Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curri...Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curriculum,which included serious study of basic science for two years,followed by 'learning by doing' in the 3d and 4th clinical years. After the Flexner report in 1910 which lauded the school as an exemplary model,this became the standard curricular structure of undergraduate medical education in the US. Since its founding Hopkins,like other medical schools,has struggled with burgeoning biomedical knowledge and the tension between time and content. The last curricular revision was implemented in 1992,and had several themes,including:(1) decreased lecture time and increased small group learning; (2) early clinical experience and more ambulatory clinical experience; (3) integration of the basic sciences to improve learning and reduce redundancy; (4) development of a longitudinal course for the social sciences,(named 'The Physician and Society' course); (5) a required thesis project for graduation. All but the last were implemented. Our students have done well in this curriculum. 98-100% pass the licensing board exams,and over 90% obtain their first choice for residency positions,often in highly competitive programs such as Dermatology,Neurosurgery and Ophthalmology. Approximately 30% of graduates are listed in the AAMC faculty roster-one of the highest percentages of graduates going to academic medicine in the country.展开更多
The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial prog...The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial program coordinated activities in five large US blood centers in San Francisco,Los Angeles,Oklahoma City,Detroit,and Baltimore with a coordinating center Westat in Rockville MD.展开更多
Glaucoma service of Johns Hopkins University is currently involved in a range of research projects.This overview will cover the major clinical activities currently underway.
Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys ben...Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys benefits such as improved communication skills and personal and professional growth to physicians,medical students,and other health care providers.Narrative medicine can promote empathy and trust between patients and physicians and foster self-care.In 2014,the author and a colleague started an ongoing inter-disciplinary narrative medicine program in the Children’s Center of the Johns Hopkins Hospital called AfterWards.The program,which meets monthly,is open to all on a volunteer basis.Through literature,art,and writing,AfterWards nurtures empathy,encourages reflective practice,and builds community among a diverse group of health care providers.Through a series of lectures and workshops at Johns Hopkins Medicine,Peking Union Medical College,and Fudan Hospital in Shanghai,the author has introduced AfterWards to Chinese medical educators and clinicians.Working with Dr.Marta Hanson,she created an AfterWards Facilitator’s Guide for the use of Chinese practitioners.A recent White Paper on Chinese health care indicates that an infusion of humanities-based education,of which narrative medicine forms a part,can help rebuild patient-physician trust.Recently,there has been an increase in interest in narrative medicine in the United States and China.However,more research is needed to demonstrate the impact of programs like AfterWards.Challenges to the implementation of narrative medicine programs remain,most significantly in terms of expertise,resources,and time.展开更多
Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patien...Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.展开更多
The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral bloo...The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid develo...Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid development of artificial intelligence and the global labor market,vocational college teachers are facing challenges such as workload pressure and limited career development,which may harm their well-being.This study aims to localize the measurement method of decent work in Chinese vocational education based on the theory of the Psychology of Working Theory,and explore the relationship mechanism between organizational support,career adaptability,decent work,and job satisfaction among vocational college teachers.Methods:A cross-sectional survey was conducted with 422 HVCU teachers in China(202 male,220 female)using the localized Perceived Organizational Support Scale,Career Adaptability Scale,Decent Work Scale,and Job Satisfaction Scale.Results:The overall level of HVCU teachers’decent work was above the median(Mean=4.09,SD=0.69),laying a foundation for their SWB.Decent work significantly and positively predicted job satisfaction(β=0.620,p<0.001).Organizational support(r=0.58,p<0.001)and career adaptability(r=0.82,p<0.001)can positively affect decent work,and further improve job satisfaction(collective R2 rising from 38.3%to 41.1%).Bootstrap analysis confirmed these mediating effects were robust.Conclusions:This study confirms that the combined effects of organizational support and career adaptability can enhance decent work,further improving teachers’job satisfaction and subsequent subjective well-being.Besides,this study provides an empirical basis for improving the well-being of higher vocational teachers and the sustainable development of vocational education,and has practical significance for improving the teacher incentive policy.展开更多
Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulat...Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.展开更多
BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical...BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.展开更多
Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes...Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.展开更多
Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously...Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DP...Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).展开更多
Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studyin...Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.展开更多
Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics cl...Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.展开更多
The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic...The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic stress disorder(PTSD)could delay the potential approval of this promising treatment by several years.展开更多
Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pat...Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pathophysiological pathway frequently involves either (or a combination of) elevated serum cholesterol levels, predominantly attributed to dietary patterns characterized by extremely high levels of saturated and trans-fat consumption. Day-to-day nutritional epidemiology among university students suggests that they represent a crucial demographic for the study of preventive interventions. Objective: This in-depth study and investigation were specifically aimed to quantitatively assess and compare prevailing patterns of dietary fat consumption between female students enrolled in health sciences and non-health sciences programs at major universities in Riyadh, Saudi Arabia. Methodology: This cross-sectional study was comprised of 434 Saudi female university students (age range: 18 - 25 years), utilizing a validated Block Dietary Fat Screener accompanied by anthropometric measurements and comprehensive demographic data collection. The sampling methodology consisted of a snowball technique that was spread across three major academic institutions in Riyadh. Results: Statistical analysis revealed a significant association between academic specialization and patterns of dietary fat consumption (p = 0.012). Paradoxically, students of health science exhibited a higher prevalence of very high fat intake (41.9%) compared with their non-health sciences counterparts (27.6%). Surprisingly, anthropometric stratification revealed that it was the underweight students who demonstrated very high levels of fat consumption. A notable socioeconomic gradient was observed, with students from households earning 15,000 - 20,000 SR monthly showing the highest prevalence of very high-fat consumption (47.1%), although this association did not achieve statistical significance (p = 0.104). Conclusion: These findings challenge the conventional assumption that health sciences education correlates with superior dietary behaviors. The data suggests a critical need for enhanced education in nutrition, as well as intervention using various behavioral programs across all academic disciplines, particularly those addressing the disconnect between nutritional knowledge and dietary practices among students of health sciences. Future longitudinal studies are warranted in order to elucidate the temporal relationship between academic specialization and dietary behaviors.展开更多
文摘Johns Hopkins University School of Medicine (JHUSOM) has been a leader in medical education since its inception in 1893. The influence of John Dewey on the founders of the school is evident in the design of the curriculum,which included serious study of basic science for two years,followed by 'learning by doing' in the 3d and 4th clinical years. After the Flexner report in 1910 which lauded the school as an exemplary model,this became the standard curricular structure of undergraduate medical education in the US. Since its founding Hopkins,like other medical schools,has struggled with burgeoning biomedical knowledge and the tension between time and content. The last curricular revision was implemented in 1992,and had several themes,including:(1) decreased lecture time and increased small group learning; (2) early clinical experience and more ambulatory clinical experience; (3) integration of the basic sciences to improve learning and reduce redundancy; (4) development of a longitudinal course for the social sciences,(named 'The Physician and Society' course); (5) a required thesis project for graduation. All but the last were implemented. Our students have done well in this curriculum. 98-100% pass the licensing board exams,and over 90% obtain their first choice for residency positions,often in highly competitive programs such as Dermatology,Neurosurgery and Ophthalmology. Approximately 30% of graduates are listed in the AAMC faculty roster-one of the highest percentages of graduates going to academic medicine in the country.
文摘The Retrovirus Epidemiology Donor Study (REDS) was established in 1989 with funding from the National Heart,Lung,and Blood Institute ( NHLBI ) of the National Institutes of Health in the United States.The initial program coordinated activities in five large US blood centers in San Francisco,Los Angeles,Oklahoma City,Detroit,and Baltimore with a coordinating center Westat in Rockville MD.
文摘Glaucoma service of Johns Hopkins University is currently involved in a range of research projects.This overview will cover the major clinical activities currently underway.
基金The study is financed by the grant of Johns Hopkins University School of Medicine,Baltimore,Maryland,USA.
文摘Narrative medicine is a multidisciplinary field of inquiry and practice based on the premise that medical care takes place in the context of stories.Research on narrative medicine training suggests that it conveys benefits such as improved communication skills and personal and professional growth to physicians,medical students,and other health care providers.Narrative medicine can promote empathy and trust between patients and physicians and foster self-care.In 2014,the author and a colleague started an ongoing inter-disciplinary narrative medicine program in the Children’s Center of the Johns Hopkins Hospital called AfterWards.The program,which meets monthly,is open to all on a volunteer basis.Through literature,art,and writing,AfterWards nurtures empathy,encourages reflective practice,and builds community among a diverse group of health care providers.Through a series of lectures and workshops at Johns Hopkins Medicine,Peking Union Medical College,and Fudan Hospital in Shanghai,the author has introduced AfterWards to Chinese medical educators and clinicians.Working with Dr.Marta Hanson,she created an AfterWards Facilitator’s Guide for the use of Chinese practitioners.A recent White Paper on Chinese health care indicates that an infusion of humanities-based education,of which narrative medicine forms a part,can help rebuild patient-physician trust.Recently,there has been an increase in interest in narrative medicine in the United States and China.However,more research is needed to demonstrate the impact of programs like AfterWards.Challenges to the implementation of narrative medicine programs remain,most significantly in terms of expertise,resources,and time.
