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Accuracy of next-generation sequencing for rapid diagnosis of tuberculous pleurisy: A protocol of systematic review and meta-analysis

Background Early, rapid and precise diagnosis of tuberculous pleurisy is difficult. Next-generation sequencing (NGS) has been used for the diagnosis of TB in some high-income countries. We completed the protocol of the study in order to better guide the systematic review and meta-analysis for evaluating the role of NGS in the diagnosis of tuberculous pleurisy, which was the purpose of the current study. Methods We designed and drafted this protocol as per the Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) guidelines. Three English databases (Cochrane Library, Embase and Medline via PubMed) and two Chinese databases (China National Knowledge Infrastructure and Wanfang Database) will be used to search for relevant studies. We followed the PICT principles to develop the eligibility criteria. Once the final compliant literature is identified, we will extract the valid information from the literature for statistical analysis. We will assess the quality of the included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. When there are more than 4 eligible studies, we will use Stata (version 15.0; Stata Corp., College Station, TX, the USA) with midas module to conduct the relevant meta-analysis and plot the relevant forest plots and curves. When there are less than 4 eligible studies, we will use Meta-DiSc (version 1.4) to perform the associated meta-analysis and plot the associated forest plots and curves. We will use the I2 statistic to assess heterogeneity between included studies. We will conduct meta-regression analysis, subgroup analysis and sensitivity analysis to explore possible sources of heterogeneity when significant heterogeneity exists. Systematic review registration PROSPERO Registration number: CRD42024568791

Kinetics of NS1 and anti-NS1 IgG following dengue infection reveals likely early formation of immune complexes in secondary infected patients

Factors associated with concordance of mother-child (6–23 months) dietary diversity in Sub-Saharan Africa

Background Inadequate dietary diversity is a major contributor to undernutrition, and compromises the health of both mothers and children. Available evidence demonstrates a significant association between maternal and child dietary diversity. However, there is limited evidence about the factors influencing the concordance of mother-child dietary diversity in Sub-Saharan Africa (SSA). Therefore, we investigated the factors associated with the concordance of mother-child dietary diversity in SSA. Methods A community-based cross-sectional study was conducted based on the recent Demographic and Health Surveys (DHS) data of eight Sub-Saharan African countries. A total weighted sample of 29,138 mother-child pairs within the five years preceding the survey was included. A mixed-effect binary logistic regression model was employed to identify factors associated with concordance between mother-child dietary diversity. Variable with p-value < 0.2 in the bivariable mixed-effect binary logistic regression analysis was considered for the multivariable analysis. In the multivariable mixed-effect binary logistic regression analysis, the Adjusted Odds Ratios (AOR) with 95% Confidence Intervals (CI) were reported. The percentage of agreement between mothers and children with minimum dietary diversity was assessed using kappa statistics. Results The concordance of dietary diversity between mother-child pairs in SSA was 74.48% (95% CI: 73.98, 74.98). A higher likelihood of mother-child dietary diversity concordance was significantly associated with mothers who had a primary level of education (AOR = 1.40, 95% CI: 1.31, 1.53) and those who were divorced or widowed (AOR = 1.54, 95% CI: 1.29, 1.84). Conversely, lower odds of concordance were observed among mothers with higher education (AOR = 0.75, 95% CI: 0.66, 0.85), those exposed to media (AOR = 0.78, 95% CI: 0.73, 0.83), and mothers belonging to poorer (AOR = 0.81, 95% CI: 0.74, 0.88), middle-income (AOR = 0.82, 95% CI: 0.75, 0.89), richer (AOR = 0.80, 95% CI: 0.73, 0.88), and richest (AOR = 0.75, 95% CI: 0.67, 0.83) households. Conclusion The findings highlight that the dietary diversity concordance between mother-child pairs in sub-Saharan Africa is moderate at 74.48%. However, the factors influencing concordance suggest socio-economic and educational disparities. Mothers with a primary education level and those who were divorced or widowed had higher concordance with their children’s dietary diversity, indicating their potential prioritization of family dietary habits despite limited resources or support systems. On the other hand, lower concordance among mothers with higher education and those exposed to media suggest that these groups may adopt more individualized dietary practices. Furthermore, households with higher economic status, surprisingly, exhibited lower concordance, which may indicate resource allocation differences within wealthier families or greater dietary autonomy among children. Globally, one-fourth of children aged 6–23 months and two-thirds of women of reproductive age suffer from micronutrient deficiencies, primarily due to inadequate dietary diversity [1–3]. It is estimated that 50–70% of the global disease burden is associated with poor dietary patterns and malnutrition [4]. In Low- and Middle-income Countries (LMICs), where many impoverished and rural households depend on starchy staples due to limited access to diverse foods, only 20% of children meet minimum acceptable dietary standards, exacerbating malnutrition and related health challenges [5,6]. Dietary Diversity (DD) is recognized as a key indicator of a healthy diet, reflecting the variety of food groups consumed within 24 hours [7]. According to the World Health Organization (WHO), DD serves as a proxy for child feeding practices, with consumption from at least four different food groups indicating that the child likely consumed an animal-source food, a fruit or vegetable, and a staple food such as grains, roots, or tubers [8].

