Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

Report on the 3rd Board Meeting of the International Human Phenome Consortium

Introduction The phenome is a set of measurable traits,including the physical,chemical and biological traits of individuals and populations,that result from the complex interactions of genes,epigenetics,symbiotic microorganisms,diet and environmental exposures(Jin 2021).The aim of human phe-nomics is to precisely measure the human phenotypes and to comprehensively analyze the human phenome.In doing so,we can systemically deconstruct the relationship among perceived phenotypes,compile phenotypic network,expand multi-dimensional and cross-scale correlations between macro and micro phenotypes,and eventually clarify the correlations among these phenotypes.After the completion of the Human Genome Project,there is an urgent need for discovering the multi-level association among genes,envi-ronment and phenotypes to complement the other half of the required information for human health.Therefore,Fudan University has initiated the International Human Phenome Project in 2018,providing a new opportunity for biomedical research and leading the development of biomedicine.

Radiomics for the detection of microvascular invasion in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver cancer,accounting for about 90%of liver cancer cases.It is currently the fifth most common cancer in the world and the third leading cause of cancer-related mortality.Moreover,recurrence of HCC is common.Microvascular invasion(MVI)is a major factor associated with recurrence in postoperative HCC.It is difficult to evaluate MVI using traditional imaging modalities.Currently,MVI is assessed primarily through pathological and immunohistochemical analyses of postoperative tissue samples.Needle biopsy is the primary method used to confirm MVI diagnosis before surgery.As the puncture specimens represent just a small part of the tumor,and given the heterogeneity of HCC,biopsy samples may yield false-negative results.Radiomics,an emerging,powerful,and non-invasive tool based on various imaging modalities,such as computed tomography,magnetic resonance imaging,ultrasound,and positron emission tomography,can predict the HCC-MVI status preoperatively by delineating the tumor and/or the regions at a certain distance from the surface of the tumor to extract the image features.Although positive results have been reported for radiomics,its drawbacks have limited its clinical translation.This article reviews the application of radiomics,based on various imaging modalities,in preoperative evaluation of HCC-MVI and explores future research directions that facilitate its clinical translation.

Imaging findings of immunoglobin G4-related hypophysitis:A case report

BACKGROUND Immunoglobin G4(IgG4)-related hypophysitis(IgG4-RH)is a rare form of IgG4-related disease(IgG4-RD),which often manifests as a single organ disease and is easily misdiagnosed as a pituitary tumor clinically and by imaging.There are few reports of imaging findings of IgG4-RH.Therefore,we describe a case of IgG4-RH,which mimicked a pituitary macroadenoma,that was detected by computed tomography(CT)and magnetic resonance imaging(MRI),and review the previous literature in order to further the understanding of IgG4-RH.CASE SUMMARY A 47-year-old man presented with a history of blurred vision for more than 2 mo,without other symptoms.A preoperative unenhanced CT scan revealed a slightly hyperdense mass in the sellar region measuring 2.5 cm×2.3 cm×1.8 cm,with a CT value of 45 HU.T1-weighted imaging(T1WI)and T2-weighted imaging showed iso-hypointensity,and gadolinium contrast-enhanced T1WI showed obvious homogeneous enhancement.The MRI revealed involvement of the pituitary gland and stalk.Preoperative laboratory tests revealed abnormal pituitary hormone levels,including an increased prolactin level,and decreased levels of insulin-like growth factor,dehydroepiandrosterone,and testosterone.The lesion was surgically resected.Postoperative histopathological examination of a tissue sample and an elevated serum IgG4 level confirmed the diagnosis of IgG4-RH.The patient was treated with cortisone acetate postoperatively and made a good recovery without developing any neurological deficit.CONCLUSION An elevated serum IgG4 concentration is the main clue for diagnosis of IgG4-RD.Imaging combined with laboratory testing is useful for preoperative diagnosis of IgG4-RH.

Deep Immunophenotyping of Human Whole Blood by Standardized Multi‑parametric Flow Cytometry Analyses

Immunophenotyping is proving crucial to understanding the role of the immune system in health and disease.High-through-put flow cytometry has been used extensively to reveal changes in immune cell composition and function at the single-cell level.Here,we describe six optimized 11-color flow cytometry panels for deep immunophenotyping of human whole blood.A total of 51 surface antibodies,which are readily available and validated,were selected to identify the key immune cell populations and evaluate their functional state in a single assay.The gating strategies for effective flow cytometry data analysis are included in the protocol.To ensure data reproducibility,we provide detailed procedures in three parts,including(1)instrument characterization and detector gain optimization,(2)antibody titration and sample staining,and(3)data acquisition and quality checks.This standardized approach has been applied to a variety of donors for a better understanding of the complexity of the human immune system.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline:A Community‑Based Cohort Study

Cardiovascular health metrics are now widely recognized as modifable risk factors for cognitive decline and dementia.Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia.Circulating metabolites profling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.In a prospective community-based cohort in China(n=725),312 serum metabolic phenotypes were quantifed,and cardiovascular health score was calculated including smoking,exercise,sleep,diet,body mass index,blood pressure,and blood glucose.Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline.A better cardiovascular health was signifcantly associated with lower risk of concentration decline and orientation decline(hazard ratio(HR):0.84–0.90;p<0.05).Apolipoprotein-A1,high-density lipoprotein(HDL)cholesterol,cholesterol ester,and phospholipid concentrations were signifcantly associated with a lower risk of longitudinal memory and orientation decline(p<0.05 and adjusted-p<0.20).Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and-3(proportion of mediation:7.68–8.21%,both p<0.05).Cardiovascular risk factors were associated with greater risks of cognitive decline,which were found to be mediated by circulating lipoproteins,particularly the medium-size HDL components.These fndings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention.