基金supported by the Canadian Institutes of Health Research(DFD-181599)the National Institutes of Health(T32AG058527)to RJB and R0190106435 to VM.
文摘Neurodegenerative disorders represent an increasingly pertinent public health crisis.As a greater proportion of the population ages,neurodegenerative disorders and other diseases of aging place undue burdens on patients,caregivers,and healthcare workers.Alzheimer’s disease(AD)and Parkinson’s disease represent the two most common neurodegenerative disorders in the population,affecting over 65 million people,worldwide.
基金supported by Department of Defense grant HT9425-24-1-0030 a grant from the Stanley Medical Research Institute(to SS).
文摘The inability to access brain tissue has greatly hindered our ability to study and care for individuals suffering from psychiatric and neurological conditions.Critics have questioned efforts to develop peripheral blood biomarkers in neurological and psychiatric disorders based on the assertion that disease pathology is limited to the brain.The discovery that all tissues,including the brain,release extracellular vesicles(Raposo and Stoorvogel,2013)and cell free DNAs(Chan et al.,2013)into various body fluids has provided a potential way to measure activity from inaccessible tissues like the central nervous system(CNS)and has given rise to the term“liquid biopsy.”The development of liquid biopsies that can diagnose and predict the course of psychiatric and neurological disorders would be transformative.The ability to predict episodic events such as mania,depression,and risk for suicide would be particularly useful for psychiatric care as it would enable the development of interventions that prevent mortality and improve outcomes.Additionally,biomarkers that are informative about drug response and aid in treatment decisions would be a significant advance in psychiatric care as it would prevent patients from having to endure multiple courses of ineffective treatments and side effects.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
基金funded by Nanjing University of Posts and Telecommunications Humanities and Social Sciences Research Fund Project(NYY222055)Special research project on teaching reform of innovation and entrepreneurship education in Nanjing University of Posts and Telecommunications(GCSJG202528)+2 种基金General Subject of Educational Science Planning in Jiangsu Province(C/2024/01/76)General project of educational science research in Shanghai(C24288)Key funded project of Shandong Vocational Education Teaching Reform Research in 2022(2022052).
文摘Background:As an important indicator of subjective well-being(SWB),decent work is a key guarantee for the sustainable development of teachers and their psychological health and work quality.Faced with the rapid development of artificial intelligence and the global labor market,vocational college teachers are facing challenges such as workload pressure and limited career development,which may harm their well-being.This study aims to localize the measurement method of decent work in Chinese vocational education based on the theory of the Psychology of Working Theory,and explore the relationship mechanism between organizational support,career adaptability,decent work,and job satisfaction among vocational college teachers.Methods:A cross-sectional survey was conducted with 422 HVCU teachers in China(202 male,220 female)using the localized Perceived Organizational Support Scale,Career Adaptability Scale,Decent Work Scale,and Job Satisfaction Scale.Results:The overall level of HVCU teachers’decent work was above the median(Mean=4.09,SD=0.69),laying a foundation for their SWB.Decent work significantly and positively predicted job satisfaction(β=0.620,p<0.001).Organizational support(r=0.58,p<0.001)and career adaptability(r=0.82,p<0.001)can positively affect decent work,and further improve job satisfaction(collective R2 rising from 38.3%to 41.1%).Bootstrap analysis confirmed these mediating effects were robust.Conclusions:This study confirms that the combined effects of organizational support and career adaptability can enhance decent work,further improving teachers’job satisfaction and subsequent subjective well-being.Besides,this study provides an empirical basis for improving the well-being of higher vocational teachers and the sustainable development of vocational education,and has practical significance for improving the teacher incentive policy.
