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Esophageal carcinoma cuniculatum is a rare histology and can be difficult to diagnose prior to resection. To date, there have been 28 cases of resected esophageal carcinoma cuniculatum reported. Herein we describe a case found in the stomach of a patient who previously underwent a Roux-en-Y gastric bypass surgery. We report the preoperative, intraoperative, and postprocedural care. We review gross and histologic pathology.

Background/purpose: Since the introduction of virtual learning into dental education, students’ perceptions of the effectiveness of virtual versus in-person learning formats have evolved for interactive clinical case-based learning (ICCBL). This study aimed to undertake a comparative analysis of three different cohorts that received various formats of ICCBL instruction. Materials and methods: A survey was distributed to the Classes of 2023, 2024, and 2025 following each class completion of interactive clinical case-based-tutorials (ICCBT) as part of the Treatment of Active Disease (TxAD) course at Harvard School of Dental Medicine. Results: A total of eighty-five participants from the three cohorts, twenty-three students from the Class of 2023 (virtual format, 71.9 % participation rate), thirty-one students from the Class of 2024 (combination of virtual and in-person, 91.2 %), and thirty-one students from the Class of 2025 (in-person, 83.8 %) completed the post-course survey. Across three classes, all cohorts were more likely to perceive the virtual format as more effective than in-person ICCBT. In addition, the classes were more likely to prefer virtual based classes compared to in-person tutorials in the future. Conclusion: This study highlights the dynamic shifts in educational approaches to align with the evolving demands of contemporary students. Our findings show that all cohorts expressed a preference for virtual ICCBT sessions and perceived virtual ICCBT sessions as somewhat more effective for learning compared to in-person sessions. These findings challenge the notion that such sessions must be conducted in person, prompting further research and the exploration of potentially more effective and optimized educational methods.

Background/purpose: Self-assessment in dental education is considered a fundamental skill for proficient oral healthcare providers. While previous studies looked at self-assessment in education, few have done so at Japanese institutions. This study aimed to assess potential associations between gender and self-assessment skills in Japanese dental students. Materials and methods: Dental students from Niigata University (n = 301) completed preclinical prosthodontic exercises and self-assessed their practical exam performance. Three calibrated faculty evaluated students’ work using the same rubric. The difference between student self-assessment score and mean faculty grade was defined as the student-faculty (S-F) gap, indicating how accurately students evaluated their work. The gap scores were stratified by quartiles by faculty grade and by gender. Regression analysis was used to investigate potential associations. Results: Students mean S-F gap was 2.9 ± 10.5 % with a significant negative association to faculty grades (coefficient, −0.32; P

Summary: Background: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear. Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls). Findings: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03–1.57)], HGF [1.48 (1.06–2.07)], PIK3AP1 [1.22 (1.00–1.50)] and CLEC4G [1.52 (1.00–2.32)] were positively associated; HSD11B1 [0.67 (0.49–0.91)], SCF [0.68 (0.49–0.94)], and CCL25 [0.80 (0.65–0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04–1.36)] and HSD11B1 [0.91 (0.84–0.99)] were associated with endometrial cancer risk. Interpretation: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis. Funding: Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).

Summary: Abdominal and thoracic aortic aneurysms (AAAs, TAAs) remain a major cause of deaths worldwide, in part due to the lack of reliable prognostic markers or early warning signs. Sox6 has been found to regulate renin controlling blood pressure. We hypothesized that Sox6 may serve as an important regulator of the mechanisms contributing to hypertension-induced aortic aneurysms. Phenotype and laboratory-wide association scans in a clinical cohort found that SOX6 gene expression is associated with aortic aneurysm in subjects of European ancestry. Sox6 and tumor necrosis factor alpha (TNF-α) expression were upregulated in aortic tissues from patients affected by either AAA or TAA. In Sox6 knockout mice with angiotensin-II-induced AAA, we found that Sox6 plays critical role in the development and progression of AAA. Our data support a regulatory role of SOX6 in the development of hypertension-induced AAA, suggesting that Sox6 may be a therapeutic target for the treatment of aortic aneurysms.

Introduction: Patients after surgical correction of Tetralogy of Fallot (ToF) often show adverse cardiac remodeling. To better understand the underlying biological processes, we studied the relation between changes in blood biomarkers and changes in biventricular size and function as assessed by cardiac magnetic resonance imaging (CMR). Methods: This study included 50 ToF patients, who underwent blood biomarker and CMR analysis at least twice between 2002 and 2018.34 (68 %) of these patients were male. Patients had an average age of 16.1 at first visit. Biomarkers were chosen based on earlier research by our group and included: NT-proBNP, ST2, GDF-15, DLK-1, IGFBP-1/7, and FABP-4. Pearson correlations coefficients (rpearson) were determined to quantify the relationship between changes in biomarkers and CMR measurements. Results: For changes in parameters of right ventricular (RV) size significant correlations were observed with changes in NT-proBNP, ST-2, GDF-15, IGFBP7 and FABP-4 (rpearson between 0.28 and 0.51). Correlations with NT-proBNP were driven by changes in RV size induced by pulmonary valve replacement (n = 9). For LV serial size changes, significant correlations were noted with changes in NT-pro-BNP, ST-2, GDF-15 and FABP-4 (rpearson between 0.32 and 0.52). Conclusion: In clinically stable ToF patients changes in right and left ventricular size and function correlated with alterations in blood biomarkers of inflammation and immune response to stress.

Background: Between 52–86% of people who menstruate in the United States use tampons—cotton and/or rayon/viscose ‘plugs’—to absorb menstrual blood in the vagina. Tampons may contain metals from agricultural or manufacturing processes, which could be absorbed by the vagina’s highly absorptive tissue, resulting in systemic exposure. To our knowledge, no previous studies have measured metals in tampons. Objectives: We evaluated the concentrations of 16 metal(loid)s in 30 tampons from 14 tampon brands and 18 product lines and compared the concentrations by tampon characteristics. Methods: About 0.2 – 0.3 g from each tampon (n = 60 samples) were microwave-acid digested and analyzed by inductively coupled plasma mass spectrometry (ICP-MS) to determine concentrations of arsenic, barium, calcium, cadmium, cobalt, chromium, copper, iron, manganese, mercury, nickel, lead, selenium, strontium, vanadium, and zinc. We compared concentrations by several tampon characteristics (region of purchase, organic material, brand type) using median quantile mixed models. Results: We found measurable concentrations of all 16 metals assessed. We detected concentrations of several toxic metals, including elevated mean concentrations of lead (geometric mean [GM] = 120 ng/g), cadmium (GM = 6.74 ng/g), and arsenic (GM = 2.56 ng/g). Metal concentrations differed by region of tampon purchase (US versus European Union/United Kingdom), by organic versus non-organic material, and for store- versus name-brand tampons. Most metals differed by organic status; lead concentrations were higher in non-organic tampons while arsenic was higher in organic tampons. No categoriy had consistently lower concentrations of all or most metals. Discussion: Tampon use is a potential source of metal exposure. We detected all 16 metals in at least one sampled tampon, including some toxic metals like lead that has no “safe” exposure level. Future research is needed to replicate our findings and determine whether metals can leach out of tampons and cross the vaginal epithelium into systemic circulation.

