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Oligodendroglial heterogeneity in health,disease,and recovery:deeper insights into myelin dynamics

中华医学会糖尿病学分会第十六次全国学术会议

作者： YANG Li LI Hai-yan LI Hong-mei Anh Bui cHANG Ming LIU Xiao-ni Sreeneeranj Kasichayanula steven c.griffen David W.Boulton Peking University Third Hospital Bristol-Myers Squibb Discovery Medicine and clinical Pharmacology Bristol-Myers SquibbPrincetonNJUSA Global Biometric Sciences Bristol-Myers SquibbPrincetonNJUSA

Objective Dapagliflozin(DAPA),a potent and highly selective inhibitor of renal sodium-glucose cotransporter -2(SGLT2),is currently in development for the treatment of type 2 diabetes mellitus(T2DM).DAPA improves hyperglycemia by reducing renal glucose reabsorption and dose-dependently increasing urinary glucose excretion independent of insulin secretion or ***,the pharmacokinetics(PK) and pharmacodynamics(PD) of

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Neural Regeneration Research 2025年第11期20卷 3179-3192页

作者： Pieter-Jan Serneels Julie D.De Schutter Lies De Groef Lieve Moons steven Bergmans KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionNeural Circuit Development&Regeneration Research GroupLeuvenBelgium KU Leuven Leuven Brain InstituteDepartment of BiologyAnimal Physiology and Neurobiology DivisionCellular Communication&Neurodegeneration Research GroupLeuvenBelgium

Decades of research asserted that the oligodendroglial lineage comprises two cell types:oligodendrocyte precursor cells and ***,recent studies employing single-cell RNA sequencing techniques have uncovered novel cell states,prompting a revision of the existing *** forward,the oligodendroglial lineage should be delineated into five distinct cell states:oligodendrocyte precursor cells,committed oligodendrocyte precursor cells,newly formed oligodendrocytes,myelin-forming oligodendrocytes,and mature *** new classification system enables a deeper understanding of the oligodendroglia in both physiological and pathological *** this uniform terminology will facilitate comparison and integration of data across ***,including the consolidation of findings from various demyelinating models,is essential to better understand the pathogenesis of demyelinating ***,comparing injury models across species with varying regenerative capacities can provide insights that may lead to new therapeutic strategies to overcome remyelination ***,by standardizing terminology and synthesizing data from diverse studies across different animal models,we can enhance our understanding of myelin pathology in central nervous system disorders such as multiple sclerosis,Alzheimer's disease,and amyotrophic lateral sclerosis,all of which involve oligodendroglial and myelin dysfunction.

关键词： animal models demyelination fish mammals multiple sclerosis myelin neurodegeneration oligodendrocytes oligodendroglial lineage remyelination

current methods for the maturation of induced pluripotent stem cellderived cardiomyocytes

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World Journal of Stem cells 2019年第1期11卷 33-43页

作者： Pranav Machiraju steven c Greenway Departments of Pediatrics and cardiac Sciences Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of MedicineUniversity of Calgary Departments of Pediatrics Cardiac Sciences Biochemistry & Molecular Biology Alberta Children’s Hospital Research Institute Libin Cardiovascular Institute of Alberta Cumming School of Medicine University of Calgary

Induced pluripotent stem cells(iPScs) were first generated by Yamanaka and colleagues over a decade ago. Since then, iPScs have been successfully differentiated into many distinct cell types, enabling tissue-, disease-, and patientspecific in vitro modelling. cardiovascular disease is the greatest cause of mortality worldwide but encompasses rarer disorders of conduction and myocardial function for which a cellular model of study is ideal. Although methods to differentiate iPScs into beating cardiomyocytes(iPSc-cMs) have recently been adequately optimized and commercialized, the resulting cells remain largely immature with regards to their structure and function,demonstrating fetal gene expression, disorganized morphology, reliance on predominantly glycolytic metabolism and contractile characteristics that differ from those of adult cardiomyocytes. As such, disease modelling using iPSc-cMs may be inaccurate and of limited utility. However, this limitation is widely recognized, and numerous groups have made substantial progress in addressing this problem. This review highlights successful methods that have been developed for the maturation of human iPSc-cMs using small molecules,environmental manipulation and 3-dimensional(3 D) growth approaches.

