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Individual and community-level determinants of knowledge of obstetric danger signs among women in Southern Ethiopia: A multi-level mixed effect negative binomial analysis

PLoS ONE Amanuel Yoseph, Yilkal Simachew, Berhan Tsegaye et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0314916

Introduction One of the key strategies to achieve the sustainable development goal by reducing maternal deaths below 70 per 100,000 is improving knowledge of obstetric danger signs (ODS). However, mothers’ knowledge of ODS is low in general and very low in rural settings, regardless of local and national efforts in Ethiopia. Further, there is significant variation of ODS knowledge among women from region to region and urban/rural settings. Most studies are limited only to northern Ethiopia and focused on individual-level determinants. Thus, this study aimed to assess the individual and community-level determinants of knowledge of obstetrics danger signs among women who delivered in the last 12 months in the northern zone of the Sidama region, Ethiopia. Methods We conducted a community-based cross-sectional study from October 21 to November 11, 2022. A multi-stage sampling procedure was utilized to select study participants. A structured and pretested questionnaire was utilized to collect data. Open Data Kit (ODK) smartphone application was used to collect data at women’s homes. A multi-level mixed-effects negative binomial regression model was used to control effects of clusters and confounders. Results The overall response rate of this study was 99.12%. The proportion of knowledge of obstetrics danger sign was 22.3% (95% CI: 18.7, 25.9). Government-employed women [adjusted incidence ratio (AIR) = 1.37; 95% CI: 1.20, 1.56], women who had exposure to mass media (AIR = 1.16; 95% CI: 1.08, 1.25), women who had received model family training (AIR = 1.15; 95% CI: 1.10, 1.25), autonomous women (AIR = 1.34; 95% CI: 1.25, 1.46), women who had faced health problems during pregnancy (AIR = 1.21; 95% CI: 1.11, 1.32), and urban women (AIR = 1.22; 95% CI: 1.09, 1.62) were determinants positively affect knowledge of ODS. Conclusion Only one in five women has good knowledge of ODS in the study setting. Urban residence, mass media exposure, receiving model family training, facing health problems during pregnancy, and women’s autonomy were the main determinants of knowledge of ODS. Any intervention strategies should focus on multi-sectorial collaboration to address determinants of knowledge of ODS at the individual and community level. Reinforcing the existing model family training, particularly focusing on rural women and women who denied autonomy in decision-making about health care, should be considered. Awareness creation should be increased about ODS through mass media exposure.

Somatization symptomology and its association with stress in patients with irritable bowel syndrome

PLoS ONE Saira Akhlaq, Nosheen Kazmi, Syed Murtaza Hassan Kazmi et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0312506

Irritable Bowel Syndrome (IBS) patients and Somatization Symptom Disorder (SSD) patients experience somatization symptoms relative to their corresponding processes. IBS patients may also have a diagnosis of both IBS and SSD. Somatization symptoms cause significant psychological, emotional and social distress. Conversely, stress in any form is believed to contribute to IBS symptoms. Whether stress mediated somatization symptoms in patients with IBS provide a pathway for these IBS symptoms is not as well understood. This cross-sectional study was performed at Shifa International Hospital, Islamabad between March 1st, 2023, and January 14th, 2024. Purposeful sampling was done to recruit study participants from three different populations as somatization is common in all three populations. As a result, there were three different samples in the study. Participants were eligible to participate if they had a diagnosis of IBS, somatic symptom disorder (SSD), or IBS with somatization (IBS-SSD) and were currently receiving treatment at the gastroenterology outpatient clinic and/or psychiatric outpatient clinic. Patient Health Questionnaire (PHQ-15) and Somatic Stress Response Scale (SSRS) were used to assess somatic symptoms and their association of stress-related somatic symptoms. Data was entered and analyzed using descriptive and inferential statistics. Data was self-reported by the participants. The largest sample size 67(100%) was from the IBS patient population. Two other samples were small i.e., there were 21 (100%) participants in SSD sample, and a very few numbers of participants 12 (100%) in the IBS diagnosis with a comorbidity of SSD sample. Majority of the patients were young i.e., 50≤ (77.7%), (71.4%), (74.99%); and male (59.7%), (66.6%), (50.0%) from the IBS, SSD, and IBS-SSD samples. Majority of the participants in the IBS (56.7%) and SSD (61.9%) samples had a high school diploma or the equivalent. In the IBS-SSD sample, the largest percentage (41.7%) of participants had more than a bachelor’s degrees. M = 85.67 (+/-23.26) for SSRS scores and M = 17.81(+/-5.28) for PHQ-15 scores in SSD patients. M = 75.21 (+/-19.59) for SSRS scores and M = 14.76 (+/-5.07) for PHQ-15 scores in IBS patients. M = 75.17 (+/-20.55) for SSRS scores and M = 14.92 (+/-6.27) for PHQ-15 scores in IBS-SSD patients. Many participants had somatization symptoms in the severe range (≥ 15) i.e., 34(50.7%), 17(81.0%), 6(50.0%) in IBS, SSD, and IBS-SSD samples respectively. Considering the PHQ scores by age in the IBS sample, highest mean scores were observed for the highest age group (60–69 years) i.e., 16.50 (+/- 5.68) despite fewer number of participants in this age group. PHQ scores also significantly differed by education groups i.e., significant differences were observed between education group 1 and 2 as well as group 2 and 3, p<0.05. On simple linear regression, PHQ-15 scores significantly predicted variations in SSRS scores, p <0.05, R2 = 69.6% for IBS sample, R2 = 68.7% for the SSD sample, and R2 = 66.0% for patients with IBS, SSD and IBS with somatization respectively. Stress related somatic symptoms are positively correlated with somatization complaints in IBS patients. Increased somatization scores were observed in the elderly. Targeted psycho-social interventions could help mitigate the negative effects of somatization in IBS patients.

