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
N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory lo...N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates ...The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.展开更多
AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other t...AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.展开更多
Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral f...Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.展开更多
2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提...2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提高中国次季节降水预报能力提供了新途径。使用区域气候模式CWRF(regional Climate-Weather Research and Forecasting model)对中国气象局全球气候模式次季节预测系统CMA_CPSv3(China Meteorological Administration Climate Prediction System version 3)的预报结果进行中国区域动力降尺度,分析了CWRF和CMA_CPSv3模式对河南省2021年7月17—22日持续性强降水的预测效果。结果表明,区域模式和全球模式预报的降水空间分布和量级存在明显差异。尽管两个模式都低估了此次强降水过程的降水量,但总体上CWRF模式预报的降水量更大且更好地捕捉到了降水的空间分布。CWRF模式自6月26和29日起报的降水预报明显好于同一起报日CMA_CPSv3模式的预报结果。与CMA_CPSv3预报相比,CWRF显著地改善了东亚低空风场和低空急流的预报。CWRF对低空急流和水汽通量输送方向的改善尤为明显,预报的水汽在山脉的迎风坡辐合,为降水提供了有利的水汽条件。同时CWRF更好地预报了郑州上空的垂直上升运动,这些改善都有利于CWRF模式对降水有更高的预报技巧。展开更多
Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is importan...Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.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
Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals an...Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.展开更多
Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and...Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.展开更多
Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the...Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle.To comprehensively characterize the genomic variation within Bos indicus and,specifically,dairy breeds,we aim to identify non-reference sequences and construct a comprehensive pangenome.Results Five representative genomes of prominent dairy breeds,including Gir,Kankrej,Tharparkar,Sahiwal,and Red Sindhi,were sequenced using 10X Genomics‘linked-read’technology.Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome.A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods,revealing 8 Mb and 17.7 Mb of novel sequence respectively.A confident set of 6,844 Non-reference Unique Insertions(NUIs)spanning 7.57 Mb was identified through both methods,representing the pange-nome of Indian Bos indicus breeds.Comparative analysis with previously published pangenomes unveiled 2.8 Mb(37%)commonality with the Chinese indicine pangenome and only 1%commonality with the Bos taurus pange-nome.Among these,2,312 NUIs encompassing~2 Mb,were commonly found in 98 samples of the 5 breeds and des-ignated as Bos indicus Common Insertions(BICIs)in the population.Furthermore,926 BICIs were identified within 682 protein-coding genes,54 long non-coding RNAs(lncRNA),and 18 pseudogenes.These protein-coding genes were enriched for functions such as chemical synaptic transmission,cell junction organization,cell-cell adhesion,and cell morphogenesis.The protein-coding genes were found in various prominent quantitative trait locus(QTL)regions,suggesting potential roles of BICIs in traits related to milk production,reproduction,exterior,health,meat,and carcass.Notably,63.21%of the bases within the BICIs call set contained interspersed repeats,predominantly Long Inter-spersed Nuclear Elements(LINEs).Additionally,70.28%of BICIs are shared with other domesticated and wild species,highlighting their evolutionary significance.Conclusions This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India.The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.展开更多
In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)r...In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic development.The recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).展开更多
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supported by the National Institute on Aging(Nos.AG000723 and AG000578)(to VAB)the Fondation Sante(No.19656),Greece 2.0+1 种基金the National Recovery and Resilience Plan’s flagship program TAEDR-0535850the European Research Council(No.101077374-Synapto Mitophagy)(to KP)。
文摘N umerous neurological disorders negatively impact the nervous system,either through loss of neurons or by disrupting the normal functioning of neural networks.These impairments manifest as cognitive defects,memory loss,behavioral abnormalities,and motor dysfunctions.Decades of research have significantly advanced our understanding of the pathophysiology underlying neurodegene rative diseases,including Alzheimer's disease(AD),Parkinson's disease,amyotrophic lateral sclerosis,and others.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by grants PID2020-120308RB-I00 and PID2023-147802OB-I00 funded by MICIU/AEI/10.13039/501100011033FEDER,UE,by Aligning Science Across Parkinson’s(ref.ASAP-020505)through the Michael J.Fox Foundation for Parkinson’s Research+1 种基金by CiberNed Intramural Collaborative Projects(ref.PI2020/09)by the Spanish Fundación Mutua Madrile?a de Investigación Médica(to JLL)。
文摘The development of clinical candidates that modify the natural progression of sporadic Parkinson's disease and related synucleinopathies is a praiseworthy endeavor,but extremely challenging.Therapeutic candidates that were successful in preclinical Parkinson's disease animal models have repeatedly failed when tested in clinical trials.While these failures have many possible explanations,it is perhaps time to recognize that the problem lies with the animal models rather than the putative candidate.In other words,the lack of adequate animal models of Parkinson's disease currently represents the main barrier to preclinical identification of potential disease-modifying therapies likely to succeed in clinical trials.However,this barrier may be overcome by the recent introduction of novel generations of viral vectors coding for different forms of alpha-synuclein species and related genes.Although still facing several limitations,these models have managed to mimic the known neuropathological hallmarks of Parkinson's disease with unprecedented accuracy,delineating a more optimistic scenario for the near future.
