Safety and pharmacokinetics of VRC07-523LS administered via different routes and doses (HVTN 127/HPTN 087): A Phase I randomized clinical trial.

BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. METHODS AND FINDINGS: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days). CONCLUSIONS: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. TRIAL REGISTRATION: ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).

The influence of placenta microbiota of normal term pregnant women on immune regulation during pregnancy.

BACKGROUND: The concerted regulation of placenta microbiota and the immune responses secures the occurrence and development of pregnancy, while few studies reported this correlation. This study aimed to explore the relationship between the placenta microbiota and immune regulation during pregnancy. METHODS: Twenty-six healthy pregnant women scheduled for elective cesarean section in the First Affiliated Hospital of Jinan University who met the inclusion criteria were recruited. Placenta and peripheral venous blood samples were collected. Microbiota in placental tissue was detected using high-throughput sequencing. Flow cytometry was used to detect immune cells in placental tissue and peripheral venous blood. ELISA and Luminex liquid chip technology were used to detect the content of cytokines in placental tissue and peripheral venous blood, respectively. RESULTS: The placental microbiota has stimulating effects on the local immunity of the placenta and mainly stimulates the placental balance ratio CD56 + CD16 + /CD56 + CD16 and the placental macrophages, that is, it plays the role of immune protection and supporting nutrition. The stimulating effect of placental microbiota on maternal systemic immunity mainly induces peripheral Treg cells and B lymphocytes. CONCLUSION: The placental microbiota may be an important factor mediating local immune regulation in the placenta, and placental microbiota participates in the regulatory function of the maternal immune system.

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120.

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled HIV vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at two dose levels in healthy HIV-uninfected adults. Trial registration URL https://clinicaltrials.gov/ct2/show/NCT03122223 and registration number NCT03122223. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200µg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40µg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% females, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40µg gp120/AS01B group were higher than in either of the 200µg gp120 groups. CONCLUSIONS: The 40µg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses.

All HER2-negative breast cancer patients need gBRCA testing: cost-effectiveness and clinical benefits.

BACKGROUND: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA). METHODS: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2. RESULTS: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively. DISCUSSION: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA.

Serum Anion Gap Level Predicts All-Cause Mortality in Septic Patients: A Retrospective Study Based on the MIMIC III Database.

PURPOSE: Sepsis is a significant threat in the intensive care unit (ICU) worldwide because it has high morbidity and mortality rates. Early recognition and diagnosis of sepsis are essential for the prevention of adverse outcomes. The present study aimed to quantitatively assess the association between serum anion gap (AG) levels and 30- and 90-day all-cause mortality among sepsis patients. METHODS: Clinical data of patients diagnosed with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between serum AG levels and all-cause mortality. A receiver operating characteristic (ROC) curve was drawn to quantify the efficacy of using the serum AG level to predict all-cause mortality. RESULTS: A total of 3811 patients were included in the study. The Kaplan-Meier curves showed that patients with higher serum AG levels had a shorter survival time than those with lower levels. Serum AG levels were found to be highly effective in predicting all-cause mortality secondary to sepsis (30-day: AUROC = 0.703; 90-day: AUROC = 0.696). The Cox regression model further indicated that the serum AG level was an independent risk factor for 30- and 90-day mortality in sepsis (HR 3.44, 95% CI 2.97-3.99 for 30-day; HR 3.17, 95% CI 2.76-3.65 for 90-day, P < 0.001 for both). CONCLUSIONS: High serum AG may be considered as an alternative parameter for predicting the death risk in sepsis when other variables are not immediately available. Prospective large-scale studies are needed to support its predictive value in the clinic.

Where does fear originate in the brain? A coordinate-based meta-analysis of explicit and implicit fear processing.

