In this paper, we use a stochastic partial differential equation (SPDE) as a model for the density of a population under the influence of random external forces/stimuli given by the environment. We study statistical properties for two crucial parameters of the SPDE that describe the dynamic of the system. To do that we use the Galerkin projection to transform the problem, passing from the SPDE to a system of independent SDEs; in this manner, we are able to find the Maximum likelihood estimator of the parameters. We validate the method by using simulations of the SDEs. We prove consistency and asymptotic normality of the estimators; the latter is showed using the Malliavin-Stein method. We illustrate our results with numerical experiments.

Mangrove and seaweed ecosystems, as integral components of blue carbon habitats, play pivotal roles in global carbon sequestration and coastal protection, showcasing unique environmental dynamics and biological diversity. This study explores seaweed and mangrove-associated bacterial communities and their functional dynamics in Goa coastal habitats, highlighting their critical ecological roles within blue carbon habitats. Physicochemical analysis revealed contrasting environmental conditions, with the seaweed ecosystem experiencing stable marine influences and the mangrove ecosystem subject to dynamic terrestrial-aquatic interactions. Elevated levels of pathogenic bacteria in both ecosystems indicate significant pollution from anthropogenic activities. Advanced metagenomic techniques, including Illumina’s 16S V3-V4 amplicon sequencing, were employed to assess bacterial diversity. The seaweed ecosystems were predominated by Proteobacteria, Cyanobacteria, and Actinobacteria, crucial for nutrient cycling and organic matter decomposition. In contrast, mangrove ecosystems displayed a more complex microbiota, represented by Firmicutes, adapted to anaerobic conditions. Core microbiome analysis revealed the prevalence of the pathogen Pleurocapsa in seaweeds, suggesting ecosystem health decline, while mangrove microbiomes showed the dominance of genera such as Bacillus and Clostridium, which are key in processing organic material under low-oxygen conditions. Notably, Clostridium levels indicated faecal contamination, underscoring the impact of external pollution. Functional pathway analysis conducted with PICRUSt2 analysis elucidated the metabolic specializations of the microbiomes. Seaweed-associated microbiomes excelled in carbohydrate metabolism, cellular growth and death and environmental information processing, whereas mangrove microbiomes showed advanced capabilities in carbohydrate metabolism, xenobiotics biodegradation and complex organic compound metabolism such as terpenoids and polyketides, reflecting complex microbial dynamics and pollution in mangroves. The findings emphasize the urgent need for effective conservation strategies to protect these vital ecosystems against the rising threats of anthropogenic pressures pollution, and climate change. An enhanced understanding of microbial dynamics and functional capabilities is essential for implementing informed management practices, ensuring the conservation and restoration of these critical blue carbon ecosystems.

Rationale: Mass spectrometry (MS) is introduced to high school students in the UK in many pre-university course syllabi. As such, we have identified the use of MS as a key technique that should be taught practically to undergraduates from the outset of their studies. This mini‑review describes how we introduce and develop students’ use of MS throughout our three‑year undergraduate spiral curriculum practical program, using atmospheric pressure chemical ionisation MS (APCI/MS). Methods: We have used an Advion Expression L spectrometer, fitted with an atmospheric solids analysis probe or a Plate Express TLC sampler for sample introduction. Results: We have successfully demonstrated the use of APCI-MS in a range of practicals and experiments covering organic and organometallic chemistries, with large cohorts of students gaining hands‑on instrumental experience in authentic research settings. Conclusions: APCI-MS has proven to be an easy-to-use and valuable addition to our undergraduate practical course. The robustness of the spectrometer enables routine use by large cohorts of students with minimal supervision, and routine maintenance can be carried out by non-specialist technicians. Students can readily process and interpret results for a series of routine analyses, as well as demonstrate uses in problem-solving exercises.

A document by Bahar Darouei. Click on the document to view its contents.

Donor and recipient HCMV-seropositive (D+R+) lung transplant recipients (LTRs) often harbour multiple human cytomegalovirus (HCMV) strains, likely due to transmitted donor (D) strains and reactivated recipient (R) strains. To date, the extent and timely occurrence of each likely source in shaping the post-transplantation (post-Tx) strain population is unknown. Here, we deciphered the D and R origin of the post-Tx HCMV strain composition in blood, bronchoalveolar lavage (BAL), and CD45+ BAL cell subsets. We investigated either D and/or R formalin-fixed paraffin-embedded blocks or fresh D lung tissue from four D+R+ LTRs obtained prior to transplantation. HCMV strains were characterised by short amplicon deep sequencing. In two LTRs, we show that the transplanted lung is reseeded by R strains within the first six months after transplantation, likely by infiltrating CD14+ CD163+/- alveolar macrophages. In three LTRs, we demonstrate both rapid D-strain dissemination and persistence in the transplanted lung for >1 year post-Tx. Broad inter-host diversity contrasts with intra-host genotype sequence stability upon transmission, during follow-up and across compartments. In D+R+ LTRs, HCMV strains of both, D and R origin can emerge first and dominate long‑term in subsequent episodes of infection, suggesting no replication advantage of one source over the other despite pre-existing R strain-specific immunity.

