Novel detoxifier of spironolactone against triptolide-induced hepatotoxicity through inhibition of RPB1 degradation.

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide. AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings. MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining. RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA. CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.

Crise global da atenção primária à saúde / Global crisis in primary health care / Crisis global de la atención primaria

Enquanto no Norte Global se discute uma crise na Atenção Primária à Saúde, a maioria dos países nunca chegou a constituir sistemas de saúde baseados propriamente numa atenção primária robusta. Nesse cenário, o Brasil apresenta uma tendência mais favorável, com conquistas importantes para a atenção primária e a medicina de família e comunidade nos últimos dez anos. Restam desafios a serem superados para que o Sistema Único de Saúde alcance níveis satisfatórios de acesso a seus serviços, com profissionais adequadamente formados e valorizados pela população.

While the Global North is discussing a crisis in primary health care, the majority of countries have never managed to establish health systems based on robust primary care. Brazil presents a more favorable trend, with important achievements for primary care and family practice over the last ten years. There are still challenges to be overcome so that the Unified Health System achieves satisfactory levels of access to its services, with professionals who are properly trained and valued by the public.

Mientras que en el Norte Global se habla de una crisis de la atención primaria, la mayoría de los países nunca han creado realmente sistemas sanitarios basados en una atención primaria robusta. Brasil, muestra una tendencia más favorable, con importantes logros para la atención primaria y la medicina familiar y comunitaria en los últimos diez años. Aún quedan retos por superar para que el Sistema Único de Salud alcance niveles satisfactorios de acceso a sus servicios, con profesionales debidamente formados y valorados por la población.

Polish translation, cultural adaptation, and validity confirmation of the Scored Patient-Generated Subjective Global Assessment.

PURPOSE: The Scored Patient-Generated Subjective Global Assessment (PG-SGA©) is a validated nutritional screening, assessment, triage, and monitoring tool. The aim of this study was to perform translation, cultural adaptation, linguistic, and content validation of the translated and culturally adapted version of the PG-SGA for the Polish setting. METHODS: The study was performed in concordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles. Patients (n = 174) and healthcare professionals (HCPs, n = 188) participated in the study. Comprehensibility and difficulty were assessed by patients for the PG-SGA Short Form, and by HCPs for the professional component. Content validity was assessed for the full PG-SGA by HCPs only. Evaluations were operationalized by a 4-point scale. Item and scale indices were calculated using the average item ratings divided by the number of respondents. Item indices < 0.78 required further analysis of the item, while scale indices ≥ 0.90 were defined as excellent and 0.80-0.89 as acceptable. RESULTS: The PG-SGA Short Form was rated as excellent for content validity (Scale-CVI = 0.90) by HCPs and easy to comprehend (Scale-CI = 0.96) and use (Scale-DI = 0.94) by patients. The professional component of the PG-SGA was perceived as acceptable for content validity (Scale-CVI = 0.80), comprehension (Scale-CI = 0.87), and difficulty (Scale-DI = 0.80). The physical exam was rated the least comprehensible and the most difficult, and with the lowest content validity. We found significant differences in scale indices (p < 0.05 for all) between HCPs with different professions and between those being familiar with PG-SGA and not. CONCLUSION: Translation and cultural adaptation of the PG-SGA for the Polish setting preserved the purpose and conceptual meaning of the original PG-SGA. Validation revealed that the Polish version of PG-SGA is well understood and easy to complete by patients and professionals, and is considered relevant by professionals. However, detailed results indicate the need for appropriate training of the Polish HCPs, especially physicians and nurses, mainly in the worksheets related to the metabolic demand and physical exam.

The global burden of cardiovascular disease attributable to diet low in fiber among people aged 60 years and older, 1990-2019: an age-period-cohort analysis of the global burden of disease study.