Alzheimer's disease (AD) is the most common global dementia and is universally fatal. Most late-stage AD disease-modifying therapies are intravenous and target amyloid beta (Aβ), with only modest effects on disease progression: there remains a high unmet need for convenient, safe, and effective therapeutics. Senescent cells (SC) and the senescence-associated secretory phenotype (SASP) drive AD pathology and increase with AD severity. Preclinical senolytic studies have shown improvements in neuroinflammation, tau, Aβ, and CNS damage; most were conducted in transgenic rodent models with uncertain human translational relevance. In this study, aged cynomolgus monkeys had significant elevation of biomarkers of senescence, SASP, and neurological damage. Intermittent treatment with the senolytic navitoclax induced modest reversible thrombocytopenia; no serious drug-related toxicity was noted. Navitoclax reduced several senescence and SASP biomarkers, with CSF concentrations sufficient for senolysis. Finally, navitoclax reduced TSPO-PET frontal cortex binding and showed trends of improvement in CSF biomarkers of neuroinflammation, neuronal damage, and synaptic dysfunction. Overall, navitoclax administration was safe and well tolerated in aged monkeys, inducing trends of biomarker changes relevant to human neurodegenerative disease.

Introduction: Stroke is one of the leading causes of mortality and disability in the world, with clinical manifestations and severe complications that they negatively affect the patient's recovery, contributing to an uncertain prognosis and difficult decisions with bioethical dilemmas such as artificial nutrition in the context of severe stroke. Presentation of the case: A 49-year-old patient with a Cerebrovascular Accident in a chronic vegetative state, tracheostomy, and gastrostomy user, admitted for infectious complications, whom, under therapeutic proportionality, the decision is made, shared by medical staff and family, to withdraw artificial nutrition. Conclusions: Difficult decision-making involves multiple challenges for both the health personnel and the patient and his or her environment. It must be guided by bioethical principles and proportionality in favor of the quality of life and the patient's benefit.

Background: Little is known regarding the characteristics, treatment patterns, and outcomes in patients with adult congenital heart disease (ACHD) admitted to cardiac intensive care units (CICUs). Objectives: The authors sought to better define the contemporary epidemiology, treatment patterns, and outcomes of ACHD admissions in the CICU. Methods: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Participating centers contributed prospective data from consecutive admissions during 2-month annual snapshots from 2017 to 2022. We analyzed characteristics and outcomes of admissions with ACHD compared with those without ACHD. Multivariable logistic regression was used to assess mortality in ACHD vs non-ACHD admissions. Results: Of 23,299 CICU admissions across 42 sites, there were 441 (1.9%) ACHD admissions. Shunt lesions were most common (46.1%), followed by right-sided lesions (29.5%) and complex lesions (28.7%). ACHD admissions were younger (median age 46 vs 67 years) than non-ACHD admissions. ACHD admissions were more commonly for heart failure (21.3% vs 15.7%, P

Summary: Background: Variants in GABRB2, encoding the β2 subunit of the γ-aminobutyric acid type A (GABAA) receptor, can result in a diverse range of conditions, ranging from febrile seizures to severe developmental and epileptic encephalopathies. However, the mechanisms underlying the risk of developing milder vs more severe forms of disorder remain unclear. In this study, we conducted a comprehensive genotype–phenotype correlation analysis in a cohort of individuals with GABRB2 variants. Methods: Genetic and electroclinical data of 42 individuals harbouring 26 different GABRB2 variants were collected and accompanied by electrophysiological analysis of the effects of the variants on receptor function. Findings: Electrophysiological assessments of α1β2γ2 receptors revealed that 25/26 variants caused dysfunction to core receptor properties such as GABA sensitivity. Of these, 17 resulted in gain-of-function (GOF) while eight yielded loss-of-function traits (LOF). Genotype-phenotype correlation analysis revealed that individuals harbouring GOF variants suffered from severe developmental delay/intellectual disability (DD/ID, 74%), movement disorders such as dystonia or dyskinesia (59%), microcephaly (50%) and high risk of early mortality (26%). Conversely, LOF variants were associated with milder disease manifestations. Individuals with these variants typically exhibited fever-triggered seizures (92%), milder degrees of DD/ID (85%), and maintained ambulatory function (85%). Notably, severe movement disorders or microcephaly were not reported in individuals with loss-of-function variants. Interpretation: The data reveals that genetic variants in GABRB2 can lead to both gain and loss-of-function, and this divergence is correlated with distinct disease manifestations. Utilising this information, we constructed a diagnostic flowchart that aids in predicting the pathogenicity of recently identified variants by considering clinical phenotypes. Funding: This work was funded by the Australian National Health & Medical Research Council, the Novo Nordisk Foundation and The Lundbeck Foundation.

Background: Autoantibodies to type I interferons have been identified in association with a variety of inflammatory and autoimmune diseases. Type I interferons have demonstrated inhibitory effects on mast cell proliferation and degranulation. Systemic mastocytosis (SM) is a disease characterized by increased mast cell burden and mediator release. Whether autoantibodies to type I interferon are present in the sera of patients with SM, and if so, whether they correlate with characteristics of disease, is unknown. Objective: The purpose of this study was to determine whether autoantibodies to type I interferons are observed in the sera of patients with SM, and if so, whether they correlate with biomarkers of disease severity. Methods: We analyzed sera from 89 patients with SM for concentrations of autoantibodies to type I interferon by using a multiplex particle-based assay and signal neutralization capacity by using a STAT1 activity assay and then compared these measurements with those in a database of information on 1284 healthy controls. Results: Our cohort was predominantly female (57.3%), with a median age of 56 years. Of the cohort members, 13 produced autoantibodies to IFN-β, 3 to IFN-ω, and 0 to IFN-α. None of the 13 sera demonstrated signal neutralization. Neither autoantibody concentration nor signaling inhibition measurements correlated with tryptase concentrations or D816V allele burden. Conclusion: Although a small subpopulation of patients with SM have autoantibodies to type I interferons, there was no correlation between autoantibody production and signaling inhibition. These data are consistent with the conclusion that autoantibodies to type I interferon do not play a significant role in the pathogenesis or severity of SM.

Post-traumatic stress disorder (PTSD) is a mental disorder linked to neurochemical, hypothalamic-pituitary-adrenal (HPA)-axis dysregulations, inflammatory and pro-oxidant challenges in response to traumatic events. It is one of the leading causes of neurocognitive declines, hence prompting the need for a pharmacological intervention. However, the impact of diosgenin, a naturally occurring steroidal saponin with adaptogenic-like action, on PTSD-induced neuropsychiatric disturbances and its underlying mechanisms are unknown. In this study, we investigated the outcome of diosgenin treatment in a multimodal traumatic, single prolonged stress (SPS)-induced PTSD in mice. Following the SPS-induced 7 days of PTSD, mice (n = 9) were thereafter treated with diosgenin (25 and 50 mg/kg) or fluoxetine (10 mg/kg) orally from days 8–20 (14 days). Locomotory, cognitive-, depressive- and anxiety-like behaviors were investigated. We assayed for changes in adrenal weight, serum glucose and corticosterone concentrations. Neurochemical, inflammatory, oxido-nitrergic dysfunctions and monoamine oxidase-B and acetylcholinesterase activities, were measured in the striatum, prefrontal-cortex and hippocampus. The results revealed that the SPS challenge inhibited locomotor, spatial/non-spatial memory functions, increased anxiety and depressive-like features, which were reversed by diosgenin. Diosgenin reduced SPS-induced increased monoamine oxidase-B, acetylcholinesterase activities, TNF-α, IL-6, malondialdehyde and nitrite levels in the striatum, prefrontal-cortex and hippocampus. Antioxidants such as glutathione, superoxide-dismutase, and catalase levels in SPS-mice brains were increased by diosgenin. Moreover, diosgenin attenuated SPS-induced hyper-HPA-axis mediation of PTSD by decreasing serum corticosterone, glucose levels and adrenal gland hypertrophy. Herewith, we suggest that diosgenin convenes adaptogenic-like protection against mice exposed to PTSD by enhancing antioxidant machinery, neurochemical modulations, and inhibition of oxido-nitrergic, inflammatory, and HPA-axis dysfunctions.

