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Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a “genomically unstable” cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients’ well-being.

Background: An increasing proportion of visits are now delivered via a virtual platform. Virtual visits are limited by the lack of important components of cardiovascular assessment such as physician examination and electrocardiogram. Objectives: The purpose of this study was to evaluate the quality of care delivered by virtual visits compared to office-based visits among adults who sought care for three common cardiac-related symptoms: dyspnea, dizziness, or palpitations. Methods: Retrospective cohort study of 992,526 outpatient visits between January 1, 2017, and December 31, 2021, within an integrated health system, including 356,159 visits for dyspnea, 412,913 for dizziness, and 223,454 for palpitations. We compared the differences in patient characteristics associated with telemedicine visits versus in-office visits, evaluated the referral rates for noninvasive cardiac testing, and examined the association between virtual visits and 30-day clinical outcomes. Results: Among 992,526 visits, 71.5% were office visits, 25.8% telephone visits, and 2.7% video visits. Median age was 59 (IQR: 43-72) years, and 63.1% were women. Patient characteristics associated with increased likelihood of virtual visits included younger age, female sex, being non-Hispanic Black, and being from lower-income households. No association was observed between visit types and 30-day cardiovascular hospitalization for patients with dizziness or palpitations. However, for patients with dyspnea, evaluation via virtual visits was associated with a higher risk of 30-day hospitalization for heart failure (aOR: 1.25; 95% CI: 1.16-1.36 for telephone visits; aOR: 1.45; 95% CI: 1.17-1.80 for video visits). Compared to office-based visits, patients with dyspnea were less likely to be referred for echocardiogram with telephone (aOR: 0.73; 95% CI: 0.72-0.75) or video visits (aOR: 0.92; 95% CI: 0.87-0.98). Conclusions: Virtual visits may be appropriate for some clinical concerns but not all. Optimal alignment of clinical conditions with appropriate care modalities is an important component of a successful telemedicine strategy.

The Sb2WO6 photocatalyst is synthesized by introducing oxygen vacancies through acetylene annealing. The number of oxygen vacancies can be adjusted by varying the annealing duration. Oxygen vacancy defects in Sb2WO6 change the surface chemical properties, enhance the separation of carriers, broaden the absorption of visible light, and activate the catalytic sites, resulting in overall enhancement of the photocatalytic properties. The significance of surface oxygen vacancies and pertinent mechanisms of photocatalytic oxidation are described. Our results reveal a promising method to improve the properties of Sb2WO6-based materials for applications such as the treatment of wastewater.

Background and objectives: To evaluate the prognostic value of an integrated model consisting of tumour response to induction chemotherapy (IC) and gross tumour volume (GTV) after IC in nasopharyngeal carcinoma (NPC) and elucidate optimal cumulative cisplatin dose (CCD) in concurrent chemoradiotherapy (CCRT) for different subgroups. Design and methods: This retrospective study enrolled 896 patients with NPC diagnosed from 2010 to 2017 receiving IC plus radiotherapy. The primary endpoint was disease-free survival (DFS). Cut-off points for GTV were combined with IC response to develop an integrated model. Propensity score matching (PSM) was used to adjust for potential confounders. Survival outcomes and acute toxicity were compared between the different CCD groups. Results: Unsatisfactory IC response and large GTV after IC were correlated with poor survival outcomes; the AUC increased to 0.668 when these factors were incorporated. The integrated model classified patients into three groups. After PSM, radiotherapy alone and CCRT demonstrated similar efficacy in the low-risk group (complete response (CR)/partial response (PR) and GTV 200 mg/m 2 and 101–200 mg/m 2 increased the 5-year DFS rates (83.7% vs 81.1% vs 65.3%, p = 0.042). In the high-risk group (stable disease/progressive disease and any GTV), the use of different CCDs did not result in significantly different survival outcomes ( p = 0.793). Additionally, high CCD was significantly associated with increased incidence of grade 1–4 acute toxicity. Conclusion: The integrated model incorporating IC response and GTV after IC demonstrates satisfactory value in risk stratification and the potential to guide individualised decision-making in CCD selection. Balancing toxicity and efficacy, RT alone seems to be the optimal treatment for patients in low-risk groups and 200 mg/m 2 might be the optimal dose for intermediate-risk groups. Moreover, increasing CCD does not benefit patients in high-risk groups, and treatment options for these patients require further consideration.

