministry of Health formed the COVID-19 incident management committee to address infections. Testing was initiated at the National Public Health Laboratory, and through training and investment, expanded to 11 additional sites. Genomic surveillance was established to monitor circulating genotypes. A comprehensive data management system was implemented to track infections from patient to reporting, ensuring effective monitoring and response. Results The enhanced laboratory capacity identified 26,439 confirmed SARS-CoV-2 cases, resulting in 1,361 deaths and a case fatality rate (CFR) of 5.15%. A total of 344,002 suspected samples were tested within the country. Genomic surveillance was initiated in March, 2022, and the first results were reported in Agoust, 2022. The e-SPAR tool assessment demonstrated a significant improvement in laboratory capacity, rising from 27% in 2018 to 56% in 2021, marking an overall improvement of 210%. Discussion Somalia has made notable strides in enhancing and expanding in-country molecular diagnostic capacity, enabling swift COVID-19 diagnosis. This capacity is being expanded to encompass other pathogens as part of an integrated disease surveillance program. The objective is to enhance response capabilities to emerging pathogen outbreaks. The implementation of a data management system has improved data monitoring and evaluation, serving as a crucial foundation for Labs

Objective: To establish a prediction Nomogram based on prognostic factors for children with hemophagocytic lymphohistiocytosis (HLH). Methods: A retrospective analysis of pediatric HLH cases diagnosed at the Affiliated Hospital of Zunyi Medical University between January 2012 and December 2022 was conducted. Cox regression analysis was used to identify prognostic factors for pediatric HLH patients. The C-index, ROC curve, and AUC were used to evaluate the discrimination of the model. The DCA was used to evaluate the clinical application value of the model. Results: A total of 133 cases of secondary pediatric HLH patients were included in this study, with 45 deaths and 88 survivors. Univariate analysis showed that age ≤ 2 years, PLT ≤ 50×10 9/L, HB ≤90 g/L, AST ≥ 200 U/L, CK-MB ≥ 50 U/L, LDH ≥ 1000 U/L, SF ≥1500 μg/L, PT ≥ 20 s, APTT ≥ 40 s, hypoalbuminemia, hypofibrinogenemia, mechanical ventilation, splenomegaly, ARDS, respiratory failure,CNSL, shock, DIC, pulmonary hemorrhage, and gastrointestinal bleeding are risk factors for the survival of those secondary pediatric HLH patients ( P <0.05), while blood purification therapy may be a protective factor for HLH prognosis ( P = 0.049). Multivariable Cox showed that CNSL (HR = 3.18, 95%CI = 1.72-5.89), PLT ≤ 50×10^9/L (HR = 2.16, 95%CI = 1.11-4.19), hypoalbuminemia (HR=2.65, 95%CI=1.14-5.17), and hypofibrinogenemia (HR = 2.48, 95%CI = 1.19-5.14) were independent risk factors for the outcome of children with HLH, while the use of blood purification therapy (HR = 0.32, 95%CI = 0.16-0.64) was an independent protective factor. A Nomogram prediction model was constructed using R software, and the ROC curve , C-index, and calibration curve showed good discrimination and fit of the model. The DCA curve showed that the model had good clinical applicability. Finally, based on the Nomogram score and HR value, the subjects were divided into three groups, and it was found that the mortality rate in the high-risk group was significantly higher than that in the low-risk group. Conclusion: The development of a Nomogram to predict the prognosis of secondary pediatric HLH patients has good discrimination and accuracy and may have good clinical application value.

Despite of the many progresses with alignment algorithms, aligning divergent protein sequences including those sharing less than 20-35% pairwise identity (so called “twilight zone”) remains a difficult problem. Many alignment algorithms have been using substitution matrices since their creation in the 1970’s to generate alignments. These matrices however do not work well within the twilight zone. We developed PEbA for Protein Embedding based Alignments. Similar to the traditional Smith-Waterman algorithm, PEbA uses a dynamic programming algorithm but the matching score of amino acids is based on their embeddings from a protein language model. We tested PEbA on benchmark alignments and the results showed that PEbA greatly outperformed BLOSUM substitution matrix-based pairwise alignments, achieving different levels of improvements of the alignment quality for pairs of sequences with different levels of similarity (over five times as well for pairs of sequences with <10% identity). We compared PEbA with embeddings generated by different protein language models (ProtT5 and ESM-2) and found that ProtT5-XL-U50 produced the most useful embeddings for aligning protein sequences. PEbA even outperformed DEDAL, a recently developed deep learning model that was created specifically for aligning protein sequences, particularly on longer alignments and sequences with low pairwise identity. Our results suggested that general purpose protein language models provide useful contextual information for accurate protein alignments.