Effect of the COVID-19 pandemic on colorectal cancer screening in two university-affiliated health care systems

PLoS ONE Vinod Kumar, Lilian Golzarri-Arroyo, Sarah Roth et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0317057

Objectives In two large university affiliated healthcare systems, we examined trends in colorectal cancer (CRC) screening both prior to and during the COVID-19 pandemic to compare the trends in non-invasive screening tests and colonoscopy. Materials and methods In this retrospective time-trend analysis, we obtained the numbers of colonoscopies and non-invasive tests performed monthly during the pandemic and the year prior to it. We obtained colonoscopy data from five endoscopy units with the indication determined by dual independent review. Monthly numbers of completed fecal immunochemical (FIT) and FIT-DNA tests were obtained from the electronic medical records of both health systems. Trends in testing, numbers, and stage of incident CRCs diagnosed during the 30-month interval were examined using Poisson regression and logistic regression, respectively. Results From January 2019 to June 2021, we identified 16,939 FIT tests, 2,942 FIT-DNA tests, and 38,332 colonoscopies from the two health systems, and 368 colorectal cancers (105 early stage, 263 advanced stage) from the private hospital system. Overall colonoscopy volume declined by 18.7% (from 16,483 to 13,393) in 2020 compared to 2019 in both health systems, returning to baseline in 2021. Non-invasive tests declined by 21.9% in 2020, but increased in 2021 due to greater use of FIT/DNA. Compared to 2019, incident CRCs declined in 2020 but rebounded in 2021, with no difference in early versus late-stage cancers. Conclusions These trends in CRC screening tests may be useful for modeling the effects of the pandemic on the longer-term outcomes of CRC incidence and mortality.

Preventing zoonotic spillover through regulatory frameworks governing wildlife trade: A scoping review

PLoS ONE Raphael Aguiar, Ryan Gray, Eduardo Gallo-Cajiao et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0312012

Wildlife trade can create adverse impacts for biodiversity and human health globally, including increased risks for zoonotic spillover that can lead to pandemics. Institutional responses to zoonotic threats posed by wildlife trade are diverse; understanding regulations governing wildlife trade is an important step for effective zoonotic spillover prevention measures. In this review, we focused on peer-reviewed studies and grey literature conducted on regulatory approaches that govern domestic and international wildlife trade in order to assess the role of local, national and global-level institutions in the prevention of zoonotic spillover and infection transmission between humans. The five-stage scoping review protocol described by Arksey and O’Malley to map key concepts and main sources and types of evidence available was followed to understand and analyze empirical evidence from peer-reviewed studies and grey literature conducted on regulatory approaches that govern domestic and international wildlife. Sources were included if they discuss at least one of three points: regulatory approaches governing the wild animal trade, including wild animal markets, traditional medicine or exotic pets; regulatory approaches governing importation of wild animals and the international wildlife supply chain; or the role of local, national, and global-level institutions in regulating wild animal trade for food, traditional medicine or exotic pets. A total of 1598 sources were retrieved, from which 32 sources were included in the final review (30 studies + 2 grey literature reports). Based on published literature, regulations governing wildlife trade are inconsistent within and between countries. Organizations regulating wildlife trade may have competing interests, which can lead to fragmentation and a lack in coordination and oversight. National compliance with international regulations can be an issue. Reducing the probability of spillover events in wildlife trade is key to prevent future pandemics. Our results indicate a need for enhanced regulatory harmonization within and between national and supranational regulations. Coordination and collaboration for prevention of zoonotic infection and spillover may be enhanced through future research focused on the effectiveness of timely Information sharing and global- and national- level harmonization of wildlife trade regulations.

