Search Results (260)

This grounded theory study examines how 40 married couples (N = 80) successfully maintained sexual abstinence until marriage, focusing on the strategies, relational processes, and spiritual commitments that sustained this non-normative practice. Because premarital abstinence is statistically uncommon among African Americans, this sample functions as a critical case context—offering a high-contrast environment in which grounded theory can clearly illuminate the relational and spiritual mechanisms that support abstinence maintenance. Using in-depth individual and dyadic interviews, the study explores how couples upheld abstinence in contexts where it was often encouraged within religious settings yet rarely modeled by parents, mentors, or peers. Findings revealed four interrelated processes: (a) a shared spiritual “why” grounded in sacred meaning, (b) mutual commitment and accountability, (c) proactive boundary-setting and trigger management, and (d) grace-based resilience and recommitment after lapses. Together, these processes illustrate the Premarital Sexual Abstinence Sustainability Model through which couples co-manage temptation and align their behaviors with shared spiritual values. Despite limited examples in their communities, many participants reported becoming perceived role models within their families and faith settings, demonstrating how new behavioral templates emerge when social models are absent. Overall, as the first study of its kind to document how abstaining couples sustain their commitment and experience success, this work offers new implications for research, relationship education, counseling, and faith-based program development. Full article

Insect hemocytic cell lines offer substantial advantages over primary, in vivo hemocyte cultures, fundamentally transforming experimental approaches in cellular immunology and related fields. Selected Malacosoma disstria cell lines were characterized for optimal growth temperatures, morphogenesis, blebbing, extracellular enzyme profiles, and their interactions with material (polystyrene) and microbial (Bacillus subtilis) surfaces. The adhesive hemocyte lines UA-Md221 and Md108 showed optimal growth at 28 °C, whereas UA-Md203 and Md66 grew best at 21 °C, with Md66 tolerating 21–28 °C. Md108 demonstrated a broader temperature tolerance than other adherent cultures. Both Md108 and UA-Md221 adhered to polystyrene within 24 h post-subculturing, although protease-induced morphological changes in modified Grace’s medium continued through 48 h and 72 h, respectively. Culture quality was monitored by assessing the release of multiple enzymes, including alkaline and acid phosphatases, esterases and lipases, aminopeptidases, proteases, glycosidases, and hydrolases from the cell lines at 50% confluency in modified Grace’s medium. Fetal bovine serum showed elevated esterase lipase (C8) and phosphoamidase activities when diluted in Grace’s medium and phosphate buffered saline (PBS). Exposure to dead B. subtilis suspended in PBS induced quantitative and qualitative alterations in the enzyme secretion profiles of Md66 and Md108 cultures. We conclude that semi-quantitative assessments of hemocytic cell lines can provide valuable insights for the time window of each enzyme release, revealing immune and metabolic signaling patterns. Full article

A point-of-care (POC) HIV drug resistance (HIV-DR) test is needed for low- and middle-income countries (LMICs). Oligonucleotide Ligation Assay (OLA)-Simple, designed as a near-POC HIV-DR test, was assessed for its overall usability in Kenya by technicians with and without molecular laboratory PCR experience. Further, its diagnostic accuracy was evaluated by PCR-experienced technicians utilizing 147 plasma samples with known Sanger sequence genotypes—based on seven major HIV-DR mutations of nucleotide and non-nucleoside reverse transcriptase inhibitors. Thirteen laboratory technicians were recruited, including five with prior PCR experience. Twelve technicians completed the training and attained OLA-Simple testing competency, ten of whom were able to perform the OLA-Simple test within 6 h. Technicians’ survey feedback indicated the user-friendliness of OLA-Simple, citing straightforward reagent reconstitution, concise instructions in prompts, and a shorter sample-to-result test time compared to standard genotyping assays. Of the 147 archived plasma samples tested, 132 (90%) yielded interpretable results. OLA-Simple assay demonstrated a sensitivity of 97.3% (95% CI 94.5, 98.9), a specificity of 97.2% (95% CI 95.5, 98.3), and a percent agreement of 97.1% (95% CI 95.9, 98.2) compared to Sanger sequencing. This evaluation found that OLA-Simple was user-friendly among intended end-users and performed well. LMIC HIV programs would benefit from strategizing on case-use scenarios for such near-POC HIV-DR assays to improve HIV outcomes. Full article

