bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and imaging characteristics of cerebral small vessel disease in a Colombian population aged 40 years and older
Authors: Rodriguez Laura , Araujo Ana T , D Vera Daniela , Rodríguez Gelvez Adriana , Camacho Paul A , Mantilla Daniel E , Mantilla Juan C
Published: March 2024

Cerebral small vessel disease is a major contributor to both brain aging and cognitive decline. This study aimed to determine the prevalence of cerebral small vessel disease in a Colombian population over 40 years of age who attended a Radiology and Diagnostic Imaging service for brain MRI between October 2018 and March 2019. This was an observational, cross-sectional and analytical study of 710 adult patients over 40 years of age who attended the Radiology and Diagnostic Imaging service for a brain MRI. The analysed data were obtained from an anonymized database of the service. We studied 710 MRI scans of patients aged between 40 and 104 years. The most frequent risk factor was hypertension (36.2%). Brain abnormalities associated with cerebral small vessel disease, such as white matter hyperintensities, were seen in 56.20% of the population, and brain atrophy was observed in 12.96%. Brain disease prevalence increased with age (23.18% for those aged 55 years, 54.49% for those aged 55–64 years, 69.8% for those aged 65–74 years and 90.53% for those older than 75 years). The prevalence of cerebral small vessel disease in our population was similar to that reported in the world literature, as were the prevalence of the evaluated cardiovascular risk factors. Additionally, we identified an association between hypertension and advanced age with cerebral small vessel disease, with white matter hyperintensities being the most characteristic finding.
Exploring public perception and willingness to pay for a renewable source of energy: evidence from an emerging economy of renewable-energy development
Authors: Bashir Mohammed J K , Abdelhak Senadjki , Salah Wael A , Abuhelwa Mai
Published: March 2024

The study focuses on the transition from conventional energy sources to sustainable renewable energy (RE) in Palestine, particularly in the West Bank and Gaza Strip. The research aims to understand the relationship between key factors and residents’ willingness to invest in the RE sector, with a specific focus on the impact of education. Using the unified theory of acceptance and use of technology, the study analyzes data from 400 residents through a questionnaire and employs ordinary least-squares regression analysis with Eviews 12. The key findings indicate that residents’ inclination to invest in RE is significantly influenced by factors such as resource availability, knowledge level and power outages. Moreover, the study suggests that educated residents are more likely to invest in RE when factors such as knowledge, effort expectation, enabling conditions and resource availability are relatively high. The conclusion emphasizes the importance of policymakers’ allocating sufficient funds to research and development to promote technological innovation in RE sources, thereby enhancing the population’s energy efficiency.
Pre- and intra-operative risk factors predict postoperative respiratory failure after minimally invasive oesophagectomy
Authors: Yu Boyao , Liu Zhichao , Zhang Long , Pan Jie , Jiang Chao , Li Chunguang , Li Zhigang
Published: March 2024

OBJECTIVES

Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample.

METHODS

We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method.

RESULTS

This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality.

CONCLUSIONS

Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.
Do genetic loci that cause reproductive isolation in the lab inhibit gene flow in nature?
Authors: Frayer Megan E , Payseur Bret A
Published: March 2024

The genetic dissection of reproductive barriers between diverging lineages provides enticing clues into the origin of species. One strategy uses linkage analysis in experimental crosses to identify genomic locations involved in phenotypes that mediate reproductive isolation. A second framework searches for genomic regions that show reduced rates of exchange across natural hybrid zones. It is often assumed that these approaches will point to the same loci, but this assumption is rarely tested. In this perspective, we discuss the factors that determine whether loci connected to postzygotic reproductive barriers in the laboratory are inferred to reduce gene flow in nature. We synthesize data on the genetics of postzygotic isolation in house mice, one of the most intensively studied systems in speciation genetics. In a rare empirical comparison, we measure the correspondence of loci tied to postzygotic barriers via genetic mapping in the laboratory and loci at which gene flow is inhibited across a natural hybrid zone. We find no evidence that the two sets of loci overlap beyond what is expected by chance. In light of these results, we recommend avenues for empirical and theoretical research to resolve the potential incongruence between the two predominant strategies for understanding the genetics of speciation.
SecMet-FISH: labeling, visualization, and enumeration of secondary metabolite producing microorganisms
Authors: Buijs Yannick , Geers Aileen Ute , Nita Iuliana , Strube Mikael Lenz , Bentzon-Tilia Mikkel
Published: March 2024