OBJECTIVES: This study aimed to quantify the global cardiovascular disease (CVD) burden attributable to diet low in fiber among adults aged 60 years and older using data from the Global Burden of Disease (GBD) Study 2019. METHODS: We extracted data on CVD mortality, disability-adjusted life-years (DALYs), and risk-factor exposures from the GBD 2019 study for people aged 60 and older. Age-period-cohort models were used to estimate the overall annual percentage change in mortality and DALY rate (net drift, % per year), mortality and DALY rate for each age group from 1990 to 2019 (local drift, % per year), longitudinal age-specific rate corrected for period bias (age effect), and mortality and Daly rate for each age group from 1990 to 2019 (local drift, % per year). And period/cohort relative risk (period/cohort effect). RESULTS: From 1990 to 2019, global age-standardized cardiovascular disease (CVD) mortality rates attributable to low dietary fiber intake decreased by 2.37% per year, while disability-adjusted life years (DALYs) fell by 2.48% annually. Decreases were observed across all sociodemographic index regions, with fastest declines in high and high-middle SDI areas. CVD mortality and DALY rates attributable to low fiber increased exponentially with age, peaking at 85-89 years, and were higher in men than women. Regarding period effects, mortality and DALY rates declined since 2000, reaching nadirs in 2015-2019. For birth cohort patterns, risks attributable to low fiber intake peaked among early 1900s births and subsequently fell, with more pronounced reductions over time in women. CONCLUSIONS: Low dietary fiber intake is a leading contributor to the global cardiovascular disease burden, accounting for substantial mortality and disability specifically among older adults over recent decades.

Burden of metabolic syndrome in the global adult HIV-infected population: a systematic review and meta-analysis.

BACKGROUND: Metabolic syndrome (MetS) elevates the risk of heart disease and stroke. In recent decades, the escalating prevalence of MetS among people living with HIV/AIDS (PLWHA) has garnered global attention. Despite MetS development being associated with both traditional and HIV-related factors, evidence from prior studies has shown variability across geographical regions. This study aimed to conduct a systematic review and meta-analysis of MetS burdens in adult PLWHA at the regional and global levels, focusing on the common effect size of HIV infection and antiretroviral therapy (ART) on MetS. METHODS: This review followed the PRISMA 2020 guidelines. A comprehensive search and review of original articles related to MetS and HIV published in peer-reviewed journals between January 2000 and December 2023 were conducted. A random effects model was used to calculate the pooled prevalence/incidence of MetS and the common effect size of HIV infection and ART exposure on MetS. RESULTS: A total of 102 studies from five continents comprising 78,700 HIV-infected participants were included. The overall pooled prevalence of MetS was 25.3%, 25.6% for PLWHA on ART, and 18.5% for those not receiving treatment. The pooled incidence of MetS, calculated from five studies, was 9.19 per 100 person-years. The highest pooled prevalence of MetS was observed in the Americas (30.4%), followed by the Southeast Asia/Western Pacific regions (26.7%). HIV-infected individuals had 1.6 times greater odds of having MetS than non-HIV-infected individuals did (pooled OR = 1.604; 95% CI 1.154-2.230), and ART exposure had 1.5 times greater odds of having MetS than nontreatment had (pooled OR = 1.504; 95% CI 1.217-1.859). CONCLUSIONS: HIV infection and ART exposure contribute significantly to the increased burden of MetS. Regions with a high burden of HIV and MetS should prioritize awareness and integrated care plans for major noncommunicable diseases (NCDs), such as heart disease and stroke. The implementation of integrated care for HIV/AIDS patients and NCDs is essential for addressing the high burden of multimorbidity in PLWHA. REGISTRATION NUMBER: INPLASY202290018.

Future Directions for Gestational Trophoblastic Disease.

Gestational trophoblastic disease encompasses a spectrum of premalignant and malignant conditions. While centralized care models significantly improve survival rates, many countries still lack such specialized centers, leading to preventable deaths. Current research focuses on refining diagnostic and treatment methods, aiming to better predict the risk of malignancy and reduce the need for aggressive therapies. Immunotherapy has emerged as a promising treatment modality, offering high cure rates with fewer side effects compared to traditional chemotherapy. Global efforts must continue to expand access to specialized care and integrate new therapies to improve outcomes and reduce treatment-related harm.

Comparison of global transcriptomes for nontyphoidal Salmonella clinical isolates from pediatric patients with and without bacteremia after their interaction with human intestinal epithelial cells in vitro.