文摘AIM: To determine the prevalence of unsuspected thyroid nodules on contrast enhanced 16and 64-modified discrete cosine transform (MDCT) of the chest, in a population of adult outpatients imaged for indications other than thyroid disease. METHODS: This retrospective study involved review of intravascular contrast-enhanced MDCT scans of the chest from 3077 consecutive adult outpatients, to identify unsuspected thyroid nodules. Exclusion criteria included history of thyroid cancer, known thyroid nodules or thyroid disease and risk factors for thyroid cancer, as evidenced by their medical records. One of 9 radiologists recorded number of nodules, location and bidirectional measurement of largest nodule, as well as amount of thyroid visualized on the chest computed tomography (CT). Presence of nodule was correlated with age, gender, race and percentage of thyroid imaged. RESULTS: A total of 2510 (2510/3077 or 81.6%) study subjects were included in the data analysis; among them,one or more nodules were identified in 629 subjects (629/2510 or 25.1%), with 242 (242/629 or 38.5%) having multiple nodules. Patients with nodule(s) were significantly older than those without (64 ± 13 years vs 58 ± 14 years, P < 0.0001), and female gender was associated with presence of nodule(s) (373/1222 or 30.5% vs 256/1288 or 19.9%, P < 0.0001). Women were also more likely having multiple nodules (167/373 or 44.8%) compared to men (75/256 or 29.3%, P < 0.0001). The majority of nodules (427/629 or 67.9%) were less than 1 cm. CONCLUSION: This retrospective review revealed a prevalence of 25.1% for unsuspected thyroid nodules on contrast-enhanced chest CT.
基金the support from the National Science Foundation of China(Grants Nos.61401117 and 61201017)the Fundamental Research Funds for the Central Universities(Grants Nos.HIT.IBRSEM.201303 and HIT.IBRSEM.B.201401).
文摘Near-infrared spectroscopy(NIRS)can provide the hemodynamics information based on the hemoglobin concentration representing the blood oxygen metabolism of the cerebral cortical,which can be deployed for the cerebral function study.However,NIRS-based cerebral function detection accuracy can be signi¯cantly in°uenced by the physiological activities such as cardic cycle,respiration,spontaneous low-frequency oscillation and ultra-low frequency oscillation.The distribution difference of the capillary,artery and vein leads to the heterogeneity feature of the cerebral tissues.In the case that the heterogeneity is not serious,good detection accuracy and stable performance can be achieved through the regression analysis as the reference signal can well represent the interference in the measurement signal when conducting the multi-distance measurement approach.The direct use of the reference signal to estimate the interference is not able to achieve good performance in the case that the heterogeneity is serious.In this study,the cerebral function activity signal is extracted using recursive least square(RLS)method based on the multi-distance measurement method in which the reference signal is processed by ensemble empirical mode decomposition(EEMD)algorithm.The temporal and dimensional correlation of the neighboring sampling values are applied to estimate the interference in the measurement signal.Monte Carlo simulation based on a heterogeneous model is adopted here to investigate the effectiveness of this methodology.The results show that this methodology can effectively suppress the physiological interference and improve the detection accuracy of cerebral activity signal.
文摘2021年7月17—22日河南省发生了一次历史罕见的持续性强降水,造成了巨大的经济损失。目前极端降水预报仍是次季节气候预测研究的热点和难点。区域气候模式有着比全球模式更精细的空间分辨率和更为完善的物理过程参数化方案,为进一步提高中国次季节降水预报能力提供了新途径。使用区域气候模式CWRF(regional Climate-Weather Research and Forecasting model)对中国气象局全球气候模式次季节预测系统CMA_CPSv3(China Meteorological Administration Climate Prediction System version 3)的预报结果进行中国区域动力降尺度,分析了CWRF和CMA_CPSv3模式对河南省2021年7月17—22日持续性强降水的预测效果。结果表明,区域模式和全球模式预报的降水空间分布和量级存在明显差异。尽管两个模式都低估了此次强降水过程的降水量,但总体上CWRF模式预报的降水量更大且更好地捕捉到了降水的空间分布。CWRF模式自6月26和29日起报的降水预报明显好于同一起报日CMA_CPSv3模式的预报结果。与CMA_CPSv3预报相比,CWRF显著地改善了东亚低空风场和低空急流的预报。CWRF对低空急流和水汽通量输送方向的改善尤为明显,预报的水汽在山脉的迎风坡辐合,为降水提供了有利的水汽条件。同时CWRF更好地预报了郑州上空的垂直上升运动,这些改善都有利于CWRF模式对降水有更高的预报技巧。
文摘Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other symptoms.The accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced EUS.Clinical studies have reported varying diagnostic and adverse event rates with these modalities.In addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different recommendations.In this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.