Our understanding of the role of secondary metabolites in microbial communities is challenged by intrinsic limitations of culturing bacteria under laboratory conditions and hence cultivation independent approaches are needed. Here, we present a protocol termed Secondary Metabolite FISH (SecMet-FISH), combining advantages of gene-targeted fluorescence in situ hybridization (geneFISH) with in-solution methods (in-solution FISH) to detect and quantify cells based on their genetic capacity to produce secondary metabolites. The approach capitalizes on the conserved nature of biosynthetic gene clusters (BGCs) encoding adenylation (AD) and ketosynthase (KS) domains, and thus selectively targets the genetic basis of non-ribosomal peptide and polyketide biosynthesis. The concept relies on the generation of amplicon pools using degenerate primers broadly targeting AD and KS domains followed by fluorescent labeling, detection, and quantification. Initially, we obtained AD and KS amplicons from Pseuodoalteromonas rubra, which allowed us to successfully label and visualize BGCs within P. rubra cells, demonstrating the feasibility of SecMet-FISH. Next, we adapted the protocol and optimized it for hybridization in both Gram-negative and Gram-positive bacterial cell suspensions, enabling high-throughput single cell analysis by flow cytometry. Ultimately, we used SecMet-FISH to successfully distinguish secondary metabolite producers from non-producers in a five-member synthetic community.
Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome
Authors: Sember Eileen , Chennakesavula Ranga , Beard Breanna , Opoola Mubaraq , Hwangbo Dae-Sung
Published: March 2024

Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in the WRN gene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS. In this study, using the null mutant flies (WRNexoΔ) for the gene WRNexo (CG7670), homologous to the exonuclease domain of WRN in humans, we examined how diets affect the lifespan, stress resistance, and sleep/wake patterns of a Drosophila model of WS. We observed that dietary restriction (DR), one of the most robust nongenetic interventions to extend lifespan in animal models, failed to extend the lifespan of WRNexoΔ mutant flies and even had a detrimental effect in females. Interestingly, the mean lifespan of WRNexoΔ mutant flies was not reduced on a protein-rich diet compared to that of wild-type (WT) flies. Compared to WT control flies, the mutant flies also exhibited altered responses to DR in their resistance to starvation and oxidative stress, as well as changes in sleep/wake patterns. These findings show that the WRN protein is necessary for mediating the effects of DR and suggest that the exonuclease domain of WRN plays an important role in metabolism in addition to its primary role in DNA-repair and genome stability.
Harnessing the predicted maize pan-interactome for putative gene function prediction and prioritization of candidate genes for important traits
Authors: Poretsky Elly , Cagirici Halise Busra , Andorf Carson M , Sen Taner Z
Published: March 2024

The recent assembly and annotation of the 26 maize nested association mapping population founder inbreds have enabled large-scale pan-genomic comparative studies. These studies have expanded our understanding of agronomically important traits by integrating pan-transcriptomic data with trait-specific gene candidates from previous association mapping results. In contrast to the availability of pan-transcriptomic data, obtaining reliable protein–protein interaction (PPI) data has remained a challenge due to its high cost and complexity. We generated predicted PPI networks for each of the 26 genomes using the established STRING database. The individual genome-interactomes were then integrated to generate core- and pan-interactomes. We deployed the PPI clustering algorithm ClusterONE to identify numerous PPI clusters that were functionally annotated using gene ontology (GO) functional enrichment, demonstrating a diverse range of enriched GO terms across different clusters. Additional cluster annotations were generated by integrating gene coexpression data and gene description annotations, providing additional useful information. We show that the functionally annotated PPI clusters establish a useful framework for protein function prediction and prioritization of candidate genes of interest. Our study not only provides a comprehensive resource of predicted PPI networks for 26 maize genomes but also offers annotated interactome clusters for predicting protein functions and prioritizing gene candidates. The source code for the Python implementation of the analysis workflow and a standalone web application for accessing the analysis results are available at https://github.com/eporetsky/PanPPI.
Analysis of wave propagation in non-isothermal poroelastic solids saturated by two-phase fluids
Authors: Santos J E , Savioli G B , Ba J
Published: March 2024

This work presents a model to characterize the behaviour of waves propagating in non-isothermal poroelastic solids saturated by two-phase fluids. The dynamic differential equations include the poroelasticity and heat equations with the solid, fluid and thermal fields combined using coupling terms. A plane wave analysis shows that five waves can propagate, three compressional, one fast (P1) and two slow (P2, P3), a shear fast (S) and a thermal slow (T). P2, P3 and T are diffusive waves at low frequencies, while P1 and S behave as propagating waves. The T wave is coupled with the compressional waves and uncoupled with the S wave. The plane wave analysis applied to a real sandstone saturated with gas–water mixtures compares phase velocities and attenuation factors for two-phase and effective single-phase fluids, considering or neglecting the coupling terms. It is observed that P1 and P2 waves have higher velocities for coupled cases, while P3 and T waves exhibit the opposite behaviour. Furthermore the plane wave analysis is performed in the coupled case for oil–water and gas–water two-phase fluids, with compressional waves exhibiting higher velocities for gas–water than for oil–water mixtures. The propagation of waves in a 1-D thermo-poroelastic medium saturated by a gas–water mixture is presented and analysed using a finite element procedure. Considering temperature may become important in high-pressure high-temperature hydrocarbon and geothermal reservoirs.
A simple weighting method for inverting earthquake source parameters using geodetic multisource data under Bayesian algorithm
Authors: Xi Can , Wang Leyang , Zhao Xiong , Sun Zhanglin , Zhao Weifeng , Pang Ming , Wu Fei
Published: March 2024