The traditional Chinese medicine (TCM) industry is critical to not only for public health but also for economic growth. According to the European Union (EU) directives, under the EU framework for (traditional) herbal medicinal products, herbal medicines with long history of use can be registered in EU. However, there is a condition in this directive in which only those that have at least 10–15 years in the EU market are accepted for registration and/or marketing authorization. In author opinion, the condition of 10–15 years of use in EU countries set within the EU regulatory framework is with consideration of the genetic differences which can result in variation in adverse drug responses among different world populations. With this concept in mind, it is reasonable to project the principal of the EU directive to the Asian countries where TCM is originated. Countries like China, Singapore, Japan and South Korea that have well established drug registration framework are in best position in executing the best practice and facilitate harmonization of registration for TCM within the region. Furthermore, the registration process itself allows more safety and efficacy data to be collected systemically before and after product registration/marketing authorization. These are valuable information for future drug development. The therapeutic value of TCM is limitless, it has been left out in the EU regulatory framework, and the opportunity for it to be expanded and carried forward in modern medicines is shadowed by the limited number of TCM that are qualified to be registered under the EU regulatory framework. An early establishment of a harmonized risk-based registration process for TCM in Asian countries is important. This will strengthen the database to substantiate the history of safe use and further preserving and expanding the therapeutic values of TCM within and beyond the Asian region.

Objective(s): The complexity of aortic arch reconstruction due to diverse 3-dimensional geometrical abnormalities is a major challenge. This study introduces 3-dimensional printed tissue-engineered vascular grafts, which can fit patient-specific dimensions, optimize hemodynamics, exhibit antithrombotic and anti-infective properties, and accommodate growth. Methods: We procured cardiac magnetic resonance imaging with 4-dimensional flow for native porcine anatomy (n = 10), from which we designed tissue-engineered vascular grafts for the distal aortic arch, 4 weeks before surgery. An optimal shape of the curved vascular graft was designed using computer-aided design informed by computational fluid dynamics analysis. Grafts were manufactured and implanted into the distal aortic arch of porcine models, and postoperative cardiac magnetic resonance imaging data were collected. Pre- and postimplant hemodynamic data and histology were analyzed. Results: Postoperative magnetic resonance imaging of all pigs with 1:1 ratio of polycaprolactone and poly-L-lactide-co-ε-caprolactone demonstrated no specific dilatation or stenosis of the graft, revealing a positive growth trend in the graft area from the day after surgery to 3 months later, with maintaining a similar shape. The peak wall shear stress of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft portion did not change significantly between the day after surgery and 3 months later. Immunohistochemistry showed endothelization and smooth muscle layer formation without calcification of the polycaprolactone/poly-L-lactide-co-ε-caprolactone graft. Conclusions: Our patient-specific polycaprolactone/poly-L-lactide-co-ε-caprolactone tissue-engineered vascular grafts demonstrated optimal anatomical fit maintaining ideal hemodynamics and neotissue formation in a porcine model. This study provides a proof of concept of patient-specific tissue-engineered vascular grafts for aortic arch reconstruction.

This paper studies the fresh and mechanical properties of high-strength concrete (HSC) by incorporating recycled concrete aggregates (RCA) of varying sizes and concentrations. The recycled aggregate concrete (RAC) was prepared by partially replacing RCA with natural coarse aggregate (NCA) at 0%, 15%, 30%, and 45%, with aggregate sizes ranging from 5 to 12 and 12–20-mm. Fresh concrete properties, such as slump, Kelly ball, compacting factor, K-slump, and fresh density, were tested to determine the influence of RCA size and concentration. In addition, the mechanical properties were studied through the execution of compressive, split-tensile, and stress-strain tests. The test results revealed that increasing the RCA concentration declines the fresh and hardened properties of HSC. In the fresh concrete experimentation, the 12–20 mm aggregate size RAC mixes exhibited greater workability than the 5–12 mm aggregate mixes. On the contrary, 5–12 mm aggregate mixes RAC had higher compressive and split-tensile strength and a higher modulus of elasticity than 12–20 mm aggregate mixes concrete. When it comes to sustainability, the study found that the smaller size range of RAC produces inferior embodied CO2 (eCO2) and provides a cost-effective and sustainable solution for the construction industry.

Background: Entrustable Professional Activities (EPAs) allow for the assessment of specific, observable, essential tasks in medical education. Since being developed in non-surgical fields, EPA assessments have been implemented in surgery to explore intraoperative entrustment. However, assessment burden is a significant problem for faculty, and it is unknown whether EPA assessments enable formative technical feedback. EPAs' formative utility could inform how surgical programs facilitate technical feedback for trainees. We aimed to assess the extent to which narrative comments provided through the Fellowship Council (FC) EPA assessments contained technical feedback. Methods: The FC previously collected EPA assessments for subspecialty surgical fellows from September 2020 to October 2022. Two raters reviewed assessments' narrative comments for inclusion of each skill area that makes up part of the Objective Structured Assessment of Technical Skills (OSATS). A third rater reconciled discrepant ratings. Results: During the study period, there were 3302 completed EPA assessments, including 1191 fellow self-assessments, 1124 faculty assessments, and 987 assessments without an identified assessor role. We found that assessments' narrative comments related to a median of two of the seven OSATS areas (IQR:1–2). There were no comments relevant to any of the seven OSATS areas in 16.0 % of all assessments. Conclusions: In this review of narrative comments for EPA assessments from the FC, we found that limited technical feedback of the kind included in the OSATS was provided in many assessments. These results suggest benefit to adjusting the EPA form, enhancing faculty development, or continuing additional types of targeted technical assessment intraoperatively. Key message: This analysis of narrative comments from fellowship EPA assessments showed that many assessments included limited technical feedback. To allow for continued technical feedback for fellows, these results highlight the need for further refinements of the EPA assessment form, additional faculty development, or ongoing use of other types of technical assessment.

The full-grouted sleeve connection (FGSC) is widely used in prefabricated structural connections, but the complexity of the grouting process often leads to defects, primarily grouting voids. The mechanical properties of FGSCs with these defects under fire exposure are not well understood. This study examines 144 FGSCs with various grouting voids exposed to specific temperatures before cooling to room temperature for static tensile testing. Key parameters include defect type, volume defect rates, and temperature. The study identifies two primary failure modes: rebar tensile and pull-out failures, influenced by void size, distribution, and temperature. Below 300 °C, tensile failure occurs when the defect rate is ≤0.05; above this rate, pull-out failure dominates. Above 300 °C, all specimens exhibit pull-out failure. Specimens with concentrated voids show lower bearing capacities. The research provides a bond stress-slip constitutive model for FGSCs and a fitting formula for characteristic points. A neural network model predicts the ultimate bond stress based on defect type, volume defect rate, temperature, and grouting material strength, with sensitivity analysis indicating the volume defect rate as a critical factor. This work offers a comprehensive theoretical foundation for studying the impact of grouting defects on FGSCs' post-fire mechanical properties.