文摘Metastatic brain tumors undergo profound metabolic-epigenetic reprogramming driven by the unique constraints of the brain microenvironment.Hypoxia-inducible factor-1α(HIF1α)enhances glycolytic flux,lactate accumulation,and histone lactylation,collectively supporting metastatic colonization and immune evasion.Key metabolites including acetyl-CoA,S-adenosylmethionine(SAM),α-ketoglutarate(α-KG),fumarate,and 2-hydroxyglutarate(2-HG)-directly modify chromatin states by regulating histone acetyltransferases,DNA/histone methyltransferases,andα-KG dependent dioxygenases such as Ten-Eleven Translocation(TET)enzymes and lysine demethylases(KDMs).These metabolic shifts result in aberrant DNA methylation,histone lysine residue at position 27 on Histone H3(H3K27)trimethylation,and depletion of 5-hydroxymethylcytosine(5hmC),all of which are hallmark epigenetic alterations in brain metastasis and primary Central Nervous System(CNS)tumors.Additionally,the blood-brain barrier(BBB)and blood-tumor barrier(BTB)impose nutrient restrictions and induce metabolic dependency on glutamine,acetate,and lactate shuttling,thereby reshaping epigenetic enzyme activity.We synthesize current mechanistic evidence showing how metabolic pressures in the brain microenvironment remodel the epigenome to promote tumor plasticity,stemness,and therapeutic resistance.Understanding these coupled pathways reveals vulnerable nodes such as HIF1αsignaling,α-KG-dependent demethylation,and lactate-driven epigenetic remodeling that may be exploited for targeted treatment of metastatic brain tumors.The present review aims to provide in-depth insights into epigenetic regulation,including chromatin and histone modifications as well as noncoding RNAs and metabolic reprogramming,highlighting how the two interplay in the development and progression of metastatic brain tumors and their therapeutic potential.
文摘BACKGROUND Acute liver failure(ALF)is a life-threatening multisystemic condition with high short-term mortality.With the growing prevalence of obesity and metabolic syndrome,it is important to investigate the clinical implications of high body mass index(BMI)on survival outcomes in ALF.AIM To explore the impact of overweight and obesity on the clinical outcomes of patients with ALF.METHODS A retrospective observational cohort study was conducted involving patients with ALF admitted to the Johns Hopkins Health System between January 1,2000 and May 1,2020.We performed Cox proportional hazards regression to identify outcomes,including the need for liver transplantation(LT)or all-cause mortality.RESULTS A total of 196 patients were included,the median age was 43.5 years,63.3%were female,and 59.7%were of Caucasian ethnicity.Acetaminophen-induced ALF was the most common etiology(45%).The mean BMI was significantly greater among patients who underwent LT or died(29.64 kg/m^(2)vs 26.59 kg/m^(2),P=0.008)than among survivors.Patients with overweight and obesity had a higher risk of all-cause mortality or need for LT by 2.22-fold(95%CI:1.30-3.78)and 2.04-fold(95%CI:1.29-3.39),respectively.Elevated BMI was associated with renal failure and higher grades of hepatic encephalopathy.Derangements in serologic markers,including alanine transaminase,lactate,and ammonia,were associated with a mortality risk or need for LT.CONCLUSION In this large,retrospective study,with a diverse cohort of United States patients,Overweight and obese were independently associated with an increased risk of all-cause mortality or need for LT.This work highlights the importance of closely monitoring ALF patients who are overweight or obese for adverse complications and measures to improve outcomes in this vulnerable patient population.
基金funded by Humanities and Social Sciences Foundation and Natural Science Foundation of Nanjing University of Posts and Telecommunications(NYY222055,NY224176)General Subject of Educational Science Planning in Jiangsu Province(C/2024/01/76)National Natural Science Foundation of China(62307025).
文摘Objectives:Teachers are facing unprecedented new challenges leading them to face an increasing number of tasks that are not part of their job,as well as having to cope with the additional skills acquisition that comes with non-traditional forms of teaching and learning,and increased work pressure leading to an increase in the rate of teachers leaving the profession.Therefore,this study aims to explore the mechanism of the career calling on job burnout through career adaptability and work engagement.Methods:This study conducted a cross-sectional survey of 465 primary and secondary school teachers(PSST)in China's Mainland from the perspective of work adjustment and used structural equation modeling(SEM)to examine the mediating roles of career adaptability and work engagement in the relationship between teachers’career calling and job burnout.Results:The results show that PSSTs are above average in career calling,career adaptability,and work engagement,while job burnout is below average.A significant positive or negative correlation exists between career calling,career adaptability,work engagement,and job burnout.The result of path analysis indicates that career adaptability and work engagement exert an indirect influence on the job burnout of PSST through three paths:namely,the independent intermediary role of career adaptability(EV=−0.144),the independent intermediary role of work engagement(EV=0.172)and the chain intermediary role of the two(EV=0.176).Conclusion:This study emphasizes the importance of career adaptability and work engagement in teacher development in regulating career calling and job burnout.Therefore,on the one hand,we think that if managers want to reduce teachers’job burnout,they need to pay more attention to teachers’career adaptability and work engagement,rather than relying solely on teachers’career calling.On the other hand,it is to remind teachers not to rely on their adjustment to adapt to the work,but also to need outside help as much as possible.
基金supported by the Hyperbaric Med School of the Department of Biomedical Sciences at the University of Padova,the Italian Air Force,and the Institute of Clinical Physiology(Milan)-National Research Council(IFC-CNR).