BACKGROUND: Nontyphoidal Salmonella (NTS) outbreaks of invasive diseases are increasing. Whether the genetic diversity of invasive NTS correlates with the clinical characteristics and bacteremia development in NTS infections remains unclear. In this study, we compared the global transcriptomes between bacteremic and nonbacteremic NTS strains after their interaction with human intestinal epithelial cells in vitro. METHODS: We selected clinical isolates obtained from stool and blood samples of patients with or without bacteremia and patients with high and low C-reactive protein (CRP) levels. The bacterial RNA samples were isolated after coculturing with Caco-2 cells for RNA sequencing and subsequent analyses. RESULTS: CRP is an unreliable predictive maker for NTS bacteremia with a median CRP level of 1.6 mg/dL. Certain Salmonella Pathogenicity Island (SPI)-1 genes (sipC, sipA, sicA, sipD, and sipB), SPI-2 genes (ssaP, ssrA, and ssaS), and six SPI-4 genes (siiA, siiB, siiC, siiD, siiE, and siiF) remained upregulated in the bacteremic blood-derived strains but significantly downregulated in the nonbacteremic strains after their interaction with Caco-2 cells. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis identified that arginine biosynthesis, ascorbate and aldarate metabolism, and phosphotransferase system pathways were activated in bacteremic NTS strains after Caco-2 cell priming. CONCLUSION: CRP levels were not correlated with bacteremia development. Significant regulation of certain SPI genes in bacteremic NTS strains after Caco-2 cell priming; bacteremia development might be influenced by the host immune response and the extent to which specific metabolism pathways in NTS strains can be prevented from invading the bloodstream.

Global-scale water security and desertification management amidst climate change.

Deserts and semi-arid environments are habitats to rare species, rich cultural heritage, and essential ecological processes. Approximately 46% of the world's surface area is covered by drylands (arid, semi-arid, and dry sub-humid areas), where 3 billion people live and unfortunately witness water insecurity and desertification implications. In this context, the present study argued that reduced dryland ecosystem services and decreased ecosystem health have resulted from the individual and compounding impacts of desertification, water scarcity, and climate change. At 1.5 °C, 2 °C, and 3 °C of global warming, under the shared socio-economic pathway SSP2, the number of people living in drylands who will be affected by various effects on water, energy, and land sectors is projected to reach 951 million, 1152 million, and 1285 million, respectively. Due to combinations of land use change, rainfall variations, fire suppression, and CO2 fertilization, as well as unsustainable management, widespread woody encroachment has occurred in many shrublands and savannas in Africa, Australia, North America, and South America. This has altered biodiversity and reduces ecosystem services, such as water availability and grazing potential. The north side of the Mediterranean, southern Africa, and North and South America are projected to have the most semiarid expansion. Contrarily, drylands are expected to shrink in India, northern China, eastern equatorial Africa, and the southern Sahara. Growing research evidence highlights the adoption of policy frameworks deriving the solutions from soil land management (SLM), indigenous and local knowledge (ILK), early warning systems coupled with adaptation and mitigation responses, and targets of sustainable development goals (SDGs).

Value for money of medicine sampling and quality testing: evidence from Indonesia.

BACKGROUND: Substandard and falsified medicines (SFMs) are a public health concern of global importance. Postmarket surveillance in the form of medicine sampling and quality testing can prevent and detect SFM, however, there is remarkably scarce evidence about the cost and value for money of these activities: how much do they cost and how effective are they in detecting SFM? METHODS: Between February and October 2022, Systematic Tracking of At Risk Medicines (STARmeds) collected and analysed for quality 1274 samples of 5 medicines from physical and online retail outlets in 7 Indonesian districts. We collated data on the resources consumed by STARmeds, related to all stages of medicines sampling and quality testing including design, fieldwork and laboratory analysis. We used activity-based costing principles to calculate the financial and economic cost of medicine quality surveillance from the perspective of a hypothetical medicines' regulator. We calculated the cost per day and per week of fieldwork, per sample collected and per substandard sample. We used bootstrapping to capture uncertainty in the number of samples collected, by seller location type (urban, rural and online). RESULTS: The total cost of sampling and testing medicines from the market was US$712 964 (current 2022 values). Laboratory costs represented the largest share (70%), followed by other direct costs (12%) and indirect costs (7%). On average, it costs STARmeds US$479 (95% CI US$462 to US$516) to collect one medicine sample and US$5990 (95% CI US$5601 to US$6258) to identify one substandard sample. CONCLUSION: Our findings bring urgently needed and novel information on the cost and value for money of medicine quality surveillance. These may support planning and budgeting of the Indonesian pharmaceutical regulator, but also of regulators and researchers elsewhere, particularly in low-income and middle-income settings, as well as international organisations with health regulation and quality of care remits.

