Introduction: The risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death. Methods: This multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome. Results: Of 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 ( P < 0.0001 and P = 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression ( P = 0.012 and P = 0.027, respectively). Conclusions: Expression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.

Authors

Background and Aims: The long-term respiratory sequelae of COVID-19 infection in children remain poorly understood and may differ across countries. This study aims to investigate the respiratory sequelae, including residual respiratory symptoms and pulmonary function in Thai children. The secondary aim is to identify factors associated with the respiratory sequelae. Materials and Methods: This is an observational study involving 56 healthy children, aged between 7-18 years, who were diagnosed with COVID-19 infection from July 2021 to February 2023. Clinical data relating to COVID-19 infection and persistent symptoms after the infection were assessed after the infection up to six months. Spirometry was performed to assess pulmonary function. Results: Post COVID-19 symptoms were identified in 14 patients (25%), with fatigue, cough, and dyspnea being common symptoms (28-35%). A significant correlation was found between post COVID-19 symptoms and pneumonia (OR = 6.00, 95%CI [1.54,23.33], p=0.01). Abnormal pulmonary function was identified in 10 patients (17.8%) with obstructive impairment being the most common. However, there were no significant association between clinical factors and pulmonary function impairment. Conclusion: Prolonged respiratory symptoms and abnormal pulmonary function following COVID-19 infection are not uncommon in children. The post COVID-19 symptoms are possibly associated with COVID-19 pneumonia.

Objectives: Although the mortality rate of pediatric acute respiratory distress syndrome (PARDS) continues to decrease, the increased incidence of clinical sequelae in survivors has become a focus of clinical practice. This study aimed to determine the functional status of PARDS survivors at hospital discharge using the Functional Status Scale and to identify risk factors associated with mortality. Methods: We retrospectively analyzed the clinical data of patients with PARDS assessed upon admission and discharge from our hospital’s pediatric intensive care unit between January 2013 and January 2020. Patients were categorized into survival and non-survival groups for intergroup clinical characteristics and therapeutic intervention comparisons. Results: Of the 149 study participants, 96 (64.4%) died during hospitalization, and 53 (35.6%) survived until discharge. Severe PARDS, defined as an oxygenation index score of ≥16, was an independent risk factor for mortality. Although surviving participants showed improvements in their clinical status, the new morbidity rate at discharge was 24.5%, with respiratory, feeding, and motor functions being the domains most affected. Conclusion: Severe PARDS was an independent risk factor for mortality. Despite the PARDS survival rate for the participants being 33.33%, approximately a quarter of survivors experienced new morbidities after discharge. The most affected functions included those related to respiration, feeding, and motor activity; therefore, special attention should be given to maintaining these functions in survivors.

Background: Among patients with cystic fibrosis (CF), methicillin-resistant Staphylococcus aureus (MRSA)-associated acute pulmonary exacerbations (APEs) are increasing in prevalence and can cause rapid declines in lung function and mortality. Limited data exist on the preferred treatment of MRSA-associated APEs, with vancomycin often considered first-line. Given the potential toxicities and intolerances associated with vancomycin, evaluating alternative therapies such as doxycycline is warranted. Methods: This evaluation is a multicenter retrospective cohort study of adult and pediatric patients with a CF diagnosis who received greater than 48 hrs of either vancomycin or doxycycline to treat MRSA-associated APEs. The primary outcome was the incidence of patients with a return to ≥90% of baseline forced expiratory volume in the first second (FEV 1). Results: 229 patient encounters were screened of which 89 met inclusion criteria (n = 26, vancomycin; n = 63, doxycycline). There were no differences between vancomycin and doxycycline for the primary outcome: 18/26, (69.2%) in the vancomycin group versus 51/63 (81.0%) in the doxycycline group (p = 0.23). Conclusions: Doxycycline was comparable to vancomycin in the rate of return to ≥90% of baseline FEV 1 and for all secondary efficacy outcomes. While the results of this study are limited by the small sample size, retrospective design, and lack of power, the findings suggest doxycycline may be a reasonable alternative to vancomycin for MRSA-associated APEs, particularly in patients who may not tolerate vancomycin or who require concomitant nephrotoxins such as intravenous aminoglycosides.