This study focuses on the actual project of rural road ‘concrete to asphalt’ pavement renovation, deeply integrating the design concept of full structure regeneration and the innovation of in-situ regeneration technology for old cement pavement. Through the life cycle assessment method, an environmental impact quantification assessment model is used. Based on the analysis of the environmental benefits of traditional pavement renovation technology (using multi-hammer crushed stone and hot mix asphalt production technology), the environmental advantages of the full-structure regeneration technology scheme are outlined, including the recycling of recycled asphalt pavement materials, application of emulsified asphalt plant mixing cold regeneration technology, and implementation of resonance crushed stone on-site regeneration technology. At the same time, sensitivity analysis methods are used to deeply analyze the sensitivity of changes in parameters such as surface and base thickness, transportation distance, and environmental factors to the overall environmental impact. The research results indicate that the optimization plan can achieve a 57.97 % reduction in total energy consumption and a 71.45 % reduction in total carbon emissions. Additionally, the recycling and utilization of RAP materials significantly reduce the demand for new mineral materials and asphalt. For a 1-kilometer road surface, mineral materials save up to 82.39 % and asphalt saves up to 27.11 %. The energy consumption and carbon emissions generated during the raw material production stage in both schemes contribute the most to the environmental impact of road construction. The analysis found that the environmental benefits of the optimization plan mainly come from the recycling of the old cement concrete pavement as the base layer after resonance crushing, as well as the use of emulsified asphalt mixture cold recycling instead of the lower layer of hot mix asphalt concrete, achieving full-scale recycling of the pavement renovation. The relevant findings provide a data foundation or the improvement and upgrading of energy-saving and emission reduction technologies in road surface renovation and offer valuable insights for future research on sustainable road surface renovation strategies.

Summary: Human neural organoid models have become an important tool for studying neurobiology. However, improving the representativeness of neural cell populations in such organoids remains a major effort. In this work, we compared Matrigel, a commercially available matrix, to a neural cadherin (N-cadherin) peptide-functionalized gelatin methacryloyl hydrogel (termed GelMA-Cad) for culturing cortical neural organoids. We determined that peptide presentation can tune cell fate and diversity in gelatin-based matrices during differentiation. Of particular note, cortical organoids cultured in GelMA-Cad hydrogels mapped more closely to human fetal populations and produced neurons with more spontaneous excitatory postsynaptic currents relative to Matrigel. These results provide compelling evidence that matrix-tethered signaling peptides can influence neural organoid differentiation, opening an avenue to control stem cell fate. Moreover, outcomes from this work showcase the technical utility of GelMA-Cad as a simple and defined hydrogel alternative to Matrigel for neural organoid culture.

Background: Exposure to antiretrovirals at or early after HIV acquisition can suppress viral replication and blunt antibody (Ab) responses; a reduced HIV detectability could impact diagnosis and blood donation screening. Methods: We used three antigen (Ag)/Ab assays and one nucleic acid test (NAT) to analyze samples collected in pre-exposure prophylaxis (PrEP) trials (iPrEx; Partners PrEP) before infection detection by Ab-only rapid diagnostic tests (RDTs), and in early antiretroviral treatment (ART) initiation studies (RV254; SIPP). Results: Reactivity using NAT and Ag/Ab assays in samples collected up to 8 weeks prior to the first reactive RDT from 251 PrEP trials participants varied between 49-61% for active PrEP users and between 27-37% for placebo users. Among RV254 participants, reactivity in Ag/Ab assays was

Background: Citropsis articulata Swingle & Kellerman (Family Rutaceae) is a renowned African traditional medicinal plant for the management of erectile dysfunction. The root bark is more commonly used than the leaves. Little has been done to evaluate the pharmacognostical parameters of both parts. Purpose: The aim of this study was to determine the pharmacognostical parameters of C. articulata leaves and root bark. Methods: The plant parts were collected, washed, dried, and extracted by decoction and soxhlation. The World Health Organisation quality control methods for herbal materials were generally followed for the pharmacognostical evaluation of the root bark and leaf. This involved macroscopic and microscopic analysis, physicochemical analysis, hemolytic activity, and phytochemical analysis. Results: Macroscopically, the distillate of the root bark showed a fluorescent blue colour under ultra violet light of wavelength 254 nm. Microscopic examination revealed the presence of cellulose, lignified, suberized and cuticular cell walls. Numerous aleurone grains were noted in the root bark. Phytochemical analysis showed the presence of reducing sugars, free amino acids, L-arginine, coumarin, glycosides, phenols, phytosterols, saponins, steroids, tannins, terpenoids, alkaloids and flavonoids. Thin layer and high performance liquid fingerprints were also developed. The C. articulata root bark decoction and Soxhlet extracts contained 12.35 ± 0.05, and 110.00 ± 0.03 while the leaf decoction and Soxhlet extracts contained 4.97 ± 0.03 and 39.65 ± 0.00 mg/g diosgenin equivalent saponins respectively. The L-arginine content for the dried root bark decoction and Soxhlet was 2681 ± 7.29, 1660 ± 2.99 µg/g, while that for the leaf decoction and Soxhlet extracts was 135.60 ± 8.28, and 130.20 ± 2.83 µg/g respectively. Conclusion: This study distinguished the root bark and leaf of Citropsis articulata and offered vital information for the quality control and standardization of the plant materials.

Background: The All of Us Research Program aims to collect longitudinal health-related data from a million individuals in the United States. An inherent challenge of a non-probability sampling strategy through voluntary participation in All of Us is that findings may not be nationally representative for addressing health and health care at the population level. We generated survey weights for the All of Us data that can be used to address the challenge. Research design: We developed raked weights using demographic, health, and socioeconomic variables available in both the 2020 National Health Interview Survey (NHIS) and All of Us. We then compared the unweighted and weighted prevalence of a set of health-related variables (health behaviors, health conditions, and health insurance coverage) estimated from All of Us data with the weighted prevalence estimates obtained from NHIS data. Subjects: The sample included 100,391 All of Us participants 18 years of age and older with complete data collected between May 2017 and January 2022 across the United States. Results: Final variables in the raking procedure included age, sex, race/ethnicity, region of residence, annual household income, and home ownership. The mean percentage difference between known proportions obtained from the NHIS and All of Us was reduced by 18.89% for health-related variables after applying the raked weights. Conclusions: Raking improved the comparability of prevalence estimates obtained from All of Us to known national prevalence estimates. Refining the process of variable selection for raking may further improve the comparability between All of Us and nationally representative data.