Processing of fear is of crucial importance for human survival and it can generally occur at explicit and implicit conditions. It is worth noting that explicit and implicit fear processing produces different behavioral and neurophysiological outcomes. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta-analysis to identify: (a) the "core" network of fear processing in healthy individuals; (b) common and specific neural activations associated with explicit and implicit processing of fear. Following PRISMA guidelines, a total of 92 fMRI and PET studies were included in the meta-analysis. The overall analysis show that the core fear network comprises the amygdala, pulvinar, and fronto-occipital regions. Both implicit and explicit fear processing activated amygdala, declive, fusiform gyrus, and middle frontal gyrus, suggesting that these two types of fear processing share a common neural substrate. Explicit fear processing elicited more activations at the pulvinar and parahippocampal gyrus, suggesting visual attention/orientation and contextual association play important roles during explicit fear processing. In contrast, implicit fear processing elicited more activations at the cerebellum-amygdala-cortical pathway, indicating an 'alarm' system underlying implicit fear processing. These findings have shed light on the neural mechanism underlying fear processing at different levels of awareness.

Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.

Inflammation secondary to tissue injuries serves as a double-edged sword that determines the prognosis of tissue repair. As one of the most important enzymes controlling the inflammation process by producing leukotrienes, 5-lipoxygenase (5-LOX, also called 5-LO) has been one of the therapeutic targets in regulating inflammation for a long time. Although a large number of 5-LOX inhibitors have been explored, only a few of them can be applied clinically. Surprisingly, phosphorylation of 5-LOX reveals great significance in regulating the subcellular localization of 5-LOX, which has proven to be an important mechanism underlying the enzymatic activities of 5-LOX. There are at least three phosphorylation sites in 5-LOX jointly to determine the final inflammatory outcomes, and adjustment of phosphorylation of 5-LOX at different phosphorylation sites brings hope to provide an unrecognized means to regulate inflammation. The present review intends to shed more lights into the set-point-like mechanisms of phosphorylation of 5-LOX and its possible clinical application by summarizing the biological properties of 5-LOX, the relationship of 5-LOX with neurodegenerative diseases and brain injuries, the phosphorylation of 5-LOX at different sites, the regulatory effects and mechanisms of phosphorylated 5-LOX upon inflammation, as well as the potential anti-inflammatory application through balancing the phosphorylation-depended set-point.

Effects of an orally supplemented probiotic on the autophagy protein LC3 and Beclin1 in placentas undergoing spontaneous delivery during normal pregnancy.

BACKGROUND: Probiotic supplementation has been shown to be beneficial and is now widely promoted as an auxiliary medicine for maternal health, but the underlying mechanism is still unclear. Thus, this study aimed to explore the effects of probiotic supplementation on the placental autophagy-related proteins LC3 and Beclin1. METHOD: A population-based cohort of specimens was collected under sterile conditions from 37 healthy nulliparous pregnant women who underwent systemic examination and delivered at the First Affiliated Hospital of Jinan University (Guangzhou, China). At 32 weeks of gestation, the pregnant women in the probiotic group were orally supplemented with golden bifid, and the pregnant women in the control group received no probiotic. Pregnant women with pregnancy-associated complications were excluded in the follow-up period, and 25 pregnant women undergoing spontaneous delivery were enrolled. The placental tissue specimens were collected at term. Western blotting was used to detect the protein expression, and qRT-PCR was used to detect the mRNA expression of the placental autophagy-related proteins LC3 and Beclin1. RESULTS: ①There was no significant difference in the expression levels of either LC3 or Beclin1 protein between the two groups (P > 0.05). ②Probiotic supplementation induced a modest but not significant decrease in the content of LC3-mRNA with a significant decrease in the content of Beclin1-mRNA (P < 0.05). CONCLUSION: Our study indicates that probiotic supplementation may reduce Beclin1-mRNA levels.

The economic burden of medical treatment of children with asthma in China.

BACKGROUND: At present, there are few studies on the economic burden and medical treatment of children with asthma in China. Thus this study aimed to investigate the economic burden of medical treatment of children with asthma in China. METHOD: The 2015 China Medical Insurance Research Association (CHIRA) database was searched for patients with asthma from 0 to 14 years old. A cross-sectional study with cost analysis was conducted. RESULTS: The annual per capita direct medical cost was RMB 525 (US$75) related to asthma. Totaling 58% of the medical expenditure for asthma was covered by insurance in China, the majority of which were direct medical costs. Those that have the highest rates of using antibiotics were central China (100.0%), children aged 3 years and under (63.6%), as well as fourth-tier and fifth-tier cities (77.1%). Outpatient clinics (98.58% vs 1.42%, P < 0.01), tertiary hospitals (62.08% vs 37.92%, P < 0.01), and general hospitals (72.27% vs 27.73%, P < 0.01) were more often visited than the inpatient clinics, secondary and primary as well as the specialized clinics, respectively. CONCLUSION: The economic burden of childhood asthma in China is relatively low, and the national medical insurance reduces their economic burden to a large extent. Abuse of antibiotics in treating asthma was found in China. There remain opportunities to strengthen the hierarchical medical system, reducing hospitalization and emergency visits, and ultimately reducing the economic burden of children with asthma.

