Investigation on cost-effective composites for CO2 adsorption from post-gasification residue and metal organic framework.

Cost-effective CO2 adsorbents are gaining increasing attention as viable solutions for mitigating climate change. In this study, composites were synthesized by electrochemically combining the post-gasification residue of Macadamia nut shell with copper benzene-1,3,5-tricarboxylate (CuBTC). Among the different composites synthesized, the ratio of 1:1 between biochar and CuBTC (B 1:1) demonstrated the highest CO2 adsorption capacity. Under controlled laboratory conditions (0°C, 1 bar, without the influence of ambient moisture or CO2 diffusion limitations), B 1:1 achieved a CO2 adsorption capacity of 9.8 mmol/g, while under industrial-like conditions (25°C, 1 bar, taking into account the impact of ambient moisture and CO2 diffusion limitations within a bed of adsorbent), it reached 6.2 mmol/g. These values surpassed those reported for various advanced CO2 adsorbents investigated in previous studies. The superior performance of the B 1:1 composite can be attributed to the optimization of the number of active sites, porosity, and the preservation of the full physical and chemical surface properties of both parent materials. Furthermore, the composite exhibited a notable CO2/N2 selectivity and improved stability under moisture conditions. These favorable characteristics make B 1:1 a promising candidate for industrial applications.

Comparison of the Marginal and Internal Fit of Ceramic Laminate Veneers Fabricated with Four Different Computer-Aided Manufacturing Techniques.

Purpose: The improvement of computer-aided design and computer-aided manufacturing (CAD/CAM) has changed the methods of fabricating laminate veneers. The objectives of this study were to evaluate the marginal and internal fit of ceramic veneers manufactured with different CAD/CAM techniques. Materials and methods: A metal die was made by copying a prepared plastic maxillary central right incisor and scanned for designing a laminate veneer. One hundred laminate veneers were made with four different CAD/CAM techniques (n=25), including milled lithium disilicate (MLD), heat-pressed lithium disilicate with 3-dimensional (3D) printed wax patterns (PLD), milled zirconia (MZ), and 3Dprinted zirconia (PZ). The virtual marginal and internal fit of fabricated veneers was evaluated with digital crown fitting software. The actual marginal and internal fit was measured with the silicone replica method under a digital microscope. The measured data were analyzed using the one-way analysis of variance and the Turkey test. Results: There were significant differences in marginal and internal fit (P < 0.001) among manufacturing techniques. Both the virtual and actual marginal and internal gaps were higher in the PLD and PZ groups compared to the MLD and MZ groups. Conclusion: All four CAD/CAM techniques of manufacturing veneers, that is, milled lithium disilicate, heat-pressed lithium disilicate with 3D-printed wax patterns, milled zirconia, and 3D-printed zirconia, have clinically acceptable marginal and internal fit. Milled zirconia and lithium disilicate veneers demonstrated superior marginal and internal fit compared to 3D-printed zirconia and heat-pressed lithium disilicate veneers with 3D-printed wax patterns.

Antibiotic Management for Early-Onset Sepsis in Neonates With Gestational Ages of ≥ 34 Weeks: The Kaiser Sepsis Calculator Versus the 2010 CDC Guidelines.

INTRODUCTION: The traditional approach to neonatal early-onset sepsis (NEOS) management, involving maternal risk factors and nonspecific neonatal symptoms, usually leads to unnecessary antibiotic use. This study addresses these concerns by evaluating the Kaiser sepsis calculator (KSC) in guiding antibiotic therapy for NEOS, especially in high-incidence facilities (over 4/1,000 live births), by comparing it against the 2010 Centers for Disease Control and Prevention (CDC) guidelines for neonates ≥34 weeks with suspected sepsis, thereby emphasizing its implications for personalized patient care. METHODS: This is a prospective observational study. All neonates of 34 gestational weeks or more, presenting with either maternal risk factors or sepsis symptoms within 12 hours of birth, were included in the study. The analysis focused on antibiotic recommendations by the 2010 CDC guidelines versus those by the KSC at presumed (0.5/1,000) and actual (16/1,000) sepsis incidence rates. RESULTS: NEOS was identified in 14 cases (14.1%). Compared to the KSC, at an incidence rate of 16 per 1,000, the KSC resulted in a significant 32.3% reduction in antibiotic treatment (74 cases (74.7%) vs. 42 cases (42.4%), respectively; p < 0.001). The calculator advised immediate antibiotic utilization for 13 out of 14 (92.9%) diagnosed cases, suggesting further evaluation for the remaining cases. When a presumed incidence of 0.5/1,000 was applied, the KSC indicated antibiotics less frequently than when using the actual rate of 16/1,000 (p<0.001) with two missed NEOS cases. CONCLUSIONS: Using the KSC led to a decrease of 32 cases (32.3%) in unnecessary antibiotic prescriptions compared to adherence to 2010 CDC guidelines. However, setting a presumed incidence below the actual rate risked missing NEOS. The calculator was effective when actual local incidence rates were used, ensuring no missed cases needing antibiotics.