Summary: Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and myeloid skewing. We report that culture of bone marrow (BM) HSCs from aged mice with epidermal growth factor (EGF) suppressed myeloid skewing, increased multipotent colony formation, and increased HSC repopulation in primary and secondary transplantation assays. Mice transplanted with aged, EGF-treated HSCs displayed increased donor cell engraftment within BM HSCs and systemic administration of EGF to aged mice increased HSC self-renewal capacity in primary and secondary transplantation assays. Expression of a dominant negative EGFR in Scl/Tal1+ hematopoietic cells caused increased myeloid skewing and depletion of long term-HSCs in 15-month-old mice. EGF treatment decreased DNA damage in aged HSCs and shifted the transcriptome of aged HSCs from genes regulating cell death to genes involved in HSC self-renewal and DNA repair but had no effect on HSC senescence. These data suggest that EGFR signaling regulates the repopulating capacity of aged HSCs.

Rationale and objectives: This study aimed to assess the feasibility and image quality of free-breathing 3D isotropic zero echo time (ZTE) whole-lung imaging and explore a clinically appropriate protocol for MR lung imaging. Materials and methods: The study was approved by the local ethics committee. A total of thirty healthy volunteers were enrolled in this study from October 2022 to May 2023. Free-breathing pulmonary 3D isotropic ZTE scans were implemented with various acquisition planes and the number of excitations (NEX). ZTE images were evaluated by two radiologists for the overall Image quality and visibility of intrapulmonary structures as well as the signal-to-noise ratio (SNR) of the lung parenchyma. ZTE images with different acquisition parameters were compared. For preliminary clinical visual assessment, three patients with interstitial lung disease underwent both ZTE imaging and computed tomography (CT). Results: The overall image quality of the lung in healthy subjects was good to excellent. The visibilities of pulmonary arteries and bronchus were up to the 7th and 5th generation, respectively. The display of lung fissures was poor. The overall image quality, the visibility of the pulmonary artery, and lung fissures in the axial acquisition were better than in the coronal acquisition (P = 0.011, 0.008, 0.010, respectively) but not statistically different from those in the sagittal acquisition (all P > 0.05). Conclusion: The free-breathing pulmonary ZTE is feasible and may serve as an alternative method in chest imaging. Either axial or sagittal ZTE image acquisition would be preferred in clinical practice.

Copper tailings are a category of solid waste discharged after the beneficiation process in mining plants. The significant concern raising stringent environmental issues give impetus to explore the multi-channel utilization of copper tailings in a sustainable manner. Concerning the fact that no study has systematically compared properties of copper tailings filled (CTP) asphalt mastic with conventional limestone filler mastic (LP) at different filler-to-asphalt ratios, multiscale and multi-dimensional comparisons between the characteristics of CTP-asphalt and LP-asphalt mastics were made in this study to thoroughly explore the feasibility and potential of recycling CTP as alternative filler in asphalt materials. Four ratios from 0.3 to 1.2 were used to manufacture asphalt mastics. The in-service pavement performance of asphalt mastics including resistances to rutting, low-temperature cracking and moisture damage was explored. Finally, the environmental and economic perspectives regarding the recycling of copper tailings are analyzed. Results indicate that CTP possesses a rougher surface, a larger specific surface area, and a more uniform pore size distribution than LP, particularly across the mesopores range. These characteristics could promote the adsorption of asphalt on its particle surface, potentially leading to enhanced filler-particle interaction. Regarding pavement performance, CTP-asphalt mastic outperforms LP-asphalt mastic in terms of high-temperature performance. Meanwhile, its low-temperature performance and moisture stability are only limitedly declined with the acceptable performance. Further, heavy metals leaching tests suggest that the risk for the substantial utilization of CTP in paving asphalt is absent. The related outcomes have verified the promising potential of CTP as an alternative candidate to substitute the conventional filler in paving asphalt from comprehensive consideration of in-service performance, and environmental and economic benefits.

ABSTRACT: This study aimed to estimate genetic parameters for feeding behavior (FB) traits and to assess their genetic relationship with performance traits in group-housed broilers. In total, 99,472,151 visits were recorded for 95,711 birds between 2017 and 2022 using electronic feeders. The visits were first clustered into 2,667,617 daily observations for ten FB traits: daily feed intake (DFI), daily number of visits (NVIS), time spent at the feeders (TSF), number of visited feeders (NVF), visiting activity interval (VAI), feeding rate (FR), daily number of meals (NMEAL), average intake per meal (INTMEAL), number of visits per meal (VISMEAL) and interval between meals (MEALIVL). All FB traits were then considered as the average per bird across the feeding test period. Three growth traits (body weight at the start – SBW and at the end of the feeding test – FBW, and weight gain over the test period – BWG), and 2 feed efficiency (FE) traits (Feed Conversion Rate - FCR and Residual Feed Intake - RFI) were also recorded. The (co)variance components were estimated using multitrait animal mixed models. For growth and FE, the heritability (h2) estimates were moderate, ranging from 0.20 ± 0.01 (BWG) to 0.32 ± 0.02 (RFI). Overall, the h2 estimates for FB traits were higher than for productive traits, ranging from 0.31 ± 0.01 (DFI) to 0.56 ± 0.02 (TSF). DFI presented high genetic correlations (0.53–0.86) with all performance traits. Conversely, the remaining FB traits presented null to moderate genetic correlations with these traits, ranging from –0.38 to 0.42 for growth traits and between –0.14 and 0.25 for FE traits. Genetic selection for favorable feeding behavior is expected to exhibit a fast genetic response. The results suggest that it is possible to consider different feeding strategies without compromising the genetic progress of FE. Conversely, breeding strategies prioritizing a higher bird activity might result in lighter broiler lines in the long term, given the negative genetic correlations between visit-related traits (NV, NVF, and NMEAL) and growth traits (SBW and FBW).

Hyperphosphorylated TAR DNA-binding protein 43 (TDP-43) aggregates in the cytoplasm of neurons is the neuropathological hallmark of amyotrophic lateral sclerosis (ALS) and a group of neurodegenerative diseases collectively referred to as TDP-43 proteinopathies that includes frontotemporal dementia, Alzheimer's disease, and limbic onset age-related TDP-43 encephalopathy. The mechanism of TDP-43 phosphorylation is poorly understood. Previously we reported casein kinase 1 epsilon gene (CSNK1E gene encoding CK1ε protein) as being tightly correlated with phosphorylated TDP-43 (pTDP-43) pathology. Here we pursued studies to investigate in cellular models and in vitro how CK1ε and CK1δ (a closely related family sub-member) mediate TDP-43 phosphorylation in disease. We first validated the binding interaction between TDP-43 and either CK1δ and CK1ε using kinase activity assays and predictive bioinformatic database. We utilized novel inducible cellular models that generated translocated phosphorylated TDP-43 (pTDP-43) and cytoplasmic aggregation. Reducing CK1 kinase activity with siRNA or small molecule chemical inhibitors resulted in significant reduction of pTDP-43, in both soluble and insoluble protein fractions. We also established CK1δ and CK1ε are the primary kinases that phosphorylate TDP-43 compared to CK2α, CDC7, ERK1/2, p38α/MAPK14, and TTBK1, other identified kinases that have been implicated in TDP-43 phosphorylation. Throughout our studies, we were careful to examine both the soluble and insoluble TDP-43 protein fractions, the critical protein fractions related to protein aggregation diseases. These results identify CK1s as critical kinases involved in TDP-43 hyperphosphorylation and aggregation in cellular models and in vitro, and in turn are potential therapeutic targets by way of CK1δ/ε inhibitors.