More accurate inversion of source fault geometry and slip parameters under the constraint of the Bayesian algorithm has become a research hotspot in the field of geodetic inversion in recent years. In nonlinear inversion, the determination of the weight ratio of the joint inversion of multisource data is more complicated. In this context, this paper proposes a simple and easily generalized weighting method for inversion of source fault parameters by joint geodetic multisource data under the Bayesian framework. This method determines the relative weight ratio of multisource data by root mean square error (RMSE) value and can be extended to other nonlinear search algorithms. To verify the validity of the method in this paper, this paper first sets up four sets of simulated seismic experiment schemes. The inversion results show that the joint inversion weighting method proposed in this paper has a significant decrease in the large residual value compared with the equal weight joint inversion and the single data source joint inversion method. The east–west deformation RMSE is 0.1458 mm, the north–south deformation RMSE is 0.2119 mm and the vertical deformation RMSE is 0.2756 mm. The RMSEs of the three directions are lower than those of other schemes, indicating that the proposed method is suitable for the joint inversion of source parameters under Bayesian algorithm. To further verify the applicability of the proposed method in complex earthquakes, the source parameters of the Maduo earthquake were inverted using the method of this paper. The focal depth of the inversion results in this paper is closer to the focal depth released by the GCMT agency. In terms of strike angle and dip angle, the joint inversion in this paper is also more inclined to the GCMT results. The joint inversion results generally conform to the characteristics of left-lateral strike-slip, which shows the adaptability of this method in complex earthquakes.
A story of (in)coherence: climate adaptation for health in South African policies
Authors: Quintana Amanda V , Mayhew Susannah H , Kovats Sari , Gilson Lucy
Published: March 2024

Climate adaptation strengthens and builds the resilience of health systems to future climate-related shocks. Adaptation strategies and policies are necessary tools for governments to address the long-term impacts of climate change and enable the health system to respond to current impacts such as extreme weather events. Since 2011 South Africa has national climate change policies and adaptation strategies, yet there is uncertainty about: how these policies and plans are executed; the extent to which health policies include adaptation; and the extent of policy coherence across sectors and governance levels. A policy document analysis was conducted to examine how South African climate change, development and health policy documents reflect the health adaptation response across national and Western Cape levels and to assess the extent of coherence across key health and environment sector policy documents, including elements to respond to health-related climate risks, that can support implementation. Our findings show that overall there is incoherence in South African climate adaptation within health policy documents. Although health adaptation measures are somewhat coherent in national level policies, there is limited coherence within Western Cape provincial level documents and limited discussion on climate adaptation, especially for health. Policies reflect formal decisions and should guide decision-makers and resourcing, and sectoral policies should move beyond mere acknowledgement of adaptation responses to a tailored plan of actions that are institutionalized and location and sector specific. Activities beyond documents also impact the coherence and implementation of climate adaptation for health in South Africa. Clear climate risk-specific documents for the health sector would provide a stronger plan to support the implementation of health adaptation and contribute to building health system’s resilience.
The effects of a large-scale home visiting programme for child development on use of health services in Brazil
Authors: Viegas da Silva Eduardo , Hartwig Fernando Pires , Yousafzai Aisha , Bertoldi Andréa Dâmaso , Murray Joseph
Published: March 2024

