Controlling factors for the global meridional overturning circulation: A lesson from the Paleozoic.

The global meridional overturning circulation (GMOC) is important for redistributing heat and, thus, determining global climate, but what determines its strength over Earth's history remains unclear. On the basis of two sets of climate simulations for the Paleozoic characterized by a stable GMOC direction, our research reveals that GMOC strength primarily depends on continental configuration while climate variations have a minor impact. In the mid- to high latitudes, the volume of continents largely dictates the speed of westerly winds, which in turn controls upwelling and the strength of the GMOC. At low latitudes, open seaways also play an important role in the strength of the GMOC. An open seaway in one hemisphere allows stronger westward ocean currents, which support higher sea surface heights (SSH) in this hemisphere than that in the other. The meridional SSH gradient drives a stronger cross-equatorial flow in the upper ocean, resulting in a stronger GMOC. This latter finding enriches the current theory for GMOC.

Strengthening the WHO Regional Office for Africa (WHO AFRO) COVID-19 vaccination information system.

This manuscript describes the process and impact of strengthening the WHO Regional Office for Africa (WHO AFRO)'s COVID-19 vaccination information system. This system plays a critical role in tracking vaccination coverage, guiding resource allocation and supporting vaccination campaign roll-out for countries in the African region. Recognising existing data management issues, including complex reporting prone to human error, compromised data quality and underutilisation of collected data, WHO AFRO introduced significant system improvements during the COVID-19 pandemic. These improvements include shifting from an Excel-based to an online Azure-based data collection system, automating data processing and validation, and expansion of collected data. These changes have led to improvements in data quality and quantity including a decrease in data non-validity, missingness, and record duplication, and expansion of data collection forms to include a greater number of data fields, offering a more comprehensive understanding of vaccination efforts. Finally, the creation of accessible information products-including an interactive public dashboard, a weekly data pack and a public monthly bulletin-has improved data use and reach to relevant partners. These resources provide crucial insights into the region's vaccination progress at national and subnational levels, thereby enabling data-driven decision-making to improve programme performance. Overall, the strengthening of the WHO AFRO COVID-19 vaccination information system can serve as a model for similar efforts in other WHO regions and contexts. The impact of system strengthening on data quality demonstrated here underscores the vital role of robust data collection, capacity building and management systems in achieving high-quality data on vaccine distribution and coverage. Continued investment in information systems is essential for effective and equitable public health efforts.

Quantifying climate conditions for the formation of coals and evaporites.

Coals and evaporites are commonly used as qualitative indicators of wet and dry environments in deep-time climate studies, respectively. Here, we combine geological records with climate simulations to establish quantitative relationships of coals and evaporites with temperature and precipitation over the Phanerozoic. We show that coal records were associated with a median temperature of 25°C and precipitation of 1300 mm yr-1 before 250 Ma. Afterwards, coal records appeared with temperatures between 0°C and 21°C and precipitation of 900 mm yr-1. Evaporite records were associated with a median temperature of 27°C and precipitation of 800 mm yr-1. The most remarkable result is that net precipitation associated with coal and evaporite records remained constant across time. The results here have important implications for quantifying climate conditions for other lithologic indicators of climate and for predicting exogenetic ore deposits.

Continental drift shifts tropical rainfall by altering radiation and ocean heat transport.

Shifts in the position of the intertropical convergence zone (ITCZ) have great importance for weather, climate, and society. The ITCZ shifts have been extensively studied in current and future warmer climate; however, little is known for its migration in the past on geological time scales. Using an ensemble of climate simulations over the past 540 million years, we show that ITCZ migrations are controlled primarily by continental configuration through two competing pathways: hemispheric radiation asymmetry and cross-equatorial ocean heat transport. The hemispheric asymmetry of absorbed solar radiation is produced mainly by land-ocean albedo contrast, which can be predicted using only the landmass distribution. The cross-equatorial ocean heat transport is strongly associated with the hemispheric asymmetry of surface wind stress, which is, in turn, controlled by the hemispheric asymmetry of ocean surface area. These results allow the influence of continental evolution on global ocean-atmosphere circulations to be understood through simple mechanisms that depend primarily on the latitudinal distribution of land.