Background/Objectives: The micronutrient iron is closely connected to inflammation and is among the complex factors contributing to beta-cell failure in diabetes. High levels of dietary iron increase the risk of developing type 2 diabetes, and excessive iron uptake by beta-cells can cause oxidative stress and inhibit function. Elevated levels of proinflammatory cytokines in obese individuals, such as interleukin (IL)-1beta and IL-6, increase the risk of developing type 2 diabetes, and there is evidence that these low levels of circulating cytokines can lead to islet dysfunction. Methods: In this study, gene microarray and other data were analyzed for expression differences in islets treated for 48 h with 10 pg/mL IL-1beta + 20 pg/mL IL-6 as a model of low-grade inflammation versus untreated. Results: Three iron-associated genes were among the most cytokine-sensitive in the mouse genome: Hamp, Steap4, and Lcn2. These proteins are all involved with increasing/retaining cellular iron. We hypothesized that increased cellular iron would lead to increased susceptibility to ferroptosis. Surprisingly, 24 h pre-exposure to low-grade inflammation, which upregulates this iron-gene network, prevented subsequent erastin-induced ferroptosis. We also found that Steap4 overexpression reduced islet dysfunction caused by high-dose proinflammatory cytokines (10× low-dose), suggesting an overall protective effect. Steap4 overexpression also upregulated Hamp and Lcn2, suggesting Steap4 regulates these cytokine-sensitive iron genes.; in contrast, ferritin and ferroportin gene expression, which are not sensitive to cytokines, were unchanged. Conclusions: These data suggest an inflammation-induced network of genes involved in cellular iron uptake and retention plays a protective role in islets against oxidative stress and ferroptosis. Full article

CD19 CAR T-cell therapy has significantly improved the survival of patients with relapsed or refractory large B cell lymphoma (R/R LBCL) and is considered standard of care for eligible patients in Canada. Axicabtagene ciloleucel (axi-cel) is an autologous CAR T-cell therapy, initially approved by Health Canada for adults with R/R LBCL after 2 or more lines of therapy. This multi-centre analysis, with registry data collected from CIBMTR, aims to present a Canadian perspective on the real-world experience of axi-cel in patients with R/R LBCL. With a median follow-up of 12.4 months, the best objective response rate (ORR) and complete response (CR) rate among all patients were 77% and 59%, respectively. At 12 months, estimated progression-free survival (PFS) and overall survival (OS) were 49% and 59%, respectively. Notably, the incidence and severity of adverse events were lower in this cohort compared to ZUMA-1 and other real-world reports, with CRS occurring in 77% (grade ≥ 3, 3%) and ICANS occurring in 38% (grade ≥ 3, 10%) of patients. Outcomes remained largely consistent across patient and disease characteristics. These findings demonstrate effectiveness and safety profiles comparable to international real-world studies and the ZUMA-1 trial, supporting the use of axi-cel as an effective treatment across broad Canadian populations. Full article

Satellite attitude is critical for both satellite antenna phase center offset and phase wind-up correction. However, during the eclipse season, the nominal satellite attitude is almost impossible to maintain, and the satellite attitude variability affects the geometric distance correction of GNSS-LEO satellites, which ultimately affects the orbital accuracy of LEO satellites. To explore the impact of neglecting eclipsing attitude models on LEO satellite orbit determination, this study utilizes the attitude quaternion products provided by CNES to analyze the discrepancies between nominal attitude yaw angles and attitude quaternion-derived yaw angles. It also examines the variations in phase center offset and phase wind-up corrections, caused by neglecting eclipsing attitude models. The model is validated through orbit determination tests using onboard GRACE-FO data from days 90 to 109 of 2023. Based on these analyses, a simplified reduced-dynamic orbit determination model for LEO satellites using attitude quaternion is proposed. It is found that the phase residuals of GRACE-C and GRACE-D under the attitude quaternion strategy are reduced by 3.6% and 3.9%, respectively, and the orbital accuracies of GRACE-C and GRACE-D are improved by 7.3% and 4.5%, respectively, compared with the nominal attitude. Full article

