Do schistosome vaccine trials in mice have an intrinsic flaw that generates spurious protection data?

The laboratory mouse has been widely used to test the efficacy of schistosome vaccines and a long list of candidates has emerged from this work, many of them abundant internal proteins. These antigens do not have an additive effect when co-administered, or delivered as SWAP homogenate, a quarter of which comprises multiple candidates; the observed protection has an apparent ceiling of 40–50 %. We contend that the low level of maturation of penetrating cercariae (~32 % for Schistosoma mansoni) is a major limitation of the model since 68/100 parasites fail to mature in naïve mice due to natural causes. The pulmonary capillary bed is the obstacle encountered by schistosomula en route to the portal system. The fragility of pulmonary capillaries and their susceptibility to a cytokine-induced vascular leak syndrome have been documented. During lung transit schistosomula burst into the alveolar spaces, and possess only a limited capacity to re-enter tissues. The acquired immunity elicited by the radiation attenuated (RA) cercarial vaccine relies on a pulmonary inflammatory response, involving cytokines such as IFNγ and TNFα, to deflect additional parasites into the alveoli. A principal difference between antigen vaccine protocols and the RA vaccine is the short interval between the last antigen boost and cercarial challenge of mice (often two weeks). Thus, after antigen vaccination, challenge parasites will reach the lungs when both activated T cells and cytokine levels are maximal in the circulation. We propose that “protection” in this situation is the result of physiological effects on the pulmonary blood vessels, increasing the proportion of parasites that enter the alveoli. This hypothesis will explain why internal antigens, which are unlikely to interact with the immune response in a living schistosomulum, plus a variety of heterologous proteins, can reduce the level of maturation in a non-antigen-specific way. These proteins are “successful” precisely because they have not been selected for immunological silence. The same arguments apply to vaccine experiments with S. japonicum in the mouse model; this schistosome species seems a more robust parasite, even harder to eliminate by acquired immune responses. We propose a number of ways in which our conclusions may be tested

Review: The increasing importance of carbon nanotubes and nanostructured conducting polymers in biosensors

The growing need for analytical devices requiring smaller sample volumes, decreased power consumption and improved performance have been driving forces behind the rapid growth in nanomaterials research. Due to their dimensions, nanostructured materials display unique properties not traditionally observed in bulk materials. Characteristics such as increased surface area along with enhanced electrical/optical properties make them suitable for numerous applications such as nanoelectronics, photovoltaics and chemical/biological sensing. In this review we examine the potential that exists to use nanostructured materials for biosensor devices. By incorporating nanomaterials, it is possible to achieve enhanced sensitivity, improved response time and smaller size. Here we report some of the success that has been achieved in this area. Many nanoparticle and nanofibre geometries are particularly relevant, but in this paper we specifically focus on organic nanostructures, reviewing conducting polymer nanostructures and carbon nanotubes

AI-Driven Large Language Models in Health Consultations for HIV Patients

Chun-Yan Zhao,1,2,* Chang Song,1,2,* Tong Yang,3,* Ai-Chun Huang,1 Hang-Biao Qiang,1 Chun-Ming Gong,1 Jing-Song Chen,4 Qing-Dong Zhu1 1Department of Tuberculosis, The Fourth People’s Hospital of Nanning, Nanning, Guangxi, People’s Republic of China; 2Clinical Medical School, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Department of Rehabilitation, Hepu County People’s Hospital, Beihai, Guangxi, People’s Republic of China; 4Department of Gastroenterology, Hepu County People’s Hospital, Beihai, Guangxi, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Dong Zhu, Department of Tuberculosis, The Fourth People’s Hospital of Nanning, No. 1 Changgang Two-Li, Xingning District, Nanning, Guangxi, 530023, People’s Republic of China, Tel +86 0771-5636973, Email [email protected] Jing-Song Chen, Department of Gastroenterology, Hepu County People’s Hospital, No. 95, Dinghai North Road, Hepu County, Beihai, Guangxi, 536100, People’s Republic of China, Tel +86 0779-7106010, Email [email protected]: This study endeavors to conduct a comprehensive assessment on the performance of large language models (LLMs) in health consultation for individuals living with HIV, delve into their applicability across a diverse array of dimensions, and provide evidence-based support for clinical deployment.Patients and Methods: A 23-question multi-dimensional HIV-specific question bank was developed, covering fundamental knowledge, diagnosis, treatment, prognosis, and case analysis. Four advanced LLMs—ChatGPT-4o, Copilot, Gemini, and Claude—were tested using a multi-dimensional evaluation system assessing medical accuracy, comprehensiveness, understandability, reliability, and humanistic care (which encompasses elements such as individual needs attention, emotional support, and ethical considerations). A five-point Likert scale was employed, with three experts independently scoring. Statistical metrics (mean, standard deviation, standard error) were calculated, followed by consistency analysis, difference analysis, and post-hoc testing.Results: Claude obtained the most outstanding performance with regard to information comprehensiveness (mean score 4.333), understandability (mean score 3.797), and humanistic care (mean score 2.855); Copilot demonstrated proficiency in diagnostic questions (mean score 3.880); Gemini illustrated exceptional performance in case analysis (mean score 4.111). Based on the post-hoc analysis, Claude outperformed other models in thoroughness and humanistic care (P < 0.05). Copilot showed better performance than ChatGPT in understandability (P = 0.045), while Gemini performed significantly better than ChatGPT in case analysis (P < 0.001). It is important to note that performance varied across tasks, and humanistic care remained a consistent weak point across all models.Conclusion: The superiority of diverse models in specific tasks suggest that LLMs hold extensive application potential in the management of HIV patients. Nevertheless, their efficacy in the realm of humanistic care still needs improvement.Keywords: artificial intelligence, large language model, HIV, health consultation, performance analysi

