Application of artificial intelligence in the diagnosis and treatment of Kawasaki disease

This editorial provides commentary on an article titled"Potential and limitationsof ChatGPT and generative artificial intelligence(AI)in medical safety education"recently published in the World Journal of Clinical Cases.AI has enormous potentialfor various applications in the field of Kawasaki disease(KD).One is machinelearning(ML)to assist in the diagnosis of KD,and clinical prediction models havebeen constructed worldwide using ML;the second is using a gene signalcalculation toolbox to identify KD,which can be used to monitor key clinicalfeatures and laboratory parameters of disease severity;and the third is using deeplearning(DL)to assist in cardiac ultrasound detection.The performance of the DLalgorithm is similar to that of experienced cardiac experts in detecting coronaryartery lesions to promoting the diagnosis of KD.To effectively utilize AI in thediagnosis and treatment process of KD,it is crucial to improve the accuracy of AIdecision-making using more medical data,while addressing issues related topatient personal information protection and AI decision-making responsibility.AIprogress is expected to provide patients with accurate and effective medicalservices that will positively impact the diagnosis and treatment of KD in thefuture.

Delayed diagnosis in inflammatory bowel disease:Time to consider solutions

In this editorial,we discuss a recently published manuscript by Blüthner et al in the World Journal of Gastroenterology,with a specific focus on the delayed diagnosis of inflammatory bowel disease(IBD).IBD,which includes Crohn's disease and ulcerative colitis,is a chronic intestinal disorder.A time lag may exist between the onset of inflammation and the appearance of signs and symptoms,potentially leading to an incorrect or delayed diagnosis,a situation referred to as the delayed diagnosis of IBD.Early diagnosis is crucial for effective patient treatment and prognosis,yet delayed diagnosis remains common.The reasons for delayed diagnosis of IBD are numerous and not yet fully understood.One key factor is the nonspecific nature of IBD symptoms,which can easily be mistaken for other conditions.Additionally,the lack of specific diagnostic methods for IBD contributes to these delays.Delayed diagnosis of IBD can result in numerous adverse consequences,including increased intestinal damage,fibrosis,a higher risk of colorectal cancer,and a decrease in the quality of life of the patient.Therefore,it is essential to diagnose IBD promptly by raising physician awareness,enhancing patient education,and developing new diagnostic methods.

Physician-dependent diagnosis delay in Crohn's disease:A pseudoproposition or not?

The challenge of diagnosis delay in inflammatory bowel disease(IBD)has emerged as a significant concern for both patients and healthcare professionals.The widely accepted notion that there is an extended time frame from the onset of symptoms to the definitive diagnosis is often attributed to the heterogeneity of IBD and the non-specificity of clinical manifestations.Specific to patients with Crohn’s disease,the issue of delayed diagnosis appears to be more pronounced across different regions globally.The intricate interplay of real-world factors has led to debates regarding the primary contributors to these diagnostic delays.Drawing a comparison solely between patients and physicians and implicating the latter as the predominant influence factor may fall into a simplistic either-or logical trap that may obscure the truth.This letter,grounded in published evidence,explores areas for improvement in a forthcoming paper within the field,hoping to pinpoint the culprit behind the diagnosis delay issue for IBD patients rather than simply attributing it to so-called“physician-dependent factors”.Our objective is to motivate healthcare providers and policymakers in relevant fields to reflect on strategies for addressing this problem to reduce diagnostic delays and enhance patient outcomes.

Differential diagnosis of Crohn’s disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning

BACKGROUND Crohn’s disease(CD)is often misdiagnosed as intestinal tuberculosis(ITB).However,the treatment and prognosis of these two diseases are dramatically different.Therefore,it is important to develop a method to identify CD and ITB with high accuracy,specificity,and speed.AIM To develop a method to identify CD and ITB with high accuracy,specificity,and speed.METHODS A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB.Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis.RESULTS The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm^(-1) and 1234 cm^(-1) bands,and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy,specificity,and sensitivity of 91.84%,92.59%,and 90.90%,respectively,for the differential diagnosis of CD and ITB.CONCLUSION Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level,and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Soluble ST2:A Novel Biomarker for Diagnosis and Prognosis of Cardiovascular Disease

The increasing incidence of cardiovascular disease(CVD)is a significant global health concern,affecting millions of individuals each year.Accurate diagnosis of acute CVD poses a formidable challenge,as misdiagnosis can significantly decrease patient survival rates.Traditional biomarkers have played a vital role in the diagnosis and prognosis of CVDs,but they can be influenced by various factors,such as age,sex,and renal function.Soluble ST2(sST2)is a novel biomarker that is closely associated with different CVDs.Its low reference change value makes it suitable for continuous measurement,unaffected by age,kidney function,and other confounding factors,facilitating risk stratification of CVDs.Furthermore,the combination of sST2 with other biomarkers can enhance diagnostic accuracy and prognostic value.This review aims to provide a comprehensive overview of sST2,focusing on its diagnostic and prognostic value as a myocardial marker for different types of CVDs and discussing the current limitations of sST2.

