Oral Simnotrelvir for Adult Patients with Mild-to-Moderate Covid-19.

BACKGROUND: Simnotrelvir is an oral 3-chymotrypsin-like protease inhibitor that has been found to have in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential efficacy in a phase 1B trial. METHODS: In this phase 2-3, double-blind, randomized, placebo-controlled trial, we assigned patients who had mild-to-moderate coronavirus disease 2019 (Covid-19) and onset of symptoms within the past 3 days in a 1:1 ratio to receive 750 mg of simnotrelvir plus 100 mg of ritonavir or placebo twice daily for 5 days. The primary efficacy end point was the time to sustained resolution of symptoms, defined as the absence of 11 Covid-19-related symptoms for 2 consecutive days. Safety and changes in viral load were also assessed. RESULTS: A total of 1208 patients were enrolled at 35 sites in China; 603 were assigned to receive simnotrelvir and 605 to receive placebo. Among patients in the modified intention-to-treat population who received the first dose of trial drug or placebo within 72 hours after symptom onset, the time to sustained resolution of Covid-19 symptoms was significantly shorter in the simnotrelvir group than in the placebo group (180.1 hours [95% confidence interval {CI}, 162.1 to 201.6] vs. 216.0 hours [95% CI, 203.4 to 228.1]; median difference, -35.8 hours [95% CI, -60.1 to -12.4]; P = 0.006 by Peto-Prentice test). On day 5, the decrease in viral load from baseline was greater in the simnotrelvir group than in the placebo group (mean difference [±SE], -1.51±0.14 log10 copies per milliliter; 95% CI, -1.79 to -1.24). The incidence of adverse events during treatment was higher in the simnotrelvir group than in the placebo group (29.0% vs. 21.6%). Most adverse events were mild or moderate. CONCLUSIONS: Early administration of simnotrelvir plus ritonavir shortened the time to the resolution of symptoms among adult patients with Covid-19, without evident safety concerns. (Funded by Jiangsu Simcere Pharmaceutical; ClinicalTrials.gov number, NCT05506176.).

The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

Mpox patients' experience from infection to treatment and implications for prevention and control: A multicenter qualitative study in China.

Monkeypox (mpox), a viral zoonotic disease, is spreading worldwide. However, evidence that informs prevention and control strategies in the Asia Pacific Region is very limited. Our study aims to investigate the experiences of mpox patients from infection to treatment to provide scientific basis for the prevention and control. A multicenter qualitative design was used. A total of 15 mpox patients were recruited between July 6 and July 25, 2023, from six cities in China. Semistructured interviews were conducted by telephone and analyzed using the thematic analysis. The interview was divided into two sections: patients' experiences (prediagnosis experience, treatment-seeking experience, and quarantine experience) and advice. Prediagnosis experience was summarized into three themes: symptoms, possible routes of infection, and knowledge of mpox. Treatment-seeking experience was summarized into three themes: time of visit to hospital, diagnostic difficulties, and attitude toward diagnosis. Quarantine experience was summarized into three themes: body and mind reactions, reluctance to self-disclose infection status, and factors facilitating recovery. Themes identified from patients' advice were as follows: (1) Increase in testing channels and methods, (2) Development and introduction of vaccines, (3) Adjustment of quarantine program, (4) Improvement of treatment measures, and (5) Improvement of publicity and education. To effectively curb the mpox epidemic, structured measures are urgently needed to address the mpox-related stigma and discrimination. Targeted health education should be provided to MSM, focusing on the prevention, detection, and treatment services. Hospitals should enhance the training of clinicians in key departments including infectious disease and dermatology, to improve diagnostic capability and sensitivity. Furthermore, given the absence of specific antiviral medications, supervised home quarantine may be a good option.

iTRAQ-based proteomic study on monocyte cell model discovered an association of LAMP2 downregulation with HIV-1 latency.