The El Niño-Southern Oscillation (ENSO) phenomena, originating in the tropical Pacific region, is an interannual climate variability driven by sea surface temperature and atmospheric pressure changes that affect weather patterns globally. In Mesoamerica, ENSO can cause significant changes in rainfall patterns with major impacts on water resources. This commentary presents results from a nearly 10-yr hydrometric and tracer monitoring network across north-central Costa Rica, a region known as a headwater-dependent system. This monitoring system has recorded different El Niño and La Niña events, as well as the direct/indirect effects of several hurricane and tropical storm passages. Our results show that ENSO exerts a significant but predictable impact on rainfall anomalies, groundwater recharge, and spring discharge, as evidenced by second-order water isotope parameters (e.g., line conditioned-excess or LC-excess). The Oceanic Niño Index (ONI) is correlated with a reduction in mean annual and cold front rainfall across the headwaters of north-central Costa Rica. During El Niño conditions, rainfall is substantially reduced (by up to 69.2%) during the critical cold fronts period, subsequently limiting groundwater recharge and promoting an early onset of baseflow conditions. In contrast, La Niña is associated with increased rainfall and groundwater recharge (by up to 94.7% during active cold front periods). During La Niña, the long-term mean spring discharge (39 Ls -1) is exceeded 63-80% of the time, whereas, during El Niño, the exceedance time ranges between 26% and 44%. These stark shifts in regional hydroclimatic variability are imprinted on the hydrogen and oxygen isotopic compositions of meteoric waters. Drier conditions favored lower LC-excess in rainfall (-17.3‰) and spring water (-6.5‰), whereas wetter conditions resulted in greater values (rainfall=+17.5‰; spring water=+10.7‰). The lower and higher LC-excess values in rainfall corresponded to the very strong 2014-16 El Niño and 2018 La Niña, respectively. During the recent triple-dip 2021-23 La Niña, LC-excess exhibited a significant and consistently increasing trend. These findings highlight the importance of combining hydrometric, synoptic, and isotopic monitoring as ENSO sentinels to advance our current understanding of ENSO impacts on hydrological systems across the humid Tropics. Such information is critical to constraining 21 st century projections of future water stress across this fragile region.

Under global climate change, the temperature and precipitation on the Tibet Plateau have significantly changed, and the melting of glacier and snow has been also affected, subsequently causing changes in runoff. The assessment of runoff and its components on the Tibetan Plateau under climate change is important for water resources management and ecology conservation in alpine regions. Therefore, the Spatial Processes in Hydrology model (SPHY model), a distributed cold-zone hydrological model which contains a glacial ablation module and performs well in alpine region, was used to simulate runoff in the Yangtze River source located in the middle of the Tibetan Plateau during 2000-2020. The input data included the measured runoff from the Zhimenda hydrological station, meteorological data from 16 meteorological stations, digital elevation model (DEM) data, land use data and glacier data. And the coupled model intercomparison project 6 (CMIP6) climate model was used to predict the runoff process for the future 30 years (2020-2050). The results showed that Nash-Sutcliffe efficiency coefficient (NSE), Relative Error (RE) and coefficient of determination (R 2) in Zhimenda hydrological station for the calibration period, reached 0.900, 0.036 and 0.956, respectively, and NSE, RE and R 2 reached 0.828, 0.120 and 0.924, respectively, for the validation period, which shows that the model performed well in most years. In 2000-2020, rainfall runoff contributed most to the total runoff (60.87%), followed by baseflow (22.96%), snowmelt runoff (11.59%) and glacier runoff (4.58%) in the Yangtze River source. The runoff amount of the three source river, Dangqu River, Tuotuo River and Chumar River accounted for about 53% of the total runoff in the Yangtze River Source basin, with rainfall runoff (52.04%) contributing the most and glacier runoff (5.92%) contributing the least. Compared to the contribution of glacial runoff in the Dangqu River (8.87%) and Tuotuo River (6.59%), the proportion of glacial runoff in the Chumar River was very small (0.89%). Under the CMIP6 climate model, the mean runoff depth was predicted to increase approximately 13.5 mm from 2020-2050 compared to 2000-2020.