BackgroundPreeclampsia (PE) poses significant diagnostic and therapeutic challenges. This study aims to identify novel genes for potential diagnostic and therapeutic targets, illuminating the immune mechanisms involved.MethodsThree GEO datasets were analyzed, merging two for training set, and using the third for external validation. Intersection analysis of differentially expressed genes (DEGs) and WGCNA highlighted candidate genes. These were further refined through LASSO, SVM-RFE, and RF algorithms to identify diagnostic hub genes. Diagnostic efficacy was assessed using ROC curves. A predictive nomogram and fully Connected Neural Network (FCNN) were developed for PE prediction. ssGSEA and correlation analysis were employed to investigate the immune landscape. Further validation was provided by qRT-PCR on human placental samples.ResultFive biomarkers were identified with validation AUCs: CGB5 (0.663, 95% CI: 0.577-0.750), LEP (0.850, 95% CI: 0.792-0.908), LRRC1 (0.797, 95% CI: 0.728-0.867), PAPPA2 (0.839, 95% CI: 0.775-0.902), and SLC20A1 (0.811, 95% CI: 0.742-0.880), all of which are involved in key biological processes. The nomogram showed strong predictive power (C-index 0.873), while FCNN achieved an optimal AUC of 0.911 (95% CI: 0.732-1.000) in five-fold cross-validation. Immune infiltration analysis revealed the importance of T cell subsets, neutrophils, and NK cells in PE, linking these genes to immune mechanisms underlying PE pathogenesis.ConclusionCGB5, LEP, LRRC1, PAPPA2, and SLC20A1 are validated as key diagnostic biomarkers for PE. Nomogram and FCNN could credibly predict PE. Their association with immune infiltration underscores the crucial role of immune responses in PE pathogenesis.

Background The aim of this study is to evaluate the ability of generative artificial intelligence (AI) models to handle specialized medical knowledge and problem-solving in a formal examination context. Methods This research utilized internal medicine exam questions provided by the Taiwan Internal Medicine Society from 2020 to 2023, testing three AI models: GPT-4o, Claude_3.5 Sonnet, and Gemini Advanced models. Rejected queries for Gemini Advanced were translated into French for resubmission. Performance was assessed using IBM SPSS Statistics 26, with accuracy percentages calculated and statistical analyses such as Pearson correlation and analysis of variance (ANOVA) performed to gauge AI efficacy. Results GPT-4o’s top annual score was 86.25 in 2022, with an average of 81.97. Claude_3.5 Sonnet reached a peak score of 88.13 in 2021 and 2022, averaging 84.85, while Gemini Advanced lagged with an average score of 69.84. In specific specialties, Claude_3.5 Sonnet scored highest in Psychiatry (100%) and Nephrology (97.26%), with GPT-4o performing similarly well in Hematology & oncology (97.10%) and Nephrology (94.52%). Gemini's best scores were in Psychiatry (86.96%) and Hematology & Oncology (82.76%). Gemini Advanced models struggled with Neurology, scoring below 60%. Additionally, all models performed better on text-based questions than on image-based ones, without significant differences. Claude 3 Opus scored highest on COVID-19-related questions at 89.29%, followed by GPT-4o at 75.00% and Gemini Advanced at 67.86%. Conclusions AI models showed varied proficiency across medical specialties and question types. GPT-4o demonstrated higher image-based correction rates. Claude_3.5 Sonnet generally and consistently outperformed others, highlighting significant potential for AI in assisting medical education.