Partnership between early childhood development interventions and primary health care services can help catalyse health care uptake by socially vulnerable families. This study aimed to assess the real-life effects of a large-scale home visiting programme [Primeira Infância Melhor (PIM)] in Brazil on the use of preventive (prenatal visits, well child visits, dentist visits and vaccination) and recovery (emergency room visits and hospitalization) health services. A quasi-experiment nested in a population-based birth cohort study was conducted. The intervention group was firstly defined as all children enrolled in PIM up to age 6 months, and afterwards stratified between those enrolled during pregnancy or after birth up to 6 months. Children receiving PIM were matched with controls on propensity scores based on 27 confounders to estimate effects on health service use from prenatal to age 2 years. Double adjustment was applied in outcome Quasi-Poisson regressions. No evidence was found for effects of PIM starting anytime up to 6 months (262 pairs), or for the children enrolled only after birth (133 pairs), on outcomes occurring after age 6 months. When the programme started during pregnancy (129 pairs), there was a 13% higher prevalence of adequate prenatal visits (prevalence ratio = 1.13; 95% confidence interval 1.01–1.27), but no effect on use of any other health service. Sensitivity analyses suggested longer participation in the programme with reduced visitor turnover might improve its impact on prenatal visits. Integration between PIM and primary health care was not adequate to affect overall patterns of contacts with health services. Nevertheless, prenatal home visits showed potential to increase health service contact during a sensitive period of development, indicating the need to start such programmes before birth, when there is more time for maternal care, and family engagement in a network of services is facilitated.
Construction of a prognostic model for breast cancer based on moonlighting genes
Authors: Zhang Ming , Zhang Dejie , Wang Qicai , Lin Guoliang
Published: March 2024

Breast cancer (BRCA) is a highly heterogeneous disease, with significant differences in prognosis among patients. Existing biomarkers and prognostic models have limited ability to predict BRCA prognosis. Moonlighting genes regulate tumor progression and are associated with cancer prognosis. This study aimed to construct a moonlighting gene-based prognostic model for BRCA. We obtained differentially expressed genes (DEGs) in BRCA from The Cancer Genome Atlas and intersected them with moonlighting genes from MoonProt to acquire differential moonlighting genes. GO and KEGG results showed main enrichment of these genes in the response of BRCA cells to environmental stimuli and pentose phosphate pathway. Based on moonlighting genes, we conducted drug prediction and validated results through cellular experiments. After ABCB1 knockdown, viability and proliferation of BRCA cells were significantly enhanced. Based on differential moonlighting genes, BRCA was divided into three subgroups, among which cluster2 had the highest survival rate and immunophenoscore and relatively low tumor mutation burden. TP53 had the highest mutation frequency in cluster2 and cluster3, while PIK3CA had a higher mutation frequency in cluster1, with the majority being missense mutations. Subsequently, we established an 11-gene prognostic model in the training set based on DEGs among subgroups using univariate Cox regression, LASSO regression, and multivariable Cox regression analyses. Model prognostic performance was verified in GEO, METABRIC and ICGC validation sets. In summary, this study obtained three BRCA moonlighting gene-related subtypes and constructed an 11-gene prognostic model. The 11-gene BRCA prognostic model has good predictive performance, guiding BRCA prognosis for clinical doctors.
Co-design of an intervention to improve patient participation in discharge medication communication
Authors: Tobiano Georgia , Latimer Sharon , Manias Elizabeth , Marshall Andrea P , Rattray Megan , Jenkinson Kim , Teasdale Trudy , Wren Kellie , Chaboyer Wendy
Published: March 2024

Patients can experience medication-related harm and hospital readmission because they do not understand or adhere to post-hospital medication instructions. Increasing patient medication literacy and, in turn, participation in medication conversations could be a solution. The purposes of this study were to co-design and test an intervention to enhance patient participation in hospital discharge medication communication. In terms of methods, co-design, a collaborative approach where stakeholders design solutions to problems, was used to develop a prototype medication communication intervention. First, our consumer and healthcare professional stakeholders generated intervention ideas. Next, inpatients, opinion leaders, and academic researchers collaborated to determine the most pertinent and feasible intervention ideas. Finally, the prototype intervention was shown to six intended end-users (i.e. hospital patients) who underwent usability interviews and completed the Theoretical Framework of Acceptability questionnaire. The final intervention comprised of a suite of three websites: (i) a medication search engine; (ii) resources to help patients manage their medications once home; and (iii) a question builder tool. The intervention has been tested with intended end-users and results of the Theoretical Framework of Acceptability questionnaire have shown that the intervention is acceptable. Identified usability issues have been addressed. In conclusion, this co-designed intervention provides patients with trustworthy resources that can help them to understand medication information and ask medication-related questions, thus promoting medication literacy and patient participation. In turn, this intervention could enhance patients’ medication self-efficacy and healthcare utilization. Using a co-design approach ensured authentic consumer and other stakeholder engagement, while allowing opinion leaders and researchers to ensure that a feasible intervention was developed.
Exploration of Novelty as Part of the Player Experience of Need Satisfaction in Games
Authors: Kosa Mehmet , Uysal Ahmet
Published: March 2024