Hypertriglyceridemia (HTG) is a common cardiovascular risk factor characterized by elevated triglyceride (TG) levels. Researchers have assessed the genetic factors that influence HTG in studies focused predominantly on individuals of European ancestry. However, relatively little is known about the contribution of genetic variation of HTG in people of African ancestry (AA), potentially constraining research and treatment opportunities. Our objective was to characterize genetic profiles among individuals of AA with mild-to-moderate HTG and severe HTG versus those with normal TGs by leveraging whole-genome sequencing data and longitudinal electronic health records available in the All of Us program. We compared the enrichment of functional variants within five canonical TG metabolism genes, an AA-specific polygenic risk score for TGs, and frequencies of 145 known potentially causal TG variants between HTG patients and normal TG among a cohort of AA patients (N = 15,373). Those with mild-to-moderate HTG (N = 342) and severe HTG (N ≤ 20) were more likely to carry APOA5 p.S19W (odds ratio = 1.94, 95% confidence interval = [1.48–2.54], P = 1.63 × 10−6 and OR = 3.65, 95% confidence interval: [1.22–10.93], P = 0.02, respectively) than those with normal TG. They were also more likely to have an elevated (top 10%) polygenic risk score, elevated carriage of potentially causal variant alleles, and carry any genetic risk factor. Alternative definitions of HTG yielded comparable results. In conclusion, individuals of AA with HTG were enriched for genetic risk factors compared to individuals with normal TGs.

Objective and rationale: The study sought to explore the experiences of midwives at selected hospitals in the Ho municipality regarding work-related musculoskeletal disorders, the predisposing factors, the impacts on them, and their coping strategies to mitigate the effects of work-related musculoskeletal disorders. Methods: This study adopted a qualitative research approach with a phenomenological study design. Purposive sampling was employed in this study to select participants. Data was collected and recorded on voice recording devices from fifteen (15) midwives through an interview using a semi-structured interview guide. Data was manually transcribed and analyzed using thematic content analysis. Results: The four emerging themes include: the lived experiences of midwives regarding musculoskeletal disorders, predisposing factors contributing to musculoskeletal disorders, impact of musculoskeletal disorders, and coping strategies of midwives. These themes were further expanded by their sub-themes in describing musculoskeletal conditions, onset, understaffing of midwives, awkward posture assumption during care delivery, limited logistics, struggle with quality of life, impaired work performance, rest and good body mechanics, and teamwork. Conclusion: To lower the rate of work-related musculoskeletal disorders among midwives and increase work efficiency and productivity, educational programs on prevention and coping mechanisms for musculoskeletal disorders should be made mandatory for midwives.

Developing countries are witnessing rapid expansion of electrical infrastructure to meet increasing energy demands, prompting a critical need to assess the potential impact on avian biodiversity. Leveraging open access data, our study conducted a comprehensive assessment to detect electrocution and collision risk hotspots in Kenya while identifying raptor species highly susceptible to these risks. Through an integrated approach that considers morphological and behavioral traits of the species, environmental factors at the site, and technical parameters of the power lines, we developed risk maps and categorized raptors’ susceptibility into high, medium, and low-risk levels. Applying this framework, we identified three raptor species at high risk of electrocution; the long-crested eagle, the augur buzzard, and the steppe eagle. Meru and Kiambu counties emerged as high-risk areas due to substantial overlap between high-risk buffer zones and areas with high raptor species distribution. It is worth noting that this framework only accounts for thirteen raptor species, and there is scope to expand it in the future to include other avian species, such as storks, bustards, pelicans and flamingos, which are also susceptible to electrocution and collision incidents and measures to mitigate electrocution of raptors may not be sufficient for these other group of birds.

Fibroblast growth factors and their receptors (FGFR) have major roles in both human growth and oncogenesis. In adults, therapeutic FGFR inhibitors have been successful against tumors that carry somatic FGFR mutations. In pediatric patients, trials testing these anti-tumor FGFR inhibitor therapeutics are underway, with several recent reports suggesting modest positive responses. Herein, we report an unforeseen outcome in a pre-pubescent child with an FGFR1-mutated glioma who was successfully treated with FDA-approved erdafitinib, a pan-FGFR inhibitor approved for treatment of Bladder tumors. While on treatment with erdafitinib, the patient experienced rapid skeletal and long bone overgrowth resulting in kyphoscoliosis, reminiscent of patients with congenital loss-of-function FGFR3 mutations. We utilized normal dermal fibroblast cells established from the patient as a surrogate model to demonstrate that insulin-like growth factor 1 (IGF-1), a factor important for developmental growth of bones and tissues, can activate the PI3K/AKT pathway in erdafitinib-treated cells but not the MAPK/ERK pathway. The IGF-I-activated PI3K/AKT signaling rescued normal fibroblasts from the cytotoxic effects of erdafitinib by promoting cell survival. We, therefore, postulate that IGF-I-activated P13K/AKT signaling likely continues to promote bone elongation in the growing child, but not in adults, treated with therapeutic pan-FGFR inhibitors. Importantly, since activated MAPK signaling counters bone elongation, we further postulate that prolonged blockage of the MAPK pathway with pan-FGFR inhibitors, together with actions of growth-promoting factors including IGF-1, could explain the abnormal skeletal and axial growth suffered by our pre-pubertal patient during systemic therapeutic use of pan-FGFR inhibitors. Further studies to find more targeted, and/or appropriate dosing, of pan-FGFR inhibitor therapeutics for children are essential to avoid unexpected off-target effects as was observed in our young patient.

Introduction: Reactive stepping capacity to recover from a loss of balance declines with aging, which increases the risk of falling. To gain insight into the underlying mechanisms, we investigated whether muscle coordination patterns of reactive stepping differed between healthy young and older individuals. Methods: We performed a cross-sectional study between 15 healthy young and 14 healthy older adults. They recovered from 200 multidirectional platform translations that evoked reactive stepping responses. We determined spatiotemporal step variables and used muscle synergy analysis to characterize stance- and swing-leg muscle coordination patterns from the start of perturbation until foot landing. Results: We observed delayed step onsets in older individuals, without further spatiotemporal differences. Muscle synergy structure was not different between young and older individuals, but age-related differences were observed in the time-varying synergy activation patterns. In anterior-posterior directions, the older individuals demonstrated significantly enhanced early swing-leg synergy activation consistent with non-stepping behavior. In addition, around step onset they demonstrated increased levels of synergy coactivation (mainly around the ankle) in lateral and anterior directions, which did not appear to hamper foot clearance. Conclusion: Although synergy structure was not affected by age, the delayed step onsets and the enhanced early synergy recruitment point at a relative bias towards non-stepping behavior in older adults. They may need more time for accumulating information on the direction of perturbation and making the corresponding sensorimotor transformations before initiating the step. Future work may investigate whether perturbation-based training improves these age-related deficits.