BACKGROUND: Patients with immunodeficiency virus-1 (HIV-1) infection are challenging to be cured completely due to the existence of HIV-1 latency reservoirs. However, the knowledge of the mechanisms and biomarkers associated with HIV-1 latency is limited. Therefore, identifying proteins related to HIV-1 latency could provide new insights into the underlying mechanisms of HIV-1 latency, and ultimately contribute to the eradication of HIV reservoirs. METHODS: An Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-labeled subcellular proteomic study was performed on an HIV-1 latently infected cell model (U1, a HIV-1-integrated U937 cell line) and its control (U937). Differentially expressed proteins (DEPs) were analyzed using STRING-DB. Selected DEPs were further evaluated by western blotting and multiple reaction monitoring technology in both cell model and patient-derived cluster of differentiation 4 (CD4)+ T cells. Finally, we investigated the relationship between a specific DEP lysosome-associated membrane glycoprotein 2 (LAMP2) and HIV-1 reactivation by panobinostat or lysosome regulation by a lysosomotropic agent hydroxychloroquine in U1 and U937 cells. RESULTS: In total, 110 DEPs were identified in U1 cells comparing to U937 control cells. Bioinformatics analysis suggested associations of the altered proteins with the immune response and endosomal/lysosomal pathway. LAMP2, leukocyte surface antigen CD47, CD55, and ITGA6 were downregulated in HIV-1 latent cells. Downregulated LAMP2 was further confirmed in resting CD4+ T cells from patients with latent HIV-1 infection. Furthermore, both HIV-1 reactivation by panobinostat and stimulation with hydroxychloroquine upregulated LAMP2 expression. CONCLUSIONS: Our results indicated the involvement of the endosomal/lysosomal pathway in HIV-1 latency in macrophage cell model. The down-modulation of LAMP2 was associated with HIV latency, and the restoration of LAMP2 expression accompanied the transition of viral latency to active infection. This study provides new insights into the mechanism of HIV-1 latency and potential strategies for eradicating HIV-1 reservoirs by targeting LAMP2 expression.

Comprehensive risk factor predictions for 3-year survival among HIV-associated and disseminated cryptococcosis involving lungs and central nervous system.

BACKGROUND: The global mortality rate resulting from HIV-associated cryptococcal disease is remarkably elevated, particularly in severe cases with dissemination to the lungs and central nervous system (CNS). Regrettably, there is a dearth of predictive analysis regarding long-term survival, and few studies have conducted longitudinal follow-up assessments for comparing anti-HIV and antifungal treatments. METHODS: A cohort of 83 patients with HIV-related disseminated cryptococcosis involving the lung and CNS was studied for 3 years to examine survival. Comparative analysis of clinical and immunological parameters was performed between deceased and surviving individuals. Subsequently, multivariate Cox regression models were utilized to validate mortality predictions at 12, 24, and 36 months. RESULTS: Observed plasma cytokine levels before treatment were significantly lower for IL-1RA (p < 0.001) and MCP-1 (p < 0.05) when in the survivor group. Incorporating plasma levels of IL-1RA, IL-6, and high-risk CURB-65 score demonstrated the highest area under curve (AUC) value (0.96) for predicting 1-year mortality. For 1-, 2- and 3-year predictions, the single-factor model with IL-1RA demonstrated superior performance compared to all multiple-variate models (AUC = 0.95/0.78/0.78). CONCLUSIONS: IL-1RA is a biomarker for predicting 3-year survival. Further investigations to explore the pathogenetic role of IL-1RA in HIV-associated disseminated cryptococcosis and as a potential therapeutic target are warranted.

Role of thymosin α1 in restoring immune response in immunological nonresponders living with HIV.

BACKGROUND: Immunological nonresponders (INRs) living with HIV are at increased risk of co-infection and multiple tumors, with no effective strategy currently available to restore their T-cell immune response. This study aimed to explore the safety and efficacy of thymosin α1 in reconstituting the immune response in INRs. METHODS: INRs with CD4 + T cell counts between 100 and 350 cells/µL were enrolled and received two-staged 1.6 mg thymosin α1 subcutaneous injections for 24 weeks (daily in the first 2 weeks and biweekly in the subsequent 22 weeks) while continuing antiretroviral therapy. T cell counts and subsets, the expression of PD-1 and TIM-3 on T cells, and signal joint T cell receptor excision circles (sjTREC) at week 24 were evaluated as endpoints. RESULTS: Twenty three INRs were screened for eligibility, and 20 received treatment. The majority were male (19/20), with a median age of 48.1 years (interquartile range: 40.5-57.0) and had received antiretroviral therapy for 5.0 (3.0, 7.3) years. Multiple comparisons indicated that CD4 + T cell count and sjTREC increased after initiation of treatment, although no significant differences were observed at week 24 compared to baseline. Greatly, levels of CD4 + T cell proportion (17.2% vs. 29.1%, P < 0.001), naïve CD4 + and CD8 + T cell proportion (17.2% vs. 41.1%, P < 0.001; 13.8% vs. 26.6%, P = 0.008) significantly increased. Meanwhile, the proportion of CD4 + central memory T cells of HIV latent hosts (42.7% vs. 10.3%, P < 0.001) significantly decreased. Moreover, the expression of PD-1 on CD4 + T cells (14.1% vs. 6.5%, P < 0.001) and CD8 + T cells (8.5% vs. 4.1%, P < 0.001) decreased, but the expression of TIM-3 on T cellsremained unaltered at week 24. No severe adverse events were reported and HIV viral loads kept stable throughout the study. CONCLUSIONS: Thymosin α1 enhance CD4 + T cell count and thymic output albeit as a trend rather than an endpoint. Importantly, it improves immunosenescence and decreases immune exhaustion, warranting further investigation. TRIAL REGISTRATION: This single-arm prospective study was registered with ClinicalTrials.gov (NCT04963712) on July 15, 2021.