Insufficient LGBTQ+ education across disciplines suggested by national survey of health professionals in training

PLoS ONE Lexie Wille, Tess Jewell, Atticus Wolfe et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0316931

Health professionals often feel underprepared to treat patients who identify as lesbian, gay, bisexual, transgender, and/or queer (LGBTQ+). Additionally, lack of access to professionals who are knowledgeable about LGBTQ+ inclusive care contributes to the myriad of health disparities experienced by LGBTQ+ communities. This cross-sectional survey study explores the preparedness of healthcare profession trainees for caring for LGBTQ+ patients by quantifying the hours and quality of training health profession trainees receive in LGBTQ+ education across disciplines. We surveyed US-based health professionals in training (HPiT) across disciplines (N = 155) on their training programs’ LGBTQ+-specific curricula and educational opportunities. Ordered logistic regression analysis assessed the relationship between the number of hours of LGBTQ+-specific education and other discipline, organization, and individual factors. Respondents reported an average of 4.75 (SD = 3.04) hours devoted to LGBTQ+-specific education. Physician assistant trainees reported receiving the highest number of hours of LGBTQ+-specific education (M = 6.63, SD = 1.98), followed by psychology (M = 5.30, SD = 3.54), medical (M = 5.12, SD = 3.38), nursing (M = 4.17, SD = 3.28), and trainees in other health fields (M = 3.88, SD = 2.47). Across all disciplines, trainees rated their LGBTQ+-specific education on average as “good”. Despite rising awareness, the quantity and quality of dedicated LGBTQ+-specific education remains concerningly low across all measured disciplines and US regions. Future research must investigate strategies to overcome common barriers to increasing LGBTQ+ education in health professions training by maximizing the impact of limited hours through integrating LGBTQ+ content into existing materials, supporting trainee leadership, and implementing institutional support for educators teaching LGBTQ+ content. Regulatory bodies must reconsider the current guidance for LGBTQ+ education quantity and quality to advise institutions on best-practice guidelines to prepare trainees for LGBTQ+ patient care.

Pain management practice and associated factors among nurses working in Ethiopia: A systematic review and meta-analysis

PLoS ONE Melesse Abiye Munie, Amsalu Baylie Taye, Befkad Derese Tilahun et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0312499

Background Pain management is a crucial component of patient care that promotes relaxation, lowers complications, improves quality of life, and shortens hospital stays. Several studies assessed the nurses’ pain management practices in Ethiopia. However, the findings of these studies are highly variable and inconsistent. Therefore, the study aims to determine the overall prevalence of pain management practice and associated factors among nurses working in Ethiopia. Method The study included all observational quantitative research articles conducted among nurses in Ethiopia. We used Google Scholar, PubMed, Cochrane Library, and Scopus searching databases. The Newcastle—Ottawa Scale was used to check the study quality. Then I2 statistics and Cochran’s Q test were used to evaluate heterogeneity. The Funnel, Egger’s test, and non-parametric trim and fill effect tests were used to check publication bias by using a random effect model. Finally, we conducted subgroup analysis and sensitivity tests to evaluate statistical heterogeneity and the presence or absence of any influential study. Result In the final analysis, we included eighteen studies, and 4,213 nurses participated. The overall pooled prevalence of nurses with good pain management practice was 43.79% (95% CI: 38.52, 49.06%). In-service training AOR; 95% CI 3.21 (1.87, 4.54), good knowledge AOR; 95% CI 2.44 (1.78, 3.09), positive attitudes AOR; 95% CI 2.84 (1.24, 4.44), and pain management guidelines in health facilities AOR; 95% CI 3.46 (1.48, 5.44) were the significant associated factors with pain management practice among nurses in Ethiopia. Conclusion This study found that over half of Ethiopian nurses had poor pain management practices. Knowledge, attitude, training, and pain management guidelines in health facilities were significant factors. Therefore, health managers and stakeholders should prioritize pain management awareness, attitudes, availability of guidelines, and in-service training to improve patient care and outcomes.

Chronotherapy with Cinacalcet has a striking effect on inhibition of parathyroid gland proliferation in rats with secondary hyperparathyroidism

PLoS ONE Søren Egstrand, Maria Lerche Mace, Marya Morevati et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0316675