Discrimination of inherent characteristics of susceptible and resistant strains of Anopheles gambiae by explainable artificial intelligence analysis of flight trajectories

Abstract Understanding mosquito behaviours is vital for the development of insecticide-treated nets (ITNs), which have been successfully deployed in sub-Saharan Africa to reduce disease transmission, particularly malaria. However, rising insecticide resistance (IR) among mosquito populations, owing to genetic and behavioural changes, poses a significant challenge. We present a machine learning pipeline that successfully distinguishes between innate IR and insecticide-susceptible (IS) mosquito flight behaviours independent of insecticidal exposure by analysing trajectory data. Data-driven methods are introduced to accommodate common tracking system shortcomings that occur due to mosquito positions being occluded by the bednet or other objects. Trajectories, obtained from room-scale tracking of two IR and two IS strains around a human-baited, untreated bednet, were analysed using features such as velocity, acceleration, and geometric descriptors. Using these features, an XGBoost model achieved a balanced accuracy of 0.743 and a ROC AUC of 0.813 in classifying IR from IS mosquitoes. SHAP analysis helped decipher that IR mosquitoes tend to fly slower with more directed flight paths and lower variability than IS—traits that are likely a fitness advantage by enhancing their ability to respond more quickly to bloodmeal cues. This approach provides valuable insights based on flight behaviour that can reveal the action of interventions and insecticides on mosquito physiology.

Structures and functions of the limited natural polyclonal antibody response to parvovirus infection

Host antibody responses are key components in the protection of animals against pathogens, yet the defining properties of viral antigens and induction of B cell responses that result in varied protection are still poorly understood. Parvoviruses are simple molecular structures that display 60 repeated motifs on their capsid surface, and rapidly induce strong antibody responses that protect animals from infection. We recently showed that following canine parvovirus infection of its natural host, the polyclonal response in the sera contained only two or three dominant antibodies that bound two epitopes on the capsid. Here, we characterize key antibodies present in that immune response, identifying their sequences, defining their binding properties on the capsid by cryoelectron microscopic (cryoEM) analysis, and testing their effects on viral infectivity. Two antibodies sharing the same heavy chain bound to the side of the capsid threefold spike (B-site), while another distinct antibody bound close to the threefold axis (A-site). The epitopes of these antibodies overlapped the binding site of the host receptor, the transferrin receptor type-1, but to varying degrees. The antibodies varied widely in their neutralization efficiencies as either immunoglobulins (IgGs) or monomeric antigen-binding fragments (Fabs), which was consistent with their ability to compete for the receptor. The monoclonal antibodies characterized here matched the structures from the cryoEM analysis of polyclonal sera, including those present in a different dog than the monoclonal source. This shows that after infection, a focused response to the viral antigen is produced that protects against infection.

Encourage or inhibit: A study on the impact of corporate digital transformation on management’s tone manipulation of information disclosure

Digitalization is anticipated to substantially improve information transparency and enhance the capital market’s information environment. However, during the initial phase of digital transformation, companies face challenges in achieving high-quality information disclosure. This is because digital technology implementation and organizational adjustment are still at early stages. Concurrently, investors face difficulties in assessing the accuracy of disclosed information. This challenge provides management with the opportunity to overstate the benefits of digital transformation. This study investigates the impact of corporate digital transformation on management’s tone manipulation behavior, using a sample of Chinese A-share listed companies from 2012 to 2021. Findings indicate that corporate digital transformation significantly fosters management’s tone manipulation during its exploration phase. Media slant positively moderates this relationship. Further analysis supports the paper’s hypothesis: companies with weaker financial flexibility and lower risk information disclosure levels show a stronger positive correlation between digital transformation and tone manipulation. Concurrently, mechanism analysis reveals that management overconfidence partially mediates the relationship. This suggests that digital transformation increases managerial overconfidence, thereby promoting tone manipulation. The conclusion offers new insights into enhancing management discussion and analysis information disclosure quality from a corporate strategic transformation perspective. It serves as a valuable reference for accurately identifying misleading management signals.