Background As one of the most common and abundant internal modifications of eukaryotic mRNA, N6-methyladenosine (m6A) modifications are closely related to placental development. Ferroptosis is a newly discovered form of programmed cell death. During placental development, placental trophoblasts are susceptible to ferroptosis. However, the interactions of m6A and ferroptosis in trophoblast physiology and injury are unclear. Methods Recurrent miscarriage (RM) was selected as the main gestational disease in this study. Published data (GSE76862) were used to analyze the gene expression profiles in patients with RM. The extent of m6A modification in total RNA of villous tissues between patients with RM and healthy controls (HC) was compared. ALKBH5 (encoding AlkB homolog 5, RNA demethylase) was selected as the candidate gene for further research. Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry (IHC) confirmed the elevated expression of ALKBH5 in the cytotrophoblasts of patients with RM. Then, cell counting kit-8 assays, glutathione disulfide/glutathione quantification, 2′,7′-dichlorfluorescein-diacetate staining, and malonaldehyde assays were used to explore the alterations of ferroptosis-related characteristics following RAS-selective lethal (RSL3) stimulation after overexpression of ALKBH5. Thereafter, we re-analyzed the published RNA sequencing data upon knockdown of ALKBH5, combined with published tissue RNA-seq data, and FTL (encoding ferritin light chain) was identified as the ferroptosis-related gene in cytotrophoblasts of patients with RM that is regulated by ALKBH5. Finally, western blotting and IHC confirmed the increased expression of FTL in the cytotrophoblasts from patients with RM. Results Total m6A levels were decreased in patients with RM. The most significant differentially m6A-related gene was ALKBH5, which was increased in patients with RM. In vitro cell experiments showed that treatment with RSL3 resulted in increased cell death and upregulated ALKBH5 expression. Overexpression of ALKBH5 alleviated RSL3-induced HTR8 cell death and caused decreased levels of intracellular oxidation products. Published transcriptome sequencing revealed that FTL was the major ferroptosis-related gene regulated by ALKBH5 in the villous tissues of patients with RM. Consistent with the expression of ALKBH5, FTL was increased by RSL3-induction and increased in patients with RM. Conclusion Elevated ALKBH5 alleviated RSL3-induced cytotrophoblast cell death by promoting the expression of FTL in patients with RM. Our results supported the view that ALKBH5 is an important regulator of the ferroptosis-related etiology of RM and suggested that ALKBH5 could be responsible for epigenetic aberrations in RM pathogenesis.

BackgroundWhile sepsis, an exaggerated response to infection, can affect people of all age groups, it is more prevalent in middle-aged and older adults. Older adults suffer worse short-term and long-term outcomes than younger patients. Older sepsis survivors are commonly discharged to long-term acute care facilities, where they often die within 1 year. Those who return home from the hospital lose the momentum of physical function improvement after early inpatient rehabilitation, and often face exacerbation of comorbidities and decline in physical function. Additionally, patients who are discharged home often live at distant locations and are not able to commute to rehabilitation centers due to their poor health status. Therefore, remotely delivered exercise interventions tailored to this population hold promise to improve physical function safely and effectively after sepsis. However, this type of intervention has yet to be tested in this population. ObjectiveThis study aims to assess the safety, feasibility, and ease of recruitment and retention of participants for a remotely delivered physical activity intervention for improving physical function in middle-aged and older sepsis survivors. MethodsThe proposed intervention will be delivered through a digital health platform that comprises a patient-facing mobile app and a 12-week physical activity program specifically designed for middle-aged and older sepsis survivors with poor health status who may face challenges participating in traditional out-patient or community-based exercise interventions. This study is ongoing and plans to enroll 40 sepsis survivors aged 55 years and older who will be randomized to either a remotely delivered exercise intervention group or a control group (electronic health diary). Both groups will use a tablet containing the Health in Motion app (Blue Marble Health). The intervention group will receive a clinician-designed personalized avatar-guided home exercise program and reminders while the control group will self-report daily activities using the in-app health diary feature. ResultsThis study is the first to use a home-based, remotely monitored 12-week exercise program to improve physical function in sepsis survivors. This study will evaluate the safety, feasibility, and efficacy, providing the necessary knowledge to design and calculate power for future larger trials. ConclusionsThis study will provide important information for planning a future randomized clinical trial to test the efficacy of a remotely delivered exercise intervention in this high-risk population. Trial RegistrationClinicalTrials.gov NCT05568511; https://clinicaltrials.gov/study/NCT05568511 International Registered Report Identifier (IRRID)DERR1-10.2196/60270

Abstract The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single‐cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI‐to‐CKD model of unilateral ischemia‐reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co‐localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro‐repair subsets, whereas infiltrating monocyte‐derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling‐associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin‐like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI‐to‐CKD transition, which could be a potential therapeutic target for preventing CKD development.