Mean nocturnal baseline impedance in gastro-esophageal reflux disease diagnosis:Should we strictly follow the Lyon 2 Consensus?

Clinical practice guidelines drive clinical practice and clinicians rely to them when trying to answer their most common questions.One of the most important position papers in the field of gastro-esophageal reflux disease(GERD)is the one produced by the Lyon Consensus.Recently an updated second version has been released.Mean nocturnal baseline impedance(MNBI)was proposed by the first Consensus to act as supportive evidence for GERD diagnosis.Originally a cut-off of 2292 Ohms was proposed,a value revised in the second edition.The updated Consensus recommended that an MNBI<1500 Ohms strongly suggests GERD while a value>2500 Ohms can be used to refute GERD.The proposed cut-offs move in the correct direction by diminishing the original cut-off,nevertheless they arise from a study of normal subjects where cut-offs were provided by measuring the mean value±2SD and not in symptomatic patients.However,data exist that even symptomatic patients with inconclusive disease or reflux hypersensitivity(RH)show lower MNBI values in comparison to normal subjects or patients with functional heartburn(FH).Moreover,according to the data,MNBI,even among symptomatic patients,is affected by age and body mass index.Also,various studies have proposed different cut-offs by using receiver operating characteristic curve analysis even lower than the one proposed.Finally,no information is given for patients submitted to on-proton pump inhibitors pH-impedance studies even if new and extremely important data now exist.Therefore,even if MNBI is an extremely important tool when trying to approach patients with reflux symptoms and could distinguish conclusive GERD from RH or FH,its values should be interpreted with caution.

Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases:A prospective,blind clinical study

BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being applied for the detection of stomach and small intestinal diseases,but its application in treating esophageal diseases is not widespread.AIM To evaluate the safety and efficacy of detachable string MCE(ds-MCE)for the diagnosis of esophageal diseases.METHODS Fifty patients who had been diagnosed with esophageal diseases were pros-pectively recruited for this clinical study and underwent ds-MCE and conven-tional EGD.The primary endpoints included the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for patients with esophageal diseases.The secondary endpoints consisted of visualizing the esophageal and dentate lines,as well as the subjects'tolerance of the procedure.RESULTS Using EGD as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%,86.21%,81.82%,89.29%,and 86%,respectively.ds-MCE was more comfortable and convenient than EGD was,with 80%of patients feeling that ds-MCE examination was very comfortable or comfortable and 50%of patients believing that detachable string v examination was very convenient.CONCLUSION This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD,providing a novel noninvasive method for treating esophageal diseases.

Association of autoimmune thyroid disease with type 1 diabetes mellitus and its ultrasonic diagnosis and management

As a common hyperglycemic disease,type 1 diabetes mellitus(T1DM)is a complicated disorder that requires a lifelong insulin supply due to the immunemediated destruction of pancreaticβcells.Although it is an organ-specific autoimmune disorder,T1DM is often associated with multiple other autoimmune disorders.The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease(AITD),which mainly exhibits two extremes of phenotypes:hyperthyroidism[Graves'disease(GD)]and hypothyroidism[Hashimoto's thyroiditis,(HT)].However,the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications.Thus,routine screening of thyroid function has been recommended when T1DM is diagnosed.Here,first,we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases.Subsequently,an updated review of the association between T1DM and AITD is offered.Finally,we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD,suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Light-Activated Virtual Sensor Array with Machine Learning for Non-Invasive Diagnosis of Coronary Heart Disease

Early non-invasive diagnosis of coronary heart disease(CHD)is critical.However,it is challenging to achieve accurate CHD diagnosis via detecting breath.In this work,heterostructured complexes of black phosphorus(BP)and two-dimensional carbide and nitride(MXene)with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy.A light-activated virtual sensor array(LAVSA)based on BP/Ti_(3)C_(2)Tx was prepared under photomodulation and further assembled into an instant gas sensing platform(IGSP).In addition,a machine learning(ML)algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD.Due to the synergistic effect of BP and Ti_(3)C_(2)Tx as well as photo excitation,the synthesized heterostructured complexes exhibited higher performance than pristine Ti_(3)C_(2)Tx,with a response value 26%higher than that of pristine Ti_(3)C_(2)Tx.In addition,with the help of a pattern recognition algorithm,LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols,ketones,aldehydes,esters,and acids.Meanwhile,with the assistance of ML,the IGSP achieved 69.2%accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients.In conclusion,an immediate,low-cost,and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD,which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.