Substitution of acidic residues near the catalytic Glu131 leads to human HYAL1 activity at neutral pH via charge-charge interactions.

Human hyaluronidase 1 (HYAL1) and PH20 play vital roles in degrading hyaluronic acids through the substrate-assisted double displacement mechanism. While HYAL1, a lysosomal enzyme, functions optimally under acidic conditions, PH20, a sperm surface hyaluronidase, displays a broader pH range, from acidic to neutral. Our objective was to extend HYAL1's pH range towards neutral pH by introducing repulsive charge-charge interactions involving the catalytic Glu131, increasing its pKa as the proton donor. Substituting individual acidic residues in the ß3-loop (S77D), ß3'-ß3″ hairpin (T86D and P87E), and at Ala132 (A132D and A132E) enabled HYAL1 to demonstrate enzyme activity at pH 7, with the mutants S77D, P87E, and A132E showing the highest activity in the substrate gel assay. However, double and triple substitutions, including S77D/T86D/A132E as found in the PH20 configuration, did not result in enhanced activity compared to single substitutions. Conversely, PH20 mutants with non-acidic substitutions, such as D94S in the ß3-loop and D103T in the ß3'-ß3″ hairpin, significantly reduced activity within the pH range of 4 to 7. However, the PH20 mutant E149A, reciprocally substituted compared to A132E in HYAL1, exhibited activity similar to PH20 wild-type (WT) at pH 7. In a turbidimetric assay, HYAL1 mutants with single acidic substitutions exhibited activity similar to that of PH20 WT at pH 7. These results suggest that substituting acidic residues near Glu131 results in HYAL1 activity at neutral pH through electrostatic repulsion. This study highlights the significance of charge-charge interactions in both HYAL1 and PH20 in regulating the pH-dependent activity of hyaluronidases.

The transcription factor LBD10 sustains pollen tube growth and integrity by modulating reactive oxygen species homeostasis via the regulation of flavonol biosynthesis in Arabidopsis.

Reproduction in angiosperms relies on the precise growth of pollen tubes, facilitating the delivery of sperm cells to the ovule for double fertilization. LATERAL ORGAN BOUNDARIES DOMAIN10 (LBD10), a plant-specific transcription factor, plays a pivotal role in Arabidopsis pollen development. Here, we uncovered LBD10's function in sustaining pollen tube growth and integrity. The lbd10 mutant exhibited elevated levels of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) in both pollen grains and tubes, leading to compromised pollen tube growth. The inhibition of ROS synthesis and scavenging of excess ROS with an antioxidant treatment each alleviated these defects in lbd10. The lbd10 mutant displayed reduced flavonol accumulation in both pollen grains and tubes. All the altered phenotypes of lbd10 were complemented by expressing LBD10 under its native promoter. Exogenous application of flavonoids recused the defects in pollen tube growth and integrity in lbd10, along with reducing the excess levels of ROS and H2O2. LBD10 directly binds the promoters of key flavonol biosynthesis genes in chromatin and promotes reporter gene expression in Arabidopsis mesophyll protoplasts. Our findings indicate that LBD10 modulates ROS homeostasis by transcriptionally activating genes crucial for flavonol biosynthesis, thereby maintaining pollen tube growth and integrity.

Hemodynamic characteristics in ruptured and unruptured intracranial aneurysms: a prospective cohort study utilizing the AneurysmFlow™ tool.