Adaptive Honeypot Engagement through Reinforcement Learning of Semi-Markov Decision Processes

A honeynet is a promising active cyber defense mechanism. It reveals the fundamental Indicators of Compromise (IoCs) by luring attackers to conduct adversarial behaviors in a controlled and monitored environment. The active interaction at the honeynet brings a high reward but also introduces high implementation costs and risks of adversarial honeynet exploitation. In this work, we apply infinite-horizon Semi-Markov Decision Process (SMDP) to characterize a stochastic transition and sojourn time of attackers in the honeynet and quantify the reward-risk trade-off. In particular, we design adaptive long-term engagement policies shown to be risk-averse, cost-effective, and time-efficient. Numerical results have demonstrated that our adaptive engagement policies can quickly attract attackers to the target honeypot and engage them for a sufficiently long period to obtain worthy threat information. Meanwhile, the penetration probability is kept at a low level. The results show that the expected utility is robust against attackers of a large range of persistence and intelligence. Finally, we apply reinforcement learning to the SMDP to solve the curse of modeling. Under a prudent choice of the learning rate and exploration policy, we achieve a quick and robust convergence of the optimal policy and value.Comment: The presentation can be found at https://youtu.be/GPKT3uJtXqk. arXiv admin note: text overlap with arXiv:1907.0139

Clinical Characteristics Analysis of 30 Cases of Interferon-γ Autoantibody-Positive Patients with Concurrent Mycobacterial Infection: A 6-Year Retrospective Study

Chun-Yan Zhao,1,2,* Chang Song,1,2,* Hua-Wei He,1,* Xian-Zhen Huang,1 Xia-Yan Meng,1 Ai-Chun Huang,1 Chao-Yan Xu,1 Li-Li Luo,1 Shao-Yong Xi,3 Yan-Qun Lan,1 Wei-Wen Li,1 Yan-Rong Lin,1 Qing-Dong Zhu1 1Department of Tuberculosis, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 2Clinical Medical School, Guangxi Medical University, Nanning, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qing-Dong Zhu; Yan-Rong Lin, Department of Tuberculosis, The Fourth People’s Hospital of Nanning, No. 1 Changgang Two-Li, Xingning District, Nanning, 530023, People’s Republic of China, Tel +8615207717261 ; +860771-5636973, Email [email protected]; [email protected]: This study aimed to investigate and elucidate the clinical characteristics, immune status, infection types and patterns, treatment responses, and disease progression in patients with positive anti-interferon-gamma (IFN-γ) autoantibodies in combination with Mycobacterium infections.Patients and Methods: We conducted a retrospective analysis of clinical data from patients with positive anti-IFN-γ autoantibodies and concurrent Mycobacterial infections, including Mycobacterial infections (MTB) and non-tuberculous mycobacteria (NTM). The study included cases treated at the Fourth People’s Hospital of Nanning, Guangxi, from 2018 to 2023. Data collected comprised symptoms, clinical signs, laboratory test results, imaging findings, and other relevant clinical information. Patients were also followed up to evaluate treatment responses and long-term therapeutic outcomes.Results: A total of 30 patients with MTB and NTM infections were analyzed. The majority presented with common symptoms, such as cough, sputum production, weight loss, extrapulmonary tuberculosis (TB), and a range of opportunistic infections. Laboratory and imaging studies revealed complex infection patterns and various pathological changes. Treatment primarily involved targeted anti-infective therapy combined with immunosupportive measures. However, frequent treatment relapses and side effects were observed, resulting in two deaths.Conclusion: Immune deficiency associated with positive anti-IFN-γ autoantibodies resembles the immunosuppression seen in advanced stages of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), rendering patients highly susceptible to opportunistic infections. These infections were predominantly caused by NTM, followed by MTB and Talaromyces marneffei (TM). This represents a novel immune deficiency syndrome that predisposes patients to a spectrum of opportunistic infections.Keywords: anti-interferon-gamma autoantibodies, Mycobacterium tuberculosis, nontuberculous mycobacteria, clinical characteristics, treatmen