Secondary hyperparathyroidism (sHPT) is a significant clinical complication of CKD leading to bone abnormalities and cardiovascular disease. Current treatment based on activating the parathyroid calcium-sensing receptor (CaSR) using calcimimetics such as Cinacalcet, aims to decrease plasma PTH levels and inhibit the progression of parathyroid hyperplasia. In the present study, we found significant diurnal rhythmicity of Casr, encoding the Cinacalcet drug target in hyperplastic parathyroid glands (p = 0.006). In rats with sHPT, Cinacalcet treatment timed prior to the acrophase of Casr expression (chronotherapy: Cina1) was compared with the usual timing of treatment early in the active phase (conventional: Cina2). Without Cinacalcet treatment, induction of sHPT resulted in a significant increase in parathyroid proliferation in terms of Ki-67+ cells compared to that of control rats (p = 0.001). Conventional Cinacalcet treatment (Cina2) did not significantly reduce Ki-67 index compared to untreated rats with sHPT (p = 0.09). In contrast, chronotherapy treatment (Cina1) resulted in a marked inhibition of parathyroid proliferation by Ki-67+ cells compared to untreated rats with sHPT (p = 0.0001). We found significantly reduced parathyroid Ki-67 index using chronotherapy compared to conventional timing of Cinacalcet (Cina1 vs. Cina2: 0.92±0.14% vs. 2.46±0.37%, p = 0.006). Transcriptomic analysis showed that the reduced proliferation of Cina1 was associated with downregulation of genes involved in mitotic activity, together with an increased adaptive response of energy metabolism, as evident from upregulated pathways of Oxidative phosphorylation and TCA cycle compared to the untreated uremic group. Conclusively, it is shown that the inhibitory effect of Cinacalcet on parathyroid cell proliferation is markedly impacted by the timing of administration, suggesting a possible benefit of using chronotherapy in Cinacalcet treatment of sHPT.

Impact of CaNa2EDTA fortification on growth, antioxidant activity and stress-related gene expression in tilapia (Oreochromis niloticus) at different stocking densities paradigms

PLoS ONE Wajeeha Komal, Shafaq Fatima, Qandeel Minahal et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0316629

Increasing aquaculture production requires high-density farming, which induces stress, necessitating supplements to mitigate its effects and ensure fish health. The aim of this study was to examine how CaNa2EDTA (EDTA) affects the growth, immune response and antioxidant activity in Nile tilapia (Oreochromis niloticus). The fish were raised at three different stocking densities: low (LD = 2.00 kg/m3), medium (MD = 3.50 kg/m3), and high (HD = 5.00 kg/m3). Each density group was fed with one of four levels of EDTA supplementation (E0 = 0 g/kg, E1 = 5 g/kg, E2 = 10 g/kg, and E3 = 15 g/kg) for 60 days. Each diet was tested in triplicate (n = 66 fish per replicate in LD, 116 per replicate in MD, and 166 per replicate in HD). After 60 days, the results of this study declared that LD group showed better growth than the MD and HD groups, and among all groups, those fed the E1 diet grew better than those on other diets. The study found significant changes in the chemical composition of the fish and the activity of digestive enzymes across all treatments. Antioxidant enzyme levels and cortisol were higher in the HD group compared to the LD and MD groups. However, fish in the HD group fed the E1 diet had the lowest levels of antioxidant enzymes and cortisol. Malondialdehyde levels were higher in the HD group compared to the LD and MD groups, with the lowest levels seen in fish on the E1 diet in the HD group. The expression of Somatostatin-1 did not increase in the MD group compared to the LD and HD groups. The gene expression levels of pro-opiomelanocortin-α and Interleukin 1-β were not significantly affected by either stocking density or EDTA supplementation. In conclusion, EDTA supplementation improved growth and antioxidant response in tilapia, with the best results seen at a dose of 5 g/kg in the high-density group, suggesting that this approach could be beneficial in intensive tilapia farming.

Data transmission delay compensation algorithm for interactive communication network of offshore oil field operation scene in bad weather

PLoS ONE Jing Xiang, Xin Du Jan 06, 2025 DOI: 10.1371/journal.pone.0317137

A data transmission delay compensation algorithm for an interactive communication network of an offshore oil field operation scene in severe weather is proposed. To solve the problem of unstable microwave signals and a large amount of noise in the communication network caused by bad weather, the communication network signal denoising method based on Lagrange multiplier symplectic singular value mode decomposition is adopted, and the communication network data denoising process is realized through five steps; phase space reconstruction, symplectic geometric similarity transformation, grouping, diagonal averaging, and adaptive reconstruction. Simultaneously, the weak communication signal is compensated after being captured, that is, the characteristics of the weak signal are enhanced. On this basis, the communication network signals are collected to obtain delay information, and the data transmission delay of the communication network is predicted using the neural network algorithm based on long-term and short-term memory; Based on the prediction result of transmission delay, the PID controller is used to calculate the transmission delay compensation amount of the communication network, and the calculation result of the compensation amount is input into the delay compensator to realize transmission delay compensation. The experimental results show that the algorithm can effectively improve the quality of data transmission in the communication network and has a good delay compensation effect to ensure real-time communication.