ABSTRACT: Environmental conditions during incubation and rearing can influence stress responsivity of laying hen pullets throughout their lifespan, and therefore have important implications for their welfare. In this study, a 12:12h green LED light-dark cycle during incubation and larvae provisioning as enrichment during rearing were tested as strategies to optimize early-life conditions and thereby decrease stress responsivity in ISA Brown laying hens. A combination of parameters was measured to indicate neuronal, physiological, and behavioral changes that may affect fear and stress. The proteins calbindin D28k (calbindin1), doublecortin (DCX), and neuronal nuclein protein (NeuN) were quantified after hatch as a proxy for brain plasticity. Plasma and feather corticosterone levels were measured after hatch and at the end of the rearing phase, and fearfulness was investigated through a series of behavioral tests (i.e., voluntary approach, open field, tonic immobility, and manual restraint tests). No effects of light during incubation were found on calbindin1, DCX, or NeuN. Neither of the treatments affected corticosterone levels in blood plasma and feathers. Light-incubated pullets showed less fearfulness towards humans in the voluntary approach test, but not in the other behavioral tests reported in this study. Larvae provisioning had no effect on behavior. Our study showed minor effects of light during incubation and no effects of enrichment during rearing on stress responsivity of laying hen pullets. The small effects may be explained by the enriched rearing conditions for all birds in this experiment (low stocking density, natural daylight, and 24/7 classical music). Given the promising results of lighted incubation in other studies, which were mostly performed in broiler chickens, and evidence regarding the positive effects of enrichment during rearing, the potential of these strategies to improve laying hen welfare needs to be explored further.

S U M M A R Y: Hepatitis B Virus (HBV) was recognized many decades ago as an important occupational hazard for Health Care Workers (HCWs) globally. HCWs who are directly involved in patient care and are in continuous contact with blood or body fluids have an increased risk of occupationally acquiring the virus. The risk of HCWs in highly endemic areas is greater due to the greater prevalence of infection in the general population. Recommendations are available to guide HBV prevention activities or practices among HCWs. These include the use of the hepatitis B vaccine as a preexposure prophylaxis and the use of hepatitis B immunoglobulin alone or hepatitis B immunoglobulin plus the vaccine as postexposure prophylaxis. The uptake of preexposure prophylaxis has been observed to be low in resource-poor settings where the disease is highly endemic. Postexposure prophylaxis has become the remedy for preventing occupational transmission of HBV in these settings.This review aimed to summarize the available evidence on the risk of transmission of HBV infection, the burden of infection and recommendations for pre- and postexposure prophylaxis for the prevention of occupational acquisition of HBV among HCWs. We conducted a narrative review to summarize the evidence available on the recommended steps of HBV exposure management and the utilization of post-exposure prophylaxis (PEP) for HBV. A comprehensive search was conducted in PubMed, Science Direct, Google Scholar, and Africa Journals Online (AJOL) databases. The keywords used were hepatitis B, hepatitis B virus postexposure prophylaxis, occupational exposures, and recommendations for postexposure to hepatitis B virus. We gleaned evidence from the literature sources and summarized the concepts related to exposure forms, postexposure prophylaxis management pathways and recommendations for the utilization of postexposure prophylaxis among exposed healthcare workers.From the synthesis of evidence, we conclude that HBV infection is a life-threatening condition. However, the disease is preventable by using the HBV vaccine as a preexposure prophylaxis measure. An effective postexposure prophylaxis management program is also available, and the last resort to preventing occupational transmission of HBV among HCWs who non-responders are, or who fail to vaccinate completely against HBV. Irrespective of the availability of these lifesaving interventions, the use of pre- and post-exposure prophylaxis among HCWs in highly endemic regions is suboptimal. Many barriers operating at the individual HCW and health facility levels have been identified as impacting the successful use of HBV preventive measures.

Adopting One Health approaches is key for addressing interconnected health challenges. Yet, how to best put One Health into practice in research-for-development initiatives aiming to ‘deliver impacts’ remains unclear. Drawing on the CGIAR Initiative on One Health – a global initiative to address zoonotic diseases, antimicrobial resistance, and food and water safety – we reflect on challenges during program conception and implementation, prompting us to suggest improvements in multisectoral collaboration, coordination, and communication. Our approach involves conducting a researcher-centered process evaluation, comprising individual interviews that are subsequently thematically analyzed and synthesized. The key takeaway is that limited time for planning processes and short program timelines compared to envisioned development impacts may impede research-for-development efforts. Yet, collaborative work can be successful when adequate time and resources are allocated for planning with minimal disruption throughout implementation. Additionally, due to the multifaceted nature of One Health initiatives, it is important to pay attention to co-benefits and trade-offs, where taking action in one aspect may yield advantages and disadvantages in another, aiding to identify sustainable One Health development pathways. Forming close partnerships with national governments and local stakeholders is essential not only to promote sustainability but also to ensure local relevance, enhancing the potential for meaningful impact. Finally, regularly assessing progress toward development goals is critical as development stands as an overarching objective.

This article investigates the complex ways that social conditions and illness experiences interact with cancer in a marginalised population. Drawing on the theoretical framework of syndemics, we explore how people living in circumstances of homelessness and severe substance use in Denmark experience and manage their cancer illness. We draw upon qualitative, partly longitudinal, interviews with marginalised people with current or previous cancer illness. Participants suffered from a wide range of physical and mental conditions alongside their cancer illness and substance use. Adverse interactions between these conditions delayed, complicated, or hindered both the cancer diagnosis and the cancer treatment of participants. Surprisingly, for some, the cancer diagnosis also contributed to temporary periods of stability. Nevertheless, disadvantaged social conditions of chaotic, unwanted housing conditions, fragile social relations and social isolation worked to aggravate participants' cancer trajectories and general life situation. Participants' cancer experiences were cases of syndemic suffering that took on a distinct direction in which cancer created cyclical rounds of suffering due to the many late effects of the illness and treatment. The article demonstrates how marginalised people’s cancer experiences are inextricably linked to, and shaped by, the social and health inequities characterising their lives.

ChatGPT, a chatbot developed by OpenAI, has gained widespread popularity and media attention since its release in November 2022. However, little hard evidence is available regarding its perception in various sources. In this paper, we analyze over 300,000 tweets and more than 150 scientific papers to investigate how ChatGPT is perceived and discussed. Our findings show that ChatGPT is generally viewed as of high quality, with positive sentiment and emotions of joy dominating social media. Its perception has slightly decreased since its debut, however, with joy decreasing and (negative) surprise on the rise, and it is perceived more negatively in languages other than English. In recent scientific papers, ChatGPT is characterized as a great opportunity across various fields including the medical domain, but also as a threat concerning ethics and receives mixed assessments for education. Our comprehensive meta-analysis of ChatGPT’s perception after 2.5 months since its release can contribute to shaping the public debate and informing its future development. We make our data available.11 https://github.com/NL2G/ChatGPTReview.

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR. Both proteins consist of seven epitopes, separated by the GPGPG linker, and a carboxy-terminal 6 × -histidine tag. The molecular weights of the final proteins rDME-C and rDME-BR are 16.83 kDa and 16.80 kDa, respectively, both with an isoelectric point of 6.35. The distinguishing factor between the two proteins lies in the origin of their epitope sequences, where rDME-C is based on the reference dengue proteome, while rDME-BR utilizes sequences from prevalent Dengue genotypes in Brazil from 2008 to 2019. PyMol analysis revealed exposure of epitopes in the secondary structure. Successful expression of the antigens was achieved in soluble form and fluorescence experiments indicated a disordered structure. In subsequent testing, rDME-BR and rDME-C antigens were assessed using an indirect Elisa protocol against Dengue infected serum, previously examined with a commercial diagnostic test. Optimal concentrations for antigens were determined at 10 µg/mL for rDME-BR and 30 µg/mL for rDME-C, with serum dilutions ranging from 1:50 to 1:100. Both antigens effectively detected IgM and IgG antibodies in Dengue fever patients, with rDME-BR exhibiting higher sensitivity. Our in-house test showed a sensitivity of 77.3 % and 82.6 % and a specificity of 89.4 % and 71.4 % for rDME-C and rDEM-BR antigens. No cross-reactivity was observed with serum from Zika-infected mice but with COVID-19 serum samples. Our findings underscore the utility of synthetic biology in crafting Dengue-specific multiepitope proteins and hold promise for precise clinical diagnosis and monitoring responses to emerging Dengue vaccines.