The mediating role of behavioral systems in linking physical activity and anxiety symptoms in college students

Factors affecting prognosis in traumatic cerebral contusions: A protocol for a systematic review and meta-analysis

Background Traumatic cerebral contusion (CC) is a severe type of injury among traumatic brain injury (TBI) patients. Individuals with traumatic CC typically exhibit rapid deterioration in their condition, leading to increased mortality rates. Despite this, there is a gap in evidence-based research. This study aims to identify the risk factors associated with adverse outcomes in patients with traumatic CC, with a particular focus on relevant biomarkers. Mortality will be the primary outcome, while the Glasgow Coma Scale (GCS) score will be considered as a secondary outcome. Methods and analysis We intend to conduct a comprehensive search through multiple Chinese and English repositories, covering the duration from the establishment of these databases up to the current era, in order to pinpoint appropriate studies. Additionally, a manual search of the references within the included literature and other pertinent works will be undertaken. The primary endpoint of this study will be the survival status of patients with traumatic brain contusion. Meta-analysis will be executed using STATA 16.0 (Stata Corporation, College Station, TX). Article selection and data extraction will be performed independently by two reviewers. The assessment of bias risks will be conducted via the Cochrane Collaboration’s tool. Depending on the heterogeneity evaluation, either a fixed-effect model or a random-effects model will be applied. Subgroup and sensitivity analyses will be conducted as needed. The examination of publication bias will be carried out, and the quality of evidence for the primary outcomes will be graded. Trial registration number: CRD42023389456

Combined bio fortification of spinach plant through foliar spraying with iodine and selenium elements

Effect of drainage layers on water retention of potting media in containers

Excess water retention in the potting medium can be a significant problem for plants grown in containers due to the volume of saturated medium which forms above the drainage hole. Adding a layer of coarse material like gravel or sand at the bottom is a common practise among gardeners with the aim of improving drainage, but some researchers have argued that such layers will raise the saturated area and in fact increase water retention. Two different depths and four different materials of drainage layer were tested with three different potting media to determine the water retention in the container after saturating and draining freely. For loamless organic media, almost all types of drainage layer reduced overall water retention in the container compared to controls. For loam-based media, most drainage layers had no effect on the overall water retention. Two simple models were also used to estimate the water retention in the media alone, excluding the drainage layer itself. All drainage layers reduced water retention of loamless organic media, according to both models. There was disagreement between the two models applied to loam-based media, and further study is required to determine the most accurate. Both models showed that some drainage layers with smaller particle sizes reduced water retention in loam-based media, but disagreed on the effect of drainage layers with larger particle sizes. Overall, any drainage layer was likely to reduce water retention of any medium, and almost never increased it. Thicker drainage layers were more effective than thinner layers, with the most effective substrate depending on the potting media used. A 60 mm layer of coarse sand was the most universally-effective drainage layer with all potting media tested.

A deep learning based prediction model for effective elastic properties of porous materials

Impact of β-defensin 103 (DEFB103) copy number variation on bull sperm parameters and post-insemination uterine gene expression

Pregnancy rates for elite bulls used in artificial insemination (AI) can vary significantly and therefore the identification of molecular markers for fertility and targets to improve bull selection is important. β-defensin peptides have diverse regulatory roles in sperm function across multiple species but the role of copy number variation (CNV) on fertility parameters has not been previously evaluated. In this study, Holstein-Friesian bulls were screened based on reliable field fertility data to identify two groups (High and Low fertility (HF and LF, respectively)) of n = 10 bulls/group which were genotyped for β-defensin 103 (DEFB103) gene CNV by droplet digital PCR. Overall, low DEFB103 copy number (CN) was associated with increased sperm motility across all bulls (n = 20, p < 0.05). As genetic diversity of DEFB103 CN was only apparent in the LF group, three bulls per CNV class (low, intermediate and high CN) were chosen for more detailed comparative functional analysis. Sperm from low CN bulls exhibited higher binding to the oviductal epithelium, while high CN increased sperm membrane fluidity in vitro (p < 0.05). To investigate the functional effect of DEFB103 CNV on the uterine response in vivo, 18 heifers were inseminated with sperm from bulls with low, intermediate and high CN. Transcriptomic analysis on uterine tissue harvested 12 h post-insemination showed differential expression of 58 genes (FDR < 0.1) involved in sperm migration, immune signalling and chemotaxis. Although field fertility results from a complex number of interactive factors, these novel results suggest a contributory role for DEFB103 CN in both sperm function and the uterine response to bull sperm, thereby potentially contributing to pregnancy outcomes in cattle. Further analysis of the role of CNV in additional β-defensin genes in bull fertility is now warranted.