Aim Tragic incidents in Phase I trials have been cited to suggest that trials put participants at high levels of risk. This meta-analysis aimed to evaluate risks to Phase I trial participants at the Fortrea Clinical Research Unit (FCRU) (UK) between 2016-2021. Methods Sixty-Five FCRU Phase I trials enrolling 3194 participants were included (99% healthy volunteers). Analysed trials tested active drugs, had finalised clinical study reports (CSRs), and standardised AE reporting procedures. Data on drug type, study design, participant numbers, and AEs were extracted from CSRs. A chi-square test of homogeneity tested mild, moderate, and severe AE probability distributions between placebo and active groups. A negative binomial regression examined relationships of administration route (parenteral vs non-parenteral), drug type (small molecule vs biologic), and trial type (First in Human (FIH) vs non-FIH) to number of AEs reported. Results Over 55% of participants reported at least one AE. 5051 AEs were reported; classified as mild (90.1%), moderate (9.4%), severe (0.4%), or unknown (0.1%). Proportion of AEs by severity category was similar between active and placebo groups (χ2(2)=3.942, p=0.139). Fifteen serious AEs were reported. Parenteral administration and biological drugs had no significant effect on AE incidence. FIH trials were a significant predictor of lower AE risk. Conclusion AEs were commonly reported in these Phase I trials. Trial features perceived to increase AE risks (parenteral administration, biologic drugs) did not and AE risk in FIH trials was lower compared with non-FIH trials. The trials analysed posed a low risk of serious harm to participants.

Osteopoikilosis, the incidental finding of a rare bone dysplasia: a case report

Mucormycosis is an invasive fungal infection with considerably high mortality rates in immunocompromised individuals. Due to COVID-19 pandemic, the disease has resurfaced recently and lack of appropriate antifungals resulted in a poor outcome in patients. The iron uptake mechanism in Rhizopus delemar, the predominant causal agent is crucial for its survival and pathogenesis in human host. The current study focuses on the structural dynamics of high affinity iron permease (Ftr1) which act as a virulence factor in this fatal fungal disease. Ftr1 is a transmembrane protein which is responsible for the transport of Fe 3+ ion from the extracellular milieu to the cytoplasm under iron-starving conditions in Rhizopus. In this work, the three-dimensional modelling of Ftr1 was carried out and it was found to possess seven transmembrane helices with N-terminal lying in the extracellular region and C-terminal in the intracellular region. Moreover, the present study delineates the interaction of glutamic acid residues, found in the REGLE motif of the fourth transmembrane helix with Fe 3+. The molecular dynamics (MD) simulation study revealed that the glycine present in the motif destabilizes the helix thereby bringing E157 closer to the positively charged ion. Understanding the interaction between Fe 3+ ion and Ftr1 would be helpful in designing effective small molecule drugs against this novel therapeutic target for treating mucormycosis.

Hofmeister effect is a famous physical chemistry phenomenon that was reported a hundred years ago, which firstly refers to the action of certain salts to decrease the solubility of proteins while others increase. The Hofmeister effect on the luminescent properties of cationic organic fluorophore is still obscure, especially for their room temperature phosphorescence (RTP). Herein, hydrophilic groups (quaternization pyridine) were introduced into carbazole molecules to obtain a series of carbazole derivatives (named CZ-Py +) with different counter anions in the Hofmeister series. These carbazole derivatives displayed tunable fluorescent color from cyan to yellow in the solid state following the Hofmeister sequence and anti-Hofmeister behavior in aqueous solution. Moreover, RTP material with tunable emission color and lifetime was achieved by doping CZ-Py + with Hofmeister series anion in polymethyl methacrylate (PMMA) and polyvinyl alcohol (PVA), which displayed good performance in time getting information encryption and anti-counterfeiting.

Advances in next-generation sequencing have allowed the use of DNA obtained from unusual sources for wildlife studies. However, these samples have been used predominantly to sequence mitochondrial DNA for species identification while population genetics analyses have been rare. Since next-generation sequencing allows indiscriminate detection of all DNA fragments in a sample, technically it should be possible to sequence whole genomes of animals from environmental samples. Here we used a blood-feeding insect, tsetse fly, to target whole genome sequences of wild animals. Using pools of flies, we compared the ability to recover genomic data from hosts using the short-read sequencing (Illumina) and adaptive sampling of long-read data generated using Oxford nanopore technology (ONT). We found that most of the short-read data (85-99%) was dominated by tsetse fly DNA and that adaptive sampling on the ONT platform did not substantially reduce this proportion. However, once tsetse reads were removed, the remaining data for both platforms tended to belong to the dominant host expected in the tsetse fly blood meal. Reads mapping to elephants, warthogs and giraffes were recovered more reliably than for buffalo, and there was high variance in the contribution of DNA by individual flies to the pools, suggesting that there are host specific biases. We were able to identify over 300,000 SNPs for elephants, which we used to estimate the allele frequencies and expected heterozygosity for the population. Overall, our results show that at least for certain wild mammals, it is possible to recover genome-wide host data from blood-feeding insects.