Long-wavelength fluorescence of carbon dots (CDs) show the great importance in multiple fields, especially for the biochemical sensing. Here we proposed one type of CDs doped with nitrogen and sulfur through the hydrothermal method, which exhibited the obvious yel-low-fluorescence in aqueous. Importantly, their fluorescence intensity of CDs decreased with pH decreasing in the acidic range, thus a linear relationship between pH and fluorescence intensity was established, and exhibiting the potential of pH sensing. Additionally, in-troducing tigecycline into CDs resulted in their decreased fluorescence, thus we further established a strategy of detecting tigecycline with the concentration range of 200 μM to 7 nM. Meanwhile, we elucidated the static quenching as the major mechanism for CDs responding tigecycline, which was induced by the formed new complex between CDs and tigecycline. Furthermore, the practicality of the method was verified by examining the recovery of tigecycline in the actual lake-water samples.

The conservation and management of large carnivores is a challenging task for researchers seeking to foster human-wildlife coexistence. Agent-based models (ABMs) allow researchers to design realistic simulations of their study system, including environmental, anthropogenic and ecological agents and their characteristics to examine interactions at landscape scales and investigate how interventions may alter potential outcomes. Including high-resolution Geographic Information Systems (GIS) data and real-world ecological data streams in ABMs represents an innovative approach for site-specific investigations into how best to manage the return of large carnivores. We used GIS-integrated ABMs to study the outcome of wolf reintroduction to Ireland’s national parks with respect to wolf ecology and wolf-livestock interactions. We introduced management strategies and policy interventions to assess how wolf-livestock interactions could be influenced by wildlife managers and whether outcomes were site-specific. Our study found that wolves could persist past the initial introduction in each protected area regardless of which reintroduction strategy is utilised, however, human-wildlife conflict warning signs emerged. Wolves extensively disperse outside protected areas, den-sites are located close (c. 1.5km) to park boundaries and livestock-depredations do occur. Management and policy interventions significantly reduced the likelihood of human-wildlife conflict by reducing the number of livestock depredations and creating ecological buffers that reduce wolf-human interactions, however, the individual characteristics of the protected area determined the success of each management and policy intervention. This analysis reveals nuanced differences in the response of each study area to the same management and policy interventions, demonstrating that the outcome of management and policy interventions is highly dependent on specific ecological conditions captured in GIS data. This underscores the importance of integrating high-resolution GIS data into ecological ABMs and the power that such integration can bring to these models for delivering tailored recommendations to decision-makers enabling human-wildlife coexistence with large carnivores in complex landscapes.