Discovery and characterization of a novel telomerase alternative splicing isoform that protects lung cancer cells from chemotherapy induced cell death

Abstract All cancer cells must adopt a telomere maintenance mechanism to achieve replicative immortality. Most human cancer cells utilize the enzyme telomerase to maintain telomeres. Alternative splicing of TERT regulates the amount and function of telomerase, however many alternative splicing isoforms of TERT have unknown functions. Single molecule long read RNA/cDNA sequencing of TERT revealed 45 TERT mRNA variants including 13 known and 32 novel variants. Among the variants, TERT Delta 2–4, which lacks exons 2–4 but retains the original open reading frame, was selected for further study. Induced pluripotent stem cells and cancer cells express higher levels of TERT Delta 2–4 compared to primary human bronchial epithelial cells. Overexpression of TERT Delta 2–4 enhanced clonogenicity and resistance to cisplatin-induced cell death. Knockdown of endogenous TERT Delta 2–4 in Calu-6 cells reduced clonogenicity and resistance to cisplatin. Our results suggest that TERT Delta 2–4 enhances cancer cells’ resistance to cell death. RNA sequencing following knockdown of Delta 2–4 TERT indicates that translation is downregulated and that mitochondrial related proteins are upregulated compared to controls. Overall, our data indicate that TERT produces many isoforms that influence the function of TERT and the abundance and activity of telomerase.

Fetal genetic factors in pregnancy loss: Insights from a meta-analysis and effectiveness of whole exome sequencing

Spontaneous pregnancy loss commonly occurs during the first trimester and can be caused by various factors including chromosomal abnormalities and submicroscopic aberrations. After the first trimester, the etiology of most pregnancy losses remains undetermined. This study aims to fill this gap by an in-depth investigation of the fetal genome and its effect on pregnancy outcome. Data from 1016 spontaneously aborted fetuses previously referred for genetic testing (2017–2023) were used for meta-analysis. Fetuses were categorized based on gestational age and genetic test result. Additionally, 35 second-third trimester fetuses, that were spontaneously aborted, terminated or died neonatally, with abnormal ultrasounds and unrevealing routine genetic testing were collected. Trio-based whole-exome sequencing was performed for identification of fetal variants that may have caused the pregnancy loss. The meta-analysis revealed that 822 of 1016 fetuses (80.91%) were aborted during the first trimester, with 569 of 822 (69.22%) successfully diagnosed using conventional genetic testing. The remaining 194 fetuses (19.09%) were aborted during the second-third trimester. Of the 194 second-third trimester aborted fetuses, 163 (84.02%) lacked genetic diagnosis using conventional testing (karyotype and array-CGH). Aneuploidies were the leading cause of spontaneous pregnancy loss in both first and second-third trimester fetuses followed by polyploidies. Thus, the meta-analysis demonstrated that undiagnosed second-third trimester pregnancy losses are more likely to benefit from further genetic investigation. Application of whole exome sequencing on second-third trimester pregnancy losses, revealed causative variants in 6 of 33 families (18.18%), in genes linked to Mendelian disorders associated with the phenotypes of interest. Pathogenic findings were identified in two additional families in heterozygosity in genes following autosomal recessive inheritance. Accurate identification of variants in such genes creates new genotype-in utero phenotype associations, with the prospect of new additions in preconception/prenatal diagnostic panels. This study highlights the importance of whole exome sequencing in resolving undiagnosed pregnancy losses.