Intestinal Behçet's disease: A review of clinical diagnosis and treatment

Behçet's disease(BD)is a chronic inflammatory disorder prone to frequent re-currences,with a high predilection for intestinal involvement.However,the ef-ficacy and long-term effects of surgical treatment for intestinal BD are unknown.In the current issue of World J Gastrointest Surg,Park et al conducted a retrospec-tive analysis of 31 patients with intestinal BD who received surgical treatment.They found that elevated C-reactive protein levels and emergency surgery were poor prognostic factors for postoperative recurrence,emphasizing the adverse impact of severe inflammation on the prognosis of patients with intestinal BD.This work has clinical significance for evaluating the postoperative condition of intestinal BD.The editorial attempts to summarize the clinical diagnosis and treatment of intestinal BD,focusing on the impact of adverse factors on surgical outcomes.We hope this review will facilitate more precise postoperative management of patients with intestinal BD by clinicians.

Colliding Bodies Optimization with Machine Learning Based Parkinson’s Disease Diagnosis

Parkinson’s disease(PD)is one of the primary vital degenerative diseases that affect the Central Nervous System among elderly patients.It affect their quality of life drastically and millions of seniors are diagnosed with PD every year worldwide.Several models have been presented earlier to detect the PD using various types of measurement data like speech,gait patterns,etc.Early identification of PD is important owing to the fact that the patient can offer important details which helps in slowing down the progress of PD.The recently-emerging Deep Learning(DL)models can leverage the past data to detect and classify PD.With this motivation,the current study develops a novel Colliding Bodies Optimization Algorithm with Optimal Kernel Extreme Learning Machine(CBO-OKELM)for diagnosis and classification of PD.The goal of the proposed CBO-OKELM technique is to identify whether PD exists or not.CBO-OKELM technique involves the design of Colliding Bodies Optimization-based Feature Selection(CBO-FS)technique for optimal subset of features.In addition,Water Strider Algorithm(WSA)with Kernel Extreme Learning Machine(KELM)model is also developed for the classification of PD.CBO algorithm is used to elect the optimal set of fea-tures whereas WSA is utilized for parameter tuning of KELM model which alto-gether helps in accomplishing the maximum PD diagnostic performance.The experimental analysis was conducted for CBO-OKELM technique against four benchmark datasets and the model portrayed better performance such as 95.68%,96.34%,92.49%,and 92.36%on Speech PD,Voice PD,Hand PD Mean-der,and Hand PD Spiral datasets respectively.

Olfactory dysfunction and its related molecular mechanisms in Parkinson’s disease

Changes in olfactory function are considered to be early biomarkers of Parkinson’s disease.Olfactory dysfunction is one of the earliest non-motor features of Parkinson’s disease,appearing in about 90%of patients with early-stage Parkinson’s disease,and can often predate the diagnosis by years.Therefore,olfactory dysfunction should be considered a reliable marker of the disease.However,the mechanisms responsible for olfactory dysfunction are currently unknown.In this article,we clearly explain the pathology and medical definition of olfactory function as a biomarker for early-stage Parkinson’s disease.On the basis of the findings of clinical olfactory function tests and animal model experiments as well as neurotransmitter expression levels,we further characterize the relationship between olfactory dysfunction and neurodegenerative diseases as well as the molecular mechanisms underlying olfactory dysfunction in the pathology of early-stage Parkinson’s disease.The findings highlighted in this review suggest that olfactory dysfunction is an important biomarker for preclinical-stage Parkinson’s disease.Therefore,therapeutic drugs targeting non-motor symptoms such as olfactory dysfunction in the early stage of Parkinson’s disease may prevent or delay dopaminergic neurodegeneration and reduce motor symptoms,highlighting the potential of identifying effective targets for treating Parkinson’s disease by inhibiting the deterioration of olfactory dysfunction.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Gut microbiota dysbiosis contributes toα-synuclein-related pathology associated with C/EBPβ/AEP signaling activation in a mouse model of Parkinson’s disease

Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.

Interplay between the glymphatic system and neurotoxic proteins in Parkinson’s disease and related disorders:current knowledge and future directions

Parkinson’s disease is a common neurodegenerative disorder that is associated with abnormal aggregation and accumulation of neurotoxic proteins,includingα-synuclein,amyloid-β,and tau,in addition to the impaired elimination of these neurotoxic protein.Atypical parkinsonism,which has the same clinical presentation and neuropathology as Parkinson’s disease,expands the disease landscape within the continuum of Parkinson’s disease and related disorders.The glymphatic system is a waste clearance system in the brain,which is responsible for eliminating the neurotoxic proteins from the interstitial fluid.Impairment of the glymphatic system has been proposed as a significant contributor to the development and progression of neurodegenerative disease,as it exacerbates the aggregation of neurotoxic proteins and deteriorates neuronal damage.Therefore,impairment of the glymphatic system could be considered as the final common pathway to neurodegeneration.Previous evidence has provided initial insights into the potential effect of the impaired glymphatic system on Parkinson’s disease and related disorders;however,many unanswered questions remain.This review aims to provide a comprehensive summary of the growing literature on the glymphatic system in Parkinson’s disease and related disorders.The focus of this review is on identifying the manifestations and mechanisms of interplay between the glymphatic system and neurotoxic proteins,including loss of polarization of aquaporin-4 in astrocytic endfeet,sleep and circadian rhythms,neuroinflammation,astrogliosis,and gliosis.This review further delves into the underlying pathophysiology of the glymphatic system in Parkinson’s disease and related disorders,and the potential implications of targeting the glymphatic system as a novel and promising therapeutic strategy.