Pterostilbene protects against H2 O2 -induced oxidative stress by regulating GAS6/Axl signaling in HL-1 cells.

Pterostilbene (PTE, trans-3,5-dimethoxy-4'-hydroxystilbene), a natural plant polyphenol, possesses numerous pharmacological effects, including antioxidant, antidiabetic, antiatherosclerotic, and neuroprotective aspects. This study aims to investigate whether PTE plays a protective role against oxidative stress injury by GAS6/Axl signaling pathway in cardiomyocytes. Hydrogen peroxide (H2 O2 )-induced oxidative stress HL-1 cells were used as models. The mechanism by which PTE protected oxidative stress is investigated by combining cell viability, cell ROS levels, apoptosis assay, molecular docking, quantitative real-time PCR, and western blot analysis. GAS6 shRNA was performed to investigate the involvement of GAS6/Axl pathways in PTE's protective role. The results showed that PTE treatment improved the cell morphology and viability, and inhibited the apoptosis rate and ROS levels in H2 O2 -injured HL-1 cells. Particularly, PTE treatment upregulated the levels of GAS6, Axl, and markers related to oxidative stress, apoptosis, and mitochondrial function related. Molecular docking showed that PTE and GAS6 have good binding ability. Taken together, PTE plays a protective role against oxidative stress injury through inhibiting oxidative stress and apoptosis and improving mitochondrial function. Particularly, GAS6/Axl axis is the surprisingly prominent in the PTE-mediated pleiotropic effects.

Construction and efficacy testing of DNA vaccines containing HLA-A*02:01-restricted SARS-CoV-2 T-cell epitopes predicted by immunoinformatics.

Vaccines play essential roles in the fight against the COVID-19 pandemic. The development and assessment of COVID-19 vaccines have generally focused on the induction and boosting of neutralizing antibodies targeting the SARS-CoV-2 spike (S) protein. Due to rapid and continuous variation in the S protein, such vaccines need to be regularly updated to match newly emerged dominant variants. T-cell vaccines that target MHC I- or II-restricted epitopes in both structural and non-structural viral proteins have the potential to induce broadly cross-protective and long-lasting responses. In this work, the entire proteome encoded by SARS-CoV-2 (Wuhan-hu-1) is subjected to immunoinformatics-based prediction of HLA-A*02:01-restricted epitopes. The immunogenicity of the predicted epitopes is evaluated using peripheral blood mononuclear cells from convalescent Wuhan-hu-1-infected patients. Furthermore, predicted epitopes that are conserved across major SARS-CoV-2 lineages and variants are used to construct DNA vaccines expressing multi-epitope polypeptides. Most importantly, two DNA vaccine constructs induce epitope-specific CD8 + T-cell responses in a mouse model of HLA-A*02:01 restriction and protect immunized mice from challenge with Wuhan-hu-1 virus after hACE2 transduction. These data provide candidate T-cell epitopes useful for the development of T-cell vaccines against SARS-CoV-2 and demonstrate a strategy for quick T-cell vaccine candidate development applicable to other emerging pathogens.

Renal safety of tenofovir alafenamide-based antiretroviral therapy in people with HIV: A mini-review.

Antiretroviral therapy (ART) has significantly enhanced the outlook for people with HIV(PWH), yet certain ART medications can adversely affect the renal function of these patients. Of particular concern is the nephrotoxicity associated with tenofovir disoproxil fumarate (TDF). Compared to TDF, tenofovir alafenamide (TAF), another prodrug of tenofovir (TFV), results in lower TFV plasma levels, thereby alleviating the TFV-associated mitochondrial toxicity on proximal renal tubular cells. Currently, numerous clinical trials and real-world studies have demonstrated the favorable renal safety profile of ART regimens incorporating TAF for PWH. This paper seeks to consolidate the available evidence regarding the renal safety of TAF-based regimens in PWH, encompassing both the general PWH and those with renal impairment or predisposing factors, in order to offer recommendations and insights for TAF clinical application.

Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.

Proposal to apply a "Positive Emotion, Engagement, Relationships, Meaning, and Accomplishment (PERMA)" based approach to manage the COVID-19-related mental health problems in the era of long COVID.

Long COVID (LC)-related health problems are highly concerned. Many patients seem to have "recovered" from an acute SARS-CoV-2 infection, however, they might experience various symptoms, almost involving all organs and systems. Of those, neuropsychiatric symptoms like depression, anxiety, and post-traumatic stress disorder (PTSD) are not rare. These problems significantly impact the quality of life (QOL) of patients, family, and caregivers, even lead a tragic suicide outcome. Other than the conventional psychological and medical approaches, here, we proposal a positive emotion, engagement, relationships, meaning, and accomplishment (PERMA)-based approach to fight against these COVID-19-related mental health problems (CRMHPs). This approach is characterized by positive psychological interventions and self-achievements, which has been proved to be a powerful tool against mood disorders in common people. Nowadays, abolishment of certain prophylactic measures (such as isolation, lockdown, compulsorily wearing a mask and maintaining social distance, measures to avoid crowding) enables us to have more opportunities to contact patients and implement the PERMA-based approach to the patients with CRMHPs. We believe that application of PERMA-based approach is conducive to alleviate the influence of the CRMHPs and improve their QOL.

Camera-Based Seismocardiogram for Heart Rate Variability Monitoring.

Heart rate variability (HRV) is a crucial metric that quantifies the variation between consecutive heartbeats, serving as a significant indicator of autonomic nervous system (ANS) activity. It has found widespread applications in clinical diagnosis, treatment, and prevention of cardiovascular diseases. In this study, we proposed an optical model for defocused speckle imaging, to simultaneously incorporate out-of-plane translation and rotation-induced motion for highly-sensitive non-contact seismocardiogram (SCG) measurement. Using electrocardiogram (ECG) signals as the gold standard, we evaluated the performance of photoplethysmogram (PPG) signals and speckle-based SCG signals in assessing HRV. The results indicated that the HRV parameters measured from SCG signals extracted from laser speckle videos showed higher consistency with the results obtained from the ECG signals compared to PPG signals. Additionally, we confirmed that even when clothing obstructed the measurement site, the efficacy of SCG signals extracted from the motion of laser speckle patterns persisted in assessing the HRV levels. This demonstrates the robustness of camera-based non-contact SCG in monitoring HRV, highlighting its potential as a reliable, non-contact alternative to traditional contact-PPG sensors.

Multispectral Depolarization Based Living-Skin Detection: A New Measurement Principle.

Camera-based photoplethysmographic imaging enabled the segmentation of living-skin tissues in a video, but it has inherent limitations to be used in real-life applications such as video health monitoring and face anti-spoofing. Inspired by the use of polarization for improving vital signs monitoring (i.e. specular reflection removal), we observed that skin tissues have an attractive property of wavelength-dependent depolarization due to its multi-layer structure containing different absorbing chromophores, i.e. polarized light photons with longer wavelengths (R) have deeper skin penetrability and thus experience thorougher depolarization than those with shorter wavelengths (G and B). Thus we proposed a novel dual-polarization setup and an elegant algorithm (named "MSD") that exploits the nature of multispectral depolarization of skin tissues to detect living-skin pixels, which only requires two images sampled at the parallel and cross polarizations to estimate the characteristic chromaticity changes (R/G) caused by tissue depolarization. Our proposal was verified in both the laboratory and hospital settings (ICU and NICU) focused on anti-spoofing and patient skin segmentation. The clinical experiments in ICU also indicate the potential of MSD for skin perfusion analysis, which may lead to a new diagnostic imaging approach in the future.

Living-Skin Detection based on Spatio-Temporal Analysis of Structured Light Pattern.