An improved A* algorithm for generating four-track trajectory planning to adapt to longitudinal rugged terrain

Evaluation of psychiatric conditions in asymptomatic outpatient clinic patients

Introduction A significant part of the internal medicine outpatient clinic burden consists of patients who are asymptomatic and intend to have routine check-up tests. In this study, we aimed to investigate the relationship between visit frequency within a year and the undiagnosed anxiety, depressive mood or obsessive-compulsive disorder. Methods We included in our study 129 participants who applied for routine check-up tests to our hospital’s internal medicine outpatient clinic, without any complaint and known diseases. Individuals were divided into two groups: Group 1 comprised individuals who applied once a year, whereas Group 2 included those who applied more than once a year. Participants underwent routine blood testing, and their mental health was assessed with the Beck`s Depression Inventory (BDI), Beck`s Anxiety Inventory (BAI), and Vancouver Obsessinal Compulsive Inventory (VOCI). Results 66% of the 129 participants included in the study were female (n = 85/44, p < 0.001). When laboratory parameters were examined, no significant difference was found except serum vitamin D levels (14.5/19.8 µg/L, p = 0.024, respectively). BDI and BAI scores were statistically significantly higher in Group 2 (10/14, p = 0.032, 11/13.5, p = 0.027, respectively). There was no difference between the two groups in terms of VOCI scores. Conclusion Asymptomatic patients who are visiting clinics for routine checkups constitute a significant part of the outpatient clinic workload. Assessing the mental health of patients who are attending frequently might be helpful in reducing this burden as well as in diagnosing and initiating treatment of undiagnosed underlying mental disorders. To ensure timely referrals of these patients to psychiatry, an adequate referral system and awareness of early signs of anxiety and depression among healthcare professionals are needed.

The role of RNA structural motifs in RNA-lipid raft interaction

Effects of pressure on the survival and viability of cancer cells in vitro: An analytical study

Intense cancer research is underway to discover possible therapies but no major breakthrough appears to be in sight in terms of its cure when diagnosed late. The cytostatic and growth inhibitory effect of high pressure on cells is well documented. In the present study, two cancer cell lines viz. MDA-MB-231 (breast carcinoma) and A549 (lung carcinoma) and one normal cell line (Vero) were subjected to increased pressure of 18 psi in a specially constructed pressure chamber. It was found that a pressure of 18 psi induced a significant change in the growth parameters of both cancer cell lines versus normal cells. Exposure to increased pressure greatly increased the proportion of MDA-MB-231 cells in the S phase while concurrently reducing the number of cells in the G0/G1 phase as compared to their untreated counterparts. SEM and AFM analysis revealed presence of characteristic ‘pores’ and ‘pits’ on the cell surface of pressure-treated versus untreated cancer cells. TEM analysis also revealed significant intracellular differences between pressure-treated and untreated cancer cells. Hyperbaric nitrogen therapy is proposed as a novel cancer-treatment modality involving administration of N2 at the tumor site in murine models of breast and lung cancer. This would eventually pave the way for development of a device effective treatment strategy for human tumors in future.

Mechanism of calcitonin gene related peptide against acute pancreatitis in rats by modulating amino acid metabolism based on metabonomics

Astragalus polyphenols attenuates doxorubicin-induced cardiotoxicity by activating the PI3K/AKT/NRF2 pathway

Background Doxorubicin (DOX) is a powerful chemotherapeutic agent commonly employed in cancer treatment. However, its clinical utility is constrained by dose-dependent cardiotoxicity, which can result in heart failure and sudden cardiac death. The molecular mechanisms of DOX-induced cardiotoxicity (DIC) include oxidative stress, mitochondrial dysfunction, and the activation of cell death pathways, including ferroptosis. There is an urgent need for effective therapeutic strategies to mitigate DIC. Methods This study investigates the cardioprotective effects of Astragalus Polyphenols (ASP), a bioactive compound extracted from Astragalus membranaceus. In the context of DIC, we utilized AC16 and H9C2 cardiomyocytes to establish a DIC model and assessed the effects of ASP on cell viability, oxidative stress, mitochondrial function, and the PI3K/AKT/NRF2 signaling pathway. The expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), markers of cardiac injury, was also evaluated. Results ASP treatment significantly reversed DOX-induced reductions in cell viability and mitochondrial membrane potential (MMP) while also decreasing the levels of reactive oxygen species (ROS). Additionally, ASP also downregulated the expression of ANP and BNP, indicating a protective effect on cardiomyocytes. Furthermore, ASP activated the PI3K/AKT/NRF2 pathway, which was suppressed by DOX. Inhibition of this pathway using LY294002 and ML385 abolishes the protective effects of ASP, suggesting that ASP mediates its effects through the PI3K/AKT/NRF2 signaling axis. Conclusion ASP exhibits a protective effect against DOX-induced cardiotoxicity by regulating the PI3K/AKT/NRF2 pathway to reduce oxidative stress and preserve mitochondrial function. These findings suggest that ASP may serve as a potential therapeutic agent to alleviate DIC. Our results provide a novel strategy to protect the heart in patients undergoing DOX chemotherapy.