Need for novelty has been proposed as a potential candidate to be a basic psychological need, in addition to autonomy, competence, and relatedness in the Self-Determination Theory literature. In this paper, we investigate the need for novelty in the video gaming domain, and examine whether it differentiates as a distinct construct from the other three basic needs of autonomy, competence and relatedness. To be able to test this, we examined whether novelty uniquely predicts context specific outcomes, such as concentration, satisfaction and commitment in games. We conducted an online survey with 390 online video game players. Regression analyses showed that need for novelty indeed emerges as a distinct construct, and uniquely predicts positive outcomes. This study provides initial support for novelty as a basic psychological need that is needed for players' intrinsic motivation, and shows the importance of novelty in online video gaming. We discuss new avenues for research related to need for novelty and how consideration of novelty may impact game design.
Sustainable pig diets: partial grain replacement with former food products and its impact on meat quality
Authors: Tretola Marco , Mazzoleni Sharon , Silacci Paolo , Dubois Sébastien , Proserpio Cristina , Pagliarini Ella , Bernardi Cristian E M , Pinotti Luciano , Bee Giuseppe
Published: March 2024

This study investigated the effects of salty and sugary former foodstuff products (FFPs) on the quality traits and meat composition of 36 male castrated pigs (Swiss Large White breed) as well as sensory characteristics of the loins. The animals were fed three different diets for both the growing (G) and finishing (F) phases: (1) a standard diet (ST), 0% FFPs; (2) a diet with 30% of sugary FFPs (e.g., chocolate, biscuits, cakes) as a replacement for traditional ingredients (SU); and (3) a diet with 30% of salty FFPs (e.g., bread, pasta, and breadsticks) as a replacement for traditional ingredients (SA). For a comprehensive assessment of meat quality, protein and fat content in the LD were analyzed. AA and FA profile were determined both in the LD and backfat. Meat quality traits such as pH and temperature, thawing, cooking and drip losses, and shear force have been evaluated. Then, pork loins have been assessed for sensory attributes by a trained sensory panel. The SA diet decreased 20:5 n-3 levels (P < 0.001) in the muscle and 22:5 n-3 levels (P < 0.05) in both muscle and backfat but increased (P < 0.05) the ratio of mono-unsaturated to saturated fatty acids compared to the ST group. Both the SU and SA diets elevated (P < 0.001) the n-6:n-3 fatty acids ratio compared to the ST diet. Dietary treatments did not affect other meat quality traits. Regarding sensory attributes, the loin from pigs fed with SU and SA diets were sweeter (P < 0.001). Loins of SA pigs were more tender (P < 0.001), had a more intense pork aroma (P < 0.001) and had more flavor (P < 0.01) compared to ST loins. Overall, the use of FFPs affected the fatty acid profile of pork while improving the sensory quality of the loins, with no negative effects observed on the technological and nutritional quality of the meat.
α-Pyrrolidinohexanophenone (α-PHP) vs. α-pyrrolidinoisohexanophenone (α-PiHP): A toxicological investigation about plasma concentrations and behavior in forensic routine cases
Authors: Brueckner Isabel , Welter-Luedeke Jessica , Zangl Anna , Graw Matthias , Paul Liane D
Published: March 2024

New psychoactive substances (NPS), like pyrrolidinophenones, are still very present on the illegal drug market. The presented study reports on two members of this substance group, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP), which occurred in forensic routine cases in the last 6 years. α-PHP could be detected predominantly by a validated liquid chromatography–tandem mass spectrometry (LC–MS-MS) method in 33 authentic human plasma samples and α-PiHP in 8. α-PHP concentrations ranged from ca. 0.75 to 128 µg/L (mean: 23.2, median: 16.3) and α-PiHP concentrations from 7.33 to 118 µg/L (mean: 44.7, median: 33.7, quantified via α-PHP). Individuals were predominantly male and middle aged. As different studies have shown, some pyrrolidinophenones are able to cause aggressive behavior. Therefore, we set out to investigate the relation of α-PHP and α-PiHP plasma concentrations and the behavior of the consumers, reported by police and medical experts. Part of the subjects showed aggressive behavior, including agitation and restlessness. Lethargic and unremarkable behavior might be explained by co-consumption of other drugs, such as opiates/opioids, benzodiazepines, pregabalin or alcohol as well as by drug tolerance and subacute effects of stimulants. Multi-drug use could be detected in all cases; also stimulating substances and multiple different pyrrolidinophenones were determined. Nevertheless, users of α-PHP and α-PiHP showed a tendency to act aggressively, possibly triggered by a high selectivity for dopamine transporter inhibition. In accordance, committed offenses were often violent crimes. This might be considered in terms of toxicological assessment of criminal responsibility and driving ability.
Atypical postmortem redistribution in chronic methadone consumers
Authors: Garneau Béatrice , Roy Cynthia , Motard Julie , Desharnais Brigitte , Bouchard Corinne , Mireault Pascal
Published: March 2024

Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26–0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as antemortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)—clearly demonstrating that cardiac blood methadone concentration is more representative of the antemortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation—particularly for cases of chronic methadone users.
Detection, exploitation and mitigation of memory errors
Authors: Llorente-Vazquez Oscar , Santos-Grueiro Igor , Pastor-Lopez Iker , Garcia Bringas Pablo
Published: March 2024

Software vulnerabilities are the root cause for a multitude of security problems in computer systems. Owing to their efficiency and tight control over low-level system resources, the C and C++ programming languages are extensively used for a myriad of purposes, from implementing operating system kernels to user-space applications. However, insufficient or improper memory management frequently leads to invalid memory accesses, eventually resulting in memory corruption vulnerabilities. These vulnerabilities are used as a foothold for elaborated attacks that bypass existing defense methods. In this paper, we summarise the main memory safety violation types (i.e. memory errors), and analyse how they are exploited by attackers and the main mitigation methods proposed in the research community. We further systematise the most relevant techniques with regards to memory corruption identification in current programs.
Towards enhanced monitoring framework with smart predictions
Authors: Calabrò Antonello , Daoudagh Said , Marchetti Eda
Published: March 2024

Context: Predicting security and trust vulnerabilities and issues is crucial for IoT interconnected systems and ecosystems, especially when integrating new, third-party or open-source components. Objective: One way to ensure timely predictions is by using a smart monitoring framework to continuously verify functional and non-functional property violations during the executions of the systems and their components. Method: This paper presents a set of guidelines for the Smart Monitoring Framework definition and its application process. Results and Conclusion: The paper provides the reference architecture of the Smart Monitoring Framework and its possible implementation to promptly detect suspicious behavior or property violations. The paper also illustrates how the provided implementation satisfies the defined guidelines by design.
Using design of experiments to guide genetic optimization of engineered metabolic pathways
Authors: Moon Seonyun , Saboe Anna , Smanski Michael J
Published: March 2024

Design of experiments (DoE) is a term used to describe the application of statistical approaches to interrogate the impact of many variables on the performance of a multivariate system. It is commonly used for process optimization in fields such as chemical engineering and material science. Recent advances in the ability to quantitatively control the expression of genes in biological systems open up the possibility to apply DoE for genetic optimization. In this review targeted to genetic and metabolic engineers, we introduce several approaches in DoE at a high level and describe instances wherein these were applied to interrogate or optimize engineered genetic systems. We discuss the challenges of applying DoE and propose strategies to mitigate these challenges.

One-Sentence Summary

This is a review of literature related to applying Design of Experiments for genetic optimization.
Comparative transcriptomic and metabolomics analysis of modified atmosphere responses in Tribolium castaneum (Coleoptera: Tenebrionidae)
Authors: Zhou Min , Pan Biying , Guan Liwen , Wang Yuanyuan , Xu Kangkang , Wang Shigui , Tang Bin , Li Can
Published: March 2024

Modified atmosphere is effective in controlling Tribolium castaneum Herbst, but it has adaptations. Comprehending the potential mechanism of resistance to T. castaneum in a modified atmosphere will help advance related management methods. This study conducted a comparative transcriptomic and metabolomic analysis to understand the physiological mechanism of T. castaneum in adapting to CO2 stress. Results showed that there were a large number of differentially expressed genes (DEGs) in T. castaneum treated with different concentrations of CO2. Gene ontology (GO) analysis revealed significant enrichment of DEGs mainly in binding, catalytic activity, cell, membrane, membrane part, protein-containing complex, biological regulation, and cellular and metabolic process. Kyoto Encyclopedia of Genes and Genomes analysis showed that different treatments had different effects on the metabolic pathways of T. castaneum. DEGs induced by 25% CO2 were involved in arginine and proline metabolism, and 50% air + 50% CO2 treatment affected most kinds of metabolic pathways, mainly the signal transduction pathway, including PI3K-Akt signaling pathway, AMPK signaling pathway, neurotrophin signaling pathway, insulin signaling pathway, and thyroid hormone signaling. Ribosome and DNA replication were enriched under high CO2 stress (75% and 95%). The metabolomics revealed that different concentrations of CO2 treatments might inhibit the growth of T. castaneum through acidosis, or they may adapt to anoxic conditions through histamine and N-acetylhistamine. Multiple analyses have shown significant changes in histamine and N-acetylhistamine levels, as well as their associated genes, with increasing CO2 concentration. In conclusion, this study comprehensively revealed the molecular mechanism of T. castaneum responding to CO2 stress and provided the basis for an effectively modified atmosphere in the T. castaneum.
New records of three parasitoids, Pteroptrix chinensis, Aphytis hispanicus, and Marlattiella prima (Hymenoptera: Aphelinidae) associated with an exotic scale, Lopholeucaspis japonica (Hemiptera: Diaspididae) in Tennessee
Authors: Daniel Johnson Alfred , Woolley James B , Addesso Karla M
Published: March 2024

