Humoral Research Articles

A Multi-Functional Nanoadjuvant Coupling Manganese with Toll-Like 9 Agonist Stimulates Potent Innate and Adaptive Anti-Tumor Immunity.

The effectiveness of Toll-like 9 agonists (CpG) as an adjuvant for tumor immunotherapy is restricted due to their insufficient ability to activate anti-tumor immunity. To address that, the common nutrient metal ions are explored (Mn2+, Cu2+, Ca2+, Mg2+, Zn2+, Fe3+, and Al3+), identifying Mn2+ as a key enhancer of CpG to mediate immune activation by augmenting the STING-NF-κB pathway. Mn2+ and CpG are then self-assembled with epigallocatechin gallate (EGCG) into a nanoadjuvant MPN/CpG. Local delivery of MPN/CpG effectively inhibits tumor growth in a B16 melanoma-bearing mouse model, reshaping the tumor microenvironment (TME) by repolarizing M2-type tumor-associated macrophages (TAMs) to an M1-type and boosting intra-tumoral infiltration of CD8+/CD4+ T lymphocytes and DCs. Furthermore, compared to free CpG, MPN/CpG exhibits heightened accumulation in lymph nodes, enhancing CpG uptake and DC activation, consequently inducing significant antigen-specific cytotoxic CD8+ T cell immune response and humoral immunity. In a prophylactic tumor-bearing mouse model, MPN/CpG vaccination with OVA antigen significantly delays B16-OVA melanoma growth and extends mouse survival. These findings underscore the potential of MPN/CpG as a multifunctional adjuvant platform to drive powerful innate and adaptive immunity and regulate TME against tumors.

Human body temperature and cardiovascular response to changes in ambient temperature and body posture

Health problems due to heat or cold exposure is closely related not only to body temperature (BT) but also to blood flow rate (BFR) and blood pressure (BP). Therefore, it is necessary to understand the physiological mechanisms of the human body, such as how these physiological quantities change and how they affect each other. In this study, to clarify the physiological mechanisms of the human body, we measured the whole-body distribution of BT and BFR, as well as BP, heart rate, and metabolic rate under changes in ambient temperature and body posture. A total of 19 subjects were tested in three cases, including the temperature up-step and down-step cases, where the ambient temperature changed from 28 °C to 38 °C or 18 °C in the supine position, and the posture change case, where the posture changed alternately between the supine and standing positions at an ambient temperature of 28 °C. The results showed that the core temperature was efficiently maintained due to BFR regulation, especially in the extremities, in response to changes in ambient temperature. Additionally, changes in cerebral BFR in response to changes in posture were suppressed due to regulation of BFR, especially in the lower limbs, and heart rate. Furthermore, in the extremities, the BFR not only in the skin but also in the subcutaneous tissue and muscle was estimated to increase in hot environments and decrease in cold environments.

CPT2-mediated Fatty Acid Oxidation Is Dispensable for Humoral Immunity.

B cell activation is accompanied by dynamic metabolic reprogramming, supported by a multitude of nutrients that include glucose, amino acids, and fatty acids. Although several studies have indicated that fatty acid mitochondrial oxidation is critical for immune cell functions, contradictory findings have been reported. Carnitine palmitoyltransferase II (CPT2) is a critical enzyme for long-chain fatty acid oxidation in mitochondria. In this study, we test the requirement of CPT2 for humoral immunity using a mouse model with a lymphocyte-specific deletion of CPT2. Stable [13C] isotope tracing reveals highly reduced fatty acid-derived citrate production in CPT2-deficient B cells. Yet, CPT2 deficiency has no significant impact on B cell development, B cell activation, germinal center formation, and Ab production upon either thymus-dependent or -independent Ag challenges. Together, our findings indicate that CPT2-mediated fatty acid oxidation is dispensable for humoral immunity, highlighting the metabolic flexibility of lymphocytes.