A New Era of Epidemiology: Digital Epidemiology for Investigating the COVID-19 Outbreak in China.

A novel pneumonia-like coronavirus disease (COVID-19) caused by a novel coronavirus named SARS-CoV-2 has swept across China and the world. Public health measures that were effective in previous infection outbreaks (eg, wearing a face mask, quarantining) were implemented in this outbreak. Available multidimensional social network data that take advantage of the recent rapid development of information and communication technologies allow for an exploration of disease spread and control via a modernized epidemiological approach. By using spatiotemporal data and real-time information, we can provide more accurate estimates of disease spread patterns related to human activities and enable more efficient responses to the outbreak. Two real cases during the COVID-19 outbreak demonstrated the application of emerging technologies and digital data in monitoring human movements related to disease spread. Although the ethical issues related to using digital epidemiology are still under debate, the cases reported in this article may enable the identification of more effective public health measures, as well as future applications of such digitally directed epidemiological approaches in controlling infectious disease outbreaks, which offer an alternative and modern outlook on addressing the long-standing challenges in population health.

An Innovative Artificial Intelligence-Based App for the Diagnosis of Gestational Diabetes Mellitus (GDM-AI): Development Study.

BACKGROUND: Gestational diabetes mellitus (GDM) can cause adverse consequences to both mothers and their newborns. However, pregnant women living in low- and middle-income areas or countries often fail to receive early clinical interventions at local medical facilities due to restricted availability of GDM diagnosis. The outstanding performance of artificial intelligence (AI) in disease diagnosis in previous studies demonstrates its promising applications in GDM diagnosis. OBJECTIVE: This study aims to investigate the implementation of a well-performing AI algorithm in GDM diagnosis in a setting, which requires fewer medical equipment and staff and to establish an app based on the AI algorithm. This study also explores possible progress if our app is widely used. METHODS: An AI model that included 9 algorithms was trained on 12,304 pregnant outpatients with their consent who received a test for GDM in the obstetrics and gynecology department of the First Affiliated Hospital of Jinan University, a local hospital in South China, between November 2010 and October 2017. GDM was diagnosed according to American Diabetes Association (ADA) 2011 diagnostic criteria. Age and fasting blood glucose were chosen as critical parameters. For validation, we performed k-fold cross-validation (k=5) for the internal dataset and an external validation dataset that included 1655 cases from the Prince of Wales Hospital, the affiliated teaching hospital of the Chinese University of Hong Kong, a non-local hospital. Accuracy, sensitivity, and other criteria were calculated for each algorithm. RESULTS: The areas under the receiver operating characteristic curve (AUROC) of external validation dataset for support vector machine (SVM), random forest, AdaBoost, k-nearest neighbors (kNN), naive Bayes (NB), decision tree, logistic regression (LR), eXtreme gradient boosting (XGBoost), and gradient boosting decision tree (GBDT) were 0.780, 0.657, 0.736, 0.669, 0.774, 0.614, 0.769, 0.742, and 0.757, respectively. SVM also retained high performance in other criteria. The specificity for SVM retained 100% in the external validation set with an accuracy of 88.7%. CONCLUSIONS: Our prospective and multicenter study is the first clinical study that supports the GDM diagnosis for pregnant women in resource-limited areas, using only fasting blood glucose value, patients' age, and a smartphone connected to the internet. Our study proved that SVM can achieve accurate diagnosis with less operation cost and higher efficacy. Our study (referred to as GDM-AI study, ie, the study of AI-based diagnosis of GDM) also shows our app has a promising future in improving the quality of maternal health for pregnant women, precision medicine, and long-distance medical care. We recommend future work should expand the dataset scope and replicate the process to validate the performance of the AI algorithms.

Maximum diversity weighting for biomarkers with application in HIV-1 vaccine studies.