Toll-like receptors (TLRs) are major players of the innate immune system – recognizing pathogens and differentiating self/non-self components of immunity. These proteins are present either on the plasma membrane or endosome and recognise pathogens at their extracellular domains. They are also characterised by a single transmembrane helix and an intracellular TIR domain. Few TIRs directly invoke downstream signalling, while others require other TIR domains of adaptors like TRAM and TRIF. On recognizing pathogenic lipopolysaccharides (LPS), TLR4 dimerises and interacts with the intracellular TRAM dimer through the TIR domain to further recruit TRIF molecules. We have performed an in-depth study of the effect of two mutations, P116H and C117H, at the dimeric region of the adaptor TRAM, which are known to abrogate downstream signalling. We modelled the structure and performed molecular dynamics studies to infer the structural changes occurring across the trajectory due to the point mutations in order to decipher the structural basis of this dramatic effect. We observed that these mutations led to increased RoG (Radius of Gyration) of the complex and resulted in several changes to the interaction energy values when compared against the wild type and few positive control mutants. We identified highly interacting residues as hubs and few such hubs that were lost in the mutant dimers. Further, changes in the protein residue path, hampering the information flow between the crucial AEDD and TS sites, happen for the mutants. Overall, we show that such residue changes can have subtle but long-distance effects, impacting the signaling path allosterically.

Atrial fibrillation (AF) is the most common arrhythmia. It is associated with increased stroke risks, thromboembolism, and other complications, which are great life and economic burdens for patients. In recent years, with the maturity of percutaneous catheter radiofrequency ablation (RFA) technology, it has become a first-line therapy for AF. However, some patients still experience AF recurrence (AFR) after RFA, which can cause serious consequences. Therefore, it is crucial to identify appropriate parameters that can predict the prognosis. Here, we reviewed possible predicting indicators for AFR, focusing on all the electrocardiogram indicators, such as P wave duration, PR interval and so on. It may provide valuable information for guiding clinical works.

Background and Aims: The relationship between SARS-CoV-2 infection and ICD shock remains unclear. We analyzed the characteristics of patients received shocks after SARS-CoV-2 infection to explore causes of these shocks to provide information for subsequent treatment. Methods: We retrospectively analyzed data from seven patients who hospitalized the First People’s Hospital of Yunnan Province between December 2022 and January 2023 after experiencing ICD shock or ventricular arrhythmias following SARS-CoV-2 infection. We collected baseline information i.e., age and sex, device type, arrhythmia type, comorbidities, etc to analyze the causes of electrical shocks. Results: All patients’ devices were implanted in our hospital. The patients’ mean age was 67±10 years. Four underwent implantation for primary prevention, and three for secondary prevention. These patients received 80 ICD shocks after SARS-CoV-2 infection, 71 (88.75%) nine (11.25%) of which were treatment for ventricular tachycardia and atrial fibrillation, respectively. There were 54 antitachycardia pacing(ATP) treatments, which forty-eight arrhythmic events were terminated through antitachycardia pacing and six not. Laboratory tests conducted upon admission revealed that six patients had blood potassium levels below 4.0 mmol/L. Five patients had blood calcium levels below 2.11 mmol/L. Four of seven patients had elevated troponin concentrations (0.030–0.297 ng/mL). All patients had significantly elevated N-terminal pro-B-type natriuretic peptide levels (608.8–25,758 pg/mL). Six patients had a QT interval of > 440 ms and a mean QT interval of 460±46 ms. Conclusion: SARS-CoV-2 infection may be associated with ICD shock. Clinicians should pay close attention to patients with implanted devices after SARS-CoV-2 infection and actively eliminate arrhythmogenic triggers to minimize the likelihood of ICD shock.