Draft Genome of White-blotched River Stingray Provides Novel Clues for Niche Adaptation and Skeleton Formation

The white-blotched river stingray(Potamotrygon leopoldi)is a cartilaginous fish native to the Xingu River,a tributary of the Amazon River system.As a rare freshwater-dwelling cartilaginous fish in the Potamotrygonidae family in which no member has the genome sequencing information available,P.leopoldi provides the evolutionary details in fish phylogeny,niche adaptation,and skeleton formation.In this study,we present its draft genome of 4.11 Gb comprising 16,227 contigs and 13,238 scaffolds,with contig N50 of 3937 kb and scaffold N50 of 5675 kb in size.Our analysis shows that P.leopoldi is a slow-evolving fish that diverged from elephant sharks about 96 million years ago.Moreover,two gene families related to the immune system(immunoglobulin heavy constant delta genes and T-cell receptor alpha/delta variable genes)exhibit expansion in P.leopoldi only.We also identified the Hox gene clusters in P.leopoldi and discovered that seven Hox genes shared by five representative fish species are missing in P.leopoldi.The RNA sequencing data from P.leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum when compared to mammals.Our functional studies suggest that lack of the gc gene encoding vitamin D-binding protein in cartilaginous fishes(both P.leopoldi and Callorhinchus milii)could partly explain the absence of hard bone in their endoskeleton.Overall,this genome resource provides new insights into the niche adaptation,body plan,and skeleton formation of P.leopoldi,as well as the genome evolution in cartilaginous fishes.

Identification of Germline Mutations in East‑Asian Young Never‑Smokers with Lung Adenocarcinoma by Whole‑Exome Sequencing

Recently,an increasing number of young never-smokers are diagnosed with lung cancer.The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers.Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40.Whole-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood cells.As a result,3,481 single nucleotide variants were identified.By bioinformatical tools and the published gene list associated with genetic predisposition of cancer,pathogenic variants were detected in ten germline genes:ATR,FANCD2,FANCE,GATA2,HFE,MSH2,PDGFRA,PMS2,SDHB,and WAS.Patients with pathogenic variants were more likely to occur in females(9/10,90.0%)and have stage IV lung adenocarcinoma(4/10,40%).Furthermore,germline muta-tions in 17 genes(ASB18,B3GALT5,CLEC4F,COL6A6,CYP4B1,C6orf132,EXO1,GATA4,HCK,KCP,NPHP4,PIGX,PPIL2,PPP1R3G,RRBP1,SALL4,and TTC28),which occurred in at least two patients,displayed potentially pathogenic effects.Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological processes.The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers,which sheds a light on prevention and early diagnosis of lung cancer.

Welcome to the Phenomics Journal

The term‘phenomics’,first coined by Dr.Steven A.Garan in 1996,describes the measurement of phenomes.The phenome is a set of measurable traits,including the physical,chemical and biological traits of individuals and populations,that result from the complex interactions of genes,epigenetics,symbiotic microorganisms,diet and environmental exposures.The high-throughput approaches implied by the term‘deep phenotyping’have attracted much attention in the fields of functional genomics,pharmaceutical science,biomedical engineering,phylogenetics and disease genomics in humans and model organisms.

Genome assembly and transcriptome analysis provide insights into the antischistosome mechanism of Microtus fortis

Microtus fortis is the only mammalian host that exhibits intrinsic resistance against Schistosoma japonicum infection.However,the underlying molecular mechanisms of this resistance are not yet known.Here,we perform the first de novo genome assembly of M.fortis,comprehensive gene annotation analysis,and evolution analysis.Furthermore,we compare the recovery rate of schistosomes,pathological changes,and liver transcriptomes between M.fortis and mice at different time points after infection.We observe that the time and type of immune response in M.fortis are different from those in mice.M.fortis activates immune and inflammatory responses on the 10th day post infection,such as leukocyte extravasation,antibody activation,Fc-gamma receptor-mediated phagocytosis,and the interferon signaling cascade,which play important roles in preventing the development of schistosomes.In contrast,an intense immune response occurrs in mice at the late stages of infection and could not eliminate schistosomes.Infected mice suffer severe pathological injury and continuous decreases in cell cycle,lipid metabolism,and other functions.Our findings offer new insights into the intrinsic resistance mechanism of M.fortis against schistosome infection.The genome sequence also provides the basis for future studies of other important traits in M.fortis.