COVID-19 Mortality and Progress Toward Vaccinating Older Adults - World Health Organization, Worldwide, 2020-2022.

After the emergence of SARS-CoV-2 in late 2019, transmission expanded globally, and on January 30, 2020, COVID-19 was declared a public health emergency of international concern.* Analysis of the early Wuhan, China outbreak (1), subsequently confirmed by multiple other studies (2,3), found that 80% of deaths occurred among persons aged ≥60 years. In anticipation of the time needed for the global vaccine supply to meet all needs, the World Health Organization (WHO) published the Strategic Advisory Group of Experts on Immunization (SAGE) Values Framework and a roadmap for prioritizing use of COVID-19 vaccines in late 2020 (4,5), followed by a strategy brief to outline urgent actions in October 2021.† WHO described the general principles, objectives, and priorities needed to support country planning of vaccine rollout to minimize severe disease and death. A July 2022 update to the strategy brief§ prioritized vaccination of populations at increased risk, including older adults,¶ with the goal of 100% coverage with a complete COVID-19 vaccination series** for at-risk populations. Using available public data on COVID-19 mortality (reported deaths and model estimates) for 2020 and 2021 and the most recent reported COVID-19 vaccination coverage data from WHO, investigators performed descriptive analyses to examine age-specific mortality and global vaccination rollout among older adults (as defined by each country), stratified by country World Bank income status. Data quality and COVID-19 death reporting frequency varied by data source; however, persons aged ≥60 years accounted for >80% of the overall COVID-19 mortality across all income groups, with upper- and lower-middle-income countries accounting for 80% of the overall estimated excess mortality. Effective COVID-19 vaccines were authorized for use in December 2020, with global supply scaled up sufficiently to meet country needs by late 2021 (6). COVID-19 vaccines are safe and highly effective in reducing severe COVID-19, hospitalizations, and mortality (7,8); nevertheless, country-reported median completed primary series coverage among adults aged ≥60 years only reached 76% by the end of 2022, substantially below the WHO goal, especially in middle- and low-income countries. Increased efforts are needed to increase primary series and booster dose coverage among all older adults as recommended by WHO and national health authorities.

CDC's COVID-19 International Vaccine Implementation and Evaluation Program and Lessons from Earlier Vaccine Introductions.

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.

A high-resolution climate simulation dataset for the past 540 million years.

The Phanerozoic Eon has witnessed considerable changes in the climate system as well as abundant animals and plant life. Therefore, the evolution of the climate system in this Eon is worthy of extensive research. Only by studying climate changes in the past can we understand the driving mechanisms for climate changes in the future and make reliable climate projections. Apart from observational paleoclimate proxy datasets, climate simulations provide an alternative approach to investigate past climate conditions of the Earth, especially for long time span in the deep past. Here we perform 55 snapshot simulations for the past 540 million years, with a 10-million-year interval, using the Community Earth System Model version 1.2.2 (CESM1.2.2). The climate simulation dataset includes global distributions of monthly surface temperatures and precipitation, with a 1° horizontal resolution of 0.9° × 1.25° in latitude and longitude. This open access climate dataset is useful for multidisciplinary research, such as paleoclimate, geology, geochemistry, and paleontology.

[Clinical Characteristic of "triple-negative" Essential Thrombocythaemia Patients and Mutation Analysis by Targeted Sequencing].