ETL: From the German Health Data Lab data formats to the OMOP Common Data Model

PLoS ONE Melissa Finster, Maxim Moinat, Elham Taghizadeh Jan 06, 2025 DOI: 10.1371/journal.pone.0311511

Objective The German Health Data Lab is going to provide access to German statutory health insurance claims data ranging from 2009 to the present for research purposes. Due to evolving data formats within the German Health Data Lab, there is a need to standardize this data into a Common Data Model to facilitate collaborative health research and minimize the need for researchers to adapt to multiple data formats. For this purpose we selected transforming the data to the Observational Medical Outcomes Partnership Common Data Model. Methods We developed an Extract, Transform, and Load (ETL) pipeline for two distinct German Health Data Lab data formats: Format 1 (2009-2016) and Format 3 (2019 onwards). Due to the identical format structure of Format 1 and Format 2 (2017 -2018), the ETL pipeline of Format 1 can be applied on Format 2 as well. Our ETL process, supported by Observational Health Data Sciences and Informatics tools, includes specification development, SQL skeleton creation, and concept mapping. We detail the process characteristics and present a quality assessment that includes field coverage and concept mapping accuracy using example data. Results For Format 1, we achieved a field coverage of 92.7%. The Data Quality Dashboard showed 100.0% conformance and 80.6% completeness, although plausibility checks were disabled. The mapping coverage for the Condition domain was low at 18.3% due to invalid codes and missing mappings in the provided example data. For Format 3, the field coverage was 86.2%, with Data Quality Dashboard reporting 99.3% conformance and 75.9% completeness. The Procedure domain had very low mapping coverage (2.2%) due to the use of mocked data and unmapped local concepts The Condition domain results with 99.8% of unique codes mapped. The absence of real data limits the comprehensive assessment of quality. Conclusion The ETL process effectively transforms the data with high field coverage and conformance. It simplifies data utilization for German Health Data Lab users and enhances the use of OHDSI analysis tools. This initiative represents a significant step towards facilitating cross-border research in Europe by providing publicly available, standardized ETL processes (https://github.com/FraunhoferMEVIS/ETLfromHDLtoOMOP) and evaluations of their performance.

Effect of power training on function and body composition in older women with probable sarcopenia. A study protocol for a randomized controlled trial

PLoS ONE Luis Polo-Ferrero, Susana Saez-Gutierrez, Arturo Dávila-Marcos et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0313072

Background Sarcopenia is a clinical syndrome characterized by the loss of muscle mass and strength. Hormonal changes that occur early in women may influence protein synthesis and promote muscle atrophy, leading to probable sarcopenia, defined as a loss of muscle strength without an obvious decrease in muscle mass. Various types of exercise have already proven effective in treating sarcopenia. Power training (PT), a subtype of resistance training performed at high speed, has not yet been studied in this population group. Methods A randomized controlled trial will be conducted with three parallel groups: a PT group, a multicomponent training (MT) group, and a no-exercise group. The inclusion criteria will be women over 65 years of age who meet the diagnostic criteria for probable sarcopenia (Hand grip test less than 16 kg and Five Times Sit to Stand Test more than 15 s) according to the European Working Group on Sarcopenia in Older People (EWGSOP2). Two assessments will be conducted at the beginning and at the end of the 32 weeks of intervention, in which variables of body composition (muscle, fat and weight) and functionality (strength and physical performance) will be collected. There will be 3 sessions of 50 minutes per week in each intervention group. The masking strategy will be double-blind. The analysis of intergroup differences will be conducted using multivariate and univariate analysis of variance (MANOVA and ANOVA), as well as pairwise comparisons (Bonferroni corrections). Changes in the degree of sarcopenia and how many women eliminate the risk of sarcopenia (no probable sarcopenia) after the different interventions will be tested. Discussion The study aims to investigate the impact of PT in older women at risk of sarcopenia. The expected results are that PT will significantly improve functionality and body composition compared to other forms of exercise (MT) and no physical activity. The results may represent a significant advance in understanding and addressing sarcopenia before it becomes established, providing preventive treatment and new tools whose clinical applicability has been studied. Trial registration The clinical trial was prospectively registered at ClinicalTrials.gov Identifier: NCT05870046.

Sequence and biochemical analysis of vaccinia virus A32 protein: Implications for in vitro stability and coiled-coil motif mediated regulation of the DNA-dependent ATPase activity

PLoS ONE Uma Ramakrishnan, Tanvi Aggarwal, Kiran Kondabagil Jan 06, 2025 DOI: 10.1371/journal.pone.0316818

Nucleocytoplasmic large DNA viruses (NCLDVs) have massive genome and particle sizes compared to other known viruses. NCLDVs, including poxviruses, encode ATPases of the FtsK/HerA superfamily to facilitate genome encapsidation. However, their biochemical and structural characteristics are yet to be discerned. In this study, we demonstrate that the viral ATPases are significantly shorter than their bacterial homologs, representing the minimal ATPase core of the FtsK/HerA superfamily. We analysed the sequence and secondary structural features of the vaccinia virus A32 protein and determined their roles in the protein’s ATPase activity. We sought to purify A32 by various techniques and noted that recombinant A32 expressed in E. coli is highly insoluble and unstable in solution. N-terminal fusion with the thioredoxin solubility tag could alleviate this issue to some extent, but subsequent tag cleavage results in increased susceptibility to precipitation and degradation. We have also predicted a highly conserved coiled-coil motif (CCM) towards the C-terminus of vaccinia virus A32. ATPase activity of A32 is known to increase in the presence of DNA. Comparative analysis of the wildtype protein versus its CCM mutants suggests that this DNA dependence of A32’s ATPase activity is likely regulated by the CCM. We demonstrate that oligomerization of A32, mediated by the CCM, is required for its DNA-binding but is not dependent on ATP- or DNA-binding. Our findings suggest a key role of the CCM, and thus, higher-order structure formation in the regulated ATPase activity of A32, providing new opportunities for further detailed characterization of the poxvirus genome packaging process.

