We offer a new approach to deal with the pointwise convergence of FourierLaplace series on the unit sphere of even-dimensional Euclidean spaces. By using spherical monogenics defined through the generalized Cauchy-Rie...We offer a new approach to deal with the pointwise convergence of FourierLaplace series on the unit sphere of even-dimensional Euclidean spaces. By using spherical monogenics defined through the generalized Cauchy-Riemann operator, we obtain the spherical monogenic expansions of square integrable functions on the unit sphere. Based on the generalization of Fueter＇s theorem inducing monogenic functions from holomorphic functions in the complex plane and the classical Carleson＇s theorem, a pointwise convergence theorem on the new expansion is proved. The result is a generalization of Carleson＇s theorem to the higher dimensional Euclidean spaces. The approach is simpler than those by using special functions, which may have the advantage to induce the singular integral approach for pointwise convergence problems on the spheres.展开更多
New higher-dimensional distributions have been introduced in the framework of Clifford analysis in previous papers by Brackx, Delanghe and Sommen. Those distributions were defined using spherical co-ordinates, the ＂f...New higher-dimensional distributions have been introduced in the framework of Clifford analysis in previous papers by Brackx, Delanghe and Sommen. Those distributions were defined using spherical co-ordinates, the ＂finite part＂ distribution Fp x＋^μ on the real line and the generalized spherical means involving vector-valued spherical monogenics. In this paper, we make a second generalization, leading to new families of distributions, based on the generalized spherical means involving a multivector-valued spherical monogenic. At the same time, as a result of our attempt at keeping the paper self-contained, it offers an overview of the results found so far.展开更多
Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to spe...Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.展开更多
With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuab...With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuable for developmental biology studies and preclinical therapeutic validation.Its rapid life cycle,optical transparency,and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses.Utilizing zebrafish models,researchers have elucidated fundamental mechanisms governing islet development,β-cell dysfunction,and metabolic dysregulation.These experimental systems have significantly advanced our understanding of various diabetes subtypes,including type 1,type 2,gestational,and monogenic forms,while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy.Recent model refinements,particularly in simulating monogenic disorders and pregnancy-associated metabolic changes,promise to deepen our comprehension of disease pathophysiology and therapeutic interventions.Nevertheless,a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions,factors that may influence translational applicability.Despite these constraints,zebrafish-based research continues to provide an indispensable platform for diabetes investigation,holding significant promise for alleviating the escalating global burden of this metabolic disorder.展开更多
BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its ...BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.展开更多
BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the...BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the causative genes of this disorder.CASE SUMMARY A 30-year-old woman presented with irregular black pigmentation spots to our department.Upon examination,the pigmentations were found to be especially dense on the extremities and the face.She had no family history of inbreeding,nor any previous chemical exposure.Genetic testing confirmed that the disease occu-rred because the patient has a SASH1 gene mutation.Following the use of assisted reproductive technology and preimplantation genetic testing for monogenic disorders,the patient give birth to a health baby.CONCLUSION Using assisted reproductive technology/preimplantation genetic testing for monogenic disorders is an option for DUH patients to reduce the risk of trans-mitting the pathogenic variant to their offspring.展开更多
Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease result...Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease resulting from pa-thogenic mutations causing impairment in the protective mechanism of the GIT.Around 10%-15%of patients with very early onset IBDs may have an underlying monogenic condition.Monogenic IBD is very different from complex forms of polygenic IBD in the underlying molecular basis of uncontrolled intestinal inflam-mation,age of onset,extraintestinal comorbidities as well as treatment modality.An in-depth understanding of this distinct form of IBD is essential for deciding an appropriate therapeutic approach as well as prognostication.In this review,we aim to discuss about the epidemiology,clinical presentation,diagnostic approach,therapeutic challenges and latest advances in patients with monogenic IBD.展开更多
Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases,...Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.展开更多
Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early det...Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.展开更多
Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of mon...Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The disease spectrum encompasses maturity-onset diabetes of the young(MODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDM)-a heterogeneous group of severe hyperglycemic disorders in infants.Mitochondrial diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of diabetes.The clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.展开更多
Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 46...Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.展开更多
AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHO...AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHODS A retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing. RESULTS A total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn's disease(CD) or CDlike intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients(16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo(interquartile range(IQR): 4 to 78) and 43.5 mo(IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group(P = 0.001). However, there were no significant differences between weight-forage and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency. CONCLUSION A high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.展开更多
Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis bu...Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.展开更多
Appealing to the Clifford analysis and matching pursuits, we study the adaptive decompositions of functions of several variables of finite energy under the dictionaries consisting of shifted Cauchy kernels. This is a ...Appealing to the Clifford analysis and matching pursuits, we study the adaptive decompositions of functions of several variables of finite energy under the dictionaries consisting of shifted Cauchy kernels. This is a realization of matching pursuits among shifted Cauchy kernels in higher-dimensional spaces. It offers a method to process signals in arbitrary dimensions.展开更多
Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early d...Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.展开更多
Monogenic lines,which carried 23 genes for blast resistance were tested and used donors to transfer resistance genes by crossing method.The results under blast nursery revealed that 9 genes from 23 genes were suscepti...Monogenic lines,which carried 23 genes for blast resistance were tested and used donors to transfer resistance genes by crossing method.The results under blast nursery revealed that 9 genes from 23 genes were susceptible to highly susceptible under the three locations(Sakha,Gemmeza,and Zarzoura in Egypt);Pia,Pik,Pik-p,Piz-t,Pita,Pi b,Pi,Pi 19 and Pi 20.While,the genes Pii,Pik-s,Pik-h,Pi z,Piz-5,Pi sh,Pi 3,Pi 1,Pi 5,Pi 7,Pi 9,Pi 12,Pikm and Pita-2 were highly resistant at the same locations.Clustering analysis confirmed the results,which divided into two groups;the first one included all the susceptible genes,while the second one included the resistance genes.In the greenhouse test,the reaction pattern of five races produced 100%resistance under artificial inoculation with eight genes showing complete resistance to all isolates.The completely resistant genes:Pii,Pik-s,Piz,Piz-5(=bi2)(t),Pita(=Pi4)(t),Pita,Pi b and Pi1 as well as clustering analysis confirmed the results.In the F1 crosses,the results showed all the 25 crosses were resistant for leaf blast disease under field conditions.While,the results in F2 population showed seven crosses with segregation ratio of 15(R):1(S),two cross gave segregated ratio of 3 R:1 S and one gave 13:3.For the identification of blast resistance genes in the parental lines,the marker K3959,linked to Pik-s gene and the variety IRBLKS-F5 carry this gene,which was from the monogenic line.The results showed that four genotypes;Sakha 105,Sakha 103,Sakha 106 and IRBLKS-F5 were carrying Pik-s gene,while was absent in the Sakha 101,Sakha 104,IRBL5-M,IRBL9-W,IRBLTACP1 and IRBL9-W(R)genotypes.As for Pi 5 gene,the results showed that it was present in Sakha 103 and Sakha 104 varieties and absent in the rest of the genotypes.In addition,Pita-Pita-2 gene was found in the three Egyptian genotypes(Sakha 105,Sakha 101 and Sakha 104)plus IRBLTACP1 monogenetic.In F2 generation,six populations were used to study the inheritance of blast resistance and specific primers to confirm the ratio and identify the resistance genes.However,the ratios in molecular markers were the same of the ratio under field evaluation in the most population studies.These findings would facilitate in breeding programs for gene pyramiding and gene accumulation to produce durable resistance for blast using those genotypes.展开更多
Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses ...Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses to optimise glycaemic control.Most clinical guidelines on the management of diabetes mellitus(DM)provide only broad principles on diabetes care,and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently.Therefore,a proper understanding of the pathobiology,clinical situation,and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care.With the aid of five unique cases of DM[(1)Medically managed type 2 diabetes mellitus(T2DM)with severe obesity;(2)Management of T2DM with unreliable glycated haemoglobin(HbA1c);(3)Obesity in a patient with type 1 diabetes mellitus(T1DM);and(4)Late diagnosis and subsequent management of monogenic diabetes and 5.Sudden worsening of well-controlled T2DM)]we elaborate on the importance of individualised diabetes care and the practicalities in these situations.The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.展开更多
Previous studies have documented the occurrence of glyphosate-resistant （GR） goosegrass （Eleusine indica （L.） Gaertn.） and, in at least some cases, resistance is due to an altered target site. Research was perfo...Previous studies have documented the occurrence of glyphosate-resistant （GR） goosegrass （Eleusine indica （L.） Gaertn.） and, in at least some cases, resistance is due to an altered target site. Research was performed to determine if an altered target site was responsible for GR in a Tennessee, United States goosegrass population （TennGR）. DNA sequencing revealed a mutation in TennGR plants conferring the Prol06Ser 5-enolpyruvylshikimate-3-phosphate synthase （EPSPS） substitution previously identified in other GR populations. F2 populations were derived from TennGR plants crossed with plants from a glyphosate-susceptible population （TennGS） and analyzed for their response to glyphosate and genotyped at the EPSPS locus. Plants from the F2 populations segregated 1：2：1 sensitive：intermediate：resistant in response to a selec- tive dose of glyphosate, and these responses co-segregated with the EPSPS genotypes （PP106, PS106, and SS106）. To separately investigate the effect of the Prol06Ser substitution on GR, glyphosate dose-response curves and 50% effective dose （EDso） values were compared among the three genotypes and the two parental populations. The SS106 genotype was 3.4-fold resistant relative to the PP106 genotype, identical to the resistance level obtained when comparing the resistant and susceptible parental populations. We conclude that the mutation conferring a Prol06Ser EPSPS mutation is solely responsible for GR in the TennGR goosegrass population.展开更多
Left ventricular(LV)dysfunction is mainly assessed by global contractile indices such as ejection fraction and LV Volumes in cardiac MRI.While these indices give information about the presence or not of LV alteration,...Left ventricular(LV)dysfunction is mainly assessed by global contractile indices such as ejection fraction and LV Volumes in cardiac MRI.While these indices give information about the presence or not of LV alteration,they are not able to identify the location and the size of such alteration.The aim of this study is to compare the performance of three parametric imaging techniques used in cardiac MRI for the regional quantification of cardiac dysfunction.The proposed approaches were evaluated on 20 patients with myocardial infarction and 20 subjects with normal function.Three parametric images approaches:covariance analysis,parametric images based on Hilbert transform and those based on the monogenic signal were evaluated using cine-MRI frames acquired in three planes of views.The results show that parametric images generated from the monogenic signal were superior in term of sensitivity(89.69%),specificity(86.51%)and accuracy(89.06%)to those based on covariance analysis and Hilbert transform in the detection of contractile dysfunction related to myocardial infarction.Therefore,the parametric image based on the monogenic signal is likely to provide additional regional indices about LV dysfunction and it may be used in clinical practice as a tool for the analysis of the myocardial alterations.展开更多
基金Sponsored by Research Grant of the University of Macao No. RG024/03-04S/QT/FST
文摘We offer a new approach to deal with the pointwise convergence of FourierLaplace series on the unit sphere of even-dimensional Euclidean spaces. By using spherical monogenics defined through the generalized Cauchy-Riemann operator, we obtain the spherical monogenic expansions of square integrable functions on the unit sphere. Based on the generalization of Fueter＇s theorem inducing monogenic functions from holomorphic functions in the complex plane and the classical Carleson＇s theorem, a pointwise convergence theorem on the new expansion is proved. The result is a generalization of Carleson＇s theorem to the higher dimensional Euclidean spaces. The approach is simpler than those by using special functions, which may have the advantage to induce the singular integral approach for pointwise convergence problems on the spheres.
文摘New higher-dimensional distributions have been introduced in the framework of Clifford analysis in previous papers by Brackx, Delanghe and Sommen. Those distributions were defined using spherical co-ordinates, the ＂finite part＂ distribution Fp x＋^μ on the real line and the generalized spherical means involving vector-valued spherical monogenics. In this paper, we make a second generalization, leading to new families of distributions, based on the generalized spherical means involving a multivector-valued spherical monogenic. At the same time, as a result of our attempt at keeping the paper self-contained, it offers an overview of the results found so far.