Real-Time Precise Orbit Determination (RTPOD) of Low Earth Orbit (LEO) satellites relies primarily on onboard GNSS observations and may suffer from degraded performance when observation geometry weakens or tracking conditions deteriorate within satellite formations. To enhance the robustness and accuracy of RTPOD under such conditions, a cooperative Extended Kalman Filter (EKF) framework that fuses onboard GNSS and inter-satellite link (ISL) range measurements is established, integrated with an iterative Detection, Identification, and Adaptation (DIA) quality control algorithm. By introducing high-precision ISL range measurements, the strategy increases observation redundancy, improves the effective observation geometry, and provides strong relative position constraints among LEO satellites. This constraint strengthens solution stability and convergence, while simultaneously enhancing the sensitivity of the DIA-based quality control to observation outliers. The proposed strategy is validated in a simulated real-time environment using Centre National d’Etudes Spatiales (CNES) real-time products and onboard observations of the GRACE-FO mission. The results demonstrate comprehensive performance enhancements for both satellites over the experimental period. For the GRACE-D satellite, which suffers from about 17% data loss and a cycle slip ratio several times higher than that of GRACE-C, the mean orbit accuracy improves by 39% (from 13.1 cm to 8.0 cm), and the average convergence time is shortened by 44.3%. In comparison, the GRACE-C satellite achieves a 4.2% mean accuracy refinement and a 1.3% reduction in convergence time. These findings reveal a cooperative stabilization mechanism, where the high-precision spatiotemporal reference is transferred from the robust node to the degraded node via inter-satellite range measurements. This study demonstrates the effectiveness of the proposed method in enhancing the robustness and stability of formation orbit determination and provides algorithmic validation for future RTPOD of LEO satellite formations or large-scale constellations. Full article

Glioblastoma is the most aggressive primary brain malignancy, characterised by extensive intra-tumoural heterogeneity, therapy resistance, and a profoundly immunosuppressive tumour microenvironment. The galectin family, a group of β-galactoside-binding lectins, has emerged as a key regulator of tumour biology, influencing oncogenesis, immune modulation, and therapy resistance. In this study, we performed an integrative bioinformatics analysis to systematically evaluate the expression patterns, prognostic significance, genetic alterations, and functional roles of galectin family members in glioblastoma. We utilised publicly available genomic datasets and computational tools to perform our analysis, including UALCAN, GEPIA, cBioPortal, STRING, GeneMANIA, DAVID, and TIMER. We identified LGALS1, LGALS3, and LGALS9 as significantly upregulated in glioblastoma, with their overexpression correlating with adverse patient survival. Functional enrichment analysis highlighted galectin-mediated pathways involved in extracellular matrix remodelling, immune dysregulation, tumour-promoting pathways, and protein processing, suggesting their pivotal role in glioblastoma pathogenesis. We also show that transcriptional and immunological signatures suggest that galectins may regulate glioblastoma immunosuppression, extracellular matrix remodelling, and protein homeostasis. Our findings provide novel insights into the oncogenic and immunoregulatory roles of galectins in glioblastoma, establishing their potential as prognostic biomarkers and therapeutic targets. Full article

Background/objectives: Understanding the immune landscape in cervical cancer is critical to the development of improved therapeutics. This study investigated the immune microenvironment in early-stage cervical cancer with a focus on B and T cell immune aggregates, i.e., lymphoid aggregates (LAs) and tertiary lymphoid structures (TLSs). Methods: Using multispectral imaging, we interrogated a cohort of patients with clinical stage I squamous or adenocarcinoma of the cervix with a focus on T and B cell spatial location and organization. Despite early-stage disease, recurrence was common at 37%, highlighting the need to identify patients at high risk for recurrence. Results: We demonstrated that high CD8+ T cell infiltration correlated significantly with improved overall survival (OS), particularly in patients with adenocarcinoma histology. CD8+ T cells colocalized with B cells, suggesting the formation of a more sophisticated cellular neighborhood, i.e., TLS, which has prognostic benefit in other solid tumors. CXCL13, a chemokine associated with TLS formation, correlated with improved recurrence-free survival. The combination of high CXCL13 and lymphoid structures correlated with improved OS. However, most immune structures in cervical cancer were lymphoid aggregates (LAs) that lack features of more developed TLS, such as high endothelial venules (HEVs) and germinal centers (GCs), highlighting a lack of full immune activation in this microenvironment. Validation in The Cancer Genome Atlas (TCGA) cohort illustrated similar trends in survival. Conclusions: Collectively, this work demonstrates the prognostic significance of immune infiltration and eventual TLS induction in early cervical cancer and presents potential future therapeutic targets. Full article