A survey for parasitoids of Lopholeucaspis japonica Cockerell (Hemiptera: Diaspididae), an exotic scale of woody ornamentals, resulted in the discovery of 3 species of aphelinid parasitoid wasps, Pteroptrix chinensis (Howard), Aphytis hispanicus (Mercet), and Marlattiella prima Howard. This serves as the first report of these parasitoids reared from a host in the state of Tennessee, USA. Despite routine pesticide applications in the surveyed nursery and directed treatments of the infested plants to control the scale outbreak, the percentage of parasitized scale in privet and euonymus shrubs averaged 7.0% and 7.9%, respectively. These parasitoids may be useful in the natural or managed control of this pest in the United States, but additional research is needed to understand how these parasitoids contribute to the control of L. japonica in the landscape and how nursery production practices can be modified to promote parasitoid populations.
Implementing the human right to science in the context of health-related data processing
Authors: Molnár-Gábor Fruzsina
Published: March 2024

This paper contributes to the exploration of the potential application of duties related to the diligent anticipation of the (imminent) harms and (potential) benefits to humans that scientific innovation engenders to health-related contexts. In particular, it addresses the intersection between the human right to science and health-related data processing, which plays a key role in the production, translation and implementation of biomedical knowledge. The first part of the paper provides a brief recap of the interpretation of the right to science based on Art. 15 (1) (b) of the United Nations International Covenant on Economic, Social and Cultural Rights (hereafter ICESCR or Covenant) and the resulting obligations for States in the context of health and related data processing. The second part of the paper defines the relevance of the ICESCR for EU Member States and the European Union. In the third part, theses are put forward on how the human right to science and the obligations under Art. 15 (1) (b) ICESCR influence the interpretation and application of the General Data Protection Regulation as secondary EU law. By examining the justifications for using the right to science to interpret EU data protection law and by providing interpretation and application guidance on the main data protection principles in the area of health-related data processing, taking this right into account, the aim is to shape the EU data governance framework to meet the requirements of this human right. In doing so, the paper aims to close the gaps in the interpretation and application of the main rules of EU data protection law. Such standardization in the health-related context can contribute to a coherent interpretation and application of existing rules by referring to this emerging human right. Against this background, the paper identifies governance measures that the EU legislator could take to guide the processing of health-related data in line with the requirements of the right to science.
Randomized trial promoting cancer genetic risk assessment when genetic counseling cost removed: 1-year follow-up
Authors: An Jinghua , McDougall Jean , Lin Yong , Lu Shou-En , Walters Scott T , Heidt Emily , Stroup Antoinette , Paddock Lisa , Grumet Sherry , Toppmeyer Deborah , Kinney Anita Y
Published: March 2024

Purpose

Cancer genetic risk assessment (CGRA) is recommended for women with ovarian and high-risk breast cancer. However, the underutilization of CGRA has long been documented, and cost has been a major barrier. In this randomized controlled trial, a tailored counseling and navigation (TCN) intervention significantly improved CGRA uptake at 6-month follow-up, compared with targeted print (TP) and usual care (UC). We aimed to examine the effect of removing genetic counseling costs on CGRA uptake by 12 months.

Methods

We recruited racially and geographically diverse women with breast and ovarian cancer from cancer registries in Colorado, New Jersey, and New Mexico. Participants assigned to TCN received telephone-based psychoeducation and navigation. After 6 months, the trial provided free genetic counseling to participants in all arms.

Results

At 12 months, more women in TCN obtained CGRA (26.6%) than those in TP (11.0%; odds ratio [OR] = 2.77, 95% confidence interval [CI] = 1.56 to 4.89) and UC (12.2%; OR = 2.46, 95% CI = 1.41 to 4.29). There were no significant differences in CGRA uptake between TP and UC. The Kaplan-Meier curve shows that the divergence of cumulative incidence slopes (TCN vs UC, TCN vs TP) appears primarily within the initial 6 months.

Conclusion

TCN significantly increased CGRA uptake at the 12-month follow-up. Directly removing the costs of genetic counseling attenuated the effects of TCN, highlighting the critical enabling role played by cost coverage. Future policies and interventions should address multilevel cost-related barriers to expand patients’ access to CGRA.

Trial Registration

This trial was registered with the NIH clinical trial registry, clinicaltrials.gov, NCT03326713. https://clinicaltrials.gov/ct2/show/NCT03326713.
Biopsychosocial determinants of sexual health in older age: the role of health-related, relationship, and psychosexual factors
Authors: Vasconcelos Priscila A , Paúl Constança , Nobre Pedro J
Published: March 2024

Background

Given the unprecedented aging of the population and the increased focus on overall well-being in older age, investigating the determining factors of sexual well-being in older adults becomes essential as it offers insights into promoting healthy aging and overall quality of life.