In vitro and in silico analyses of amino acid substitution effects at the conserved N-linked glycosylation site in hepatitis B virus surface protein on antigenicity, immunogenicity, HBV replication and secretion

PLoS ONE Patcharin Tepjanta, Thammakorn Saethang, Kazuhito Fujiyama et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0316328

The "a" determinant, a highly conformational region within the hepatitis B virus large surface protein (LHBs), is crucial for antibody neutralization and diagnostic assays. Mutations in this area can lead to conformational changes, resulting in vaccination failure, diagnostic evasion, and disease progression. The "a" determinant of LHBs contains a conserved N-linked glycosylation site at N320, but the mechanisms of glycosylation in LHBs remain unclear. This study aimed to investigate the impact of amino acid substitutions at N320 on antigenicity, three-dimensional (3D) structures of LHBs, immunogenic epitopes, and HBV DNA levels. LHBs were mutated by substituting asparagine 320 with proline, cysteine, lysine, and glutamine. The reactivity of the mutants with antibodies was evaluated by western blotting and immunofluorescence staining. Results showed increased binding affinity in N320C, N320Q, and particularly N320P mutants compared to the wild type, likely attributed to conformational changes predicted by the I-TASSER server and further refined by the GalaxyRefine server. Analysis conducted using the IEDB server indicated that the N320P mutation increased the antigenic index, whereas the N320C mutation significantly decreased it. Conversely, the N320K and N320Q mutations exhibited minor effects on antigenicity. Our observations also identified N320P as a potential B-cell epitope and a binding epitope for MHC-I (T-cell epitope). Furthermore, mutating the conserved N-linked glycosylation site at position N320 to proline significantly increased the secretion of HBV DNA in virions. This study enhances our understanding of the impact of a single amino acid mutation at N320 on antibody interaction, LHBs conformation, immunogenicity, and HBV DNA replication. These insights hold promise for advancements in HBsAg detection and the development of vaccines against hepatitis B virus.

LBNP: Learning features between neighboring points for point cloud classification

PLoS ONE Lei Wang, Ming Huang, Zhenqing Yang et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0314086

Inspired by classical works, when constructing local relationships in point clouds, there is always a geometric description of the central point and its neighboring points. However, the basic geometric representation of the central point and its neighborhood is insufficient. Drawing inspiration from local binary pattern algorithms used in image processing, we propose a novel method for representing point cloud neighborhoods, which we call Point Cloud Local Auxiliary Block (PLAB). This module explores useful neighborhood features by learning the relationships between neighboring points, thereby enhancing the learning capability of the model. In addition, we propose a pure Transformer structure that takes into account both local and global features, called Dual Attention Layer (DAL), which enables the network to learn valuable global features as well as local features in the aggregated feature space. Experimental results show that our method performs well on both coarse- and fine-grained point cloud datasets. We will publish the code and all experimental training logs on GitHub.

An E-Delphi study to facilitate animal welfare assessment in Italian zoos and aquaria

PLoS ONE Barbara de Mori, Elena Mercugliano, Adriana F. Cerizza et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0309760

Ensuring animal welfare is a key aspect of animal management in zoological facilities and aquaria, representing a pivotal facet of their mission. Italy currently lacks a comprehensive and valuable assessment methodology for evaluating the welfare of captive animals. To address this gap, the present study aimed to identify the most important criteria that should be considered in the welfare management and assessment of animals housed in Italian zoos and aquaria. To pinpoint this issue, we engaged experts with diverse backgrounds, structuring their communication throughout an iterative process, by applying the Delphi methodology. A pilot and three Delphi rounds were administered online to 74 experts, asking them to a) validate relevant topics derived from current legislation and guidelines divided into three clusters: Care, Wellbeing, and Regulation; b) assess the relevance of these topics across taxonomic groups; c) propose and confirm indicators for each identified topic; d) suggest and refine a list of questions for animal welfare assessment. The results were three lists of questions, one for each cluster, with a total of 80 topics, 174 indicators, and 272 questions identified by the experts. The aspects included in these lists offer valuable insights into the main aspects experts consider relevant for captive animal welfare. Despite the complexity of animal welfare and the huge amount of species hosted in zoos limiting the possibility to cover this aspect with a single expert consultation, this project actively addresses the urgent need for standardization in animal welfare assessment, contributing to the ongoing development of zoological regulations in Italy. This is especially important given the current limited legislative framework, underscoring the link between animal welfare and successful ex-situ species conservation. These questions can be the basis of fine-tuned protocols to be tested in future projects aiming at animal welfare self-assessment, thus supporting authority inspection processes.