关键词： Induced pluripotent stem cells Induced pluripotent stem cell-derived cardiomyocytes Regenerative medicine Stem cell biology Translational research

Trends and seasonality in hospitalizations for acute alcohol-related and biliary pancreatitis in the USA

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Hepatobiliary & Pancreatic Diseases International 2021年第2期20卷 173-181页

作者： Artem Shmelev Anne M Sill Tiffany Horrigan steven c cunningham Department of Surgery Saint Agnes HealthcareBaltimoreMDUSA

Background:The incidence of acute pancreatitis(AP)is characterized by circannual and geographical *** aim of this study was to describe seasonal variation and trends in hospitalizations for AP in the USA with respect to AP ***:The Nationwide Inpatient Sample data(2000–2016)from the Healthcare cost and Utilization Project were *** study population included all primary hospitalizations for *** AP(BAP)and alcohol-induced AP(AAP)were distinguished by diagnostic and procedural IcD *** trend decomposition was ***:There was a linear increase in annual incidence(per 100000 population)of AAP in the USA(from 17.0 in 2000 to 22.9 in 2016),while incidence of BAP,equaled 19.9 in 2000,peaked at 22.1 in 2006 and decreased to 17.4 in *** incidence demonstrated 18%annual incidence amplitude with summer peak and winter trough,more prominent in *** 2016,within AAP,the highest incidence(per 100000 population)was noted among African-Americans(up to 50.4),followed by males aged 56–70 years(26.5)and Asians of low income(25.5);within BAP,above the average incidence was observed in Hispanic(up to 25.8)and Asian(up to 25.0)*** most consistent and rapid increase in AP incidence was noted in males aged 56–70 years with an alcoholic etiology(average 6%annual incidence growth).conclusions:The incidence and annual trends of AP vary significantly among demographic and socioeconomic groups and this knowledge may be useful for the planning of healthcare resources and identification of at-risk populations.

关键词： Pancreatitis Alcoholic pancreatitis Incidence Seasonal variation

Subspecialty radiology and surgery

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Hepatobiliary & Pancreatic Diseases International 2013年第2期12卷 122-124页

作者： steven c cunningham Saleem Farooqui Departments of Surgery and Radiology Saint Agnes Hospital

The Master said: "Yu! Shall I teach you the meaning of knowledge?When you know a thing to recognize that you know it; and when you do not, to know that you do not know

关键词： Subspecialty radiology and surgery FNH

Detecting accidental punctures and lacerations during cholecystectomy in large datasets: Two methods of analysis

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Hepatobiliary & Pancreatic Diseases International 2018年第5期17卷 430-436页

作者： Artem Shmelev Anne M Sill Gopal c Kowdley Juan A Sanchez steven c cunningham Department of Surgery Saint Agnes Hospital and Cancer Center

Background: After the Institute of Medicine(IOM) report To Err Is Human highlighted the impact of medical errors, the Agency for Healthcare Research and Quality(AHRQ) developed Patient-Safety Indicators(PSI) to improve quality by identifying potential inpatient safety problems. PSI-15 was created to study accidental punctures and lacerations(APL), but PSI-15 may underestimate APLs in populations of patients. This study compares PSI-15 with a more inclusive approach using a novel composite of secondary diagnostic and procedural codes. Methods: We used Nationwide Inpatient Sample(NIS) data(20 0 0–2012) from AHRQ’s Healthcare cost and Utilization Project(H-cUP). We analyzed PSI-15-positive and-negative cholecystectomies. cross tabulations identified codes that were significantly more frequent among PSI-15-positive cases; these secondary diagnostic and procedural codes were selected as candidate members of a composite marker(cM) of APL. We chose cholecystectomy patients for study because this is one of the most common general operations, and the large size of NIS allows for meaningful analysis of infrequent occurrences such as APL rates. Results: cM identified 1.13 times more APLs than did PSI-15. Patients with cM-detected APLs were significantly older and had worse mortality, comorbidities, lengths of stay, and charges than those detected with PSI-15. Further comparison of these two approaches revealed that time-series analysis for both APL markers revealed parallel trends, with inflections in 2007, and lowest APL rates in July. conclusions: Although cM may yield more false positives, it appears more inclusive, identifying more clinically significant APLs, than PSI-15. Both measures presented similar trends over time, arguing against inflation in PSI-15 reporting. While arguably less specific, cM may increase sensitivity for detecting APL events during cholecystectomies. These results may inform the interpretation of other large population studies of APLs following abd

关键词： cholecystectomy Patient safety Accidental lacerations AHRQ PSI-15

Using modeling and simulation and artificial intelligence to improve complex adaptive systems engineering

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International Journal of Modeling, Simulation, and Scientific computing 2022年第2期13卷 70-90页

作者： Andreas Tolk Philip Barry steven c.Doskey The MITRE corporation 1001 Research Park Blvd#220 CharlottesvilleVA 22911USA George Mason University 4400 University DrFairfax VA 22030USA The MITRE corporation 7525 Colshire DrMcLean VA 22102USA

Systems engineering practices are evolving to address fast-changing needs in fielding complex *** needs create an environment in which system needs evolve or change too quickly to be tracked or managed by humans’natural *** propose that systems engineering must aid systems engineering managers by providing architectural alternatives and design ***,as systems become more complex and dynamic,there is an increased need to identify hidden risks,model emergent behav-ior,and expose hidden patterns in the behavior of *** engineering needs to evolve to build fast-fielded,resilient,and adaptive systems that leverage posi-tive reinforcement feedback loops with multiple experimental and real-world information *** very basis of systems engineering must evolve from today’s development paradigms to a future that leverages modeling,simulation,and artificial intelligence to drastically improve the capability and agility for developing new *** paper proposes a common way forward to enable this new form of complex adaptive systems engineering.