With new emerging diseases such as COVID-19 and an increasing incidence of cancer, there remains a significant need for investigating new therapeutic options to treat a wide range of ailments and disorders. Peppermint (Mentha × piperita) and white snakeroot (Ageratina altissima) have been used medicinally by native people in the Midwestern United States for centuries. However, the antiproliferative and antimicrobial properties of the aqueous extracts of these plants remain unclear. In this study, we evaluate the therapeutic potential of peppermint and white snakeroot aqueous leaf extracts by examining their activity against mammalian cancer cells, bacteria, and viruses. Both peppermint and snakeroot extracts showed no reductions in viability at concentrations lower than 25 mg/mL and 10 mg/mL, respectively, in two different cancer lines, HEp-2 and DBT-9 cells, in vitro. While treatment with the snakeroot extract resulted in significant disruption to cytoskeletal organization in HEp-2 cells at a concentration of 10 mg/mL, peppermint and snakeroot extracts did not have a major impact on the viability or proliferation of the cancer cell lines tested. Peppermint and snakeroot were then evaluated for antibacterial activity against four different bacterial pathogens. Significant inhibition of bacterial replication was observed for E. coli (at concentrations greater than 0.1 mg/mL) and S. aureus (at concentrations greater than 1 mg/mL) treated with either peppermint or snakeroot extracts. No significant activity was observed against the bacterial strains P. aeruginosa and S. pyogenes. Peppermint (EC₅₀ = 2.36 mg/mL) and snakeroot (EC₅₀ = 2.64 mg/mL) significantly reduce infectivity and replication (at concentrations above 0.2 mg/mL) of the major human pathogen, human respiratory syncytial virus (hRSV). However, testing for antiviral activity against a mouse coronavirus (murine hepatitis virus, MHV) showed no impact on replication at concentrations up to 2.5 mg/mL. Lastly, chemical analysis of the extracts identified several prominent compounds, which were subsequently evaluated for their biological contributions to the observed plant extract phenotypes. Two of the identified compounds, 1,8-cineole (Eucalyptol) and menthol, show significant antimicrobial activity. We report that aqueous extracts of peppermint and white snakeroot exhibit specific antibacterial and antiviral activities that support further investigation for therapeutic potential. Full article

Background: The GRACE score is widely used to estimate early mortality in acute coronary syndromes (ACS), yet its ability to capture the complex interaction between inflammation, hepatic dysfunction, renal impairment, and myocardial injury remains limited. Integrating biomarkers that reflect these complementary physiological pathways may enhance risk prediction and allow earlier identification of high-risk patients. This study evaluated whether a multi-biomarker model incorporating the C-reactive protein/albumin ratio (CAR), the albumin–bilirubin (ALBI) score, and the blood urea nitrogen/creatinine (BUN/Cr) ratio provides incremental prognostic value beyond the GRACE score and traditional cardiac markers. Methods: This retrospective study included patients hospitalized with ACS. Baseline laboratory results were used to calculate CAR, ALBI, and BUN/Cr ratios. Troponin and hemoglobin values were recorded as standard cardiac and hematologic indicators. The primary outcome was in-hospital mortality. Logistic regression models, receiver operating characteristic (ROC) curve analysis, and comparisons of area under the curve (AUC) were performed to determine whether the multi-biomarker model improved risk stratification beyond the GRACE score alone. Results: Higher CAR, ALBI, and BUN/Cr values were each associated with increased in-hospital mortality. When combined with the GRACE score, the multi-biomarker model significantly improved predictive accuracy. The integrated model demonstrated a higher AUC compared with GRACE alone, indicating incremental prognostic value across inflammatory, hepatic, and renal pathways. Conclusions: A multi-biomarker strategy combining CAR, ALBI, and BUN/Cr ratios enhances early mortality prediction beyond the GRACE score in patients with ACS. Incorporating these readily available laboratory indices may help clinicians identify high-risk patients more precisely at the time of hospital admission. Full article