A 32-year-old female patient presented with palpitations and chest discomfort. The patient had a history of pericardiotomy due to pericardial effusion. Multimodal imaging, including echocardiography, cardiac magnetic resonance (CMR), and coronary computed tomography angiography (CCTA) were used showing a pericardial cyst as the cause of the symptoms. Furthermore its location and potential complications were accurately defined. The patient underwent successful surgical resection of the cyst, and histopathological analysis confirmed a bronchogenic cyst, a very rare congenital malformation. The article discusses the rarity of bronchogenic cysts in the pericardium and the importance of accurate diagnosis and appropriate treatment.

As detection technology continually advances, the survivability of targets on the battlefield is significantly challenged. Therefore, microwave absorbers with stealth capabilities have become a focal point of research in modern military science. To address the issues of narrow bandwidth and complex structures in existing absorbers, we propose a model for an ultra-wideband absorber based on a hybrid structure. In this study, we design, manufacture, and characterize a polarization-insensitive ultra-wideband absorber (PIUWA), which demonstrates impressive absorptivity of over 90% across a range of 4-24.53GHz (a fractional bandwidth of 144%). This is achieved by inducing multiple resonance peaks within the hybrid structure. Moreover, the subwavelength periodicity of the PIUWA theoretically contributes to its angular stability under full-wave polarizations. We observed that absorption performance remains stable under incident conditions within 45 degrees. Furthermore, the operational mechanism of the PIUWA is elucidated through an equivalent circuit model, with design validity confirmed via experimental measurements. This study paves the way for the design and fabrication of ultra-wideband microwave absorbers that offer high absorptivity, robust angular stability, and simpler assembly processes, thereby broadening the potential for application in other absorber types.

In Mexico, the BA.4 and BA.5 Omicron variants dominated the fifth epidemic wave (summer 2022), superseding BA.2, which had circulated during the inter-wave period. The present study uses genome sequencing and statistical and phylogenetic analyses to examine these variants’ prevalence, distribution, and genetic diversity in Mexico from April to August 2022. Over 35% of the sequenced genomes in this period corresponded to the BA.2 variant, 8% to the BA.4, and 56% to the BA.5 variant. Multiple subvariants were identified, but only BA.2.9, BA.2.12.1, BA.5.1, BA.5.2, BA.5.2.1, and BA.4.1 circulated throughout the fifth wave across the entire country, not forming geographical clusters. Contrastingly, other subvariants exhibited a geographically restricted distribution, most notably in the Southeast region, which showed a distinct subvariant dynamic. This study supports previous results showing that this region may be a major entry point and may have contributed to the introduction and evolution of novel variants in Mexico. Furthermore, a differential distribution was observed for certain subvariants among specific States throughout time, which may have contributed to the overall increased diversity observed during this wave compared to the previous one. This study highlights the importance of sustaining genomic surveillance to identify novel variants that may impact public health.