文摘Monogenic diabetes is a heterogeneous disorder characterized by hyperglycemia arising from defects in a single gene.Maturity-onset diabetes of the young(MODY)is the most common type with 14 subtypes,each linked to specific mutations affecting insulin synthesis,secretion and glucose regulation.Common traits across MODY subtypes include early-onset diabetes,a family history of autosomal dominant diabetes,lack of features of insulin resistance,and absent islet cell autoimmunity.Many cases are misdiagnosed as type 1 and type 2 diabetes mellitus.Biomarkers and scoring systems can help identify candidates for genetic testing.GCK-MODY,a common subtype,manifests as mild hyperglycemia and doesn’t require treatment except during pregnancy.In contrast,mutations in HNF4A,HNF1A,and HNF1B genes lead to progressive beta-cell failure and similar risks of complications as type 2 diabetes mellitus.Neonatal diabetes mellitus(NDM)is a rare form of monogenic diabetes that usually presents within the first six months.Half of the cases are lifelong,while others experience transient remission.Permanent NDM is most commonly due to activating mutations in genes encoding the adenosine triphosphate-sensitive potassium channel(KCNJ11 or ABCC8)and can be transitioned to sulfonylurea after confirmation of diagnosis.Thus,in many cases,monogenic diabetes offers an opportunity to provide precision treatment.The scope has broadened with next-generation sequencing(NGS)technologies,replacing older methods like Sanger sequencing.NGS can be for targeted gene panels,whole-exome sequencing(WES),or whole-genome sequencing.Targeted gene panels offer specific information efficiently,while WES provides comprehensive data but comes with bioinformatic challenges.The surge in testing has also led to an increase in variants of unknown significance(VUS).Deciding whether VUS is disease-causing or benign can be challenging.Computational models,functional studies,and clinical knowledge help to determine pathogenicity.Advances in genetic testing technologies offer hope for improved diagnosis and personalized treatment but also raise concerns about interpretation and ethics.
基金Supported by Natural Science Foundation of Zhejiang Province,China,No.LQ24H070007。
文摘With diabetes currently affecting 537 million people globally,innovative research approaches are urgently required.Zebrafish(Danio rerio)has emerged as a pivotal model organism in diabetes research,particularly valuable for developmental biology studies and preclinical therapeutic validation.Its rapid life cycle,optical transparency,and genetic tractability collectively enable efficient longitudinal observation of pathological progression and pharmacological responses.Utilizing zebrafish models,researchers have elucidated fundamental mechanisms governing islet development,β-cell dysfunction,and metabolic dysregulation.These experimental systems have significantly advanced our understanding of various diabetes subtypes,including type 1,type 2,gestational,and monogenic forms,while also facilitating mechanistic studies of diabetic complications such as retinopathy and nephropathy.Recent model refinements,particularly in simulating monogenic disorders and pregnancy-associated metabolic changes,promise to deepen our comprehension of disease pathophysiology and therapeutic interventions.Nevertheless,a persistent limitation lies in their incomplete recapitulation of human-specific physiological complexity and multi-organ metabolic interactions,factors that may influence translational applicability.Despite these constraints,zebrafish-based research continues to provide an indispensable platform for diabetes investigation,holding significant promise for alleviating the escalating global burden of this metabolic disorder.
基金Supported by Beijing Holistic Integrative Medicine Association Clinical Research Funding Program,No.ZHKY-2024-2209.