BACKGROUND: Essential thrombocythemia is a subgroup of myeloproliferative neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are closely related with the pathogenesis of myeloproliferative neoplasms. All these mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a small proportion of essential thrombocythemia patients does not display such mutations. The pathogenesis of "triple-negative" form of essential thrombocythemia remains unknown. OBJECTIVE: To investigate the clinical characteristics of triple-negative essential thrombocythemia and related mutation genes. METHODS: To identify the mutations associated with triple-negative essential thrombocythemia, next-generation sequencing was used to conduct targeted sequencing of 360 genes in samples from 68 patients. RESULTS: At least one missense mutation was detected in all the patients and all the detected genes. After screening the data, it was observed that 10 genes with the 10 highest mutation were follows: FLT3, SH2B3, ASXL1, ADAMTS1, TET2, TP53, EGFR, CUX1, GATA2, and MPL.When only rare genes (i.e., with a frequency in Asian populations lower than 5%, as estimated by the 1000 Genomes Project) were analyzed, the most frequently mutated genes in the patients were TET2 (33.82%), SH2B3(29.41%), and ASXL1 (23.53%). Our study identified some mutations that did not previously reported. Although all these mutations need further validation, high incidence rates may indicate relevance of the respective mutations to essential thrombocythemia pathogenesis. Some of the detected mutations have been previously reported; these mutations were also found in a large proportion of our subjects. CONCLUSION: whole-exon sequencing can provide a higher level of accuracy for gene mutation analysis and assist in identifying mutations that contribute to illustrate the pathogenesis of essential thrombocythemia.

ASXL1 mutations in Chinese patients with essential thrombocythemia.

Essential thrombocythemia (ET) is characterized by thrombotic and hemorrhagic events. The association of clinical characteristics of Chinese ET patients and additional sex combs like 1 (ASXL1) mutations in these patients has remained to be elucidated. In the present study, 72 newly diagnosed Chinese ET patients were enrolled to determine ASXL1 mutations. Mutations in ASXL1, Janus kinase (JAK)2, calreticulin (CALR) and myeloproliferative leukemia (MPL) genes were detected using Sanger sequencing, and data were statistically analyzed. The frequencies of ASXL1, JAK2 V617F, CALR and MPL W515 mutations in ET patients were 19.4% (14/72), 29.2% (21/72), 31.9% (23/72) and 0% (0/72), respectively. Of note, 28 ET patients (38.9%) were negative for JAK2, CALR and MPL mutations; these patients were classified as triple-negative (TN). The frequency of ASXL1 mutations in patients with JAK2 V617F, CALR and TN mutations was 23.8% (5/21), 21.7% (5/23) and 14.3% (4/28), respectively. ASXL1-mutant patients exhibited significant propensities for thrombotic events compared with the ASXL1 wild-type (wt) cohort (42.9 vs. 12.1%; P=0.021). In addition, JAK2 V617F-mutant patients had a higher mean age compared with CALR-mutant (64.76 vs. 52.96 years; P=0.008) or TN patients (64.76 vs. 51.14 years; P=0.002). Furthermore, more white blood cells in the peripheral blood (PB) were observed in JAK2 V617F-mutant patients compared with those in TN patients (12.40 vs. 8.20×109/l; P=0.02). In addition, CALR-mutant patients exhibited more platelets (PLT) in PB than JAK2 V617F-mutant patients (787.91 vs. 562.17×109/l; P=0.047). TN patients had a significantly lower incidence of clinical symptoms, including dizziness, palpitation and chest congestion compared with CALR- or JAK2 V617F-mutant patients (14.1 vs. 39.1%; P=0.043 and 14.1 vs. 38.1%; P=0.050). No significant difference in progression-free survival was observed between ASXL1-mutant and ASXL1-wt patients (P=0.590). In conclusion, ASXL1-mutant ET patients are prone to experiencing thrombotic events. There was no significant difference in the occurrence of thrombotic events among CARL-mutant, JAK2 V617F-mutant and TN patients. Furthermore, ASXL1-mutant/TN patients exhibited a higher number of PLT than ASXL1/JAK2 V617F-double mutant patients. Therefore, ASXL1 mutations may be a risk factor for the occurrence of thrombotic events in ET patients.