Living-skin detection is an important step for imaging photoplethysmography and biometric anti-spoofing. In this paper, we propose a new approach that exploits spatio-temporal characteristics of structured light patterns projected on the skin surface for living-skin detection. We observed that due to the interactions between laser photons and tissues inside a multi-layer skin structure, the frequency-domain sharpness feature of laser spots on skin and non-skin surfaces exhibits clear difference. Additionally, the subtle physiological motion of living-skin causes laser interference, leading to brightness fluctuations of laser spots projected on the skin surface. Based on these two observations, we designed a new living-skin detection algorithm to distinguish skin from non-skin using spatio-temporal features of structured laser spots. Experiments in the dark chamber and Neonatal Intensive Care Unit (NICU) demonstrated that the proposed setup and method performed well, achieving a precision of 85.32%, recall of 83.87%, and F1-score of 83.03% averaged over these two scenes. Compared to the approach that only leverages the property of multilayer skin structure, the hybrid approach obtains an averaged improvement of 8.18% in precision, 3.93% in recall, and 8.64% in F1-score. These results validate the efficacy of using frequency domain sharpness and brightness fluctuations to augment the features of living-skin tissues irradiated by structured light, providing a solid basis for structured light based physiological imaging. Our code is available at: https://github.com/contactless-healthcare/Structured-light-based-Living-skin-Detection.

Notch RGB-camera based SpO2 estimation: a clinical trial in a neonatal intensive care unit.

Regular and narrow-band RGB cameras are recently explored for contactless SpO2 monitoring. Regular RGB cameras with cross-band overlap provide a high signal-to-noise-ratio (SNR) in measuring the photoplethysmographic signals but possess high dependency on the spectra of incident light, whereas narrow-band RGB cameras have better spectral independence but lower SNR especially in dim lighting conditions, such as in the neonatal intensive care unit (NICU). This paper proposes a notch RGB camera based SpO2 measurement approach that uses an optical notch filter to attenuate the wavelengths of 580-605 nm of a regular RGB camera to improve the spectral independence while maintaining high SNR in signal measurement. The proposed setup was validated in the lab condition (e.g. dark chamber) against the existing solutions for visible-light based camera-SpO2 measurement and further verified in the NICU on preterm infants. The clinical trial conducted in the NICU with 22 preterm infants shows that the notch RGB camera can achieve a mean absolute error (MAE) less than 4% for SpO2 measurement. This is the first showcase of continuous monitoring of absolute camera-SpO2 values in the NICU.

Evolving immune evasion and transmissibility of SARS-CoV-2: The emergence of JN.1 variant and its global impact.

The continuous evolution of SARS-CoV-2 variants constitutes a significant impediment to the public health. The World Health Organization (WHO) has designated the SARS-CoV-2 variant JN.1, which has evolved from its progenitor BA.2.86, as a Variant of Interest (VOI) in light of its enhanced immune evasion and transmissibility. The proliferating dissemination of JN.1 globally accentuates its competitive superiority and the potential to instigate fresh surges of infection, notably among cohorts previously infected by antecedent variants. Notably, prevailing evidence does not corroborate an increase in pathogenicity associated with JN.1, and antiviral agents retain their antiviral activity against both BA.2.86 and JN.1. The sustained effectiveness of antiviral agents offers a beacon of hope. Nonetheless, the variant's adeptness at eluding the immunoprotective effects conferred by extant vaccines highlights the imperative for the development of more effective vaccines and therapeutic approaches. Overall, the distinct evolutionary trajectories of BA.2.86 and JN.1 underscore the necessity for ongoing surveillance and scholarly inquiry to elucidate their implications for the pandemic's evolution, which requires the international communities to foster collaboration through the sharing of data, exchange of insights, and collective scientific endeavors.

LSTM-Based Prediction Model for Tuberculosis Among HIV-Infected Patients Using Structured Electronic Medical Records: A Retrospective Machine Learning Study.