Introduction The prevalence of chronic conditions is increasing. Given that the majority of chronic patients are managed by primary healthcare providers, there is a need to integrate primary care with public health to address the prevailing situation and enhance patient outcomes. The purpose of this study is to establish, implement and evaluate an integrated primary care and public health model in China for patients with chronic conditions.Methods This prospective, multicentre and observational study will be conducted at 12 township hospitals on patients (n=7200) diagnosed with chronic conditions (hypertensive, diabetic or stroke). Participants were divided into two groups: pilot areas and mainstream areas follow-up groups. The primary outcome will be the difference in the proportion of controlled chronic conditions among the two groups. Secondary outcomes will be the differences in mean change in diastolic and systolic blood pressures, fasting glucose, total cholesterol and triglyceride, death from any cause and participant-reported physical and psychological health status.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology. We plan to publish the results of this study in a peer-reviewed journal article.

Abstract Despite docetaxel combined with cisplatin and 5‐fluorouracil (TPF) being the established treatment for advanced nasopharyngeal carcinoma (NPC), there are patients who do not respond positively to this form of therapy. However, the mechanisms underlying this lack of benefit remain unclear. DCAF7 is identified as a chemoresistance gene attenuating the response to TPF therapy in NPC patients. DCAF7 promotes the cisplatin resistance and metastasis of NPC cells in vitro and in vivo. Mechanistically, DCAF7 serves as a scaffold protein that facilitates the interaction between USP10 and G3BP1, leading to the elimination of K48‐linked ubiquitin moieties from Lys76 of G3BP1. This process helps prevent the degradation of G3BP1 via the ubiquitin‒proteasome pathway and promotes the formation of stress granule (SG)‐like structures. Moreover, knockdown of G3BP1 successfully reversed the formation of SG‐like structures and the oncogenic effects of DCAF7. Significantly, NPC patients with increased levels of DCAF7 showed a high risk of metastasis, and elevated DCAF7 levels are linked to an unfavorable prognosis. The study reveals DCAF7 as a crucial gene for cisplatin resistance and offers further understanding of how chemoresistance develops in NPC. The DCAF7‐USP10‐G3BP1 axis contains potential targets and biomarkers for NPC treatment.

PurposeThe present longitudinal study aimed to evaluate the potential impact of modern radiotherapy (RT) techniques on quality of life (QOL) in patients with head and neck (HNC) cancer.Materials and methodsIn this single-center prospective study, participants were asked to complete QOL questionnaires that included the EORTC QLQ-C30, QLQ-H&N 35 and utility score by time trade-off (TTO) at three time points (2 weeks, 3 months and 6 months) after completion of RT. All patients were treated by modern RT techniques [volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT)]. Patients who developed recurrence or died before the 6-month follow-up were excluded. Linear mixed models with random intercepts for participants and restricted maximum likelihood estimates were used to assess the effect of our study variables (age, sex, primary site, cancer stage, treatment, radiation dose and radiation method). Overall changes in QOL, utility scores and symptom burdens at different time points were tested using paired t tests.ResultsA total of 45 patients were recruited from 2022 to 2023. Those who completed the surveys at 2 weeks with at least 1 follow-up (30 patients, 67%) were enrolled in the final analysis. The majority of these 30 patients were men (76.7%), had oral cancer (40%), had stage III or IV disease (60%), received surgical intervention (63%) and were treated with chemoradiation (80%). A curative total dose of 66 to 70 Gy was delivered to 23 (76.7%) patients, half of whom received HT. Patients who received chemotherapy had significantly lower global QoL scales (mean difference, 27.94; 95% CI, 9.33-46.55; p=0.005). Global QOL, physical function, symptoms of sticky saliva, cough, feelings of illness and weight loss improved significantly between 2 weeks and 3 months. There was no significant difference between 3 and 6 months. Interestingly, improvements in social function, social contact, pain and nutrition reached significance at 6 months. Subgroup analysis revealed greater pain relief over time for patients who underwent HT (p=0.030). Moreover, patients who participated in swallowing rehabilitation programs had a greater decrease in nausea and vomiting (p=0.036).ConclusionHNC patients treated with modern RT techniques experience improved QOL and physical function over time. The most significant improvement occurs between 2 weeks and 3 months, after which the improvement plateaus. However, social function, social contact, pain and nutrition may require longer recovery intervals after treatment. HT with daily image guidance could provide a therapeutic opportunity for improving pain relief in patients with HNC.