Clinical Characteristic of "triple-negative" Essential Thrombocythaemia Patients and Mutation Analysis by Targeted Sequencing / 中国实验血液学杂志

<p><b>BACKGROUND</b>Essential thrombocythemia is a subgroup of myeloproliferative neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are closely related with the pathogenesis of myeloproliferative neoplasms. All these mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a small proportion of essential thrombocythemia patients does not display such mutations. The pathogenesis of "triple-negative" form of essential thrombocythemia remains unknown.</p><p><b>OBJECTIVE</b>To investigate the clinical characteristics of triple-negative essential thrombocythemia and related mutation genes.</p><p><b>METHODS</b>To identify the mutations associated with triple-negative essential thrombocythemia, next-generation sequencing was used to conduct targeted sequencing of 360 genes in samples from 68 patients.</p><p><b>RESULTS</b>At least one missense mutation was detected in all the patients and all the detected genes. After screening the data, it was observed that 10 genes with the 10 highest mutation were follows: FLT3, SH2B3, ASXL1, ADAMTS1, TET2, TP53, EGFR, CUX1, GATA2, and MPL.When only rare genes (i.e., with a frequency in Asian populations lower than 5%, as estimated by the 1000 Genomes Project) were analyzed, the most frequently mutated genes in the patients were TET2 (33.82%), SH2B3(29.41%), and ASXL1 (23.53%). Our study identified some mutations that did not previously reported. Although all these mutations need further validation, high incidence rates may indicate relevance of the respective mutations to essential thrombocythemia pathogenesis. Some of the detected mutations have been previously reported; these mutations were also found in a large proportion of our subjects.</p><p><b>CONCLUSION</b>whole-exon sequencing can provide a higher level of accuracy for gene mutation analysis and assist in identifying mutations that contribute to illustrate the pathogenesis of essential thrombocythemia.</p>

The value of platelet count in predicting the efficacy of rituximab treatment in adult patients with chronic primary immune thrombocytopenia / 中华血液学杂志

Objective: To investigate the value of platelet count in predicting the efficacy of rituximab treatment in chronic primary immune thrombocytopenia (ITP). Methods: A retrospective study was conducted in 103 chronic ITP patients hospitalized in our medical center between January 2011 and December 2014. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of platelet count in different time points were analyzed for the predictor of treatment response. Optimal cutoff values were established using ROC analysis. Results: A total of 103 patients were included in the study. There were 46 males and 57 females, with a median age of 30 (18-67) years. At day 1, 3 and 7 after the first dose of rituximab, there was no significant difference in platelet counts between the success group (PLT≥50×10(9)/L after treatment) and the failure group (PLT≤50×10(9)/L after treatment) (P>0.05). At day 14 after rituximab treatment (PTD 14), platelet counts became significantly different in the success and failure groups[41(8-384)×10(9)/L vs 23(0-106)×10(9)/L, P=0.003], and remained different thereafter, with increasing significance in the subsequent follow-ups. Patients were divided further using an optimal cut-off platelet count of 50×10(9)/L on PTD 14, PTD 30, and PTD 60, and PPV and NPV values were calculated for predicting eventual success and failure. Conclusion: Response can be predicted by obtaining platelet counts at 14, 30 and 60 days after rituximab treatment. The study proposed a protocol that guides patient monitoring and management planning.

[Clinical Characteristics and Long-Term Outcome of 125 Chinese Young Patients with Essential Thrombocythemia].