关键词： complex systems digital twin systems engineering

HIDA scan for functional gallbladder disorder： ensure that you know how the scan was done

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Hepatobiliary & Pancreatic Diseases International 2017年第2期16卷 197-201页

作者： Naeem Goussous Hadia Maqsood Ethan Spiegler Gopal c Kowdley steven c cunningham Department of Surgery Saint Agnes Hospital Baltimore USA Department of Nuclear Medicine Saint Agnes Hospital Baltimore USA

BAcKGROUND： Despite the increasing use of fatty meal（FM） as a substitute for cholecystokinin（ccK） in pain reproduction during hepato-imino-diacetic acid（HIDA） scan in functional gallbladder disorder, there are no studies comparing the differences between ccK and FM. The present study was to compare the efficacy of FM in comparison of ccK in FGBD application. METHODS： Patients undergoing HIDA scans from August 2013 to May 2014 were divided into two groups： those undergoing ccK-stimulated HIDA scan versus FM-stimulated HIDA scan. These groups were compared according to demographics and HIDA ***： Of 153 patients, 70 received ccK and 83 FM. There was no difference regarding age, gender, gallstones, gallbladder ejection fraction and time to visualization. However, significantly more of the patients receiving ccK than FM experienced pain reproduction（61% vs 30%, P〈0.01）.cONcLUSIONS： Stimulation of gallbladder contractility with a FM during HIDA is less than half as likely to reproduce biliary symptoms compared to ccK, despite similar ejection fractions and other parameters. It is essential that providers account for this difference when counseling patients regarding cholecystectomy for functional gallbladder disorder.

关键词： gallbladder dysfunction biliary dyskinesia cholecystokinin hepato-imino-diacetic acid

Stem cell Ophthalmology Treatment Study (ScOTS)： bone marrow-derived stem cells in the treatment of Leber＇s hereditary optic neuropathy

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Neural Regeneration Research 2016年第10期11卷 1685-1694页

作者： Jeffrey N. Weiss steven Levy Susan c. Benes Retina Associates of South Florida 5800 Colonial Drive Suite 300 Margate FL USA MD Stem cells 3 Sylvan Road South Westport CT USA The Eye center of columbus The Ohio State University Columbus OH USA

The Stem cell Ophthalmology Treatment Study （ScOTS） is currently the largest-scale stem cell ophthal- mology trial registered at *** （identifier： NcT01920867）. ScOTS utilizes autologous bone marrow-derived stem cells （BMScs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMScs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMScs as provided in ScOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.

关键词： nerve regeneration Leber's hereditary optic neuropathy mitochondrial disease optic neuropathy bone marrow derived stem cells blindness visual loss neural regeneration

Minimally invasive and open gallbladder cancer resections: 30-vs 90-day mortality

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Hepatobiliary & Pancreatic Diseases International 2017年第4期16卷 405-411页

作者： Naeem Goussous Motahar Hosseini Anne M Sill steven c cunningham Department of Surgery Saint Agnes HospitalBaltimoreMDUSA

BAcKGROUND:Minimally invasive surgery is increasingly used for gallbladder cancer *** mortality at 30 days is low,but 90-day mortality is ***:Using National cancer Database(1998-2012),all resection patients were ***-and 90-day mortality rates were ***:A total of 36 067 patients were identified,19 139(53%) of whom underwent *** age was 71 years and 70.7% were ***-day mortality following surgical resection was 2.3-fold higher than 30-mortality(17.1% vs 7.4%).There was a statistically significant increase in 30-and 90-day mortality with poorly differentiated tumors,presence of lymphovascular invasion,tumor stage,incomplete surgical resection and low-volume centers(Pction between 2010 and 2012,the 90-day mortality was 2.8-fold higher than the 30-day mortality(12.0% vs 4.3%).cONcLUSIONS:Ninety-day mortality following gallbladder cancer resection is significantly higher than 30-day *** mortality is associated with tumor grade,lymphovascular invasion,tumor stage,type and completeness of surgical resection as well as type and volume of facility.

关键词： gallbladder cancer laparoscopic minimally invasive survival radical cholecystectomy complications