Title pageTitle of the article: The Association of Thrombophilia and Pregnancy: Six Pregnancies with recurrent fetal deformities: A Case Report

Background Voriconazole (VCZ) is a first-line treatment drug for invasive fungal disease, with narrow therapeutic window and significant inter-individual variability. VCZ is primarily metabolized by liver, which declines with age. For elderly patients, physiological and pathological factors lead to more pronounced fluctuations in VCZ plasma concentrations. Thus, it is crucial to establish a model that accurately predicts VCZ plasma concentration in elderly patients. Methods A retrospective study was performed incorporating 32 variables, including population pharmacokinetics (PPK) parameters derived from the PPK model. Recursive Feature Elimination with Cross-Validation was used for feature selection. Multiple algorithms were selected and combined into an ensemble model, and the model was interpreted by Shapley Additive exPlanations. Results The predictive performance of machine learning was greatly improved after inclusion of PPK parameters. The composition of XGBoost, RF, and CatBoost (1:1:8) with the highest R2 (0.828) was determined as the final ensemble model. Feature selection greatly simplified the model from 31 variables to 9 variables without compromising its performance. The R2, mean square error, mean absolute error, and accuracy (± 30%) of external validation were 0.633, 1.094, 2.286, and 71.05%, respectively. Conclusions Our study is the first to include PPK parameters as new factors for machine learning modeling to predict VCZ plasma concentrations in elderly patients. The model underwent optimization through feature selection. Our model provides a reference for individualized dosing of VCZ in clinical practice, enhancing the efficacy and safety of VCZ treatment in elderly patients. Keywords: voriconazole, elderly patients, machine learning, population pharmacokinetics, precision medicine

Saliva has emerged as a promising diagnostic resource due to its accessibility, non-invasiveness, and repeatability, enabling early disease detection and timely intervention. However, current studies often overlook the distinction between whole saliva (WS) and cell-free saliva (CFS). This study aims to compare the proteomic profiles of WS and CFS, both with and without low-abundance proteins enrichment using nanoparticles, employing DIA-MS technology. Our findings reveal a substantial enhancement in the detectability of low-abundance proteins in saliva with utilization of nanoparticles, enabling identification of 12%-15% low-abundance proteins previously undetectable in WS or CFS. In total, 3817 saliva proteins were identified, with 3413 found in WS and 2340 in CFS. More interestingly, we found that it wasn’t the similarity of the samples that did the clustering, but rather it depended more on the different detection methods and sample types. And the predominant functions of the identified proteins in WS were related to oxidative phosphorylation and neurodegenerations, whereas those in CFS were primarily associated with nitrogen and glycosaminoglycan metabolism. And both exhibited functions in immune response and proteasome. This study represents the first comparison of WS and CFS, providing valuable experimental evidence for guiding the selection of research subjects in future salivomics studies.

Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial haemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes. Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation and neuronal signaling. Here we investigated activity-based protein profiling (ABPP) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS). Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism.

HVLA Manipulation Intervention Resulting in Severe Vertebral Artery Dissection: A Case Report

Natural Killer (NK) cells, integral to the innate immune system, are notable in cell therapies because for their applicability in allogeneic treatments, distinguishing them from T cells typically employed in conventional cell therapies. However, their limited half-life poses a challenge for therapy. Although attempts to leverage feeder cells are common, safer methods are needed to mitigate the associated risks. In our study, an upregulation in the expression of 4-1BBL in Colo-205 cells under extracellular stresses such as hypoxia and cytochalasin D was observed. This enhanced binding to the 4-1BB receptors on NK cells promotes proliferation in NK cells. Elevated CD56 expression of a marker strongly linked to NK cell proliferation in co-culture further supports this process. Applying extracellular stressors, specifically hypoxia and cytochalasin D, to Colo-205 cells successfully tailored feeder cells, significantly enhancing NK cell proliferation.

This article presents an open-source network simulator and digital twin focused on Metropolitan Area Networks (MAN). Our tool is capable of estimating average latency and delay percentiles between every pair of nodes with minimal computational effort, with the ultimate goal to see if the MAN is capable of supporting emerging services and applications that have strict latency requirements. We show that probability bounds like Vysochanskij–Petunin’s inequality can be used to quickly estimate latency bounds with minimal computational effort. Theoretical results are validated with extensive simulations leveraging the simmer package, an open-source Discrete Event Simulator (DES) written in R, along with igraph for visualization of networks and shortest path calculations. The code is publicly available as open-source, and published in Github for the research community to use and build upon.

Application of perioperativetransesophageal echocardiography in resection ofpulmonary artery sarcoma: a case report