文摘BACKGROUND Wolfram syndrome is a rare autosomal recessive genetic disorder characterized by early-onset diabetes and progressive neurodegeneration,most notably sensorineural hearing loss and optic atrophy.Because its initial manifestations are usually similar to those of type 1 diabetes,the diagnosis may be delayed until other manifestations appear.Pathogenic variations of the WFS1 gene can disrupt endoplasmic reticulum function and cellular homeostasis,but the complete mutation spectrum of WFS1 has not been fully determined.Early identification of monogenic diabetes caused by Wolfram syndrome is of vital importance,as it enables the provision of targeted multidisciplinary care and genetic counseling for affected families.CASE SUMMARY A 2-year-old Han Chinese girl was admitted with a 1-month history of polydipsia,polyuria,and polyphagia,and was diagnosed with diabetic ketoacidosis and impaired insulin secretion.Sensorineural hearing loss was also detected.Wholeexome sequencing identified a previously unreported heterozygous mutation,WFS1 c.986T>C(p.Phe329Ser),in the patient and her father,confirming the diagnosis of Wolfram syndrome.Bioinformatic analysis supported the likely pathogenicity of this mutation.In silico pathogenicity predictors(REVEL,SIFT,Poly-Phen-2,MutationTaster,and GERP+)supported a deleterious effect on wolframin structure and function.The patient was initially treated with intravenous insulin and fluid resuscitation,then transitioned to a basal–bolus insulin regimen.Glycemic control was subsequently maintained with continuous subcutaneous insulin infusion and intermittent subcutaneous injections.At the 1-and 6-month follow-ups,blood glucose remained well controlled(hemoglobin A1c:5.89%and 6.58%,respectively),with no evidence of organ dysfunction or further complications.CONCLUSION This case identifies WFS1 c.986T>C(p.Phe329Ser)as a novel pathogenic variant causing Wolfram syndrome.It highlights the importance of early genetic testing in pediatric patients with atypical diabetes presentations to enable timely diagnosis,individualized therapy,and comprehensive family support.
文摘BACKGROUND Dyschromatosis universalis hereditaria(DUH)is a rare type of autosomal dominant inheritance disease.It has varying gene mutation sites among different ethnicities.SASH1 and ABCB6 have been identified as the causative genes of this disorder.CASE SUMMARY A 30-year-old woman presented with irregular black pigmentation spots to our department.Upon examination,the pigmentations were found to be especially dense on the extremities and the face.She had no family history of inbreeding,nor any previous chemical exposure.Genetic testing confirmed that the disease occu-rred because the patient has a SASH1 gene mutation.Following the use of assisted reproductive technology and preimplantation genetic testing for monogenic disorders,the patient give birth to a health baby.CONCLUSION Using assisted reproductive technology/preimplantation genetic testing for monogenic disorders is an option for DUH patients to reduce the risk of trans-mitting the pathogenic variant to their offspring.
文摘Inflammatory bowel disease(IBD)is a group of chronic disorders that cause relapsing inflammation in the gastrointestinal tract(GIT).It results either from gene-environment interactions or as a monogenic disease resulting from pa-thogenic mutations causing impairment in the protective mechanism of the GIT.Around 10%-15%of patients with very early onset IBDs may have an underlying monogenic condition.Monogenic IBD is very different from complex forms of polygenic IBD in the underlying molecular basis of uncontrolled intestinal inflam-mation,age of onset,extraintestinal comorbidities as well as treatment modality.An in-depth understanding of this distinct form of IBD is essential for deciding an appropriate therapeutic approach as well as prognostication.In this review,we aim to discuss about the epidemiology,clinical presentation,diagnostic approach,therapeutic challenges and latest advances in patients with monogenic IBD.
文摘Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.
文摘Monogenic diabetes is caused by one or even more genetic variations,which may be uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1%to 5%of children,and early detection and genetically focused treatment of neonatal diabetes and maturity-onset diabetes of the young can significantly improve long-term health and well-being.The etiology of monogenic diabetes in childhood is primarily attributed to genetic variations affecting the regulatory genes responsible for beta-cell activity.In rare instances,mutations leading to severe insulin resistance can also result in the development of diabetes.Individuals diagnosed with specific types of monogenic diabetes,which are commonly found,can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguish individuals with type 1 or 2 diabetes from those more prone to monogenic diabetes.Genetic screening with appropriate findings and interpretations is essential to establish a prognosis and to guide the choice of therapies and management of these interrelated ailments.This review aims to design a comprehensive literature summarizing genetic insights into monogenetic diabetes in children and adolescents as well as summarizing their diagnosis and management.