BACKGROUND AND PURPOSE: Hemodynamic factors significantly influence the onset, progression, and rupture of intracranial aneurysms (IAs). Current rupture risk prediction scores focus primarily on the clinical, anatomical and morphological aspects. This study aimed to investigate the hemodynamic characteristics differences between ruptured and unruptured IAs. MATERIALS AND METHODS: Conducted from July 2021 to July 2022, this prospective cohort study involved patients with ruptured and unruptured IAs undergoing digital subtraction angiography (DSA). Hemodynamic characteristics were assessed using the AneurysmFlow™ tool. Hemodynamic, clinical, anatomical and morphological parameters were compared between ruptured and unruptured IA groups. RESULTS: The study included 127 patients with 135 aneurysms (67 ruptured, 68 unruptured). Complex flow patterns (type 3 and 4) were observed more frequently in ruptured aneurysms compared to unruptured aneurysms (odds ratio [OR], 5.57; 95% confidence interval [CI], 2.49-12.45; P < 0.001) in univariate analysis, and were also more common in unruptured aneurysms associated with daughter sacs features (P = 0.015). The mean aneurysm flow amplitude (MAFA) was lower in ruptured aneurysms, and associated with lower flow velocity in the parent artery related to vasospasm. MAFA in the aneurysmal dome or any additional daughter sacs was lowest compared to other regions inside the aneurysms. The technical failure rate of AneurysmFlow™ measurements was 8.5% (12 out of 139 patients). Additionally, hypertension (OR, 0.42; 95% CI, 0.30-0.54; P < 0.001), bifurcation location (AcomA/ACA/MCA/PcomA/posterior circulation) (OR, 0.17; 95% CI, 0.05-0.29; P = 0.005), and irregular shape (OR, 0.19; 95% CI, 0.05-0.35; P = 0.012) were identified as independently associated with rupture. CONCLUSIONS: Complex flow patterns identified on the AneurysmFlow™ tool are significantly more common in ruptured and unruptured aneurysms associated with daughter sac features. The lowest MAFA in the aneurysmal dome and daughter sacs likely indicates specific pathophysiological changes within the aneurysm wall associated with rupture incidence. Hypertension, bifurcation location, and an irregular shape are independently associated with the risk of rupture. Further multicenter studies with larger sample sizes are needed to validate these findings. ABBREVIATIONS: ACA = anterior cerebral artery; AcomA = anterior communicating artery; IAs = intracranial aneurysms; ICA = internal carotid artery; MAFA = mean aneurysm flow amplitude; MCA = middle cerebral artery; PcomA = posterior communicating artery; RIAs = ruptured intracranial aneurysms; SAH = subarachnoid hemorrhage; UIAs = unruptured intracranial aneurysms.

Changes in the Quality of Life and Nutrition Markers in Transition From End-Stage Kidney Disease to Kidney Transplantation: Insights From a Vietnamese Cohort.

Background Malnutrition is strongly associated with lower quality of life (QoL) and lower survival rates in patients with end-stage kidney disease. However, the impact of renal transplantation on nutrition factors and QoL is unclear. Therefore, this study aims to assess changes in QoL and investigate the relationships with nutrition factors among kidney transplant recipients (KTRs). Materials and methods A longitudinal study included 86 dialysis patients aged 18-65 years who underwent primary kidney transplantation (KTx) and were followed up for one year. Body weight, biochemical parameters, and QoL data were collected before transplantation (T0) and at six months (T6) and 12 months (T12) post-transplantation. Effect size (ES) was used to measure the impact of KTx on QoL and nutritional status from T0 to T12. The predictors of QoL were calculated with ß-coefficients and p<0.05 in linear regression. Results The ES of transplantation on the QoL of KTRs was large, at 1.1 for health change, 0.9 for physical health, and moderate (0.7) for mental health (MH) over one year. Hemoglobin and malnourished were affected by KTx, with ES being 2.4 and 0.6, respectively. Linear regression showed that physical health was predicted by hemoglobin (ß=0.12, p<0.01), phosphorus (ß=7.82, p<0.05), and dose of mycophenolate mofetil (MMF) (ß=-0.01, p<0.05). Mental health was predicted by obesity (ß=-7.63, p<0.05), hemoglobin (ß=0.11, p<0.05), and phosphorus (ß=8.49, p<0.01). Health change was indicated by nutritional risk index (NRI) score (ß=0.47, p<0.05), total cholesterol (ß=3.39, p<0.01), and kidney function (ß=0.15, p<0.05). Conclusions The transition from end-stage kidney disease to transplantation has positive impacts on QoL and nutrition markers. Nutritional status, kidney function, and the dose of mycophenolate mofetil are significant determinants of QoL in KTRs.