Continued Immunotherapy of Patient with Lung Cancer with COVID-19 InfectionJiadi Gan1, Jiaxuan Wu1, Huohuo Zhang1, Weimin Li#1 Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Center of Precision Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, ChinaFinancial/nonfinancial disclosures: None declared.FUNDING/SUPPORT: This work was supported by the Clinical Research Incubation Project of West China Hospital of Sichuan University (2018HXFH012), the National Natural Science Foundation of China (82200078)Address for correspondence: Weimin Li, MD, PhD, Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Center of Precision Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. E-mail:weimi003@scu.edu.cn.To the Editor :The COVID-19 pandemic has infected over 763.7 million people globally, causing over 6.9 million deaths (https://covid19.who.int/; accessed 15 April 2023). Omicron has received much attention for just 2 weeks after its appearance on November 11th, 2021 for its rapidly spreaded variants infectivity. The emerging of new variants of SARS-CoV-2 become the predominant strains during the pandemic. Similar with comorbidities such as diabetes and cardiovascular disease1, patients with cancer seems to be highly risk of acute respiratory syndrome coronavirus 2 (SARS-CoV-2)2.A major consideration in the delivery of cancer care is to balance the duration of delaying the cancer-directed therapy. SARS-CoV-2 can mediated immune system activation by triggerring cytokine release3, which may lead to a great potential for treating SARS-CoV-2 infections by targeting immune related receptors. To mild to moderate COVID-19 or asymptomatic positive SARS-CoV-2 patients, the NCCN Guidelines recommend considerring holding immune checkpoint inhibitors therapy for at least 10 days and until improvement of symptoms (https://www.nccn.org). Whether checkpoint inhibitor treatment lead to a better or worse outcome maintain controversial. Here, we report the management of three lung cancer patients during Omicron period through a multidisciplinary perspective on the basis of clinical experience and the available data in the literature, the general characteristic of patients were showed in Table 1 .The first case is a 65-year-old male, 30 years of smoking history, with a 1.8cm*1.3cm right lower lobe node, with liver and multiple bone metastases. Liver lesion puncture biopsy prompt neuroendocrine tumor. Next generation sequencing (NGS) detection indicated no oncogenic mutations. The patient had symptoms of fatigue and fever and performed rapid test of nasopharyngeal swab for respiratory SARS-CoV-2 viruse, which prompt strongly positive. He commenced with slurryMab combined with etoposide and carboplatin as first-line therapy. A computed tomography (CT) scan of the chest revealed lesion reduction after 3 months, with disease assessment of partial response (PR) (Figure 1B ). The second case was a 63-year-old Chinese male ex-smoker presented with a pulmonary mass in the right lobe lung apex mass discovered on chest enhanced-CT scan, with bilateral lung and bone metastasis. Histologic examination of the biopsy samples at lung mass led to the diagnosis of advanced lung squamous carcinoma. COVID-19 nucleic acid test prompt positive. He signed informed consent and was treated with was treated with Pembrolizumab+Vibostolimab. CT scan after 2 month showed obvious shrinkage in lung mass, contributing to PR (Figure 1B ). The patient reported feeling better after and no side effects occurred. The third was a 70-year-old male never-smoker referred to a local hospital for repetitive cough in June 2022. Chest-CT scan revealed a pulmonary mass in the left upper lobe and left pleural thickening. Cerebral magnetic resonance image demonstrated no brain metastasis and bone imag revealed multiple bone metastases. Biopsy on lung tissue demonstrated squamous carcinoma and subsequent targeted NGS detected no oncogenic mutations. Then the patient started duvalizumab combined with albumin paclitaxel and carboplatin as first-line therapy for four circles and single-agent duvalizumab maintenance for two cycles. Nasal swab was positive for COVID-19 in January 12th, 2023. He received nirmatrelvir plus ritonavirand for strongly positive of COVID-19 nucleic acid test with low Ct value. The clinical cough symptom of patients improved two days later and he continued receiving duvalizumab maintenance treatment. Stable lung lesions were shown through CT scan after 1 months and no novel added COVID-19 symptoms presented (Figure 1B ). Above patients manifest no viral symptom after active treatment with checkpoint inhibitor and continue to receive anti-tumor treatment (Figure 1A ).The cancer patients receiving antitumour treatments should be strictly screened for COVID-19 infection during epidemic period and avoid treatments causing immunosuppression or decrease the dosages of medication. These cases emphasized immunotherapy has no detrimental effect on the outcome of mild to moderate patients with COVID-19.

Internet-of-Things (IoT) networks are characterized by low-powered nodes with limited computational power and storage capacity. Consequently, protocols dedicated to Low Power and Lossy networks (LLNs) are designed to support communication in such resource-constrained nodes. One such protocol is Routing Protocol for Low-Power and lossy networks (RPL) which builds and maintains routes in RPL-based networks, leading to optimized routing and lower network overhead. However, the RPL-based protocol has several internal and external vulnerabilities that must be explored and addressed. Therefore, the present study illustrates the impact of several RPL-based attacks, including DIS attack, version number attack, decreased rank attack, and WPS attack, by employing the Contiki Cooja network simulator with specific simulation scenarios. In addition, we conduct a comparative analysis of the RPL-based attacks and find that the WPS attack results in the highest packet loss rate of 26%, whereas the DIS attack, version number attack, and rank attack result in packet loss rates of 17%, 15%, and 13%, respectively.