1. Alpine plants possess unique traits owing to their adaptation to alpine environments. However, it remains unknown whether leaf trait relationships of alpine plants can be captured by the two general trait dimensions of organ size and resource economics. 2. We hypothesized that, beyond the trait dimensions of leaf size and resource economics, non-structured carbohydrates (NSCs) would reflect an important dimension of cold-tolerance in alpine plants. 3. We measured 12 leaf traits critical to leaf construction, growth, and stress resistance in 225 site species, ranging from 7 sites along the alpine steppes to alpine meadows on the Tibetan Plateau. We also examined the cold-tolerance of 11 species at one of these sites by estimating the lethal temperature causing 50% frost damage (LT50). We investigated the variation and potential leaf trait dimensions of alpine plants and verified whether the third leaf trait dimension is related to cold-tolerance by analyzing the relationships of NSCs and LT50. 4. The majority of variations in 12 leaf traits of alpine plants were captured by three trait axes, in which leaf carbon (LCC) and NSCs (including starch, LSC and soluble sugars, LSS) were clustered in a new dimension (PC3) beyond leaf size and structure, and resource economics. Although LCC, LSC and LSS all showed negative correlations with MAT, a significant negative correlation was only found between LSS and LT50. It indicated that PC3 was able to reflect the cold-tolerance of alpine plants to some extent, in which LSS was the most critical trait. 5. Thus, the storage and transformation of NSCs under stressful conditions could reflect a dimension of long-term metabolic adaptation and cold-tolerance, which is an extension of the resource-utilization strategy beyond construction cost and growth. Our study suggested that NSCs should not be ignored in leaf economic spectrum for alpine plants.

J-aggregate dyes have been widely used in biomedicine, chemical engineering, etc., due to their structure and photophysical properties. J-aggregation theory describes the nearest-neighbor molecules' transition dipole moments in a sliding stacking arrangement. Recently, we found that the intervention of polyvalent anions can induce the J-aggregation of dyes via the intermolecular van der Waals interaction, which is an essential way once overlooked. Experimental results and theoretical calculations revealed that the more negatively charged or large size of anions within a specific range, the more efficiently the dye will form J-aggregates. As an application, the content of polyvalent anion salts in a salt-stressed Arabidopsis model was evaluated based on the ratiometric fluorescence emission resulting from the polyvalent anion-induced dye J-aggregation.

The efficacy of nanoparticle (NP)-based drug delivery technology is hampered by aberrant tumor stromal microenvironments (TSMs) that hinder NP transportation. Therefore, the promotion of NP permeation into deep tumor sites via the regulation of tumor microenvironments is of critical importance. Herein, we propose a potential solution using a dihydrazidine (HDZ)-loaded nanoparticle drug delivery system containing a pH-responsive, cyclic RGD peptide-modified prodrug based on doxorubicin (cRGD-Dex-DOX). With a combined experimental and theoretical approach, we find that the designed NP system can recognize the acid tumor environments and precisely release the encapsulated HDZ into tumor tissues. HDZ can notably downregulate the expression levels of hypoxia-inducible factor 1α (HIF1α), α-smooth muscle actin, and fibronectin through the dilation of tumor blood vessels. These changes in the TSMs enhance the enrichment and penetration of NPs and also unexpectedly promote the infiltration of activated T cells into tumors, suggesting that such a system may offer an effective “multifunctional therapy” through both improving the chemotherapeutic effect and enhancing the immune response to tumors. In vivo experiments on 4T1 breast cancer bearing mice indeed validate that this therapy has the most outstanding antitumor effects over all the other tested control regimens, with the lowest side effects as well.

A document by Farah Wiita. Click on the document to view its contents.

This research work presents a novel approach to combat propaganda and misinformation in the context of information warfare through the integration of a modified logistic differential equation, a Physics-Informed Neural Network (PINN), and a comprehensive parameter sensitivity analysis. The study leverages the LIAR dataset, which offers a diverse range of labelled statements reflecting real-world political discourse, making it an ideal foundation for capturing the complexities of propaganda dynamics. The modified logistic equation, incorporating parameters such as spread rate (α), decay rate (β), and growth rate (γ), is employed to capture the intricate dynamics of information spread and adoption. The PINN model uses domain knowledge and data to estimate the underlying dynamics and unknown parameters of the logistic equation. This allows for highly accurate classification and analysis of propaganda spread. Thereafter, a parameter sensitivity analysis is conducted under different attacker intensities, categorized as aggressive, neutral, and non-aggressive. Varying population sizes are considered to assess the implications of different parameter combinations. The results reveal the significant influence of the spread rate parameter (α), highlighting the aggressiveness of the attacker’s propaganda dissemination in information warfare scenarios. Furthermore, the proposed PINN-based model’s performance is evaluated against two benchmark models: a Term Frequency-Inverse Document Frequency (TF- IDF) model and the random forest classifier. The PINN model achieved an impressive accuracy rate of 97.32% on the LIAR dataset, outperforming both the TF-IDF model (93.87%) and the random forest classifier (95%). This demonstrates the superior predictive power and effectiveness of the PINN model in capturing the complexities of information spread in the realm of propaganda and misinformation. This research lays down a robust groundwork for research aimed at combating propaganda and pushing the boundaries of information warfare. It achieves this by validating the efficacy of the proposed model and showcasing its superiority when compared to existing benchmark models. The comprehensive parameter sensitivity analysis further enhances the understanding of the system’s behavior and offers insights into the impact of varying parameter values.