文摘Monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance patterns.Despite over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician awareness.The disease spectrum encompasses maturity-onset diabetes of the young(MODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDM)-a heterogeneous group of severe hyperglycemic disorders in infants.Mitochondrial diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of MODY.NDM diagnosis warrants immediate molecular genetic testing for infants under six months.Identifying these genetic defects presents a unique opportunity for precision medicine.Ongoing research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical outcomes.Identification and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of diabetes.The clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.
基金partially supported by grants from the Ministry of Science and Technology of China(2016YFC1000306)the Beijing Municipal Science and Technology Commission Foundation(Z181100001918003)+1 种基金the Beijing Municipal Commission of Health and Family Planning Foundation(2018-21141,2020-4-1144)Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201905)。
文摘Different newborn screening(NBS) programs have been practiced in many countries since the 1960 s. It is of considerable interest whether next-generation sequencing is applicable in NBS. We have developed a panel of 465 causative genes for 596 early-onset, relatively high incidence, and potentially actionable severe inherited diseases in our Newborn Screening with Targeted Sequencing(NESTS) program to screen 11,484 babies in 8 Women and Children’s hospitals nationwide in China retrospectively. The positive rate from preliminary screening of NESTS was 7.85%(902/11,484). With 45.89%(414/902) follow-up of preliminary positive cases, the overall clinically confirmative diagnosis rate of monogenic disorders was 12.07%(50/414), estimating an average of 0.95%(7.85% × 12.07%) clinical diagnosis rate, suggesting that monogenic disorders account for a considerable proportion of birth defects. The disease/gene spectrum varied in different regions of China. NESTS was implemented in a hospital by screening 3923 newborns to evaluate its clinical application. The turn-around time of a primary report, including the sequencing period of < 7 days, was within 11 days by our automatic interpretation pipeline. Our results suggest that NESTS is feasible and cost-effective as a first-tier NBS program, which will change the status of current clinical practice of NBS in China.
基金Supported by Zhejiang Province Medical Platform Backbone,No.2017KY436
文摘AIM To analyze clinical differences between monogenic and nonmonogenic very-early-onset inflammatory bowel disease(VEO-IBD) and to characterize monogenic IBD phenotypically and genotypically via genetic testing. METHODS A retrospective analysis of children aged 0 to 6 years diagnosed with VEO-IBD in a tertiary hospital in southern China from 2005 to 2017 was performed. Clinical data for VEO-IBD patients were collected, and genetic characteristics were analyzed using whole exome sequencing or target gene panel sequencing. RESULTS A total of 54 VEO-IBD patients were included in this study. A diagnosis of Crohn's disease(CD) or CDlike intestinal manifestations accounted for 72.2% of the VEO-IBD cases. Nine patients(16.7%) were identified by genetic testing as having monogenic IBD. The median age of diagnosis in the monogenic group was younger than that of the nonmonogenic IBD group, at 18 mo(interquartile range(IQR): 4 to 78) and 43.5 mo(IQR: 3 to 173), respectively; the P-value was 0.021. The incidence of perianal disease in the monogenic group was higher than that in the nonmonogenic group(P = 0.001). However, there were no significant differences between weight-forage and height-for-age Z-scores between the two groups, and similar laboratory results were obtained for the two groups. Five patients were found to have IL10 receptor mutation, two patients had chronic granulomatous disease, one patient had common variable immunodeficiency disease, and one patient had X-linked inhibitor of apoptosis protein deficiency. CONCLUSION A high proportion of monogenic IBD was observed in the VEO-IBD group, especially with disease onset before the age of 6 mo. Monogenic IBD and nonmonogenic IBD exhibited similar clinical features. Furthermore, next-generation sequencing played an important role in the diagnosis of monogenic IBD, and IL10 receptor mutation was predominant in this cohort.