Photo Visualization of Skintone Compatibility of an SPF 35 Sunscreen.

BACKGROUND: Visual casts and discoloration are common barriers to sunscreen use in melanin-rich populations. However, photoprotective measures are essential for individuals with all skin types, including darker skin. METHODS: Single-center, 7-day, open-label study of healthy adult females with Fitzpatrick Skin Types (FST) IV to VI and sensitive skin treated with once-daily daily facial moisturizer sun protection factor 35 (DFM SPF35). Subjects completed a cosmetic acceptability questionnaire at days 1 and 7. Photography using VISIA CR was performed at day 7. Adverse events were monitored throughout the study. RESULTS: Thirty-two (32) subjects participated; 31.3% had FST IV, 53.1% V, and 15.6% VI skin. DFM SPF35 was viewed as cosmetically elegant. At day 1, 96.7% of subjects agreed product was easy to apply; 90.0% reported soft skin after product use; 86.7% said it had a lightweight, non-greasy feel and hydrated the skin. At day 7, 93.7% reported no visible white residue on their skin and said the product applied easily/absorbed well. The majority (90.6%) would continue using and would recommend the product; and 87.5% reported the product blended seamlessly into their skin, which agreed with clinical photography. Responses were consistent among subjects with normal, oily, or combination skin. No adverse events were reported. CONCLUSIONS: DFM SPF35 blended well into the skin and was perceived favorably among subjects with SOC after 1 and 7 days of use. Subjects felt it had good cosmetic acceptability without unacceptable white residues or a greasy feeling. Dermatologists need to be versed in products that can be used on a variety of skin types.J Drugs Dermatol. 2024;23(7):515-518.  doi:10.36849/JDD.8223.

Involvement of D1 dopamine receptor in the nucleus of the solitary tract of rats in stress-induced hypertension and exercise.

OBJECTIVE: Chronic stress can cause hypertension, whereas daily exercise promotes healthy well being through destressing. Although the nucleus of the solitary tract (NTS) is involved in the development of hypertension, the molecular and physiological mechanisms of stress and exercise remain unclear. In this study, we tested whether gene expression in the NTS is altered by stress and daily exercise and whether this is involved in cardiovascular regulation. METHODS: We have performed RT2 Profiler PCR arrays targeting a panel of neurotransmitter receptor genes in the NTS of Wistar rats subjected to chronic restraint stress (1 h a day over 3 weeks) with or without voluntary wheel exercise. We also performed immunohistochemistry to determine whether the identified molecules were expressed at the protein level. Additionally, microinjection studies in anesthetized rats were performed to examine whether validated molecules exhibit physiological roles in cardiovascular regulation of the NTS. RESULTS: We observed that blood pressure was significantly increased by stress and the increase was suppressed by exercise. Using PCR analysis, we determined that the expression levels of four genes in the NTS, including the dopamine receptor D1 gene (Drd1), were significantly affected by stress and suppressed by exercise. We also examined dopamine D1 receptor (D1R) expression in NTS neurons and found significantly greater expression in the stressed than nonstressed animals. Furthermore, the microinjection of a D1R agonist into the NTS in anesthetized rats induced hypotensive effects. CONCLUSION: These results suggest that NTS D1R plays a role in the counteracting processes of stress-induced hypertension.

Imaging features of a rare giant intra-abdominal aggressive angiomyxoma.

Aggressive angiomyxoma (AAM) is a rare benign tumor that arises from connective tissue, prominently located in the vulva, vagina, perineum, and pelvis and is mainly found in women aged about 20-40 years old. Giant intraabdominal tumors have rarely been described. These tumors develop slowly over time and are often difficult to diagnose due to various clinical findings, especially in the early stages. Even though surgery is the primary treatment method, the possibility of complete resection is sometimes limited because the tumor tends to infiltrate nearby structures, leading to local recurrence. Only about 10% of AAM cases can be accurately diagnosed before treatment, which causes ineffective outcomes. This article demonstrates a case of giant intra-abdominal AAM precisely diagnosed by suspicious signs on CT and MRI scans before starting treatment.