OBJECTIVE: To investigate the clinical characteristics and long-term outcome of Chinese young patients (≤40 years) with essential thrombocythemia(ET), and to develop a thrombosis predicting model specific for young patients with ET, so as to provide a new evidence for risk stratification and treatment. METHODS: Medical records of 125 Chinese young patients with newly diagnosed of ET were retrospectively analyzed. RESULTS: The median age at diagnosis was 32 (18-40) years old, with 37 males and 88 females. During follow-up, 18 patients (14.4%) experienced major thrombotic events. JAK2 V617F (HR=8.895, P=0.001), history of thrombosis (HR=8.001, P<0.001) and WBC≥12.0×109/L (HR=5.225, P=0.002) were independent risk factors for thrombosis. The incidence of thrombosis and risk factors in young patients were different from that in general ET population, so a thrombosis predicting model specific for young patients with ET was developed. In this model, JAK2 V617F (score 2), history of thrombosis (score 2) and WBC≥12.0×109/L (score 1) were used to divide the patients into low risk (score 0), intermediate risk (score 1-2) and high risk (score≥3) groups. These 3 groups exhibited significantly different thrombosis-free survival (χ2=32.223, P<0.001). Antiplatelet treatment could prevent the occurrence of thrombosis (HR=0.081, P<0.001), while cytoreductive agents significantly decreased the risk of thrombosis only in intermediate and high risk groups (14.3% vs 36.4%, χ2=4.416, P=0.036). Seven patients (5.6%) evolved to myelofibrosis, and one of them finally progressed in to acute leukemia. The only risk factor for evolution was WBC≥15.0×109/L (χ2=5.434, P=0.020). Neither antiplatelet treatment nor cytoreductive agents could prevent disease progression. CONCLUSION: The incidence of thrombosis and risk factors in young patients with ET are different from that in general ET population. The thrombosis-predicting model specific for young patients with ET is useful for guiding therapeutic decisions.

Clinical Characteristics and Long-Term Outcome of 125 Chinese Young Patients with Essential Thrombocythemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinical characteristics and long-term outcome of Chinese young patients (≤40 years) with essential thrombocythemia(ET), and to develop a thrombosis predicting model specific for young patients with ET, so as to provide a new evidence for risk stratification and treatment.</p><p><b>METHODS</b>Medical records of 125 Chinese young patients with newly diagnosed of ET were retrospectively analyzed.</p><p><b>RESULTS</b>The median age at diagnosis was 32 (18-40) years old, with 37 males and 88 females. During follow-up, 18 patients (14.4%) experienced major thrombotic events. JAK2 V617F (HR=8.895, P=0.001), history of thrombosis (HR=8.001, P<0.001) and WBC≥12.0×10/L (HR=5.225, P=0.002) were independent risk factors for thrombosis. The incidence of thrombosis and risk factors in young patients were different from that in general ET population, so a thrombosis predicting model specific for young patients with ET was developed. In this model, JAK2 V617F (score 2), history of thrombosis (score 2) and WBC≥12.0×10/L (score 1) were used to divide the patients into low risk (score 0), intermediate risk (score 1-2) and high risk (score≥3) groups. These 3 groups exhibited significantly different thrombosis-free survival (χ=32.223, P<0.001). Antiplatelet treatment could prevent the occurrence of thrombosis (HR=0.081, P<0.001), while cytoreductive agents significantly decreased the risk of thrombosis only in intermediate and high risk groups (14.3% vs 36.4%, χ=4.416, P=0.036). Seven patients (5.6%) evolved to myelofibrosis, and one of them finally progressed in to acute leukemia. The only risk factor for evolution was WBC≥15.0×10/L (χ=5.434, P=0.020). Neither antiplatelet treatment nor cytoreductive agents could prevent disease progression.</p><p><b>CONCLUSION</b>The incidence of thrombosis and risk factors in young patients with ET are different from that in general ET population. The thrombosis-predicting model specific for young patients with ET is useful for guiding therapeutic decisions.</p>

PAQR3 controls autophagy by integrating AMPK signaling to enhance ATG14L-associated PI3K activity.