New Pathway for Management Studies in China: Exploring Qualitative Research Methods of Business Anthropology

Through an inventory of the existing literature body on Chinese management studies, this paper attempts to present a critical review of the phenomenon that the management studies in contemporary China over-rely on quantitative research methodology. It endeavors to demonstrate that the nature of scientific research is to innovate by seeking truth and, therefore, should not be restricted by quantitative research methods. Improve the effectiveness of academic analyses, it suggests that the scholars in China need to positively adapt the anthropological methodologies to conduct management studies and enhance the process of the localization of management science in the country. It is designed to broaden the approaches toward Chinese management studies by introducing business anthropological methods to Chinese management scholars. It adopts a comparative and case study methodology to demonstrate the limitations of quantitative methods and illustrate the effectiveness of business anthropological approaches for management studies in the Chinese context. The existing literature body demonstrates that excessive quantitative research approaches are utilized in current management studies, while scholars in China primarily ignore the effectiveness of qualitative methods. The necessity for further understanding qualitative research methods in management studies has been recognized more recently by Chinese scholars. They tend to agree that qualitative and quantitative research methodologies are merely different approaches, while the results are the same. One of the compelling new paths to improving management studies and practices is to apply anthropological research methods so that management theory in China can better explain actual human responses and factors that influence their behaviors. Anthropology has always been employed for practical applications. In addition, anthropological methods can enlarge the approaches to management studies and widen the scope for scholars to conduct their research. The combination of anthropology and management will accelerate the localization of management studies and, accordingly, speed up the systematic establishment of Chinese management theory to promote management practices in modern China. Business anthropology is emerging among some outstanding qualitative research methods in Western management studies. On the other hand, China's management science community is still a little behind in this respect. This paper is a pilot study to elaborate on business anthropology and its contribution to specific areas in management studies, such as marketing management, product design, and entrepreneurship in the Chinese context.

Delivery of SARS-CoV-2 spike and membrane genes in a single Baculoviral vector enhance the immune breadth against SARS-CoV-2 variants of concern

Although the coronavirus pandemic has ended, new variants of concern (VOCs) continue to emerge. Therefore, novel vaccines targeting VOCs are highly warranted. We initially constructed three recombinant baculovirus-vectored vaccines (AcHERV-COVID19S) carrying the spike genes of the SARS-CoV-2 prototype, Delta, and Omicron BA.1 variants. However, the SARS-CoV-2 spike gene alone could not provide protection against multiple VOCs. To develop a universal vaccine, we constructed a recombinant baculovirus-vectored vaccine (AcHERV-COVID19 OmiM) by introducing the M gene, which is conserved among VOCs, as a secondary cellular immune antigen in addition to the S gene. AcHERV-COVID19 OmiM could provide higher protection against SARS-CoV-2 variants (prototype, Delta, BA.5 and XBB.1) compared with that of AcHERV-COVID19S. The membrane protein of SARS-CoV-2 synergizes with the S gene, thereby enhancing both humoral and cellular immunity against VOCs. Although AcHERV-COVID19 OmiM may not provide sterile protection against new variants, it may help reduce symptoms and curb viral transmission.

Unveiling human biomechanics: insights into lower limb responses to disturbances that can trigger a fall

IntroductionSlip-related falls are a significant concern, particularly for vulnerable populations such as the elderly and individuals with gait disorders, necessitating effective preventive measures. This manuscript presents a biomechanical study of how the lower limbs react to perturbations that can trigger a slip-like fall, with the ultimate goal of identifying target specifications for developing a wearable robotic system for slip-like fall prevention.MethodsOur analysis provides a comprehensive understanding of the natural human biomechanical response to slip perturbations in both slipping and trailing legs, by innovatively collecting parameters from both the sagittal and frontal plane since both play pivotal roles in maintaining stability and preventing falls and thus provide new insights to fall prevention. We investigated various external factors, including gait speed, surface inclination, slipping foot, and perturbation intensity, while collecting diverse data sets encompassing kinematic, spatiotemporal parameters, electromyographic data, as well as torque, range of motion, rotations per minute, detection, and actuation times.ResultsThe biomechanical response to slip-like perturbations by the hips, knees, and ankles of the slipping leg was characterized by extension, flexion, and plantarflexion moments, respectively. In the trailing leg, responses included hip flexion, knee extension, and ankle plantarflexion. Additionally, these responses were influenced by gait speed, surface inclination, and perturbation intensity. Our study identified target range of motion parameters of 85.19°, 106.34°, and 95.23° for the hips, knees, and ankles, respectively. Furthermore, rotations per minute values ranged from 17.85 to 51.10 for the hip, 21.73 to 63.80 for the knee, and 17.52 to 57.14 for the ankle joints. Finally, flexion/extension torque values were estimated as −3.05 to 3.22 Nm/kg for the hip, −1.70 to 2.34 Nm/kg for the knee, and −2.21 to 0.90 Nm/kg for the ankle joints.DiscussionThis study contributes valuable insights into the biomechanical aspects of slip-like fall prevention and informs the development of wearable robotic systems to enhance safety in vulnerable populations.