Aim

By applying the biopsychosocial model of sexuality in older age, we aimed to identify the role of biomedical and psychosocial factors in predicting sexual well-being in partnered older adults (≥55 years old).

Methods

A total of 111 participants (mean [SD], 63.2 [5.96]) completed a self-report questionnaire assessing biopsychosocial dimensions. Bivariate correlational analyses and hierarchical multiple regression were conducted to investigate factors associated with sexual well-being. Health-related factors were entered into the first regression model. The second model included factors pertaining to relationship dimensions. Sexual beliefs were introduced in the third regression model.

Outcomes

Self-rated health, psychological distress, subjective cognitive decline, sexual beliefs, duration of the relationship, relationship satisfaction, and sexual well-being were assessed.

Results

Findings from the hierarchical regression revealed that duration of relationship [t(104) = −3.07, P < .01], relationship satisfaction [t(104) = 8.49, P < .001], and age-related sexual beliefs [t(104) = −2.75, P < .01] were significant predictors of sexual well-being of partnered older adults [F(6, 104) = 22.77, P < .001, R2 = .57], after controlling for health-related factors. These findings suggest that relationship factors and sexual beliefs play a significant role in predicting sexual well-being of older adults, above and beyond health-related dimensions.

Clinical implications

Interventional approaches aimed at promoting sexual well-being in older age might benefit from incorporating exercises that demystify age-related sexual beliefs, by normalizing changes that occur with aging and fostering positive attitudes toward sexual expression in older age; particularly for older adults in long-term relationships, relationship satisfaction must also be considered as an important intervention target.

Strengths and limitations

Further investigation using longitudinal designs is required to examine the causal links between these factors and sexual well-being in older age.

Conclusion

Findings from this study underscore the role of relationship dimensions and age-related sexual beliefs for the sexual well-being of partnered older adults.
Dorsoventrally asymmetric expression of miR319/TCP generates dorsal-specific venation patterning in petunia corolla tube
Authors: Zhang Bin , Qin Xiaoting , Han Yao , Li Mingyang , Guo Yulong
Published: March 2024

Vein-associated pigmentation (venation) is a type of floral coloration adopted by plants to attract pollinators. Several petunia (Petunia hybrida) lines generate dorsoventrally asymmetric venation patterning of the corolla tube, in which venation is only present in the dorsal tube. The molecular mechanism underlying this trait is unknown. Here, we demonstrate that miR319 is preferentially expressed in the dorsal corolla tube, leading to dorsoventrally asymmetric expression of its target genes. Transgenic lines overexpressing phy-miR319a generated uniform venation patterning of the corolla tube. Knockout of TCP genes targeted by miR319 promoted venation patterning in the ventral and dorsal tube, while overexpression of the miR319 target gene, PhTCP6, completely inhibited corolla tube venation patterning. In addition, miR319-targeted TCPs negatively regulated venation patterning, probably by repressing the regulator of venation patterning, AN4. Together, our data demonstrate that asymmetric expression of miR319 promotes venation patterning in the petunia dorsal tube alone by repressing the expression of its target TCP genes, which negatively regulate corolla tube venation patterning. These findings provide novel insights into how the dorsoventrally asymmetric distribution of venation patterning is established in zygomorphic flowers.
Microbes as a tool for the bioremediation of fish waste from the environment and the production of value-added compounds: a review
Authors: Kumari Neha , Hussain Ahmed , Ghosh Sachan Shashwati
Published: March 2024

Fish are the most edible protein source worldwide and generate several remnants such as scales, viscera, head, bone, and skin. Fish wastes are not disposed of properly, which adversely affects the environment, especially the water bodies where fish processing industries dispose of their waste. Fish waste mainly contains nitrogen, oil, fat, salts, heavy metals, and organic compounds, which increase the biological oxygen demand and chemical oxygen demand. Fish waste can degrade in various ways, such as physicochemical or by enzymatic action, but using microbes is an environmentally friendly approach that can provide valuable compounds such as products such as collagen, chitin, minerals, and fish protein concentrates. This review is designed to focus on the suitability of microbes as tools for fish waste degradation and the production of certain associated. This study also provides insight into the production of other compounds such as protease, chitinase, and chitin applicability of these products. After processing, fish waste as a microbial growth media for enzyme production since microorganisms synthesize enzymes such as proteases, protein hydrolysates, lipids, and chitinase, which have broader applications in the pharmaceutical, cosmetic, biomedical material, and food processing industries.