CD74-AKT Axis Is a Potential Therapeutic Target in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) cells are often resistant to FAS (CD95)-mediated apoptosis, but the underlying molecular mechanism(s) is not fully understood yet. Notably, the expression of the type II transmembrane protein, CD74, is correlated with chemotherapy-resistant and more invasive forms of cancers via unknown mechanisms. Here, we analyzed gene expression pattern of cancer patients and/or patient-derived xenograft (PDX) models and found that mRNA and protein levels of CD74 are highly expressed in TNBC and correlated with cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) properties. Mechanistically, we found that AKT activation is likely critical for maintaining CD74 expression and protein stability to favor its oncogenic functions. Physiologically, epidermal growth factor (EGF) along with CD74 could activate AKT signaling, likely through binding of phosphorylated AKT (S473) to CD74, whereas inhibition of AKT could impair stability of CD74. We also revealed that CD74 binds to FAS and interferes with the intrinsic signaling of FAS-mediated apoptosis. As such, selective targeting of the CD74/FAS complex using the AKT inhibitor along with the CD74-derived peptide could synergistically restore and activate FAS-mediated apoptosis. Therefore, our approach of mobilizing apoptosis pathways likely provides a rationale for TNBC treatment by targeting the CD74/FAS and CD74-AKT axes.

Recombinant Ixodes scapularis Calreticulin Binds Complement Proteins but Does Not Protect Borrelia burgdorferi from Complement Killing.

Ixodes scapularis is a blood-feeding obligate ectoparasite responsible for transmitting the Lyme disease (LD) agent, Borrelia burgdorferi. During the feeding process, I. scapularis injects B. burgdorferi into the host along with its saliva, facilitating the transmission and colonization of the LD agent. Tick calreticulin (CRT) is one of the earliest tick saliva proteins identified and is currently utilized as a biomarker for tick bites. Our recent findings revealed elevated levels of CRT in the saliva proteome of B. burgdorferi-infected I. scapularis nymphs compared to uninfected ticks. Differential precipitation of proteins (DiffPOP) and LC-MS/MS analyses were used to identify the interactions between Ixs (I. scapularis) CRT and human plasma proteins and further explore its potential role in shielding B. burgdorferi from complement killing. We observed that although yeast-expressed recombinant (r) IxsCRT binds to the C1 complex (C1q, C1r, and C1s), the activator of complement via the classical cascade, it did not inhibit the deposition of the membrane attack complex (MAC) via the classical pathway. Intriguingly, rIxsCRT binds intermediate complement proteins (C3, C5, and C9) and reduces MAC deposition through the lectin pathway. Despite the inhibition of MAC deposition in the lectin pathway, rIxsCRT did not protect a serum-sensitive B. burgdorferi strain (B314/pBBE22Luc) from complement-induced killing. As B. burgdorferi establishes a local dermal infection before disseminating to secondary organs, it is noteworthy that rIxsCRT promotes the replication of B. burgdorferi in culture. We hypothesize that rIxsCRT may contribute to the transmission and/or host colonization of B. burgdorferi by acting as a decoy activator of complement and by fostering B. burgdorferi replication at the transmission site.

Azo dye anaerobic treatment in anaerobic reactors coupled with PVA/Fe/Starch gel bead.

A novel bio-carrier, PVA/Fe/starch gel bead, was fabricated and developed to enhance the anaerobic treatment performance of synthetic azo dye-containing wastewater. PVA-gel beads with 5 % magnetite and 0.5 % starch were optimal for physical strength and treatment performance. A pair of 2 L-up-flow anaerobic sludge blankets (UASB), one with the bead (UB) and another without (U) as a controller, operated continuously at 30 °C and an HRT of 11-24 h for 302 days. UB showed better performance than U in most phases, especially with influent dye of 200 mg·L-1, suggesting a greater tolerance to dye toxicity of UB than U. Microbial analysis revealed that the PVA/Fe/starch gel beads successfully captured the dye degrader Clostridium. Diversity indices indicated that PVA/Fe/Starch gel beads effectively support microbial diversity and resilience under varying dye concentrations. Overall, these findings demonstrate the potential of PVA/Fe/Starch gel beads to improve the stability and efficiency of the dye treatment system.

Impact of peripheral thyroid hormone balance on liver fat: insights from the NutriAct trial.