Exploring the Impact of Visual and Aural Elements in Urban Parks on Human Behavior and Emotional Responses

As cities progress into high-quality developments, the demand for urban parks that enhance residents’ well-being and sustainability is increasing. Traditional visual-centric design methods no longer suffice. Given that vision and hearing are the primary sensory pathways through which people perceive their environment, exploring their relationship with landscape experiences offers a novel perspective for optimizing the audiovisual perception quality of urban parks. This study explores the relationship between visual and auditory elements and landscape experiences to optimize urban parks’ sensory quality. Using visual perception, soundscape perception, sound source perception, and behavioral vitality, this study evaluates the audiovisual perception quality of a representative wetland park in Chengdu’s ring ecological zone. By quantifying relationships between audiovisual characteristics, behavioral vitality, and emotional feedback, several emotional assessment models were constructed. The results show that lawns, pavements, and sound pressure levels significantly impact vitality. A sound pressure level of 77 dB has been identified as a critical threshold in emotional perception models. Consequently, distinct emotional prediction models can be employed to enhance landscape design across various sound pressure level zones. This research provides scientific evidence and flexible strategies for designing urban open spaces that improve landscape experiences based on multisensory perception.

Polarization of circulating Follicular Helper T cells correlates with the severity of Bullous Pemphigoid.

T-follicular-helper (Tfh) cells form a distinct population of T-helper cells with different polarizations (type 1, type 2 and type 17) that regulates humoral responses and may participate in the pathophysiology of B-cell mediated autoimmune diseases, such as bullous pemphigoid (BP), a dermatosis mediated by auto-antibodies specific for hemidesmosomal proteins. The aim was to evaluate the impact of superpotent topical corticosteroid (TCS) treatment, which is more effective and safer than high doses of oral corticosteroids and recommended first-line treatment of BP, on circulating Tfh cells. We compared by flow cytometry the frequency, polarization and activation of blood Tfh cells from patients with BP at baseline and longitudinally after initiation of TCS treatment to age- and sex-matched healthy subjects. We observed that circulating Tfh cells were more frequent in patients with BP at baseline than in healthy subjects and exhibited an activated phenotype. We further showed a decrease of type 1 and an increase of type 17 Tfh cells in the blood of patients, which resulted in a higher (type 2+type 17) to type 1 Tfh cell ratio. This ratio correlated positively with disease severity as measured by the Bullous Pemphigoid Disease Area Index. Remarkably, along TCS treatment, although the frequency of Tfh cells returned to a level similar to control, the activated phenotype persisted. Interestingly serum IL-21 levels and the Tfh cell subset ratio, similarly to disease activity and serum anti-BP180 and anti-BP230 auto-antibodies, were decreased under the TCS treatment. Overall, our findings suggest an involvement of the polarization of Tfh cells in the pathophysiology of BP and open the door to a modulation of their activity for therapeutic purposes.

COVID-19 mRNA vaccines induce robust levels of IgG but limited amounts of IgA within the oronasopharynx of young children.