Objective: We report a case of an accessory cavitated uterine mass (ACUM) in a patient with infertility and chronic pelvic pain. In addition, we summarize the literature to better characterize ACUM diagnosis and management. Design: A comprehensive literature search using the PubMed database was performed through April 2023. Historical ACUM diagnostic criteria were applied as inclusion criteria. Descriptive statistics and statistical evaluation were reported. Results: A 31-year-old nulligravid woman presented with chronic pelvic pain, dysmenorrhea, primary infertility, and history of endometriosis. Three-dimensional ultrasonography identified an ACUM and laparoscopic excision provided complete resolution of symptoms. Subsequently, she conceived without assistance twice with uncomplicated vaginal deliveries. A total of 154 articles were identified, 34 papers met inclusion criteria and were individually reviewed, consisting of 70 reported cases. The most common presenting complaints were dysmenorrhea (81.4%), chronic pelvic/abdominal pain (54.1%), and refractory pain (34.3%). Diagnostic imaging included magnetic resonance imaging (62.9%) and transvaginal ultrasound (55.7%). Management included resection via laparoscopy (75.7%) or laparotomy (18.6%), or hysterectomy (5.7%). Of cases with reported outcomes, 90.7% had complete relief of symptoms after surgery. Conclusion: ACUM often presents with dysmenorrhea, chronic pelvic pain, or abdominal pain and is identifiable on magnetic resonance imaging as a hyperenhancing mass. Three-dimensional transvaginal ultrasound can also accurately identify ACUM. A total of 90.7% of patients had complete relief of symptoms after intervention. It is important to identify ACUM early to relieve pain and reduce unnecessary interventions. Like our patient, other reports have demonstrated concomitant infertility and endometriosis. However, further investigation is needed to explore the association between infertility and ACUM.

Cryptosporidium, Giardia, and Blastocystis are significant causes of diarrhea worldwide. However, studies on their prevalence in wild animals are limited, compared to humans and domestic animals. In this study, we collected 23 stool samples from captive wild rescued animals in Boyacá, Colombia. Using conventional PCR, we detected Cryptosporidium spp., Giardia spp., and Blastocystis in over half of the samples (69.6%). Cryptosporidium spp. (43.5%) were the most commonly found, followed by Giardia spp. (39.1%) and Blastocystis (13.0%). Co-infections involving these parasites were also observed. Subsequent genotyping revealed Cryptosporidium canis and Cryptosporidium ryanae as the predominant species. These findings contribute valuable information about the ecoepidemiology of intestinal parasites in Colombian wild animals.

This paper focuses on the investigation of fresh, mechanical, and durability properties of concrete with the influence of fly ash and polypropylene fiber. In this study, cement was partially replaced by 15 % and 30 % fly ash content in weight, whereas polypropylene fiber was incorporated in concrete mixes at 0.06 %, 0.12 %, and 0.18 % by volume. Twelve concrete mix proportions were developed, and slump, density, ball penetration, and compacting factor tests were conducted to examine the fresh concrete properties. Besides, mechanical characteristics, including the uniaxial compressive and splitting tensile strength of concrete, were evaluated at 7, 28, and 90 days. Further tests of concrete durability, including rapid chloride permeability test, sorptivity, and water penetration, were performed at 90 days. The results exhibited that the incorporation of fly ash developed fresh concrete properties, while polypropylene fiber decreased the fresh characteristics of concrete. Furthermore, the combination of fly ash and polypropylene fiber in concrete was substantially attained to improve the mechanical and durability characteristics compared to the control mix. Mix proportion of 15 % fly ash and 0.12 % polypropylene fiber exhibited a pronounced influence on compressive strength, chloride permeability, sorptivity, and water penetration compared to other concrete mixtures.

Adansonia digitata, commonly known as the African Baobab plant is used widely in traditional medicine for treating of many diseases. The current study investigates the antioxidant and antimicrobial properties, and nutritional composition of the pulp and seeds from the fruit of African Baobab plant. Matured fruits were harvested and processed by separating the fruit pulp and seeds. Water, 70 % Ethanol/water mixture, and Hexane were used as solvents for extraction. Antioxidant properties of extracts in this study were investigated using the 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxidescavenging assays., Total Flavonoid Content, Total Phenolic Content, Total Tannin Content, and Total Antioxidant Capacity were also investigated. Agar Well Diffusion and Broth Dilution methods were used to estimate the antimicrobial properties of the extracts. The proximate composition of the seeds and fruit pulps was also determined. GC-MS was employed to determine the fatty acid composition. Results obtained showed the presence of Total phenolics (range 4.1–5.5 mg GAE/g), Total flavonoids (range 10.1–16.5 mg QE/g), Total Tannins (range 1.7–15.6 mg CE/g), and Antioxidants (range 2.0–14.5 mg AAE/g). The H2O2 and DPPH assays gave IC50s in the ranges of 300–1800 mg/L and 700–1600 mg/L respectively. Extract from the fruit pulp was found to inhibit the growth of a panel of 2 g-positive bacteria, 2 g-negative bacteria, and two fungi microorganisms. Fatty acids such as myristic acid, palmitic acid, and stearic acid were found to be present in oil from the seeds. Proximate components such as crude protein, crude fat, and crude fibre were found to be high. From the results, seeds and the fruit pulp of the African Baobab plant have significant antioxidant properties and can inhibit microbial growth.

Soil contamination is a growing concern for sustainable development worldwide. Conventional remediation approaches, such as using ordinary Portland cement (OPC) or lime are limited due to high CO2 emissions, energy consumption, and natural resource consumption. This paper proposes a sustainable method using CO2 and a waste from steel production (ladle slag, LS) for rapid remediation of Cr and Zn-contaminated soils. Contaminated soils spiked by Cr and Zn with various initial concentrations were treated with 10% LS and subjected to conventional and CO2 curing for different periods. The results demonstrated that LS with conventional curing could reduce leaching concentrations of Cr and Zn in contaminated soils. However, it necessitated 28 days to meet the criteria of inert waste and drinking water standards. In contrast, LS with CO2 curing required significantly less time (32 h for Cr and 8 h for Zn) to achieve lower leaching concentrations of Cr and Zn than those with 28-day conventional curing. After CO2 curing for 152 h for Cr- and 80–120 h for Zn-contaminated soils, leaching concentrations of Cr and Zn were 1.5–4 times and 6–72 times lower than those with 28-day conventional curing, respectively. Simultaneously, carbon capture was increased from 10.6% to 17.5% and 19.9%, respectively, with the initial Cr and Zn concentrations increased from 0 to 8000 mg/kg. The strength of Cr- and Zn-contaminated soils with CO2 curing also effectively enhanced up to around 3.3–3.6 times and 1.3–3.3 times higher than those with 28-day conventional curing, respectively.

Summary: Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p