While studying the association between risk of HIV-1 infection and vaccine-elicited immune responses in preventative HIV-1 vaccine recipients, we encountered a need to combine a collection of biomarkers in an unsupervised fashion with the goal of preserving signal diversity within that collection. Inspired by methods for weighting protein sequences from the biological sequence analysis literature, we propose novel methods for weighting biomarkers, which we call maximum diversity weights. These weights are defined as the weights that maximize measures of signal diversity within a collection of biomarkers. While the optimization problems do not admit analytical solutions, they are convex and hence can be solved efficiently using iterative search algorithms. Through Monte Carlo studies and a real data example from HIV-1 vaccine research, we show that using maximum diversity weights in association studies can lead to an increase in power over other commonly used weights such as uniform weights or principal component-based weights.

Medical nutrition treatment of women with gestational diabetes mellitus by a telemedicine system based on smartphones.

AIM: To explore whether WeChat platform-based treatment of women with gestational diabetes mellitus (GDM) reduces the risk of perinatal complications and explore factors affecting gestational age at delivery. METHODS: Pregnant women with GDM (n = 107) and normal glucose tolerance (n =50, group C) according to oral glucose tolerance test (OGTT) results during gestational weeks 24-28 were included. Women with GDM were divided into groups A (n =57) and B (n =50) according to informed consent. According to GDM treatment norms, group B was given routine outpatient treatment and health education guidance. In addition to the interventions in group B, group A was given access to both a smartphone-based telemedicine system and articles providing continuous health education. The PBG level in groups A and B was compared, as were differences in maternal and fetal outcomes. Data were analyzed by t-test, analysis of variance (anova), chi-square test and multiple linear regression, with P < 0.05 considered significant. RESULTS: Fasting blood glucose (FBG) and 2-h postprandial blood glucose (PBG) were significantly lower and premature delivery was significantly less likely in group A than in group B (all P < 0.05). Compared with group B, caesarean section was more likely in group A (P < 0.05). Pregnancy-induced hypertension had a higher incidence in group B than in group C (P < 0.05). Gestational age at delivery was associated with OGTT2h, premature fetal membrane rupture and self-monitoring of blood glucose. CONCLUSION: GDM treatment based on the WeChat platform effectively reduces FBG and 2-h PBG and may improve pregnancy outcomes. However, 1-h PBG was not affected by treatment. Obstetricians should consider the OGTT2h value to increase gestational age at delivery.

Pandemic Fatigue and Preferences for COVID-19 Public Health and Social Measures in China: Nationwide Discrete Choice Experiment.

BACKGROUND: Information on the public's preferences for current public health and social measures (PHSMs) and people's mental health under PHSMs is insufficient. OBJECTIVE: This study aimed to quantify the public's preferences for varied PHSMs and measure the level of pandemic fatigue in the COVID-19 normalization stage in China. METHODS: A nationwide cross-sectional study with a discrete choice experiment and psychometric scales was conducted to assess public preferences for and attitudes toward PHSMs, using the quota sampling method. The COVID-19 Pandemic Fatigue Scale (CPFS) was used to screen fatigue levels among respondents. The multinomial logit model, latent class model, and Mann-Whitney test were used for statistical analysis. We also conducted subgroup analysis based on sex, age, monthly income, mental health status, and pandemic fatigue status. RESULTS: A total of 689 respondents across China completed the survey. The discrete choice experiment revealed that respondents attached the greatest importance to the risk of COVID-19 infection within 3 months (45.53%), followed by loss of income within 3 months (30.69%). Vulnerable populations (low-income populations and elderly people) were more sensitive to the risk of infection, while younger respondents were more sensitive to income loss and preferred nonsuspension of social places and transportation. Migrants and those with pandemic fatigue had less acceptance of the mandatory booster vaccination and suspension of transportation. Additionally, a higher pandemic fatigue level was observed in female respondents, younger respondents, migrants, and relatively lower-income respondents (CPFS correlation with age: r=-0.274, P<.001; correlation with monthly income: r=-0.25, P<.001). Mandatory booster COVID-19 vaccination was also not preferred by respondents with a higher level of pandemic fatigue, while universal COVID-19 booster vaccination was preferred by respondents with a lower level of pandemic fatigue. CONCLUSIONS: Pandemic fatigue is widely prevalent in respondents across China, and respondents desired the resumption of normal social life while being confronted with the fear of COVID-19 infection in the normalization stage of COVID-19 in China. During future pandemics, the mental burden and adherence of residents should be considered for the proper implementation of PHSMs.