Understanding antibody responses to SARS-CoV-2 vaccination is crucial for refining COVID-19 immunization strategies. Generation of mucosal immune responses, including mucosal IgA, could be of potential benefit to vaccine efficacy, yet limited evidence exists regarding the production of mucosal antibodies following the administration of current mRNA vaccines to young children. We measured the levels of antibodies against SARS-CoV-2 from a cohort of children under 5 years of age (N=24) undergoing SARS-CoV-2 mRNA vaccination (serially collected, matched serum and saliva samples) or in a convenience sample of children under 5 years of age presenting to pediatric emergency department (nasal swabs, N=103). Further, we assessed salivary and nasal samples for the ability to induce SARS-CoV-2 spike-mediated neutrophil extracellular traps (NET) formation. Longitudinal analysis of post-vaccine responses in saliva revealed the induction of SARS-CoV-2 specific IgG but not IgA. Similarly, SARS-CoV-2 specific IgA was only observed in nasal samples obtained from previously infected children with or without vaccination, but not in vaccinated children without a history of infection. In addition, oronasopharyngeal samples obtained from children with prior infection were able to trigger enhanced spike-mediated NET formation, and IgA played a key role in driving this process. Despite the induction of specific IgG in the oronasal mucosa, current intramuscular vaccines have limited ability to generate mucosal IgA in young children. These results confirm the independence of mucosal IgA responses from systemic humoral responses following mRNA vaccination and suggest potential future vaccination strategies for enhancing mucosal protection in this young age group.

The metabolic profiles of endogenous and exogenous substances in a poor metabolizer of humanized CYP2D6 model

Background: Species differences in CYP2D6 drug metabolism complicate the extrapolation of in vivo pharmacokinetic data to humans and impact the prediction of drug responses. This study aimed to develop an in vivo model to predict human responses to CYP2D6 metabolized compounds and to evaluate medication risks and disease development.Methods: We used embryonic stem cell (ES) targeting and CRISPR-Cas9 technology to create a humanized CYP2D6 mouse model by inserting the human wild-type CYP2D6 gene and knocking out the mouse Cyp2d locus. Metoprolol was used as the substrate probe to examine the pharmacokinetic properties of exogenous substances, tissue distribution, and in situ metabolism of CYP2D6. Untargeted and quantitative metabolomics analyses compared endogenous substance metabolism between different species of CYP2D6 enzymes.Results: No significant differences in CYP2D6 homologous protein distribution and expression of primary metabolic organs were found between humanized CYP2D6 mice and wild-type (WT) mice. The activity and metabolic capacity of CYP2D6 in humanized mice were substantially lower than homologous Cyp2d22 of WT mice in metabolizing metoprolol. The levels of several glycerolipids and glycerophospholipid-related metabolites were down-regulated in humanized CYP2D6 mice. Triglyceride TG (14:0_22:6_22:6) was significantly downregulated in male and female humanized mice, suggesting a strong association with reduced CYP2D6 activity.Conclusions: This study established a robust animal model to investigate human CYP2D6-mediated metabolic profiles of exogenous and endogenous compounds, predict medication risks, and explore the potential roles of CYP2D6 in organ-specific toxicity and disease development.

Sequence Matters: Primary COVID-19 Vaccination after Infection Elicits Similar Anti-spike Antibody Levels, but Stronger Antibody Dependent Cell-mediated Cytotoxicity than Breakthrough Infection.

Infection before primary vaccination (herein termed "hybrid immunity") engenders robust humoral immunity and broad Ab-dependent cell-mediated cytotoxicity (ADCC) across SARS-CoV-2 variants. We measured and compared plasma IgG and IgA against Wuhan-Hu-1 and Omicron (B.1.1.529) full-length spike (FLS) and receptor binding domain after three mRNA vaccines encoding Wuhan-Hu-1 spike (S) and after Omicron breakthrough infection. We also measured IgG binding to Wuhan-Hu-1 and Omicron S1, Wuhan-Hu-1 S2 and Wuhan-Hu-1 and Omicron cell-based S. We compared ADCC using human embryonic lung fibroblast (MRC-5) cells expressing Wuhan-Hu-1 or Omicron S. The effect of Omicron breakthrough infection on IgG anti-Wuhan-Hu-1 and Omicron FLS avidity was also considered. Despite Omicron breakthrough infection increasing IgG and IgA against FLS and receptor binding domain to levels similar to those seen with hybrid immunity, there was no boost to ADCC. Preferential recognition of Wuhan-Hu-1 persisted following Omicron breakthrough infection, which increased IgG avidity against Wuhan-Hu-1 FLS. Despite similar total anti-FLS IgG levels following breakthrough infection, 4-fold higher plasma concentrations were required to elicit ADCC comparable to that elicited by hybrid immunity. The greater capacity for hybrid immunity to elicit ADCC was associated with a differential IgG reactivity pattern against S1, S2, and linear determinants throughout FLS. Immunity against SARS-CoV-2 following Omicron breakthrough infection manifests significantly less ADCC capacity than hybrid immunity. Thus, the sequence of antigenic exposure by infection versus vaccination and other factors such as severity of infection affect antiviral functions of humoral immunity in the absence of overt quantitative differences in the humoral response.

Understanding Human-Robot Interactions with a Humanoid Robot

Human responses towards robots vary from excitement and acceptance to complete rejection, and as robots become more prevalent in personal and public spaces, understanding the factors that elicit those responses is important. This research explores the factors influencing these responses, specifically in the context of human-robot collaborative tasks. Under mechatronics and robotics, the study focuses on identifying behavioural features (like triggers or positive/negative eliciting actions) and human-designed robot algorithms that elicit different human reactions. It also examines how these features interact to shape human behaviour and emotions in stressful and calm situations. I developed a study in a simulated medical setting where participants are tasked with developing dialogue scripts for a social robot. The study utilizes the NAO robot and a programmable platform called the Robot Management System developed by RobotLab. Participants will program NAO to interact with a patient, perform a checkup, and decide on actions like writing a prescription or referring the patient to medical professionals. The experiment is designed to observe how the participant interacts with the robot to complete tasks and how the robot’s design impacts the participants' perception and interaction following and during tasks. While no experimental data has been collected due to pending ethics approval, the research will provide insights into human-robot interaction, including algorithm design. This study aims to enhance our understanding of human-robot relationships, contributing to developing robotic systems that can be effectively integrated into social environments, such as healthcare settings or similar environments. These insights may inform the design and deployment of robots to ensure they support rather than disrupt social dynamics.

Investigating Human-Robot Interactions with a Quadruped Robot

Robots are becoming more prevalent in our daily lives. As robots become more common in society, we must understand how people react and interact with them. This study leverages Boston Dynamics' Spot robot to examine human responses to quadruped robots. Previous studies had Spot walking alongside participants at fixed speeds, independent of their gait. Improving upon this method, I developed a program that enables Spot to detect and follow fiducial markers (AprilTags). Using the Robot Operating System (ROS), the depth and position of the tag within the camera’s frame were extracted and translated into motion commands for the robot. The tag is attached to an apparatus on the hip that extends the tag near the subject’s knee, allowing Spot to track the participant’s trunk speed and maintain a consistent distance, offering a more adaptive walking experience. The program allows for variations in the acceleration, height, and camera selection (front/back, left/right) through a custom Graphical User Interface (GUI), allowing for diverse trial conditions. Extensive testing identified considerations to optimize the walking experience. Factors included gradual acceleration to allow Spot to react and maintain detections, and the set requirement to run only a single camera at a time for optimized processing. Additionally, keeping the tag unobstructed and square to the camera is critical to avoid failures in detection. Overall, Spot's new capabilities will assist in further studies of human and robot interactions.

Hubungan Antara Kelelahan Dengan Tingkat Kecemasan Perawat Rumah Sakit: Sebuah Tinjauan Pustaka

Fatigue can be caused by overwork, prolonged physical and mental activity, lack of rest, high stress or a combination of these factors. Work fatigue is caused by tiring and energy-draining activities, thereby reducing human alertness and response to stress. Anxiety is a common emotional disorder characterized by deep and persistent fear or worry, but without any disturbance in the assessment of reality. A nurse is someone who has graduated from a nursing school, both inside and outside of school, in accordance with the provisions of applicable laws and regulations. This article provides an explanation of work fatigue, anxiety and determines the relationship between anxiety and work fatigue specifically for nurses who work in hospitals. This research uses a qualitative approach research methodology by collecting data using structured interviews with 2 research subjects, namely nurses in the Emergency Department and Inpatient Installation who work in private hospitals in Wonogiri Regency accompanied by a literature review based on the literature. Based on literature sources, it was found that high work fatigue can cause an increased risk of anxiety disorders up to 2.7 times higher compared to subjects with lower work fatigue. From the results of interviews with the 2 research subjects, it was found that the level of work fatigue was positively related to anxiety, meaning that the higher the level of work fatigue based on the scoring of the Job Fatigue Measuring Tool Questionnaire (KAUPK2), the higher the anxiety level score based on the Hamilton Anxiety Rating Scale.