Designing of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation

PLoS ONE Md. Mijanur Rahman, Md. Habib Ullah Masum, Rehana Parvin et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0313559

Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins. We used several bioinformatics tools to predict helper T lymphocyte, cytotoxic T lymphocyte, and B-cell epitopes derived from the proteins and assessed their antigenicity, allergenicity, and toxicity. Both vaccines were constructed using selected epitopes, linkers, and adjuvants. After that, the vaccines were applied for physicochemical properties, secondary and tertiary structure predictions, and subsequent docking and simulation analyses. Accordingly, vaccine 1 (V1) and vaccine 2 (V2) showed better hydrophilicity with the grand average hydropathicity score of -0.811 and -0.648, respectively. The secondary and tertiary structures of the vaccines were also deemed satisfactory, with high stability indicated by the Ramachandran plot (V1:94.5% and V2:87.1%) and Z scores (V1: -5.15 and V2: -4.1). Docking analysis revealed substantial affinity of the vaccines towards the toll-like receptor-2 (V1: -1159.3, V2: -1246.3) and toll-like receptor-4 (V1: -1109.3, V2: -1244.8) receptors. Molecular dynamic simulation validated structural integrity and indicated varying stability throughout the simulation. Codon optimization showed significant expression of the vaccines (V1:51.88% and V2:51.63%) in E. coli vectors. Furthermore, regarding immune stimulation, the vaccines elicited significant B-cell and T-cell responses, including sustained adaptive and innate immune responses. Finally, thermodynamic predictions indicated stable mRNA structures of the vaccines (V1: -502.60 kcal/mol and V2: -450.90 kcal/mol). The proposed vaccines designed effectively targeting human papillomavirus oncoproteins have demonstrated promising results via robust immune responses, suggesting their suitability for further clinical advancement, including in vitro and in vivo experiments.

Cross-sectional study of lung cancer patients as a potential high-risk factor for abdominal aortic aneurysm

PLoS ONE Hye Ran Gwon, A La Woo, Seung Hyun Yong et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0315898

Background Abdominal aortic aneurysm (AAA) is more common in Non-small cell lung cancer (NSCLC) patients. Considering that ruptured AAA is potentially fatal, timely management of AAA would result in long-term survival benefits. We assess the prevalence and characteristics of AAA in resectable NSCLC patients who would benefit from AAA surveillance. Methods 1,019 resectable NSCLC patients in Severance and Kangbuk Samsung Hospitals were reviewed from January 2019 to November 2020. The control group comprised 2,899 cancer-free people who had a health check-up CT scan in Severance between January 2018 and December 2019. Results Among resectable primary NSCLC patients, 39/1,019 (3.8%; odds ratio [OR], 19.19; 95% confidence interval [CI], 8.10–46.46) had AAA compared with 6/2,899 (0.2%) in the control (P<0.001). In multivariable regression analysis, male (OR, 13.24; 95% CI, 1.50–117.48; P = 0.020), aging (OR, 1.10; 95% CI, 1.04–1.15; P<0.001), current smoker (OR, 4.20; 95% CI, 1.20–14.62; P = 0.024), and coronary artery disease (OR, 3.13; 95% CI, 1.48–6.62; P = 0.003) were independent risk factors for AAA in NSCLC. Conclusion The present study found that the incidence of AAA in resectable early-stage lung cancer patients was significantly higher than in the cancer-free control group. Therefore, we suggest that early-stage NSCLC patients, especially smokers older than 60 years, undergo regular AAA surveillance as part of their lung cancer monitoring.

Insights into the progressive impact of high-fat-diet induced insulin resistance on skeletal muscle and myocardium: A comprehensive study on C57BL6 mice

PLoS ONE Jingxuan Wang, Lizhi Dai, Tong Yu et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0310458