Rift Valley Fever Epizootic, Rwanda, 2022.

A Rift Valley fever epizootic affected livestock in Rwanda during March-October 2022. We confirmed 3,112 infections with the virus, including 1,342 cases, 1,254 abortions, and 516 deaths among cattle, goats, and sheep. We recommend a One Health strategy for investigations and response to protect animal and human health.

Correlation Between the Prevalence of Myasthenia Gravis and the Frequency of Class II Human Leucocyte Antigen Alleles in Various Geographical Locations Around the World.

Myasthenia gravis (MG) is an autoimmune condition characterised by muscle weakness due to antibodies produced against post-synaptic receptors. The impact of MG can be significant, especially with an ageing population. Human leukocyte antigens (HLA) are polymorphic genes associated with autoimmune conditions. Establishing the HLA alleles associated with MG may aid in the diagnosis, screening and early management of individuals at risk of MG. This research aims to establish the class II HLA alleles associated with the prevalence of MG in various regions of the world and identify the alleles that could predispose to the condition. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart and various databases including, Scopus and PubMed as well as other sources were used to find appropriate papers on HLA class II alleles associated with MG and the prevalence of MG in various countries. The frequency of selected HLA alleles in selected regions were obtained from the website, allelefrequencies.net. From this, a correlation coefficient and p-value were calculated to investigate whether the frequency of MG and the prevalence of HLA alleles had a significant association.  The results highlighted two HLA alleles, DRB1*04:04 and DRB1*03, to have a significant positive association with the prevalence of MG. The frequency of the alleles showed regional variation, with European countries, particularly Northern Europe, exhibiting the highest frequencies. A significant positive correlation between HLA-DRB1*04:04 and DRB1*03 showed with the prevalence of MG, highlighting these alleles as a possible cause of the disease. Screening for these alleles, particularly in Northern Europe, may help identify individuals susceptible to MG.

Strengthening global health resilience: Marburg virus-like particle vaccines and the One Health approach.

The Marburg virus (MARV), belonging to the Filoviridae family, poses a significant global health threat, emphasizing the urgency to develop Marburg virus-like particle (VLP) vaccines for outbreak mitigation. The virus's menacing traits accentuate the need for such vaccines, which can be addressed by VLPs that mimic its structure safely, potentially overcoming past limitations. Early Marburg vaccine endeavors and their challenges are examined in the historical perspectives section, followed by an exploration of VLPs as transformative tools, capable of eliciting immune responses without conventional risks. Noteworthy milestones and achievements in Marburg VLP vaccine development, seen through preclinical and clinical trials, indicate potential cross-protection. Ongoing challenges, encompassing durability, strain diversity, and equitable distribution, are addressed, with proposed innovations like novel adjuvant, mRNA technology, and structure-based design poised to enhance Marburg VLP vaccines. This review highlights the transformative potential of Marburg VLPs in countering the virus, showcasing global collaboration, regulatory roles, and health equity for a safer future through the harmonious interplay of science, regulation, and global efforts.

Temporal trends in cross-country inequalities of stroke and subtypes burden from 1990 to 2021: a secondary analysis of the global burden of disease study 2021.

Background: Stroke remains a significant global health challenge, with persistent disparities in burden across different countries and regions. This study aimed to assess the temporal trends in cross-country inequalities of stroke and its subtypes burden from 1990 to 2021. Methods: We conducted a secondary analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The age-standardised disability-adjusted life years (DALYs) rate (ASDR) was used to assess the burden of stroke and its subtypes (ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage) across 21 GBD regions and 204 countries. The slope index of inequality (SII) and the concentration index were calculated to quantify the absolute and relative cross-country inequalities in the burden of stroke and its subtypes, with negative values indicating a higher burden in lower socio-demographic index (SDI) countries, and positive values indicating a higher burden in higher SDI countries. Estimated annual percentage change (EAPC) was used to illustrate temporal trends at global and regional levels from 1990 to 2021. The inequality changing patterns from 1990 to 2021 were classified as worsening, improving, and shifting to higher burdens among higher or lower SDI countries. Findings: From 1990 to 2021, the ASDR of total stroke decreased from 3078.95 (95% uncertainty interval [UI]: 2893.58, 3237.34) to 1886.20 (95% UI: 1738.99, 2017.90) per 100,000 population globally. While both absolute and relative inequalities increased, with a disproportionately higher burden shouldered by countries with lower SDI. The SII of total stroke exhibited a worsening inequality among lower SDI countries, increasing by 286.97 units from -2329.47 (95% confidence interval [CI]: -2857.50, -1801.43) in 1990 to -2616.44 (95% CI: -2987.33, -2245.56) in 2021. Similarly, the concentration index of total stroke increased by 0.03 from -0.0819 (95% CI: -0.1143, -0.0495) in 1990 to -0.1119 (95% CI: -0.1478, -0.0759) in 2021. The changing patterns from 1990 to 2021 were diverse across regions, yet most regions exhibited a worsening inequality among lower SDI countries in both SII and concentration index. Southern Sub-Saharan Africa showed the largest worsening inequality in SII (EAPC: -2.15, 95% CI: -2.71, -1.57) while Central Europe showed the largest worsening inequality in concentration index (EAPC: -0.51, 95% CI: -0.58, -0.44). In 2021, the highest negative SII was observed in Oceania and the highest negative concentration index was in the Caribbean. In terms of subtypes, ischemic stroke reported a worsening inequality among lower SDI countries in SII (EAPC: -2.13, 95% CI: -2.20, -2.05) while intracerebral haemorrhage showed an improving inequality in SII (EAPC: 0.44, 95% CI: 0.40, 0.47). SII in subarachnoid haemorrhage (EAPC: -0.18, 95% CI: -0.19, -0.17) and concentration index in ischemic stroke (EAPC: -0.25, 95% CI: -0.27, -0.23) presented a shift to higher burden among lower SDI countries from 1990 to 2021. Interpretation: Although the burden of stroke and its subtypes decreased from 1990 to 2021, inequalities have persisted and even widened in some regions. Timely and effective prevention and management strategies for stroke and its subtypes are needed in specific areas to reduce the stroke burden and achieve equity in health outcomes. Funding: None.

Mobile Critical Care in Resource-Limited Settings: An Unmet Need.

Care of the critically ill in resource-limited areas, inside or outside the intensive care unit (ICU), is indispensable. Murthy and Adhikari noted that about 70% of patients in low-middle income (LMIC) areas could benefit from good critical care. Many patients in resource-limited settings still die before getting to the hospital. Investing in capacity building by strengthening and expanding ICU capability and training intensivists, critical care nurses, respiratory therapists, and other ICU staff is essential, but this process will take years. Also, having advanced healthcare facilities that are still far from remote areas will not do much to alleviate distance and mode of transportation as barriers to achieving good critical care. This paper discusses the importance of mobile critical care units (MCCUs) in supporting and enhancing existing emergency medical systems. MCCUs will be crucial in addressing critical delays in transportation and time to receive appropriate lifesaving critical care in remote areas. They are incredibly versatile and could be used to transfer severely ill patients to a higher level of care from the field, safely transfer critically ill patients between hospitals, and, sometimes, almost more importantly, provide standalone short-term critical care in regions where ICUs might be absent or immediately inaccessible. MCCUs should not be used as a substitute for primary care or to bypass readily available services at local healthcare centers. It is essential to rethink the traditional paradigm of 'prehospital care' and 'hospital care' and focus on improving the care of critically ill patients from the field to the hospital.

Catastrophic floods and antimicrobial resistance: Interconnected threats with wide-ranging impacts.

•Climate change and AMR combined worsen vulnerabilities, accelerating AMR spread.•Floods can spread AMR-related pathogens, impacting health, agriculture, and ecosystems.•Integrated strategies are needed to address climate change and AMR, enhancing sanitation.

Long-Term Outcomes Following Inguinal Hernia Repair With Mesh Performed by Medical Doctors and Surgeons in Ghana.

Objective: To assess long-term outcomes following inguinal hernia repair with mesh performed by medical doctors and surgeons in Ghana. Background: Task sharing of surgical care with nonsurgeons can increase access to essential surgery. Long-term safety and outcomes of task sharing are not well-described for hernia repair. Methods: This prospective cohort study was conducted in Ho, Ghana. After completing a training course, 3 medical doctors and 2 surgeons performed inguinal hernia repairs with mesh on men with primary, reducible hernias. The primary outcome of this study was hernia recurrence at 5 years. The noninferiority limit was 5 percentage points. Secondary endpoints included pain and self-assessed health status at 5 years. Results: A total of 242 operations in 241 participants were included, including 119 hernia repairs performed by the medical doctors and 123 performed by the surgeons. One hundred and sixty-nine participants (70.1%) were seen in follow-up at 5 years, 29 participants (12.0%) had died and 43 (17.8%) were lost to follow-up. The overall 5-year recurrence rate was 4.7% (n = 8). The absolute difference in recurrence rate between the medical doctor group (2 [2.3%]) and the surgeon group (6 [7.3%]) was -5.0 (1-tailed 95% confidence interval, -10.5; P = 0.06), demonstrating noninferiority of the medical doctors. Participants experienced improvements in groin pain and self-assessed health status that persisted at 5 years. Conclusions: Long-term outcomes of elective mesh inguinal hernia repair in men performed by medical doctors and surgeons in Ghana were excellent. Task sharing is a critical tool to address the substantial morbidity of unmet hernia surgery needs in Ghana.

Global and local feature extraction based on convolutional neural network residual learning for MR image denoising.

OBJECTIVE: Given the different noise distribution information of global and local magnetic resonance (MR) images, this study aims to extend the current work on convolutional neural networks that preserve global structure and local details in MR image denoising tasks. APPROACH: This study proposed a parallel and serial network for denoising 3D MR images, called 3D-PSNet. We use the residual depthwise separable convolution block to learn the local information of the feature map, reduce the network parameters, and thus improve the training speed and parameter efficiency. In addition, we consider the feature extraction of the global image and utilize residual dilated convolution to process the feature map to expand the receptive field of the network and avoid the loss of global information. Finally, we combine both of them to form a parallel network. What's more, we integrate reinforced residual convolution blocks with dense connections to form serial network branches, which can remove redundant information and refine features to further obtain accurate noise information. The peak signal-to-noise ratio, structural similarity index measure, and root mean square error metrics of 3D-PSNet are as high as 47.79%, 99.81%, and 0.40%, respectively, achieving competitive denoising effect on three public datasets. The ablation experiments demonstrated the effectiveness of all the designed modules regarding all the evaluated metrics in both datasets. SIGNIFICANCE: The proposed 3D-PSNet takes advantage of multi-scale receptive fields, local feature extraction and residual dense connections to more effectively restore the global structure and local fine features in MR images, and is expected to help doctors quickly and accurately diagnose patients' conditions.

Spatiotemporal trends in the burden of colorectal cancer incidence and risk factors at country level from 1990 to 2019.

BACKGROUND AND AIM: Worldwide, the incidence of colorectal cancer (CRC) continues to rise and remains a major public health concern. This study aimed to analyze the temporal and spatial trends in CRC incidence and related risk factors at the country level. METHODS: Data on CRC and related risk factors were obtained from the Global Burden of Disease Study (GBD) 2019 study. Temporal trends were evaluated using estimated annual percentage change while spatial trends were analyzed using spatial autocorrelation and autoregression. Additionally, linear mixed-effects models were employed to identify risk factors linked to CRC incidence. RESULTS: Globally, from 1990 to 2019, the incidence cases of CRC increased by 157.23%. At the national level, the incidence of CRC increased in most countries, with the highest increases of age-standardized incidence rate (ASIR) in Equatorial Guinea, Vietnam, and China. In both 1990 and 2019, global spatial clustering of CRC ASIR highlighted hotspots in Europe, characterized by elevated CRC ASIR levels. A comparative analysis of risk factors between hotspot countries and others indicated that gender and alcohol use exerted greater influence in hotspots than elsewhere. CONCLUSION: Although from 1990 to 2019, the highest growth in ASIR of CRC has been observed in African, Asian, and Latin American countries, the hotspots are still concentrated in Europe. In the identified hotspots, gender and alcohol use exert a more significant impact on CRC incidence compared with other countries. Thus, we should pay attention to countries where the CRC incidence is increasing and these risk factors.