Cardiotoxicity of Iron and Zinc and Their Association with the Mitochondrial Unfolded Protein Response in Humans.

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced ageHTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes.

Phase I Clinical Study of the Subunit Betulin-Adjuvanted Tetravalent Candidate Influenza Vaccine TetraFluBet

Objectives: This study aimed to determine the safety, tolerability and immunogenicity of TetraFluBet, an inactivated subunit influenza vaccine that contains a corpuscular immuno-adjuvant derived from natural betulin. Methods: We conducted a prospective, randomized, open-labeled, single-center, phase I trial. The study was conducted in two stages: 5 volunteers in stage I and 25 volunteers in stage II. Eligible participants received one single dose (20 μg/0.5 mL) of TetraFluBet intramuscularly. Participants were followed for adverse events and reactogenicity. Seroconversion rate, seroprotection level, geometric mean titers (GMTs) of virus-neutralizing antibodies, IFN-γ induction and cell-mediated immunity were assessed. Results: A total of 30 participants were enrolled. No vaccine-related serious adverse events were observed. The proportions of study participants with 4-fold seroconversions assessed by the HI assay (with 95% CIs) were 80.0% (62.7; 90.5), 70.0% (52.1; 83.3), 63.3% (45.5; 78.1) and 73.3% (55.6; 85.8) for influenza virus subtypes A (H1N1), A (H3N2), B1 and B2, respectively. Seroprotection levels (with 95% CIs) were 83.3% (66.4; 92.7), 83.3% (66.4; 92.7), 73.3% (55.6; 85.8) and 66.7% (48.8; 80.8), respectively. The fold increases in the GMTs of virus-neutralizing antibodies for subtype H1N1 was 6.50, for subtype H3N2 was 3.03, for subtype B1 was 3.56 and for subtype B2 was 6.07. The population of cytotoxic T-cells increased significantly in the post-vaccination period, indicating a strong CD3+CD8+ response. Conclusions: TetraFluBet tetravalent inactivated subunit vaccine with adjuvant demonstrated pronounced immunogenic properties, leading to the formation of both specific humoral and cellular immunity at a 20 μg dose.

Exploring Affective Representations in Emotional Narratives: An Exploratory Study Comparing ChatGPT and Human Responses.

While artificial Intelligence (AI) has made significant advancements, the seeming absence of its emotional ability has hindered effective communication with humans. This study explores how ChatGPT (ChatGPT-3.5 Mar 23, 2023 Version) represents affective responses to emotional narratives and compare these responses to human responses. Thirty-four participants read affect-eliciting short stories and rated their emotional responses and 10 recorded ChatGPT sessions generated responses to the stories. Classification analyses revealed the successful identification of affective categories of stories, valence, and arousal within and across sessions for ChatGPT. Classification analyses revealed the successful identification of affective categories of stories, valence, and arousal within and across sessions for ChatGPT. Classification accuracies predicting affective categories of stories, valence, and arousal of humans based on the affective ratings of ChatGPT and vice versa were not significant, indicating differences in the way the affective states were represented., indicating differences in the way the affective states were represented. These findings suggested that ChatGPT can distinguish emotional states and generate affective responses consistently, but there are differences in how the affective states are represented between ChatGPT and humans. Understanding these mechanisms is crucial for improving emotional interactions with AI.

Torque teno viruses exhaust and imprint the human immune system via the HLA-E/NKG2A axis.

The ubiquitous Torque teno virus (TTV) establishes a chronically persistent infection in the human host. TTV has not been associated with any apparent disease, but, as part of the human virome, it may confer a regulatory imprint on the human immune system with as yet unclear consequences. However, so far, only few studies have characterized the TTV-specific immune responses or the overall immunological imprints by TTV. Here, we reveal that TTV infection leads to a highly exhausted TTV-specific CD8+ T-cell response, hallmarked by decreased IFN-γ production and the expression of the inhibitory NKG2A-receptor. On a functional level, we identified a panel of highly polymorphic TTV-encoded peptides that lead to an expansion of regulatory NKG2A+ natural killer, NKG2A+CD4+, and NKG2A+CD8+ T cells via the stabilization of the non-classical HLA-E molecule. Our results thus demonstrate that TTV leads to a distinct imprint on the human immune system that may further regulate overall human immune responses in infectious, autoimmune, and malignant diseases.