OBJECTIVE: Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat. DESIGN: 502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG). METHODS: Serum levels of thyroid hormones (THs) as well as IHLs, defined via magnetic resonance spectroscopy, were measured within an euthyroid subgroup without significant alcohol consumption at baseline (n = 332) and after 12 months (n = 243). A ratio of T3/T4 was used to assess whole-body deiodinase activity. Estimates of glucose and lipid metabolism were analyzed. RESULTS: Only fT3 and T3/T4 ratios showed a significant positive correlation with IHL at baseline. We observed a significant decline in fT3, T3, fT3/fT4 ratio, and T3/T4 ratio in CG and IG after 12 months without significant differences between groups. TSH, fT4, and T4 remained stable. A larger improvement of IHL during dietary intervention was seen in those subjects with a lower decline in T3 concentrations. CONCLUSIONS: Altered TH balance indicates a possible compensatory upregulation of whole-body TH activity in subjects with increased liver fat. This might be also relevant during the improvement of hepatic steatosis.

Synthesis of magnetic Fe3O4/graphene aerogel for the removal of 2,4-dichlorophenoxyacetic acid herbicide from water.

Graphene-based aerogels are among the lightest materials in the world and have been extensively studied for environmental remediation. In this work, an Fe3O4/graphene aerogel material was synthesized using the co-precipitation method. The prepared material was characterized using X-ray diffraction (XRD), scanning electron microscopy/X-ray energy dispersive spectroscopy (FESEM/EDX), infrared spectroscopy (FT-IR), and vibration sample magnetization (VSM). The results showed that the Fe3O4 nanoparticles with a particle size of less than 100 nm were well-distributed on the surface of the graphene aerogel. The prepared Fe3O4/graphene aerogel showed effective removal of 2,4-D herbicide from the aqueous solution with a maximal adsorption capacity of approximately 42.918 mg g-1. The adsorption isotherms and kinetics were investigated to study the adsorption behaviour of the resultant material. The saturation magnetism value of the aerogel was determined to be about 20.66 emu g-1, indicating that the adsorbent could be easily collected from the solution using an external magnet. These results implied that the prepared Fe3O4/graphene aerogel could be a promising adsorbent for the removal of 2,4-D herbicide from water.

Empowering Women Living with HIV/AIDS in Vietnam: A Hybrid Online-Offline Intervention to Combat Stigma.

Women living with HIV/AIDS (WLHA) encounter numerous challenges, such as stigma and gender disparities, that hinder their access to care, especially in patriarchal societies like Vietnam. We developed a hybrid intervention with online and offline (in-person) components to empower WLHA in Vietnam. The intervention was pilot tested with 91 WLHA in Hanoi. During baseline and 4-month, study investigators delivered two in-person sessions, one Zoom session, and 15 weeks of Zalo (social media platform) discussions to enhance positive coping strategies, treatment utilization and adherence, and engagement of support from family and peers. The participants continued their Zalo discussions from 4-month to 6-month without investigators' involvement. Intervention outcomes, including active coping and perceived barriers to care, were evaluated at baseline, 4-, and 6-month surveys. Mixed-effects regression models showed that the participants' active coping significantly increased from baseline (50.5 ± 9.4) to 4-month (53.8 ± 6.2; p = 0.0001), although there was a slight decrease at 6-month (52.8 ± 7.2), the change from 4-month to 6-month was not significantly significant (p = 0.3256). There was a significant reduction in participants' perceived barriers to care, from 19.8 ± 5.2 at baseline to 17.4 ± 5.2 at 4-month (p < 0.0001), which remained stable at 17.8 ± 4.3 at 6-month (p < 0.0001 compared to baseline). This intervention presents a promising model to empower WLHA in Vietnam and potentially in similar global contexts. Future interventions could benefit from leveraging natural peer leaders and adopting a more person-centered approach to meet WLHA's varying needs.

Population-wide active case finding as a strategy to end TB.

Tuberculosis (TB) is the leading infectious cause of morbidity and mortality globally. Despite available tools for preventing, finding, and treating TB, many people with TB remain undiagnosed. In high-incidence settings, TB transmission is ubiquitous within the community, affecting both high-risk groups and the general population. In fact, most people who develop TB come from the general population. To disrupt the chain of transmission that sustains the TB epidemic, we need to find and treat everyone with infectious TB as early as possible, including those with minimal symptoms or subclinical TB who are unlikely to present for care. Important elements of an effective active case-finding strategy include effective social mobilisation and community engagement, using sensitive screening tools that can be used at scale, and embracing population-wide screening in high-incidence ('hot spot') areas. We require a better description of feasible delivery models, 'real-life' impact and cost effectiveness to enable wider implementation.