A review of the neurotransmitter system associated with cognitive function of the cerebellum in Parkinson's disease

The dichotomized brain system is a concept that was generalized from the‘dual syndrome hypothesis’to explain the heterogeneity of cognitive impairment,in which anterior and posterior brain systems are independent but partially overlap.The dopaminergic system acts on the anterior brain and is responsible for executive function,working memory,and planning.In contrast,the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function.Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease.Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections.However,whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated.Furthermore,the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear.Therefore,in this review,we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition,as reported by previous studies,and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment,as determined by functional neuroimaging.Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

Roles of neuronal lysosomes in the etiology of Parkinson’s disease

Therapeutic progress in neurodegenerative conditions such as Parkinson’s disease has been hampered by a lack of detailed knowledge of its molecular etiology.The advancements in genetics and genomics have provided fundamental insights into specific protein players and the cellular processes involved in the onset of disease.In this respect,the autophagy-lysosome system has emerged in recent years as a strong point of convergence for genetics,genomics,and pathologic indications,spanning both familial and idiopathic Parkinson’s disease.Most,if not all,genes linked to familial disease are involved,in a regulatory capacity,in lysosome function(e.g.,LRRK2,alpha-synuclein,VPS35,Parkin,and PINK1).Moreover,the majority of genomic loci associated with increased risk of idiopathic Parkinson’s cluster in lysosome biology and regulation(GBA as the prime example).Lastly,neuropathologic evidence showed alterations in lysosome markers in autoptic material that,coupled to the alpha-synuclein proteinopathy that defines the disease,strongly indicate an alteration in functionality.In this Brief Review article,I present a personal perspective on the molecular and cellular involvement of lysosome biology in Parkinson’s pathogenesis,aiming at a larger vision on the events underlying the onset of the disease.The attempts at targeting autophagy for therapeutic purposes in Parkinson’s have been mostly aimed at“indiscriminately”enhancing its activity to promote the degradation and elimination of aggregate protein accumulations,such as alpha-synuclein Lewy bodies.However,this approach is based on the assumption that protein pathology is the root cause of disease,while pre-pathology and pre-degeneration dysfunctions have been largely observed in clinical and pre-clinical settings.In addition,it has been reported that unspecific boosting of autophagy can be detrimental.Thus,it is important to understand the mechanisms of specific autophagy forms and,even more,the adjustment of specific lysosome functionalities.Indeed,lysosomes exert fine signaling capacities in addition to their catabolic roles and might participate in the regulation of neuronal and glial cell functions.Here,I discuss hypotheses on these possible mechanisms,their links with etiologic and risk factors for Parkinson’s disease,and how they could be targeted for disease-modifying purposes.

Deep brain implantable microelectrode arrays for detection and functional localization of the subthalamic nucleus in rats with Parkinson’s disease

The subthalamic nucleus(STN)is considered the best target for deep brain stimulation treatments of Parkinson’s disease(PD).It is difficult to localize the STN due to its small size and deep location.Multichannel microelectrode arrays(MEAs)can rapidly and precisely locate the STN,which is important for precise stimulation.In this paper,16-channel MEAs modified with multiwalled carbon nanotube/poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)(MWCNT/PEDOT:PSS)nanocomposites were designed and fabricated,and the accurate and rapid identification of the STN in PD rats was performed using detection sites distributed at different brain depths.These results showed that nuclei in 6-hydroxydopamine hydrobromide(6-OHDA)-lesioned brains discharged more intensely than those in unlesioned brains.In addition,the MEA simultaneously acquired neural signals from both the STN and the upper or lower boundary nuclei of the STN.Moreover,higher values of spike firing rate,spike amplitude,local field potential(LFP)power,and beta oscillations were detected in the STN of the 6-OHDA-lesioned brain,and may therefore be biomarkers of STN localization.Compared with the STNs of unlesioned brains,the power spectral density of spikes and LFPs synchronously decreased in the delta band and increased in the beta band of 6-OHDA-lesioned brains.This may be a cause of sleep and motor disorders associated with PD.Overall,this work describes a new cellular-level localization and detection method and provides a tool for future studies of deep brain nuclei.