基金supported by Ministry of Science and Technology Project (2017YFC1001302 and 2016YFC0906400)the Grant of Shanghai Brain-Intelligence Project from the Shanghai Science and Technology Committee (STCSM) (16JC1420500)Shanghai Jiao Tong University Medical Engineering Cross Research Foundation (YG2014MS07)
文摘Medical genetics is the newest cutting-edge discipline that focuses on solving medical problems using genetics knowledge and methods. In China, medical genetics research activities initiated from a poor inner basis but a prosperous outer environment. During the 40 years of reform and opening-up policy,Chinese scientists contributed significantly in the field of medical genetics, garnering considerable attention worldwide. In this review, we highlight the significant findings and/or results discovered by Chinese scientists in monogenic diseases, complex diseases, cancer, genetic diagnosis, as well as gene manipulation and gene therapy. Due to these achievements, China is widely recognized to be at the forefront of medical genetics research and development. However, the significant progress and development that has been achieved could not have been accomplished without sufficient funding and a wellconstructed logistics network. The successful implementation of translational and precise medicine sourced from medical genetics will depend on an open ethics policy and intellectual property protection,along with strong support at the national industry level.
基金supported by Macao FDCT(098/2012/A3)Research Grant of the University of Macao(UL017/08-Y4/MAT/QT01/FST)+1 种基金National Natural Science Funds for Young Scholars(10901166)Sun Yat-sen University Operating Costs of Basic ResearchProjects to Cultivate Young Teachers(11lgpy99)
文摘Appealing to the Clifford analysis and matching pursuits, we study the adaptive decompositions of functions of several variables of finite energy under the dictionaries consisting of shifted Cauchy kernels. This is a realization of matching pursuits among shifted Cauchy kernels in higher-dimensional spaces. It offers a method to process signals in arbitrary dimensions.
文摘Monogenic diabetes is caused by one or even more genetic variations, which maybe uncommon yet have a significant influence and cause diabetes at an early age.Monogenic diabetes affects 1 to 5% of children, and early detection and geneticallyfocused treatment of neonatal diabetes and maturity-onset diabetes of theyoung can significantly improve long-term health and well-being. The etiology ofmonogenic diabetes in childhood is primarily attributed to genetic variationsaffecting the regulatory genes responsible for beta-cell activity. In rare instances,mutations leading to severe insulin resistance can also result in the developmentof diabetes. Individuals diagnosed with specific types of monogenic diabetes,which are commonly found, can transition from insulin therapy to sulfonylureas,provided they maintain consistent regulation of their blood glucose levels.Scientists have successfully devised materials and methodologies to distinguishindividuals with type 1 or 2 diabetes from those more prone to monogenicdiabetes. Genetic screening with appropriate findings and interpretations isessential to establish a prognosis and to guide the choice of therapies andmanagement of these interrelated ailments. This review aims to design a comprehensiveliterature summarizing genetic insights into monogenetic diabetes inchildren and adolescents as well as summarizing their diagnosis and management.
基金Authors extend their appreciation to Deanship of Scientific Research,King Faisal University,Saudi Arabia,for supporting this research(NA000112).
文摘Monogenic lines,which carried 23 genes for blast resistance were tested and used donors to transfer resistance genes by crossing method.The results under blast nursery revealed that 9 genes from 23 genes were susceptible to highly susceptible under the three locations(Sakha,Gemmeza,and Zarzoura in Egypt);Pia,Pik,Pik-p,Piz-t,Pita,Pi b,Pi,Pi 19 and Pi 20.While,the genes Pii,Pik-s,Pik-h,Pi z,Piz-5,Pi sh,Pi 3,Pi 1,Pi 5,Pi 7,Pi 9,Pi 12,Pikm and Pita-2 were highly resistant at the same locations.Clustering analysis confirmed the results,which divided into two groups;the first one included all the susceptible genes,while the second one included the resistance genes.In the greenhouse test,the reaction pattern of five races produced 100%resistance under artificial inoculation with eight genes showing complete resistance to all isolates.The completely resistant genes:Pii,Pik-s,Piz,Piz-5(=bi2)(t),Pita(=Pi4)(t),Pita,Pi b and Pi1 as well as clustering analysis confirmed the results.In the F1 crosses,the results showed all the 25 crosses were resistant for leaf blast disease under field conditions.While,the results in F2 population showed seven crosses with segregation ratio of 15(R):1(S),two cross gave segregated ratio of 3 R:1 S and one gave 13:3.For the identification of blast resistance genes in the parental lines,the marker K3959,linked to Pik-s gene and the variety IRBLKS-F5 carry this gene,which was from the monogenic line.The results showed that four genotypes;Sakha 105,Sakha 103,Sakha 106 and IRBLKS-F5 were carrying Pik-s gene,while was absent in the Sakha 101,Sakha 104,IRBL5-M,IRBL9-W,IRBLTACP1 and IRBL9-W(R)genotypes.As for Pi 5 gene,the results showed that it was present in Sakha 103 and Sakha 104 varieties and absent in the rest of the genotypes.In addition,Pita-Pita-2 gene was found in the three Egyptian genotypes(Sakha 105,Sakha 101 and Sakha 104)plus IRBLTACP1 monogenetic.In F2 generation,six populations were used to study the inheritance of blast resistance and specific primers to confirm the ratio and identify the resistance genes.However,the ratios in molecular markers were the same of the ratio under field evaluation in the most population studies.These findings would facilitate in breeding programs for gene pyramiding and gene accumulation to produce durable resistance for blast using those genotypes.