The tubular furnace is one of the main production equipment in petrochemical industry, the main functions of which is to heat the liquid oil in multiple branch tubes in the furnace to the target temperature. Since the temperature of each branch furnace tube is affected by the feed composition, the distribution position of the furnace tube and the uneven distribution of the furnace temperature, these factors may result in the deviation of the oil outlet temperature of each branch, and the serious temperature deviation may lead to the coking of the furnace tube and even cause accidents. In order to overcome the problem of unbalanced outlet temperature of each branch tube in the tubular furnace, this paper proposes a temperature control method GSA-MPIDNN, which is based on genetic simulated annealing (GSA) algorithm to optimize multi-input multi-output proportion-integration-differentiation neural network(MPIDNN). The GSA algorithm is used to find out the optimal initial weights of the MPIDNN, to overcome the deficiency of the algorithm by manually setting the initial weights, and to improve the control performance of the MPIDNN controller on the outlet temperature of the tubular furnace. The Matlab software is used to build the mathematical model of GSA-MPIDNN controller and tubular furnace, and the results are compared and analyzed with the traditional methods such as MPIDNN, PID and fuzzy PID, etc. The results show that the convergence time and error of GSA-MPIDNN are better than the traditional methods, which verifies the effectiveness of the method.

The Fuzzy logic offers an intelligent bound for information illustration and analysis to handle quality, uncertainty, and ambiguity. Fuzzy logic is applied to combine human knowledgeable information and discrete computing. As per our study, explicit mathematical model has not been developed in the existing research work to explain the behavior of advanced system. A novel mathematical model for defining the behavior of such system has been introduced in the paper. Different techniques to calculate distance between two Intuitionistic Fuzzy Sets (IFSs) have been analyzed in the proposed model. In the proposed model a novel distance calculation technique has been introduced. The proposed technique of distance calculation can be used in medical diagnostic for decision making. Further, to analyze the outcomes of the proposed model, different possible outcomes of diagnosis with the existing techniques have been compared. By comparing the results of proposed technique with the existing techniques, 65% improvements in the decision of medical diagnosis can be achieved.

Accurate estimation of percolation is crucial for assessing landfill final cover effectiveness, designing leachate collection/treatment systems, and many other applications, such as in agriculture. Despite the importance, percolation is seldom measured due to the high cost and maintenance of lysimeters, underlining the need for skillful simulation. Process-based numerical models, despite requiring validation and numerous parameters, present an alternative for percolation simulation, though few studies have assessed their performance. This study compares percolation measured from three fully instrumented large-scale experimental plots to simulated percolation using a new version of the Soil Vegetation and Snow (SVS) land-surface model with an active soil-freezing module. Previous research indicates numerical model performance may significantly vary based on soil-related parameter values. To account for input data and parameter uncertainty, we use an ensemble simulation strategy incorporating random perturbations. The results suggest that SVS can accurately capture the seasonal patterns of percolation, including significant events during snowmelts in spring and fall, with little to no percolation in winter and summer. The continuous ranked probability skill score values for the three plots are 0.13, -0.13, and 0.33. SVS simulates near-surface soil temperature dynamics effectively (R 2 values 0.97-0.98) but underestimates temperature and has limitations in simulating soil temperature in snow-free situations in the cold season. It also overestimates soil freezing duration, revealing discrepancies in the onset and end of freezing periods compared to observed data. This study highlights the potential of land surface models for the simulation of percolation, with potential applications in the design of systems such as leachate collection and treatment. While the SVS model already provides an interesting outlook, further research is needed to address its limitations in simulating soil temperature dynamics during soil freezing periods.