Inverted Classroom Teaching of Physiology in Basic Medical Education: Bibliometric Visual Analysis.

Background: Over the last decade, there has been growing interest in inverted classroom teaching (ICT) and its various forms within the education sector. Physiology is a core course that bridges basic and clinical medicine, and ICT in physiology has been sporadically practiced to different extents globally. However, students' and teachers' responses and feedback to ICT in physiology are diverse, and the effectiveness of a modified ICT model integrated into regular teaching practice in physiology courses is difficult to assess objectively and quantitatively. Objective: This study aimed to explore the current status and development direction of ICT in physiology in basic medical education using bibliometric visual analysis of the related literature. Methods: A bibliometric analysis of the ICT-related literature in physiology published between 2000 and 2023 was performed using CiteSpace, a bibliometric visualization tool, based on the Web of Science database. Moreover, an in-depth review was performed to summarize the application of ICT in physiology courses worldwide, along with identification of research hot spots and development trends. Results: A total of 42 studies were included for this bibliometric analysis, with the year 2013 marking the commencement of the field. University staff and doctors working at affiliated hospitals represent the core authors of this field, with several research teams forming cooperative relationships and developing research networks. The development of ICT in physiology could be divided into several stages: the introduction stage (2013-2014), extensive practice stage (2015-2019), and modification and growth stage (2020-2023). Gopalan C is the author with the highest citation count of 5 cited publications and has published 14 relevant papers since 2016, with a significant surge from 2019 to 2022. Author collaboration is generally limited in this field, and most academic work has been conducted in independent teams, with minimal cross-team communication. Authors from the United States published the highest number of papers related to ICT in physiology (18 in total, accounting for over 43% of the total papers), and their intermediary centrality was 0.24, indicating strong connections both within the country and internationally. Chinese authors ranked second, publishing 8 papers in the field, although their intermediary centrality was only 0.02, suggesting limited international influence and lower overall research quality. The topics of ICT in physiology research have been multifaceted, covering active learning, autonomous learning, student performance, teaching effect, blended teaching, and others. Conclusions: This bibliometric analysis and literature review provides a comprehensive overview of the history, development process, and future direction of the field of ICT in physiology. These findings can help to strengthen academic exchange and cooperation internationally, while promoting the diversification and effectiveness of ICT in physiology through building academic communities to jointly train emerging medical talents.

A Randomised Clinical Trial of the Safety and Pharmacokinetics of VRC07-523LS Administered via Different Routes and Doses (HVTN 127/HPTN 087).

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01. Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

A real-world data validation of the value of early-stage SIR modelling to public health.

Performance of Susceptible-Infected-Recovered (SIR) model in the early stage of a novel epidemic may be hindered by data availability. Additionally, the traditional SIR model may oversimplify the disease progress, and knowledge about the virus and transmission is limited early in the epidemic, resulting in a greater uncertainty of such modelling. We aimed to investigate the impact of model inputs on the early-stage SIR projection using COVID-19 as an illustration to evaluate the application of early infection models. We constructed a modified SIR model using discrete-time Markov chain to simulate daily epidemic dynamics and estimate the number of beds needed in Wuhan in the early stage of COVID-19 epidemic. We compared eight scenarios of SIR projection to the real-world data (RWD) and used root mean square error (RMSE) to assess model performance. According to the National Health Commission, the number of beds occupied in isolation wards and ICUs due to COVID-19 in Wuhan peaked at 37,746. In our model, as the epidemic developed, we observed an increasing daily new case rate, and decreasing daily removal rate and ICU rate. This change in rates contributed to the growth in the needs of bed in both isolation wards and ICUs. Assuming a 50% diagnosis rate and 70% public health efficacy, the model based on parameters estimated using data from the day reaching 3200 to the day reaching 6400 cases returned a lowest RMSE. This model predicted 22,613 beds needed in isolation ward and ICU as on the day of RWD peak. Very early SIR model predictions based on early cumulative case data initially underestimated the number of beds needed, but the RMSEs tended to decline as more updated data were used. Very-early-stage SIR model, although simple but convenient and relatively accurate, is a useful tool to provide decisive information for the public health system and predict the trend of an epidemic of novel infectious disease in the very early stage, thus, avoiding the issue of delay-decision and extra deaths.