文摘Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses to optimise glycaemic control.Most clinical guidelines on the management of diabetes mellitus(DM)provide only broad principles on diabetes care,and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently.Therefore,a proper understanding of the pathobiology,clinical situation,and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care.With the aid of five unique cases of DM[(1)Medically managed type 2 diabetes mellitus(T2DM)with severe obesity;(2)Management of T2DM with unreliable glycated haemoglobin(HbA1c);(3)Obesity in a patient with type 1 diabetes mellitus(T1DM);and(4)Late diagnosis and subsequent management of monogenic diabetes and 5.Sudden worsening of well-controlled T2DM)]we elaborate on the importance of individualised diabetes care and the practicalities in these situations.The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.
文摘Previous studies have documented the occurrence of glyphosate-resistant （GR） goosegrass （Eleusine indica （L.） Gaertn.） and, in at least some cases, resistance is due to an altered target site. Research was performed to determine if an altered target site was responsible for GR in a Tennessee, United States goosegrass population （TennGR）. DNA sequencing revealed a mutation in TennGR plants conferring the Prol06Ser 5-enolpyruvylshikimate-3-phosphate synthase （EPSPS） substitution previously identified in other GR populations. F2 populations were derived from TennGR plants crossed with plants from a glyphosate-susceptible population （TennGS） and analyzed for their response to glyphosate and genotyped at the EPSPS locus. Plants from the F2 populations segregated 1：2：1 sensitive：intermediate：resistant in response to a selec- tive dose of glyphosate, and these responses co-segregated with the EPSPS genotypes （PP106, PS106, and SS106）. To separately investigate the effect of the Prol06Ser substitution on GR, glyphosate dose-response curves and 50% effective dose （EDso） values were compared among the three genotypes and the two parental populations. The SS106 genotype was 3.4-fold resistant relative to the PP106 genotype, identical to the resistance level obtained when comparing the resistant and susceptible parental populations. We conclude that the mutation conferring a Prol06Ser EPSPS mutation is solely responsible for GR in the TennGR goosegrass population.
基金This research received funding from Basque Country Government.
文摘Left ventricular(LV)dysfunction is mainly assessed by global contractile indices such as ejection fraction and LV Volumes in cardiac MRI.While these indices give information about the presence or not of LV alteration,they are not able to identify the location and the size of such alteration.The aim of this study is to compare the performance of three parametric imaging techniques used in cardiac MRI for the regional quantification of cardiac dysfunction.The proposed approaches were evaluated on 20 patients with myocardial infarction and 20 subjects with normal function.Three parametric images approaches:covariance analysis,parametric images based on Hilbert transform and those based on the monogenic signal were evaluated using cine-MRI frames acquired in three planes of views.The results show that parametric images generated from the monogenic signal were superior in term of sensitivity(89.69%),specificity(86.51%)and accuracy(89.06%)to those based on covariance analysis and Hilbert transform in the detection of contractile dysfunction related to myocardial infarction.Therefore,the parametric image based on the monogenic signal is likely to provide additional regional indices about LV dysfunction and it may be used in clinical practice as a tool for the analysis of the myocardial alterations.