Abstract Introduction One of the most often used OTC antipyretic and analgesic is paracetamol or acetaminophen. Though widely used, the mechanism by which it reduces fever and pain remains unknown. Although paracetamol is available in a variety of formulations, there are no set guidelines for the various formulations of paracetamol alone or in combination. Materials and Methods In Department of Pharmacology at Government Doon Medical College, the study was planned as an observational cross-sectional study. Data regarding different paracetamol dosages and dosages of paracetamol in fixed dose combinations (FDCs) with various ingredients were gathered and evaluated from the editions of Drug Today, Current Index Of Medical Specialties (CIMS), Monthly Index Of Medical Specialties (MIMS), and India 2021/2022. Results Analysing Drug Today, CIMS and MIMS, it was found, 810 formulations of paracetamol tablets are available in the Indian market, of which, 77 formulations contain only paracetamol, rest being fixed dose combinations (FDCs). Among all the available FDCs with paracetamol having 2or 3 drug formulation, among the 2 constituent FDCs group containing paracetamol, 47% drugs have paracetamol in 325 mg or less dose, whereas, 53% drugs are in clear violation of the notice by CDSCO, by containing more than 325 mg paracetamol. Conclusion In spite of widespread use there is ambiguity in paracetamol doses, as well as absence of data for few constituents in the FDCs. Thus, further research into paracetamol dosing, as well as strict regulation is the need of the hour for one of the most widely used drug.

A document by Zisong Mo. Click on the document to view its contents.

Objective: to identify lung ultrasound (LUS) findings associated to acute chest syndrome (ACS) and establish a LUS risk score for the development of ACS in children with sickle cell disease (SCD). Methods: a prospective observational study including children with SCD and signs and/or symptoms of lower airway infection were evaluated by LUS and chest radiography (CXR) at admission and 48 hours later (follow-up) and observed regarding the development of ACS during hospitalization. Results: 110 children were evaluated, of whom 66 (60%) developed ACS. At admission, LUS score greater than one showed sensitivity, specificity, and accuracy of 77.3%, 84.1% and 80.0% versus 53.0%, 100% and 71.8% on CXR. ACS diagnosis was unlikely for a LUS score of zero, likely for a score of one or two and very likely for a score greater than two. Regarding follow-up exams, LUS score greater than one showed sensitivity, specificity, and accuracy of 98.5%, 72.0% and 91.2% versus 90.2%, 100% and 92.3% on CXR. ACS diagnosis was very unlikely for a LUS score of zero, likely for a score of one and very likely for a score greater than one. Conclusion: LUS is an effective tool for the diagnosis of ACS with superior sensitivity and similar accuracy compared to CXR. The LUS score was able to assess risk for development of ACS in children with SCD and clinical suspicion of ACS.

Bile acids present important roles in the human body and changes in their pool can be used as markers for various liver pathologies. In part, the unconjugated or conjugated, secondary or primary nature of bile acids accounts for their various effect as ligands in addition to their functional effects in modulating inflammatory responses and cellular survivability. With no documented baseline levels of bile acids or their receptors in the inner ear system, some hydrophilic bile acids have been used successfully as a treatment to resolve drug induced cell damage or to ameliorate hearing loss. This review, presents both hydrophilic and hydrophobic human bile acids along with their tissue-specific ligand effects in modulating cellular integrity, bringing in consideration the possible effects and therapeutic applicability of bile acids to the inner ear tissue.

Abstract Background: There has been a decline in childhood vaccination uptake, with reports indicating that 25 million children missed out on one or more doses in 2021 . There is a need to understand the socio-behavioural drivers of vaccination uptake and to identify contextual and emerging factors that can inform demand-creation interventions. Objective: This review examined the social and behavioural factors influencing childhood vaccination intentions and uptake globally. Methods: A comprehensive search was carried out for published studies that presented data on patterns of association between socio-behavioural factors and vaccination intentions and uptake in children under five years. Studies were screened for eligibility by two reviewers, and information was collected using a standard data abstraction form. Findings: Out of 4462 records identified in the search, 82 studies were included. Emerging factors influencing vaccination uptake included gender-based factors like the mother’s financial autonomy, the number of social and formal messengers recommending vaccination, the proportion of non-conforming social network members, and the role of decisional balance and conflict as a moderator of the vaccination intention and action pathway. Conclusion: The review identified multiple behavioural and social constructs influencing vaccination intentions and uptake. The diversity of influences underscores the complexity of relationships between social-behavioural factors and vaccination uptake, which may be contributing to low vaccination uptake. More context-specific research is required to extend the geographical base and depth of evidence and to evaluate highly localised socio-behavioural interventions.