Low-carbon calcined clay-based binders for sustainable hempcrete

Abstract The building sector is responsible for approximately 40% of total anthropogenic greenhouse gas emissions and 37% of global energy consumption. Hempcrete, fabricated from industrial hemp, can offer a tremendous potential to alleviate the carbon emissions and energy usage from buildings and construction based on its carbon capture and storage capability and low thermal conductivity. However, conventional lime-based binders for hempcrete are carbon intensive. This study investigates three low carbon binder alternatives for hempcrete: HL-Ref (100% hydrated lime), HL–CC (50% hydrated lime, 50% calcined clay), HL–CC–LS (50% hydrated lime, 50% calcined clay and limestone), Geo-CC [geopolymer binder with 70% calcined clay and 30% granulated ground blast furnace slag (GGBFS)]. Compressive strength, bulk density, sound absorption coefficient, thermal conductivity, surface bond strength and crystalline phases of hempcrete were assessed and a multicriteria analysis was carried out to compare the hempcrete performance between different mix designs. Results showed that the Geo-CC hempcrete using the calcined clay/GGBFS geopolymer binder achieved the best performance in terms of compressive strength, surface bonding capacity and thermal conductivity. The performance of HL–CC–LS hempcrete also achieved outstanding properties which could not be achieved by using only calcined clay (HL–CC), highlighting the beneficial synergy between limestone and calcined clay in a lime-based system. The HL–CC–LS hempcrete achieved the best acoustic performance with the highest sound absorption coefficient.</jats:p

Suitability of calcined clay and ground granulated blast furnace slag geopolymer binder for hempcrete applications

PurposeHempcrete has the potential to reduce both CO2 emissions and energy usage in buildings. Hempcrete has a high sound absorption capacity, excellent moisture regulator and outstanding thermal insulation properties. However, hempcrete traditionally uses lime-based binders, which are carbon-intensive materials. The low-carbon binders to increase the sustainability of hempcrete are the current research gap. Geopolymer binders are low-carbon binders composed of aluminosilicate precursors dissolved in a high alkalinity solution. This study investigated the suitability of calcined clay and ground granulated blast furnace slag geopolymer binder as a low-carbon binder for hempcrete applications.Design/methodology/approachTwo types of hemp hurds with different water absorption capacity and particle size distributions were used. Hempcrete properties tested were compressive strength, bulk density, sound absorption coefficient by a two-microphone impedance tube and thermal conductivity by a Hot Disk system.FindingsThe particle size distribution and water absorption capacity of hemp hurds did not affect the compressive strength of hempcrete when following a mixing procedure, ensuring the hurds in a saturated surface dry condition. The geopolymer hempcrete achieved a compressive strength about four times higher than the reference hydrated lime hempcrete. All hempcrete specimens achieved outstanding acoustic performance. The increase in bulk density led to the decrease in the maximum sound absorption coefficient. The geopolymer hempcrete achieved the lowest thermal conductivity.Originality/valueThe outcomes of this paper reveal that the low-carbon geopolymer binder appears to be a promising option for manufacturing hempcrete, achieving significantly higher compressive strength and lower thermal conductivity than the reference hydrated lime-based hempcrete.</jats:sec

The effect of socioeconomic status on three-year mortality after first-ever ischemic stroke in Nanjing, China

BACKGROUND: Low socioeconomic status (SES) is associated with increased mortality after stroke in developed countries. This study was performed to determine whether a similar association also exists in China. METHODS: A total of 806 patients with first-ever ischemic stroke were enrolled in our study. From August 1999 to August 2005, the three-year all-cause mortality following the stroke was determined. Level of education, occupation, taxable income and housing space were used as indicators for SES. Stepwise univariate and multivariate COX proportional hazards models were used to study the association between the SES measures and the three-year mortality. RESULTS: Our analyses confirmed that occupation, taxable income and housing space were significantly associated with three-year mortality after first-ever stroke. Manual workers had a significant hazard ratio of 5.44 (95% CI 2.75 to 10.77) for death within three years when compared with non-manual workers. Those in the zero income group had a significant hazard ratio of 5.35 (95% CI 2.95 to 9.70) and those in the intermediate income group 2.10 (95% CI 1.24 to 3.58) when compared with those in the highest income group. Those in two of the three groups with the smallest housing space also had significant hazard ratios of 2.06 (95% CI 1.16 to 3.65) and 1.68 (95% CI 1.12 to 2.52) when compared with those in group with the largest housing space. These hazard ratios remained largely unchanged after multivariate adjustment for age, gender, baseline cardiovascular disease risk factors, and stroke severity. The analyses did not confirm an association with educational level. CONCLUSION: Lower SES has a negative impact on the outcome of first-ever stroke in Nanjing, China. This confirms the need to improve preventive and secondary care for stroke among low SES groups

The evolutionary history of 2,658 cancers

Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection