Estimating the burden and modeling mitigation strategies of pork-related hepatitis E virus foodborne transmission in representative European countries

Hepatitis E virus (HEV) is an emerging zoonotic pathogen posing global health burden, and the concerns in Europe are tremendously growing. Pigs serve as a main reservoir, contributing to pork-related foodborne transmission. In this study, we aim to specifically simulate this foodborne transmission route and to assess potential interventions. We firstly established a dose-response relationship between the risk of transmission to human and the amount of ingested viruses. We further estimated the incidence of HEV infection specifically attributed to pork-related foodborne transmission in four representative European countries. Finally, we demonstrated a proof-of-concept of mitigating HEV transmission by implementing vaccination in human and pig populations. Our modeling approach bears essential implications for better understanding the transmission of pork-related foodborne HEV and for developing mitigation strategies

Low-SNR Infrared Point Target Detection and Tracking via Saliency-Guided Double-Stage Particle Filter

Low signal-to-noise ratio (SNR) infrared point target detection and tracking is crucial to study regarding infrared remote sensing. In the low-SNR images, the intensive noise will submerge targets. In this letter, a saliency-guided double-stage particle filter (SGDS-PF) formed by the searching particle filter (PF) and tracking PF is proposed to detect and track targets. Before the searching PF, to suppress noise and enhance targets, the single-frame and multi-frame target accumulation methods are introduced. Besides, the likelihood estimation filter and image block segmentation are proposed to extract the likelihood saliency and obtain proper proposal density. Guided by this proposal density, the searching PF detects potential targets efficiently. Then, with the result of the searching PF, the tracking PF is adopted to track and confirm the potential targets. Finally, the path of the real targets will be output. Compared with the existing methods, the SGDS-PF optimizes the proposal density for low-SNR images. Using a few accurate particles, the searching PF detects potential targets quickly and accurately. In addition, initialized by the searching PF, the tracking PF can keep tracking targets using very few particles even under intensive noise. Furthermore, the parameters have been selected appropriately through experiments. Extensive experimental results show that the SGDS-PF has an outstanding performance in tracking precision, tracking reliability, and time consumption. The SGDS-PF outperforms the other advanced methods

A homozygous EVC mutation in a prenatal fetus with Ellis–van Creveld syndrome

Abstract Background Ellis–van Creveld (EvC) syndrome, caused by variants in EVC, is a rare genetic skeletal dysplasia. Its clinical phenotype is highly diverse. EvC syndrome is rarely reported in prenatal stages because its presentation overlaps with other diseases. Methods A Chinese pedigree diagnosed with EvC syndrome was enrolled in this study. Whole‐exome sequencing (WES) was applied in the proband to screen potential genetic variant(s), and then Sanger sequencing was used to identify the variant in family members. Minigene experiments were applied. Results WES identified a homozygous variant (NM_153717.3:c.153_174 + 42del) in EVC which was inherited from the heterozygous parents and confirmed by Sanger sequencing. Further experiments demonstrated that this variant disrupts the canonical splicing site and produces a new splicing site at NM_153717.3: c.‐164_174del, which ultimately leads to a 337 bp deletion at the 3′ end of exon 1 and loss of the start codon. Conclusion This is the first reported case of EvC syndrome based on a splicing variant and detailed delineation of the aberrant splicing effect in the fetus. Our study demonstrates the pathogenesis of this new variant, expands the spectrum of EVC mutations, and demonstrates that WES is a powerful tool in the clinical diagnosis of diseases with genetic heterogeneity

Wind-blown dust and its impacts on particulate matter pollution in Northern China : current and future scenarios

Northern China experienced two intense dust storms in March 2021, leading to reduced visibility and excessive particulate pollution. Understanding the cause of such extreme phenomena is important for further prevention. This study successfully reproduced the extreme dust storms using the Community Multiscale Air Quality model with refined bulk density of different soil types and improved spatial resolution. The wind-blown PM2.5 and PM10 are estimated to be around 15 and 120 mu g m(-3) in dust source areas (equal 9.6% and 31.0% in average of China), resulting in 1.1 and 2.0 times increases in PM2.5 and PM10 concentrations in populated regions of the Middle Yellow River Basin and the Beijing-Tianjin-Hebei area. The critical threshold friction velocity is the key parameter to judge whether wind-blown dust occurs. Dust flux is sensitive to the bulk soil density (increased by 4.2% and 12.6% for PM2.5 and PM10 after refined soil bulk density) and resolution (increased by 13.5% and 3.5% for PM2.5 and PM10 from 27 km to 9 km). Such results demonstrated the strong correlation between wind speed, frequency, and intensity of dust phenomena from 2013 to 2021. The wind speed can be further enhanced in dust source areas even in the context of a decline in the national average, leading to more frequent and persistent dust storms in March 2050. Only relying on coordinated emission reductions to mitigate climate change, wind-blown dust in northern China still poses considerable potential risks to air quality. Urgent actions should also be taken to improve land-use and land-cover to reduce the area of dust sources.Non peer reviewe

Long non-coding RNA polymorphisms on 8q24 are associated with the prognosis of gastric cancer in a Chinese population

Background Gastric cancer (GC) remains the third leading cause of cancer death in China. Although genome-wide association studies have identified the association between several single nucleotide polymorphisms (SNPs) on 8q24 and the risk of GC, the role of these SNPs in the prognosis of GC in Chinese populations has not yet been fully evaluated. Therefore, this study was conducted to explore the association between long non-coding RNA (lncRNA) polymorphisms on 8q24 and the prognosis of GC. Methods We genotyped 726 surgically resected GC patients to explore the association between eight SNPs in the lncRNAs CCAT1 (rs10087719, rs7816475), PCAT1 (rs1026411), PRNCR1 (rs12682421, rs13252298), and CASC8 (rs1562430, rs4871789, rs6983267) transcribed from the 8q24 locus and the prognosis of GC in a Chinese population. Results We found that the patients carrying rs12682421 AA genotypes survived for a shorter time than those with the GG/GA genotype (HR = 1.39, 95% confidence interval (CI) [1.09–1.78]). Compared with the CC/CT genotype, the TT genotype of rs1562430 was associated with an increased risk of death (HR = 1.38, 95% CI [1.06–1.80]). Furthermore, the results also identified the rs1026411 SNP as an independent prognostic factor for poor survival in GC patients. Patients carrying AA/AG variant genotypes had a 36% increased risk of death compared to those carrying the GG genotype (HR = 1.36, 95% CI [1.06–1.74]). These findings suggested that the rs12682421, rs1026411 and rs1562430 SNPs may contribute to the survival of GC and be prognostic markers for GC

Prognostic Value of Systemic Immune-Inflammation Index among Critically Ill Patients with Acute Kidney Injury: A Retrospective Cohort Study

Inflammation plays a significant role in the occurrence and development of acute kidney injury (AKI). Evidence regarding the prognostic effect of the systemic immune-inflammation index (SII) in critically ill patients with AKI is scarce. The aim of this study was to assess the association between SII and all-cause mortality in these patients. Detailed clinical data were extracted from the Medical Information Mart for Intensive Care Database (MIMIC)-IV. The primary outcome was set as the in-hospital mortality. A total of 10,764 AKI patients were enrolled in this study. The restricted cubic splines analyses showed a J-shaped curve between SII and the risk of in-hospital and ICU mortality. After adjusting for relevant confounders, multivariate Cox regression analysis showed that both lower and higher SII levels were associated with an elevated risk of in-hospital all-cause mortality. A similar trend was observed for ICU mortality. In summary, we found that the SII was associated in a J-shaped pattern with all-cause mortality among critically ill patients with AKI. SII appears to be have potential applications in the clinical setting as a novel and easily accessible biomarker for predicting the prognosis of AKI patients

A novel truncated variant in SPAST results in spastin accumulation and defects in microtubule dynamics

Abstract Objective Haploinsufficiency is widely accepted as the pathogenic mechanism of hereditary spastic paraplegias type 4 (SPG4). However, there are some cases that cannot be explained by reduced function of the spastin protein encoded by SPAST. The aim of this study was to identify the causative variant of SPG4 in a large Chinese family and explore its pathological mechanism. Materials and methods A five-generation family with 49 members including nine affected (4 males and 5 females) and 40 unaffected individuals in Mongolian nationality was recruited. Whole exome sequencing was employed to investigate the genetic etiology. Western blotting and immunofluorescence were used to analyze the effects of the mutant proteins in vitro. Results A novel frameshift variant NM_014946.4: c.483_484delinsC (p.Val162Leufs*2) was identified in SPAST from a pedigree with SPG4. The variant segregated with the disease in the family and thus determined as the disease-causing variant. The c.483_484delinsC variant produced two truncated mutants (mutant M1 and M87 isoforms). They accumulated to a higher level and presented increased stability than their wild-type counterparts and may lost the microtubule severing activity. Conclusion SPAST mutations leading to premature stop codons do not always act through haploinsufficiency. The potential toxicity to the corticospinal tract caused by the intracellular accumulation of truncated spastin should be considered as the pathological mechanism of SPG4

Microsatellite instability and Epstein-Barr virus combined with PD-L1 could serve as a potential strategy for predicting the prognosis and efficacy of postoperative chemotherapy in gastric cancer

Background Microsatellite instability (MSI) and Epstein-Barr virus (EBV)-positive molecular subtypes exhibit complex immune responses in gastric cancer (GC), and PD-L1 has emerged as a prognostic biomarker associated with the cancer immune microenvironment. This study aimed to determine the prognostic value of molecular subtypes and whether the addition of PD-L1 would accurately predict the prognosis and guide postoperative chemotherapy for GC patients. Methods We performed molecular subtyping of tissue microarray slides from 226 GC patients who were treated with radical gastrectomy. The MSI status and PD-L1 expression were evaluated through immunohistochemistry (IHC) and EBV status through situ hybridization. Multiplex polymerase chain reaction (PCR) was also performed on 50 cases to validate the accuracy of IHC in defining MSI status. Differences in overall survival (OS) were assessed using the Kaplan-Meier method, log-rank test and Cox proportional hazards regression model. Results Among the 226 GC patients, 52 (23.2%) patients were classified as the MSI subtype, 11 (4.9%) were EBV+ subtype, and 161 (71.9%) were MSS (Microsatellite stable) /EBV− subtype according to TCGA analysis. Two patients were both positive for MSI and EBV infection. EBV+ cases showed higher PD-L1 positivity than MSI cases and MSS/EBV− cases (81.8% vs. 50.0% vs. 35.4%, P = 0.003). Compared with the non-MSS/EBV− (MSI or EBV+ cases) subgroup, GC patients with MSS/EBV− were associated with the worst outcomes (HR = 1.610, 95% CI [1.046–2.479], P = 0.031). MSS/EBV− GCs alone could benefit from postoperative chemotherapy (HR = 0.452, 95% CI [0.299–0.682], P < 0.001), and PD-L1-positive expression could also predict a better prognosis (HR = 0.612, 95% CI [0.389–0.962], P = 0.033) in this subgroup. Considering both chemotherapy efficacy and PD-L1 expression in the MSS/EBV− subgroup, chemotherapy could improve the prognosis for PD-L1-negative MSS/EBV− GCs (HR = 0.357, 95% CI [0.217–0.587], P < 0.001) but not PD-L1-positive MSS/EBV− GCs. Conclusions Molecular subtyping combined with PD-L1 expression could serve as a potential strategy to better predict prognosis and guide postoperative chemotherapy of GC patients