Background: Both HIV and TB are chronic infectious diseases requiring long-term treatment and follow-up, resulting in extensive electronic medical records. With the exponential growth of health and medical big data, effectively extracting and analyzing these data has become the research hotspot. As a fundamental aspect of artificial intelligence, machine learning has been extensively applied in medical research, encompassing diagnosis, treatment, patient monitoring, drug development, and epidemiological investigations. This significantly enhances medical information systems and facilitates the interoperability of medical data. Methods: In our study, we analyzed longitudinal data from the electronic health records of 4540 patients, gathered from the National Clinical Research Center for Infectious Diseases in Shenzhen, China, spanning from 2017 to 2021. Initially, we employed the fine-tuned ChatGLM to structure the electronic medical records. Subsequently, we utilized a multi-layer perceptron to classify each patient and determined the presence of tuberculosis in HIV patients. Using machine learning-based natural language processing, we structured these records to build a specialized database for HIV and TB co-infection. We studied the epidemiological characteristics, focusing on incidence patterns, patient characteristics, and influencing factors, to uncover the transmission characteristics of these diseases in Shenzhen. Additionally, we used Long Short-Term Memory to create a predictive model for TB co-infection among HIV patients, based on their medical records. This model predicted the risk of TB co-infection, providing scientific evidence for clinical decision-making and enabling early detection and precise intervention. Results: Based on the refined ChatGLM model tailored for structured electronic health records, the accuracy of symptom extraction consistently surpassed 0.95 precision. Key symptoms such as diarrhea and normal showed precision rates exceeding 0.90. High scores were also achieved in recall and F1 scores. Among 4540 HIV patients, 758 were diagnosed with concurrent tuberculosis, indicating a 16.7% co-infection rate, while syphilis co-infection affected 25.1%, underscoring the prevalence of concurrent infections among HIV patients. Utilizing electronic health records, a Multilayer Perceptron classifier was developed as a benchmark against Long Short-Term Memory to predict high-risk groups for HIV and tuberculosis co-infections. The Multilayer Perceptron classifier demonstrated predictive ability with AUROC values ranging from 0.616 to 0.682 on the test set, suggesting opportunities for further optimization and generalization despite its accuracy in identifying HIV-TB co-infections. In tuberculosis intelligent diagnosis based on laboratory results, the Long Short-Term Memory showed consistent performance across 5-fold cross-validation, with AUROC values ranging from 0.827 to 0.850, indicating reliability and consistency in tuberculosis prediction. Furthermore, by optimizing classification thresholds, the model achieved an overall accuracy of 81.18% in distinguishing HIV co-infected tuberculosis from simple HIV infection. Conclusion: Combining the Multilayer Perceptron classifier with Long Short-Term Memory represented an advanced approach for effectively extracting electronic health records and utilizing it for disease prediction. This underscored the superior performance of deep learning techniques in managing both structured and unstructured medical data. Models leveraging laboratory time-series data demonstrated notably better performance compared to those relying solely on electronic health records for predicting tuberculosis incidence. This emphasized the benefits of deep learning in handling intricate medical data and provided valuable insights for healthcare providers exploring the use of deep learning in disease prediction and management.

Roadmap for ending TB in China by 2035: The challenges and strategies.

Tuberculosis (TB) is one of the top ten causes of death worldwide, taking the lives of over a million people annually. In addition to being a serious health issue, TB is also closely linked to eradicating poverty according to the Sustainable Development Goals (SDGs) of the United Nations (UN). All UN members have committed to ending the TB epidemic by 2030. China has one of the highest TB loads worldwide, ranking third in the world on many TB burden indices. The national strategy for TB control is aimed at creating a collaborative network and integrating TB treatment into the medical system. According to the WHO's global TB report, China is expected to have 748,000 new cases of TB in 2022 and an incidence of 52 cases per 100,000 people. Ending TB remains a huge challenge and requires comprehensive control strategies in China. In this work, we have discussed the challenges of TB prevention and control in China and proposed specific measures to end TB.

Repeated Omicron infection dampens immune imprinting from previous vaccination and induces broad neutralizing antibodies against Omicron sub-variants.

OBJECTIVE: Similar with influenza virus, antigenic drift is highly relevant to SARS-CoV-2 evolution, and immune imprinting has been found to limit the performance of updated vaccines based on the emerging variants of SARS-CoV-2. We aimed to investigate whether repeated exposure to Omicron variant could reduce the immune imprinting from previous vaccination. METHODS: A total of 194 participants with different status of vaccination (unvaccinated, regular vaccination and booster vaccination) confirmed for first infection and re-infection with BA.5, BF.7 and XBB variants were enrolled, and the neutralizing profiles against wild type (WT) SARS-CoV-2 and Omicron sub-variants were analyzed. RESULTS: Neutralizing potency against the corresponding infected variant is significantly hampered along with the doses of vaccination during first infection. However, for the participants with first infection of BA.5/BF.7 variants and re-infection of XBB variant, immune imprinting was obviously alleviated, indicated as significantly increased ratio of the corresponding infected variant/WT ID50 titers and higher percentage of samples with high neutralizing activities (ID50 > 500) against BA.5, BF.7 and XBB variants. Moreover, repeated Omicron infection could induce strong neutralizing potency with broad neutralizing profiles against a series of other Omicron sub-variants, both in the vaccine naive and vaccine experienced individuals. CONCLUSIONS: Our results demonstrate that repeated Omicron infection dampens immune imprinting from vaccination with WT SARS-CoV-2 and induces broad neutralizing profiles against Omicron sub-variants.