Invasive alien plants (IAPs) present a severe threat to native ecosystems and biodiversity. Comprehending the potential distribution patterns of these plant invaders and their responses to climate change is essential. Parthenium hysterophorus, native to the Americas, has become an aggressively invasive species since its introduction to China in the 1930s. This study aims to collect and reconstruct the historical occurrence and invasion of P. hysterophorus. Using the optimal MaxEnt model, the potential geographical distributions of P. hysterophorus were predicted based on screened species occurrences and environmental variables under the current and three future scenarios in the 2030s, 2050s, and 2070s (i.e., SSP1-2.6, SSP2-4.5, and SSP5-8.5), and the invasion risk of P. hysterophorus in Chinese cities, croplands, forests, and grasslands was assessed. The results show that: (1) The species initially invaded highly suitable areas and further spread to regions with non-analogous climate conditions. (2) Under the current climatic conditions, the overall potential distribution of P. hysterophorus is characterized by more in the southeast and less in the northwest. Climate variables, including mean annual temperature (bio1), precipitation in the wettest month (bio13), isothermality (bio3), and temperature seasonality (bio4), are the primary factors influencing its distribution. (3) The potential distribution of P. hysterophorus will expand further under future climate scenarios, particularly toward higher latitudes. (4) Forests and crop lands are the areas with the most serious potential invasion risk of P. hysterophorus. Therefore, we suggest that the government should strengthen the monitoring and management of P. hysterophorus to prevent its spread and protect agro-ecosystems and human habitats. Depending on the potential risk areas, measures such as quarantine, removal, and publicity should be taken to mitigate the threat of P. hysterophorus invasion and to raise awareness of P. hysterophorus invasion prevention.

Objective Routine screening for cardiovascular disease before kidney transplantation remains controversial. This study aims to compare cardiac testing rates in patients with end-stage renal disease, referred and not referred for transplantation, and assess the impact of testing on transplant wait times.Methods This is a retrospective cohort study of 22 687 end-stage renal disease patients from 2011 to 2022, within an integrated health system. Cardiac testing patterns, and the association between cardiac testing and transplant wait times and post-transplant mortality were evaluated.Results Of 22 687 patients (median age 66 years, 41.1% female), 6.9% received kidney transplants, and 21.0% underwent evaluation. Compared with dialysis patients, transplant patients had a 5.6 times higher rate of stress nuclear myocardial perfusion imaging with single-photon emission (rate ratio (RR) 5.64, 95% CI 5.37 to 5.92), a 6.5 times higher rate of stress echocardiogram (RR 6.51, 95% CI 5.65 to 7.51) and 16% higher cardiac catheterisation (RR 1.16, 95% CI 1.06 to 1.27). In contrast, revascularisation rates were significantly lower in transplant patients (RR 0.46, 95% CI 0.36 to 0.58). Transplant wait times were longer for patients who underwent stress testing (median 474 days with no testing vs 1053 days with testing) and revascularisation (1796 days for percutaneous intervention and 2164 days for coronary artery bypass surgery). No significant association was observed with 1-year post-transplant mortality (adjusted OR 1.99, 95% CI 0.46 to 8.56).Conclusions This study found a higher rate of cardiac testing in dialysis patients evaluated for kidney transplants. Cardiac testing was associated with longer transplant wait time, but no association was observed between testing and post-transplant mortality.