A sixty-year-old male presented with three-day history of a widespread erythematous rash with associated chills, paraesthesia, and haematuria. On review of medications, he had recently been commenced on Vimovo (Naproxen/Esomeprazole) 500mg/20mg twice daily for a week for back pain. Bloods showed hypereosinophilia and a moderate acute kidney injury. Histology revealed parakeratosis, mild spongiosis with eosinophils. His admission was complicated by the acute onset of rapid atrial fibrillation with acute coronary syndrome. Coronary angiogram was non-obstructive. Cardiac MRI revealed acute myocarditis. This was felt to be a complication secondary to Drug reaction with eosinophilia and systemic symptoms (DRESS). In addition to his cardiac management, he was treated with oral corticosteroids and supportive care. Naproxen/Esomeprazole was stopped. On repeat cardiac MRI 3 months later his myocarditis had resolved, and his skin remains clear. DRESS is a rare drug induced hypersensitivity reaction that includes skin eruption, haematological abnormalities, lymphadenopathy, and internal organ involvement which has morality rate of up to 10%. The objective of this case report is to highlight the significant cardiac complications that can ensue. Naproxen/Esomeprazole was the culprit drug which is rare. There has been one previous case of DRESS secondary to NSAID with myocarditis. However, it presented as cardiogenic shock. This case was complicated by arrythmia and acute coronary syndrome. DRESS warrants prompt recognition with identification of causative drug and withdrawal. Multiorgan complications can be severe, and treatment should not be delayed. DRESS should always be considered with a new onset rash in the context of a new medication.

Objective: Our study aimed to explore the mechanism network that TLR2/AP-1 combined with SOX10 to activate the MAPK pathway via CTGF in Dox-induced myocardial injury. Methods: Rats with Dox-induced myocardial injury were treated with a TLR2 inhibitor or CTGF silencing lentiviral vector. H9c2 cells were treated with genetic vectors or MAPK pathway activators. Cardiac function was tested using echocardiography and serum markers. H&E, sirius red, and TUNEL staining were used to detect myocardial pathological changes, collagen accumulation, and apoptosis. Western blot was used to detect proteins related to cardiac hypertrophy, fibrosis, apoptosis, and MAPK pathway. H9c2 cell injury was assessed by testing cell viability, LDH release, and mitochondrial membrane potential. Results: TLR2 and CTGF were highly expressed in patients with heart failure, and Dox treatment further increased their expression. Inhibiting TLR2 or silencing CTGF improved cardiac function and reduced myocardial fibrosis and apoptosis in Dox-treated rats. Silencing TLR2 alleviated Dox-induced H9c2 cell injury, which was nullified by CTGF overexpression. TLR2 activated AP-1, which cooperated with SOX10 to promote CTGF transcription. MAPK activation aggravated H9c2 cells against Dox-induced injury. Conclusions: TLR2 activates AP-1 which cooperates with SOX10 to promote CTGF transcription and subsequently activate the MAPK pathway, thereby stimulating Dox-induced myocardial injury.