文摘Dear Editor,Space flight(SF)is substantially increasing at present.The emergence of commercial suborbital SF,such as the Virgin Galactic with VSS Unity and VMS Eve spacecraft,is extending to civilians,being previously confined to military and/or professional astronauts only.This new evidence offers additional opportunities for better characterizing the impact that the transition from Earth’s 1G to microgravity in space could have on the astronauts’health while comparing well-trained subjects such as the latt er to space newcomers[1].
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
基金supported by NIH/NIAMS(P01 AG066603,R01 AR079171,R21 AR078919)NIH/NIDCR(R01 DE031488,R01 DE031028)+4 种基金Alex’s Lemonade Stand Foundation(22-26743)American Cancer Society(DBG-23-1155131-01-IBCD)the Maryland Stem Cell Research Foundation(2021-MSCRFD-5641),and Department of Defense(USAMRAA HT9425-24-1-0051)MC is supported by Merkin Peripheral Neuropathy and Nerve Regeneration Center(23-DF/C2/260)M.K.is supported by NIH(T32HD044355).
文摘Peripheral neuropathy is a common complication in diabetes,affecting around 50%of the diabetic population.Co-occurrence of diabetic peripheral neuropathy(DPN)and diabetic bone disease has led to the hypothesis that DPN influences bone metabolism,although little experimental evidence has yet supported this premise.To investigate,mice were fed a high-fat diet(HFD)followed by phenotyping of skeletal-innervating neurons and bone architectural parameters.Results showed that HFD feeding resulted in a marked decrease in skeletal innervation(69%–41%reduction in Beta-III-Tubulin-stained nerves,38%reduction in CGRP-stained nerves in long bone periosteum).
基金supported by funding from NIDCR(1R01DE027957)Maryland Stem Cell Research Fund(2022-MSCRFV-5782)the NSF GRFP and NCI(5R01CA237597-05,2R01CA196701-06A1).
文摘Calvarial nerves,along with vasculature,influence skull formation during development and following injury,but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging.Studying the spatial distribution of nerves in the skull remains a challenge due to a lack of methods to quantify 3D structures in intact bone.To visualize calvarial 3D neurovascular architecture,we imaged nerves and endothelial cells with lightsheet microscopy.
基金supported by the Neurosurgery Pain Research Institute at Johns Hopkins University and by the Lehner Family Foundation.
文摘Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.
文摘The United States Food and Drug Administration's(FDA's)August 2024 determination that an additional phase Ⅱ study will be required to consider the approval of midomafetamine for the treatment of posttraumatic stress disorder(PTSD)could delay the potential approval of this promising treatment by several years.
文摘Background: In the global burden of non-communicable diseases, the top slot among them all is occupied by various cardiovascular diseases (CVD), which also claim primacy in mortality rates. Generally speaking, the pathophysiological pathway frequently involves either (or a combination of) elevated serum cholesterol levels, predominantly attributed to dietary patterns characterized by extremely high levels of saturated and trans-fat consumption. Day-to-day nutritional epidemiology among university students suggests that they represent a crucial demographic for the study of preventive interventions. Objective: This in-depth study and investigation were specifically aimed to quantitatively assess and compare prevailing patterns of dietary fat consumption between female students enrolled in health sciences and non-health sciences programs at major universities in Riyadh, Saudi Arabia. Methodology: This cross-sectional study was comprised of 434 Saudi female university students (age range: 18 - 25 years), utilizing a validated Block Dietary Fat Screener accompanied by anthropometric measurements and comprehensive demographic data collection. The sampling methodology consisted of a snowball technique that was spread across three major academic institutions in Riyadh. Results: Statistical analysis revealed a significant association between academic specialization and patterns of dietary fat consumption (p = 0.012). Paradoxically, students of health science exhibited a higher prevalence of very high fat intake (41.9%) compared with their non-health sciences counterparts (27.6%). Surprisingly, anthropometric stratification revealed that it was the underweight students who demonstrated very high levels of fat consumption. A notable socioeconomic gradient was observed, with students from households earning 15,000 - 20,000 SR monthly showing the highest prevalence of very high-fat consumption (47.1%), although this association did not achieve statistical significance (p = 0.104). Conclusion: These findings challenge the conventional assumption that health sciences education correlates with superior dietary behaviors. The data suggests a critical need for enhanced education in nutrition, as well as intervention using various behavioral programs across all academic disciplines, particularly those addressing the disconnect between nutritional knowledge and dietary practices among students of health sciences. Future longitudinal studies are warranted in order to elucidate the temporal relationship between academic specialization and dietary behaviors.