Background: Pneumonia contributes to post-burn morbidity and mortality. Understanding the mechanisms that predispose burn patients to pneumonia is crucial to both stratifying patients at increased risk and developing targeted interventions. Methods: A prospective observational study was conducted with 47 human patients who sustained large burn injuries with serum collected on days 2 and 3 post-burn and assessed for Angiopoietin-1 (Ang-1) and -2 (Ang-2). C57BL/6 mice were subjected to either sham injury or a 12.5% total body surface area (TBSA) scald burn injury, and plasma and lungs were assessed. Results: Patients who developed pneumonia within 30 days of injury had higher serum Ang-2 and Ang-2/1 ratio on post-injury days 2 and 3. Similar to patient findings, we observed an increase in Ang-2 in burn mice compared to sham. Within the lungs of burn mice, we found significant increases in Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (TIE2) receptor transcript Tek, downstream mediators TNFAIP3 Interacting Protein 2 (Tnip2) and phosphoinositide-3-kinase regulatory subunit 1 (Pik3r1), in addition to endothelial adhesion molecules intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), along with neutrophil infiltration and markers compared to sham. Conclusions: These findings suggest that burn injury increases Angiopoetin-2 and downstream signaling in the lungs, which may contribute to post-burn pulmonary dysfunction. Further studies are necessary to understand if modulating the Ang–TIE2 axis can protect against pneumonia post-burn. Full article

This study evaluates the incidence of metabolic disorders detected from January 2005 to December 2024 and their clinical outcomes. Data were retrospectively collected from the Louisiana Newborn Screening database. Clinical outcomes were obtained through review of corresponding medical records. In addition, an electronic questionnaire assessing educational attainment and neurodevelopmental disorders was sent to the patients’ families. Of 1,230,356 infants screened, 478 were diagnosed with metabolic disorders, corresponding to an incidence of 1 in 2574 live births. The three most commonly identified conditions were biotinidase deficiency, phenylketonuria (PKU), and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). During the study period, at least 11 patients died. The program demonstrated a false-positive rate of 0.93%. Twelve patients (7%) were symptomatic before or at the time of NBS result notification. Recurrent metabolic decompensations occurred in 3 of 4 maple syrup urine disease (MSUD) cases, 7 of 7 methylmalonic acidemia (MMA) cases, 1 of 4 propionic acidemia (PA) cases and 1 of 7 urea cycle defect cases. Regarding long-term outcomes, 45.7% of survey respondents reported adverse neurodevelopmental outcomes of varying severity. Early detection and timely intervention have contributed to normal or near-normal outcomes in many cases. However, the morbidity and mortality observed in some patients despite early diagnosis highlights the severity and complexity of certain metabolic conditions. Additionally, the relatively high false positive rate underscores the need for ongoing efforts to improve the specificity of screening protocols to reduce unnecessary follow-ups and mitigate potential stress for families. Full article

Host-vector contact rates influence the spread of several vector-borne infections, including avian haemoparasites. To investigate the ecological mechanisms underlying avian disease dynamics, we examined haemoparasite prevalences in relation to bird life-history attributes. Using previously collected data of 1003 birds sampled from an Afrotropical region, we tested the hypothesis that a bird’s behavioural traits and habitat do not influence the chances of infection. Overall, infection prevalence did not differ significantly between gregarious and solitary birds, nor across association categories (wild, mixed, anthropogenic). However, significant differences in infection were detected across haemoparasite genera. Plasmodium, Haemoproteus, and Leucocytozoon showed distinct infection patterns in relation to host behavioural traits and habitats. Moreover, there were significant differences in infection prevalence based on movement patterns (resident, nomadic, migratory) and foraging strata (ground, mixed, aerial). These results enhance our avian parasitology theories, indicating that behavioural traits and habitat also have parasite-genus-dependent impacts on infection prevalence. Our research demonstrates that behavioural characteristics have an unequal impact on haemoparasite prevalence, indicating that no single factor can accurately predict the probability of infection at an Afrotropical setting. Full article