Bony changes such as glenoid bone defects and Hill-Sachs lesions are responsible for recurrent anterior shoulder dislocations. With the development of arthroscopic techniques as well as arthroscopic surgical instruments, arthroscopic repair of bony structures has become an important surgical procedure for the treatment of recurrent shoulder dislocation. In this Technical Note, we used screws to fill Hill-Sachs lesions and autologous iliac bone grafts combined with soft tissue to repair the glenoid bone defects. In the surgical procedures within the shoulder, all operations are done arthroscopically, are minimally invasive, and achieve the goal of repairing composite shoulder injuries.

Background In direct oral anticoagulant (DOAC) users with stroke due to large artery occlusion, endovascular thrombectomy is an effective treatment when intravenous thrombolytic therapy is unsuitable. The purpose of this study is to investigate the association between emergent DOAC levels and endovascular thrombectomy outcomes. Methods Participants with atrial fibrillation, who had a premorbid modified Rankin Scale score of ≤3 and had undergone endovascular thrombectomy for acute stroke, were enrolled. Drug levels upon hospital arrival were measured in the prestroke DOAC users. Head noncontrast computed tomography and computed tomographic angiography images were used to quantify thrombus permeability. The primary outcome was functional independence at 3 months (modified Rankin Scale 0–2 or a return to premorbid status for patients with a premorbid modified Rankin Scale of 3). Results The study included 250 patients (antithrombotic agent nonusers, 42.0%; oral anticoagulant users, 34.0%; and antiplatelet users, 24.0%). The primary outcomes did not differ among the 3 groups. Among oral anticoagulant users, 78.8% were DOAC users. Of the 59 DOAC users with available drug level measurements, 62.7% had low levels (

ABSTRACT Molecular methods have improved the sensitivity of the detection of pneumococcal carriage in saliva. However, they typically require sample culture enrichment and nucleic acid extraction prior to performing the detection assay and may limit scalability for extensive surveillance of pneumococcus, particularly in low-resource settings. We evaluated the performance of a DNA-extraction-free method for the detection of pneumococcus in saliva. We developed a streamlined qPCR-based protocol for the detection of pneumococcus, omitting culture enrichment and DNA extraction. Using saliva samples collected from children attending childcare centers (New Haven, CT, USA), we evaluated the detection of pneumococcus using saliva lysates as compared to purified DNA extracted from culture-enriched aliquots of the paired samples using qPCR targeting the pneumococcal piaB gene. Of the 759 saliva samples tested from 92 children [median age 3.65 years; IQR (2.46–4.78)], pneumococcus was detected in 358 (47.2%) saliva lysates prepared using the extraction-free protocol and in 369 (48.6%) DNA extracted from culture-enriched samples. We observed near-perfect agreement between the two protocols (Cohen’s kappa: 0.92; 95% CI: 0.90–0.95). Despite a high correlation between CT values generated by the two methods (r = 0.93, P < 0.0001), the CT values generated from saliva lysates were higher (lower concentration) than those from culture-enriched samples (ΔCT = 6.69, P < 0.00001). The cost of detecting pneumococcus using saliva lysates was at least fivefold lower (US$2.53) compared to the cost of the culture-enriched method (range: US$13.60–US$19.46). For pneumococcal carriage surveillance in children, our findings suggest that a DNA extraction-free approach may offer a cost-effective alternative to the resource-intensive culture-enrichment method.IMPORTANCESurveillance for carriage of pneumococcus is a key component of evaluating the performance of pneumococcal vaccines and informing new vaccination strategies. To improve the scalability of pneumococcal carriage surveillance, we show that molecular detection of pneumococcus in saliva from children can be performed without culture enrichment and DNA extraction. Our findings show that using the extraction-free method can improve surveillance efforts for pneumococcal carriage in children, overcoming the resource-intensive hurdle that comes with the use of molecular methods, particularly in low-resource settings.

Background: Global warming has provoked more co-occurrence of hot extreme and dry extreme, namely compound hot-dry events (CHDEs). However, their health impacts have seldom been investigated. This study aimed to characterize CHDEs and assess its mortality burden in China from 1990 to 2100. Methods: CHDEs were defined as a day when daily maximum temperature > its 90th percentile and Standardized Precipitation Index