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Supported by American Diabetes AssociationAmerican Heart Association+3 种基金NIH NIEHSNIH NIANIH NINDSand NIH ARRA.
文摘Diabetes mellitus(DM)is a debilitating disorder that impacts all systems of the body and has been increasing in prevalence throughout the globe.DM represents a significant clinical challenge to care for individuals and prevent the onset of chronic disability and ultimately death.Underlying cellular mechanisms for the onset and development of DM are multi-factorial in origin and involve pathways associated with the production of reactive oxygen species and the generation of oxidative stress as well as the dysfunction of mitochondrial cellular organelles,programmed cell death,and circadian rhythm impairments.These pathways can ultimately involve failure in the glymphatic pathway of the brain that is linked to circadian rhythms disorders during the loss of metabolic homeostasis.New studies incorporate a number of promising techniques to examine patients with metabolic disorders that can include machine learning and artificial intelligence pathways to potentially predict the onset of metabolic dysfunction.
基金supported by NIH funding(RF1NS110637,2RF1NS094527,R01NS110635)to JW.
文摘Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.
基金the project “Genomics for Conservation of Indigenous Cattle Breeds and for Enhancing Milk Yield, Phase-I” [BT/ PR26466/AAQ/1/704/2017], funded by the Department of Biotechnology (DBT ), Indiathe project “Identification of key molecular factors involved in resistance/susceptibility to paratuberculosis infection in indigenous breeds of cows” [BT/PR32758/AAQ/1/760/2019], which was also funded by Department of Biotechnology (DBT ), India。
文摘Background India harbors the world’s largest cattle population,encompassing over 50 distinct Bos indicus breeds.This rich genetic diversity underscores the inadequacy of a single reference genome to fully capture the genomic landscape of Indian cattle.To comprehensively characterize the genomic variation within Bos indicus and,specifically,dairy breeds,we aim to identify non-reference sequences and construct a comprehensive pangenome.Results Five representative genomes of prominent dairy breeds,including Gir,Kankrej,Tharparkar,Sahiwal,and Red Sindhi,were sequenced using 10X Genomics‘linked-read’technology.Assemblies generated from these linked-reads ranged from 2.70 Gb to 2.77 Gb,comparable to the Bos indicus Brahman reference genome.A pangenome of Bos indicus cattle was constructed by comparing the newly assembled genomes with the reference using alignment and graph-based methods,revealing 8 Mb and 17.7 Mb of novel sequence respectively.A confident set of 6,844 Non-reference Unique Insertions(NUIs)spanning 7.57 Mb was identified through both methods,representing the pange-nome of Indian Bos indicus breeds.Comparative analysis with previously published pangenomes unveiled 2.8 Mb(37%)commonality with the Chinese indicine pangenome and only 1%commonality with the Bos taurus pange-nome.Among these,2,312 NUIs encompassing~2 Mb,were commonly found in 98 samples of the 5 breeds and des-ignated as Bos indicus Common Insertions(BICIs)in the population.Furthermore,926 BICIs were identified within 682 protein-coding genes,54 long non-coding RNAs(lncRNA),and 18 pseudogenes.These protein-coding genes were enriched for functions such as chemical synaptic transmission,cell junction organization,cell-cell adhesion,and cell morphogenesis.The protein-coding genes were found in various prominent quantitative trait locus(QTL)regions,suggesting potential roles of BICIs in traits related to milk production,reproduction,exterior,health,meat,and carcass.Notably,63.21%of the bases within the BICIs call set contained interspersed repeats,predominantly Long Inter-spersed Nuclear Elements(LINEs).Additionally,70.28%of BICIs are shared with other domesticated and wild species,highlighting their evolutionary significance.Conclusions This is the first report unveiling a robust set of NUIs defining the pangenome of Bos indicus breeds of India.The analyses contribute valuable insights into the genomic landscape of desi cattle breeds.
文摘In medical research,there are times when the introduction of a new tool can launch scientific discovery in new directions.While antibody development may be considered mundane,in the field of glucocerebrosidase(GCase)research,the dearth of validated antibodies for different applications has impeded progress in studies of disease pathogenesis and therapeutic development.The recent introduction of new,rigorously evaluated antibodies can now propel research into the link between glucocerebrosidase and Parkinson’s disease(PD)as well as aspects of the pathobiology of Gaucher disease(Jong et al.,2024).