The Beclin1-VPS34 complex is recognized as a central node in regulating autophagy via interacting with diverse molecules such as ATG14L for autophagy initiation and UVRAG for autophagosome maturation. However, the underlying molecular mechanism that coordinates the timely activation of VPS34 complex is poorly understood. Here, we identify that PAQR3 governs the preferential formation and activation of ATG14L-linked VPS34 complex for autophagy initiation via two levels of regulation. Firstly, PAQR3 functions as a scaffold protein that facilitates the formation of ATG14L- but not UVRAG-linked VPS34 complex, leading to elevated capacity of PI(3)P generation ahead of starvation signals. Secondly, AMPK phosphorylates PAQR3 at threonine 32 and switches on PI(3)P production to initiate autophagosome formation swiftly after glucose starvation. Deletion of PAQR3 leads to reduction of exercise-induced autophagy in mice, accompanied by a certain degree of disaggregation of ATG14L-associated VPS34 complex. Together, this study uncovers that PAQR3 can not only enhance the capacity of pro-autophagy class III PI3K due to its scaffold function, but also integrate AMPK signal to activation of ATG14L-linked VPS34 complex upon glucose starvation.

The association between household poverty rates and tuberculosis case notification rates in Cambodia, 2010.

INTRODUCTION: Poverty is a risk factor for tuberculosis (TB); it increases the risk of infection and active disease but limits diagnostic opportunities. The role of poverty in the stagnant case detection in Cambodia is unclear. This study aims to assess the relationship between district household poverty rates and sputum-positive TB case notification rates (CNRs) in Cambodia in 2010. METHODS: Poisson regression models were used to calculate the relative risk of new sputum-positive TB CNR for Operational Districts (ODs) with different poverty rates using data from the National Centre for Tuberculosis and Leprosy Control and the National Committee for SubNational Democratic Development. Models were adjusted for other major covariates and a geographical information system was used to examine the spatial distribution of these covariates in the country. RESULTS: The univariate model showed a positive association between household poverty rates and sputum-positive TB CNRs. However, in multivariate models, after adjusting for major covariates, household poverty rates showed a significantly negative association with sputum-positive TB CNRs (relative risk [RR] = 0.95 per 5% increase in poverty rate). The negative association was stronger among males than females (RR = 0.93 versus 0.96 per 5% increase in poverty rate). Similar spatial patterns were observed between household poverty rates and other covariates, particularly OD population density. CONCLUSION: Household poverty rate is associated with a decrease in sputum-positive TB CNR in Cambodia, particularly in men. The potential of combining surveillance data and socioeconomic variables should be explored further to provide more insights for TB control programme planning.

The association between household poverty rates and tuberculosis case notification rates in Cambodia, 2010

Introduction: Poverty is a risk factor for tuberculosis (TB); it increases the risk of infection and active disease but limits diagnostic opportunities. The role of poverty in the stagnant case detection in Cambodia is unclear. This study aims to assess the relationship between district household poverty rates and sputum-positive TB case notification rates (CNRs) in Cambodia in 2010. Methods: Poisson regression models were used to calculate the relative risk of new sputum-positive TB CNR for Operational Districts (ODs) with different poverty rates using data from the National Centre for Tuberculosis and Leprosy Control and the National Committee for SubNational Democratic Development. Models were adjusted for other major covariates and a geographical information system was used to examine the spatial distribution of these covariates in the country. Results: The univariate model showed a positive association between household poverty rates and sputum-positive TB CNRs. However, in multivariate models, after adjusting for major covariates, household poverty rates showed a significantly negative association with sputum-positive TB CNRs (relative risk [RR] = 0.95 per 5% increase in poverty rate). The negative association was stronger among males than females (RR = 0.93 versus 0.96 per 5% increase in poverty rate). Similar spatial patterns were observed between household poverty rates and other covariates, particularly OD population density. Conclusion: Household poverty rate is associated with a decrease in sputum-positive TB CNR in Cambodia, particularly in men. The potential of combining surveillance data and socioeconomic variables should be explored further to provide more insights for TB control programme planning.