：Explore the digital rendering mode with texturing brush and ink effect, analyze and simulate the brush and ink characteristics of traditional Chinese ink painting, especially the art of landscape painting, and try to integrate the texture of wrinkle method synthesis map and modeling technology based on particle deposition and stacking (overlapping) to render, thus realizing the computer simulation of small freehand brushwork and large freehand brushwork (splash ink) ink effects in traditional landscape painting. This research inherits and develops the aesthetic theory and thought of traditional ink painting art, and makes some beneficial exploration in the field of digital freehand ink painting, which has positive reference value and promotion significance for the development of Chinese ink painting.

A document by Michelle Leal. Click on the document to view its contents.

This paper provides a comprehensive assessment of the up-to-date life-cycle sustainability status of cadmium-telluride based photovoltaic (PV) systems. Current production modules (Series 6 and Series 7) are analyzed in terms of their energy performance and environmental footprint and compared with the older series 4 module production and current single-crystalline-silicon (sc-Si) module production. For fixed-tilt systems with series 6 modules operating under average US irradiation of 1800 kWh/m 2/yr, the global warming potential (GWP) is reduced from 16 g CO2 eq/kWh in Series 4 systems to 10 CO2 eq/kWh in Series 6 systems. For operation in US-SW irradiation of 2300 kWh/m2 the GWP is reduced from 11 CO2eq/kWh to 8 CO2eq/kWh and for 1-axis tracking systems operating in Phoenix, Arizona with point-of array irradiation of 3051 kWh/m 2/yr the GWP is reduced to 6.5 CO2 eq/kWh. Similar reductions have happened in all environmental indicators. Energy payback times (EPBT) of currently installed systems range from 0.6 years for fixed-tilt ground-mounted installations at average U.S. irradiation at latitude tilt installations, to 0.3 years for one-axis trackers at high US-SW irradiation, considering average fossil-fuel dominated electricity grids with fuel to electricity conversion efficiency of 0.3. The resulting energy return on energy investment (EROI) also depends on the conversion efficiency of the electricity grid and on the operation life expectance. For a 30-year operational life and grid conversion efficiency of 0.3, EROI ranges from 50 (at US average irradiation) to 70 for US-SW irradiation. The EROI declines with increased grid conversion efficiency; for CdTe PV operating in south California with grid conversion efficiency of 49% the EROI is about 50 and is projected to fall to 30 when the state’s 2030 target of 80% renewable energy penetration materializes. Material alternatives that show a potential of further reductions in degradation rates and materials for enhanced encapsulation that would enable longer operation lives are also been investigated. A degradation rate of 0.3%/year, which has been verified by accelerated testing, is assumed in 30-year scenarios; this is projected to be reduced to 0.2%/yr in the near-term and potentially to 0.1%/yr in the longer term. With such low degradation rates and enhanced edge-sealing, modules can last 40- to 50-years. Consequently, all impact indicators will be proportionally reduced while EROI will increase.

Human activities have increased the intensity and frequency of natural stressors and created novel stressors, altering host-pathogen interactions, and changing the risk of emerging infectious diseases. Despite the ubiquity of such anthropogenic impacts, predicting the directionality of outcomes has proven challenging. Here, we conduct a review and meta-analysis to determine the primary mechanisms through which stressors affect host-pathogen interactions and to evaluate the impacts stress has on host fitness (survival and fecundity) and pathogen infectivity (prevalence and intensity). We assessed 891 effect sizes from 71 host species (representing seven taxonomic groups) and 78 parasite taxa from 98 studies. We found that infected and uninfected hosts had similar sensitivity to stressors and that responses varied according to stressor type. Specifically, limited resources compromised host fecundity and decreased pathogen intensity, while abiotic environmental stressors (e.g., temperature and salinity) decreased host survivorship and increased pathogen intensity, and pollution increased mortality but decreased pathogen prevalence. We then used our meta-analysis results to develop Susceptible-Infected theoretical models to illustrate scenarios where infection rates are expected to increase or decrease in response to resource limitation or environmental stress gradients. Our results carry implications for conservation and disease emergence and reveal areas for future work.