Understanding influencing attributes of COVID-19 vaccine preference and willingness-to-pay among Chinese and American middle-aged and elderly adults: A discrete choice experiment and propensity score matching study.

Background and objective: COVID-19 has imposed burdens on public health systems globally. Owing to the urgency of vaccination, this study aimed at comparing the differences in preference and willingness to pay of COVID-19 vaccine among Chinese and American middle-aged and elderly adults. Methods: A cross-sectional survey containing demographic questions, rating their acceptance of COVID-19 vaccination with and without recommendations from friends, family members or employers (the social cues referred to in our study), and a discrete choice experiment understanding COVID-19 vaccine preference and willingness to pay was conducted to collect data. Propensity score matching was utilized to adjust confounding factors of baseline characteristics and the relative importance of respondents' preference for each attribute and its level was estimated using a conditional logit model. Then, willingness to pay was calculated. Results: In total, 3,494 (2,311 and 1,183 from China and the United States, respectively) completed the questionnaire, among which 3,444 questionnaires were effective. After propensity score matching, 1,604 respondents with 802 from the US and 802 from China were included. Under the influence of the social cues, Chinese respondents' vaccine acceptance decreased from 71.70 to 70.70%, while American respondents' vaccine acceptance increased from 74.69 to 75.81%. The discrete choice experiment showed that American respondents regarded the efficacy of COVID-19 vaccine as the most important attribute, whereas Chinese respondents attached the highest importance to the cost of vaccination. But overall, the COVID-19 vaccine with the higher efficacy, the milder adverse effect, the lower cost, and the longer duration will promote the preference of the public in both countries. Additionally, the public were willing to spend the most money for a reduction in COVID-19 vaccine adverse effect from moderate to very mild (37.476USD for the United States, 140.503USD for China), followed by paying for the 1% improvement in its efficacy and paying for the one-month extension of its duration. Conclusion: Given the impact of social cues on vaccine acceptance, Chinese government should promote reasonable vaccine-related information to improve national vaccination acceptance. Meanwhile, considering the influence of COVID-19 attributes on public preference and willingness to pay, regulating the vaccine pricing, improving the efficacy of the vaccine, reducing its adverse effect, and prolonging the duration of the vaccine works will contribute to vaccine uptake.

Acceptance of and Preference for COVID-19 Vaccination in India, the United Kingdom, Germany, Italy, and Spain: An International Cross-Sectional Study.

Objective: India and Europe have large populations, a large number of Coronavirus disease 2019 (COVID-19) cases, and different healthcare systems. This study aims to investigate the differences between the hesitancy toward and preference for COVID-19 vaccines in India and four European countries, namely, the United Kingdom (UK), Germany, Italy, and Spain. Methodology: We conducted a cross-national survey for distribution in India, the UK, Germany, Italy, and Spain. More specifically, a discrete choice experiment (DCE) was conducted to evaluate vaccine preferences, and Likert scales were used to probe the underlying factors that contribute to vaccination acceptance. Propensity score matching (PSM) was performed to directly compare India and European countries. Results: A total of 2565 respondents (835 from India and 1730 from the specified countries in Europe) participated in the survey. After PSM, more than 82.5% of respondents from India positively accepted the COVID-19 vaccination, whereas 79.9% of respondents from Europe had a positive attitude; however, the proportion in Europe changed to 81.6% in cases in which the vaccine was recommended by friends, family, or employers. The DCE found that the COVID-19 vaccine efficacy was the most important factor for respondents in India and the four European nations (41.8% in India and 47.77% in Europe), followed by the vaccine cost (28.06% in India and 25.88% in Europe). Conclusion: Although most respondents in both regions showed high acceptance of COVID-19 vaccines, either due to general acceptance or acceptance as a result of social cues, the vaccination coverage rate shows apparent distinctions. Due to the differences in COVID-19 situations, public health systems, cultural backgrounds, and vaccine availability, the strategies for COVID-19 vaccine promotion should be nation-dependent.