This study aims to provide a theoretical foundation for the future management of diabetes at various stages induced by a high-fat diet. Specifically, it seeks to determine the appropriate pharmacological interventions for each phase of diabetes development and the targeted therapeutic directions at different stages of diabetes progression. This investigation employed C57BL6 mice as experimental subjects, successfully establishing an insulin resistance model through a 12-week high-fat diet. Clinical manifestations, weight, body composition, and overall health of each mouse group were observed on the first day of the 6th, 8th, 10th, and 12th week of high-fat feeding to analyze insulin resistance. Subsequently, open-field test of each mouse group, and histopathological changes in the skeletal muscle and myocardium of each mouse group, along with the detection of protein-level expression of relevant genes, were performed to assess alterations in mitochondrial energy metabolism during insulin resistance. This endeavor aims to contribute insights for future in-depth veterinary research. The outcomes demonstrated that a continuous 12-week high-fat diet successfully induced stable insulin resistance in C57BL6 mice. Following insulin resistance, the motor activity of mice decreased, gradual pathological damage and functional decline were observed in the skeletal muscle and myocardium. The insulin signaling pathway was inhibited, resulting in reduced glucose transport and increased gluconeogenesis. Additionally, mitochondrial dysfunction manifested as diminished ATP synthesis capacity, weakened mitochondrial biogenesis, reduced mitochondrial fusion, increased division, and diminished autophagy. Notably, during insulin resistance progression, skeletal muscles and myocardium in C57BL6 mice predominantly relied on glycolytic pathways for energy supply. In the early stages of insulin resistance, the glycogen synthesis pathway in C57BL6 mouse skeletal muscles was inhibited. Our findings underscore a distinct mechanism in skeletal muscle and myocardium that ensures the utilization of anaerobic fermentation to meet energy demands in instances of inadequate aerobic respiration (Fig 1).

Cost-effectiveness of the SMILE intervention compared with usual care for people with severe mental illness: A randomized clinical trial

PLoS ONE Mohamed El Alili, Berno van Meijel, Maurits W. van Tulder et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0313100

Objectives Only studying effectiveness of lifestyle interventions for people with severe mental illness (SMI) is insufficient for policy making. As budgets for healthcare are limited, policy makers face the problem of allocating scarce healthcare resources. Cost-effectiveness studies are needed, but currently cost-effectiveness studies of lifestyle interventions for people with SMI delivered in ambulatory care are limited. The aim of this current study was to evaluate the cost-effectiveness of a lifestyle intervention for people with SMI living in the Dutch community in comparison with usual care. Methods and findings An economic evaluation was performed using a societal perspective alongside the Severe Mental Illness Lifestyle Evaluation (SMILE) pragmatic cluster randomized controlled trial. The SMILE lifestyle intervention is a one-year, group-based intervention delivered by trained mental healthcare workers. Costs, body weight change and quality of life were assessed at baseline, 6 and 12 months. Mixed models were used to estimate incremental costs and effects between the treatment group and the usual care group. Overall, the SMILE intervention resulted in lower total costs compared to the usual care group (-€719, 95% CI -7133; 3897). The effect difference between the intervention and usual care groups was -3.76 (95% CI -6.30; -1.23) kilograms for body weight and -0.037 (95% CI -0.083; 0.010) for QALYs. Conclusions Overall, the SMILE intervention resulted in lower total costs compared to the usual care group and was cost-effective for body weight change. However, the SMILE intervention does not seem cost-effective with regards to QALYs. More cost-effectiveness studies in other countries and other settings are needed to gain further insight into the cost-effectiveness of lifestyle interventions for people with SMI.

Age-related variations in physical activity, happiness, and psychological well-being: Evidence from Iran

PLoS ONE Mohammad VaezMousavi, Lara Carneiro, Amir Shams et al. Jan 06, 2025 DOI: 10.1371/journal.pone.0314202

Background Physical activity (PA) is associated with higher levels of PWB and happiness. The high prevalence of physical inactivity among the Iranian population is concerning. Moreover, according to the Happiness Report 2024, Iran is ranked 100th out of 143 countries. Thus, this research aimed to study the PWB, happiness, and PA in Iranian age groups. Methods The study sampled 1,050 participants, equally divided into young, middle-aged, and elderly groups, using randomized cluster sampling from urban areas across five geographic regions in Iran. The study utilized four questionnaires: a Demographic Information Questionnaire, the International Physical Activity Questionnaire (IPAQ), Ryff’s Scales of PWB (18-item form), and the Oxford Happiness Questionnaire (OHQ). Descriptive statistics were used for summarizing data, and inferential analyses included Pearson’s correlation coefficient, one-way ANOVA, the Bonferroni test, and multivariate regression, all with a significance level set at P<0.05. Results Middle-aged individuals had the highest PA (1015.69±730.63 MET-minutes per week) and reported the highest happiness (111.97±24.08) and PWB (63.75±11.17) levels. The elderly had the lowest levels of PA (677.78±592.50 MET-minutes per week), happiness (107.63±24.01), and PWB (60.05±10.02). Statistical tests showed significant differences in PA, happiness, and PWB between the age groups (P<0.05), with no significant difference between young and elderly in PA (P>0.05). Physical activity positively correlated with happiness and PWB, especially in the elderly. Multivariate regression revealed that PA significantly predicts happiness (F = 30.993, t = 6.96, B = 0.211) and PWB (F = 86.85, t = 9.32, B = 0.004), explaining 4.4% and 8.0% of their variances, respectively. Conclusions The study concludes that increasing PA enhances happiness and PWB. Practical applications include promoting PA to improve mental health and PWB. Future research should investigate the effects of specific types of PA and explore longitudinal impacts on PWB to provide a deeper understanding of these relationships.