AUTHORSDr. Saroj Poudel Clinical Pharmacist Critical Care Medicine, Nepal Mediciti Email: itsmesarozz@gmail.comDr. Rupak Chalise Anesthesiologist Critical Care Medicine, Nepal Mediciti Email: rupak.chalise1990@gmail.comDr. Manoj Bist Medical Officer Critical Care Medicine, Nepal Mediciti Email: manojbistamanisha18@gmail.comDr. Ashim Regmi Junior Consultant Critical Care Medicine, Nepal Mediciti Email: a20regmi@gmail.comDr. Anup Ghimire Junior Consultant Critical Care Medicine, Nepal Mediciti Email: anup.login@gmail.comDr. Kishor Khanal Intensivist and ICU Coordinator Critical Care Medicine, Nepal Mediciti Email: kishorkhanal01@gmail.com

Background: Herpes simplex virus type 2 (HSV-2) infection is prevalent and a significant public health problem. Understanding its epidemiology will help assess the current HSV-2 prevention efforts and inform future interventions in China. Methods: We followed Cochrane and PRISMA guidelines for a systematic review and included publications published in Chinese and English bibliographic systems until March 18 th, 2023. We synthesized seroprevalence, sero-incidence, and proportions of HSV-2 isolated in genital ulcer disease (GUD) and genital herpes data. We used random-effects models for meta-analyses and conducted meta-regression to assess the association between population characteristics and seroprevalence. Results: Overall, 21,849 articles were identified, and 457 publications (1,051,035 participants) were included. A total of 429 studies reported the overall seroprevalence rates (939 stratified measures), 5 reported seroincidence rates, 4 reported overall proportions of HSV-2 isolation in GUD (8 stratified proportions), and 24 reported overall proportions of HSV-2 isolation in genital herpes (59 stratified proportions). Pooled HSV-2 seroprevalence among overall populations was 14.9% (95% confidence interval (CI): 13.8-16.1%) and was 7.9% (95% CI: 6.9-8.8%) among the general population. Seroprevalence was highest among key populations (e.g., female sex workers and men who have sex with men) (32.1% (95% CI: 27.8-36.5%)). Among the general population, we found northeastern regions had a higher HSV-2 seroprevalence (12.4%, 95% CI: 7.8-17.9%). HSV-2 seroprevalence also increased with age. The pooled HSV-2 seroincidence rate was 4.3 per 100 person-years (95% CI: 1.0-7.6). Pooled HSV-2 seroprevalence among GUD and genital herpes were 45.2% (95% CI: 29.0-61.9%) and 52.8% (95% CI: 46.6-59.0%), respectively. We also found higher HSV-2 seroprevalence estimates in publications published in English bibliographic databases than those in Chinese databases (20.5% vs. 13.6%, risk ratio=1.10 (1.05-1.14)), indicating a potential existence of language bias in publication. Conclusion: Around 1 in 12 among the general population and 1 in 7 among all included populations were infected with HSV-2. The data revealed vulnerability to HSV-2 infection among higher-risk populations calling for expanding the intervention to prevent HSV-2 infection. It also revealed heterogeneities in synthesized HSV-2 prevalence results, suggesting the necessity to include Chinese bibliographic databases in conducting systematic reviews and meta-analyses of this topic.

We report an hemodialysis MDR HIV-infected patient switched to fostemsavir with lenacapavir plus lamivudine for more than a year. She maintained a suppressed viral replication and didn't present any clinical or biological drug-related side effects. The combination of lenacapavir plus fostemsavir looks promising in terms of safety and efficacy even in patients with end-stage renal disease awaiting renal transplant. Both drugs are first in class ARVs so that there is no cross resistance with previous drugs, maintaining their efficacy against MDR HIV.

A document by Maria Perez Rubi. Click on the document to view its contents.