Leveraging computer vision for predicting collision risks: a cross-sectional analysis of 2019-2021 fatal collisions in the USA.

OBJECTIVE: The USA has higher rates of fatal motor vehicle collisions than most high-income countries. Previous studies examining the role of the built environment were generally limited to small geographic areas or single cities. This study aims to quantify associations between built environment characteristics and traffic collisions in the USA. METHODS: Built environment characteristics were derived from Google Street View images and summarised at the census tract level. Fatal traffic collisions were obtained from the 2019-2021 Fatality Analysis Reporting System. Fatal and non-fatal traffic collisions in Washington DC were obtained from the District Department of Transportation. Adjusted Poisson regression models examined whether built environment characteristics are related to motor vehicle collisions in the USA, controlling for census tract sociodemographic characteristics. RESULTS: Census tracts in the highest tertile of sidewalks, single-lane roads, streetlights and street greenness had 70%, 50%, 30% and 26% fewer fatal vehicle collisions compared with those in the lowest tertile. Street greenness and single-lane roads were associated with 37% and 38% fewer pedestrian-involved and cyclist-involved fatal collisions. Analyses with fatal and non-fatal collisions in Washington DC found streetlights and stop signs were associated with fewer pedestrians and cyclists-involved vehicle collisions while road construction had an adverse association. CONCLUSION: This study demonstrates the utility of using data algorithms that can automatically analyse street segments to create indicators of the built environment to enhance understanding of large-scale patterns and inform interventions to decrease road traffic injuries and fatalities.

Hu14.18K.322A Causes Direct Cell Cytotoxicity and Synergizes with Induction Chemotherapy in High-Risk Neuroblastoma.

The disialoganglioside, GD2, is a promising therapeutic target due to its overexpression in certain tumors, particularly neuroblastoma (NB), with limited expression in normal tissues. Despite progress, the intricate mechanisms of action and the full spectrum of the direct cellular responses to anti-GD2 antibodies remain incompletely understood. In this study, we examined the direct cytotoxic effects of the humanized anti-GD2 antibody hu14.18K322A (hu14) on NB cell lines, by exploring the associated cell-death pathways. Additionally, we assessed the synergy between hu14 and conventional induction chemotherapy drugs. Our results revealed that hu14 treatment induced direct cytotoxic effects in CHLA15 and SK-N-BE1 cell lines, with a pronounced impact on proliferation and colony formation. Apoptosis emerged as the predominant cell-death pathway triggered by hu14. Furthermore, we saw a reduction in GD2 surface expression in response to hu14 treatment. Hu14 demonstrated synergy with induction chemotherapy drugs with alterations in GD2 expression. Our comprehensive investigation provides valuable insights into the multifaceted effects of hu14 on NB cells, shedding light on its direct cytotoxicity, cell-death pathways, and interactions with induction chemotherapy drugs. This study contributes to the evolving understanding of anti-GD2 antibody therapy and its potential synergies with conventional treatments in the context of NB.

Thiophenyl Derivatives of Nicotinamide Are Metabolized by the NAD Salvage Pathway into Unnatural NAD Derivatives That Inhibit IMPDH and Are Toxic to Peripheral Nerve Cancers.

N-Pyridinylthiophene carboxamide (compound 21) displays activity against peripheral nerve sheath cancer cells and mouse xenografts by an unknown mechanism. Through medicinal chemistry, we identified a more active derivative, compound 9, and found that only analogues with structures similar to nicotinamide retained activity. Genetic screens using compound 9 found that both NAMPT and NMNAT1, enzymes in the NAD salvage pathway, are necessary for activity. Compound 9 is metabolized by NAMPT and NMNAT1 into an adenine dinucleotide (AD) derivative in a cell-free system, cultured cells, and mice, and inhibition of this metabolism blocked compound activity. AD analogues derived from compound 9 inhibit IMPDH in vitro and cause cell death by inhibiting IMPDH in cells. These findings nominate these compounds as preclinical candidates for the development of tumor-activated IMPDH inhibitors to treat neuronal cancers.