The impact of Germany's human papillomavirus immunization program on HPV-related anogenital diseases: a retrospective analysis of claims data from statutory health insurances.

Human papillomavirus (HPV) is the most common sexually transmitted infection, responsible for multiple HPV-related diseases, including almost all cervical cancers. The highly effective HPV vaccination has been recommended under the German HPV national immunization program (NIP) since 2007 and is reimbursed by health insurances. Vaccination uptake rates, however, remain suboptimal and data on the real-world impact of HPV vaccination in Germany are lacking. This study aims to demonstrate the population-level impact of Germany's NIP on HPV-related anogenital diseases among young women. Retrospective claims data analysis using a classic impact study design comparing disease prevalence among 28- to 33-year-old women before and after introduction of the HPV-immunization program in Germany. Claims data representing approximately two thirds of German health insurances were used. HPV-related disease outcomes included cervical cancer and high grade precancers (cervical intraepithelial neoplasia (CIN) 2+), anogenital warts, as well as vulvar, vaginal, and anal precancer/cancer. Significant declines were seen for CIN2+, anogenital warts, and vaginal precancer/cancer. Prevalence of CIN2+ declined 51.1% from 0.92% (95% CI = 0.78%, 1.08%) to 0.45% (95% CI = 0.38%, 0.53%). There was a 38.6% decline in anogenital warts prevalence from 0.44% (95% CI = 0.36%, 0.54%) to 0.27% (95% CI = 0.22%, 0.32%) and 75.0% decline in vaginal precancer/cancer prevalence from 0.04% (95% CI = 0.02%, 0.07%) to 0.01% (95% CI = 0.00%, 0.02%). The German HPV-immunization program has led to significant declines in female anogenital disease among young women in Germany, highlighting the importance of the vaccination. Moreover, the data suggest that increasing vaccination coverage in Germany could further strengthen the public-health impact of its HPV-immunization program.

Pharmacology of Adenosine A1 Receptor Agonist in a Humanized Esterase Mouse Seizure Model Following Soman Intoxication

Recently a novel genetically modified mouse strain with serum carboxylesterase knocked-out and the human acetylcholinesterase gene knocked-in (KIKO) was created to simulate human responses to nerve agent (NA) exposure and its standard medical treatment. A1 adenosine receptor (A1AR) agonist N-bicyclo-(2.2.1)-hept-2-yl-5'-chloro-5'-deoxyadenosine (ENBA) alone is a potent anticonvulsant and neuroprotectant (A/N) in both rat and KIKO mouse soman (GD) seizure models. In this study we utilized the KIKO mouse to evaluate further the basic pharmacologic A/N effects of ENBA as an adjunct to standard NA medical treatments (i.e., atropine sulfate, pralidoxime chloride [2-PAM], and midazolam). Male mice, implanted with cortical electroencephalographic (EEG) electrodes, were pretreated with asoxime (HI-6) and exposed to an epileptogenic dose of GD (33 µg/kg, s.c.) or saline (sham exposure) and then treated 15 min after seizure onset with ENBA at 15 mg/kg, i.p. (a minimum efficacy dose in suppressing NA-induced seizure) alone or as an adjunct to standard medical treatments. We collected EEG activity, seizure suppression outcomes, daily body temperature and weight, heart rate, toxic signs, neuropathology, and lethality data for up to 14 days. Without ENBA, death from NA exposure was 45%, while with ENBA, either alone or in combination with midazolam, the survival improved to 80% and 90%, respectively. Additionally, seizure was suppressed quickly and permanently, toxic signs, hypothermia, and bradycardia recovered by 48 h, and no neuropathology was evident. Our findings confirmed that ENBA is a potent A/N adjunct for delayed medical treatments of NA exposure.