In recent decades,Haiti has been subject to man-made and natural disasters that have left its citizens vulnerable to a range of shocks.With a weak state unable to protect its populace,Haitians are exposed to some of t...In recent decades,Haiti has been subject to man-made and natural disasters that have left its citizens vulnerable to a range of shocks.With a weak state unable to protect its populace,Haitians are exposed to some of the highest levels of poverty and violence in the Western Hemisphere.In recent years,Haitians have experienced two crises that this study analyzes:the instability and political violence of“peyi lòk”as well as the global pandemic of COVID-19.This community-based assessment explores the impact of these two crises on the mental health and psychological well-being of 38 Haitian university students in the understudied northern part of the country.Results indicate that both crises had similarities related to their psychological effects on young people,most notably in terms of traumatic experiences related to threats or violence,forced confinement,and large increases in population-wide uncertainty.Additionally,the extreme violence of“peyi lòk”and the widespread unpredictability of COVID-19 and its effects in the early days of the pandemic resulted in high levels of stress and fear.Both crises also resulted in extreme economic hardship for students,with many reporting difficulties accessing basic needs such as food and water.This study highlights how converging population-level crises in“complex emergencies”can heighten trauma and compromise mental health.展开更多
Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative...Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.展开更多
Purpose:Media exaggerations of health research may confuse readers’understanding,erode public trust in science and medicine,and cause disease mismanagement.This study built artificial intelligence(AI)models to automa...Purpose:Media exaggerations of health research may confuse readers’understanding,erode public trust in science and medicine,and cause disease mismanagement.This study built artificial intelligence(AI)models to automatically identify and correct news headlines exaggerating obesity-related research findings.Design/methodology/approach:We searched popular digital media outlets to collect 523 headlines exaggerating obesity-related research findings.The reasons for exaggerations include:inferring causality from observational studies,inferring human outcomes from animal research,inferring distant/end outcomes(e.g.,obesity)from immediate/intermediate outcomes(e.g.,calorie intake),and generalizing findings to the population from a subgroup or convenience sample.Each headline was paired with the title and abstract of the peer-reviewed journal publication covered by the news article.We drafted an exaggeration-free counterpart for each original headline and fined-tuned a BERT model to differentiate between them.We further fine-tuned three generative language models-BART,PEGASUS,and T5 to autogenerate exaggeration-free headlines based on a journal publication’s title and abstract.Model performance was evaluated using the ROUGE metrics by comparing model-generated headlines with journal publication titles.Findings:The fine-tuned BERT model achieved 92.5%accuracy in differentiating between exaggeration-free and original headlines.Baseline ROUGE scores averaged 0.311 for ROUGE-1,0.113 for ROUGE-2,0.253 for ROUGE-L,and 0.253 ROUGE-Lsum.PEGASUS,T5,and BART all outperformed the baseline.The best-performing BART model attained 0.447 for ROUGE-1,0.221 for ROUGE-2,0.402 for ROUGE-L,and 0.402 for ROUGE-Lsum.Originality/value:This study demonstrated the feasibility of leveraging AI to automatically identify and correct news headlines exaggerating obesity-related research findings.展开更多
Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize c...Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.展开更多
Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),se...Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)implementation.Methods:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation support.The PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity Profile.Linear mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by gender.Results:Both implementation conditions led to significant improvements in PA and SST over time(p<0.01),but DI did not improve commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary time.Conclusion:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness programming.Similarly,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and girls.Additional research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.展开更多
Bone is a highly vascularized tissue,although this aspect of bone is often overlooked.In this article,the importance of blood flow in bone repair and regeneration will be reviewed.First,the skeletal vascular anatomy,w...Bone is a highly vascularized tissue,although this aspect of bone is often overlooked.In this article,the importance of blood flow in bone repair and regeneration will be reviewed.First,the skeletal vascular anatomy,with an emphasis on long bones,the distinct mechanisms for vascularizing bone tissue,and methods for remodeling existing vasculature are discussed.Next,techniques for quantifying bone blood flow are briefly summarized.Finally,the body of experimental work that demonstrates the role of bone blood flow in fracture healing,distraction osteogenesis,osteoporosis,disuse osteopenia,and bone grafting is examined.These results illustrate that adequate bone blood flow is an important clinical consideration,particularly during bone regeneration and in at-risk patient groups.展开更多
Ovarian cystic masses include a spectrum of benign, borderline and high grade malignant neoplasms. Imaging plays a crucial role in characterization and pretreatment planning of incidentally detected or suspected adnex...Ovarian cystic masses include a spectrum of benign, borderline and high grade malignant neoplasms. Imaging plays a crucial role in characterization and pretreatment planning of incidentally detected or suspected adnexal masses, as diagnosis of ovarian malignancy at an early stage is correlated with a better prognosis. Knowledge of differential diagnosis, imaging features, management trends and an algorithmic approach of such lesions is important for optimal clinical management. This article illustrates a multi-modality approach in the diagnosis of a spectrum of ovarian cystic masses and also proposes an algorithmic approach for the diagnosis of these lesions.展开更多
Industrial grade multi-walled carbon nanotubes(IG-MWCNTs) are a low-cost substitute for commercially purified multi-walled carbon nanotubes(P-MWCNTs). In this work, IG-MWCNTs were functionalized with tetraethylenepent...Industrial grade multi-walled carbon nanotubes(IG-MWCNTs) are a low-cost substitute for commercially purified multi-walled carbon nanotubes(P-MWCNTs). In this work, IG-MWCNTs were functionalized with tetraethylenepentamine(TEPA) for CO2capture. The TEPA impregnated IG-MWCNTs were characterized with various experimental methods including N2adsorption/desorption isotherms, elemental analysis, X-ray diffraction, Fourier transform infrared spectroscopy and thermogravimetric analysis. Both the adsorption isotherms of IGMWCNTs-n and the isosteric heats of different adsorption capacities were obtained from experiments. TEPA impregnated IG-MWCNTs were also shown to have high CO2adsorption capacity comparable to that of TEPA impregnated P-MWCNTs. The adsorption capacity of IG-MWCNTs based adsorbents was in the range of 2.145 to 3.088 mmol/g, depending on adsorption temperatures. Having the advantages of low-cost and high adsorption capacity, TEPA impregnated IG-MWCNTs seem to be a promising adsorbent for CO2capture from flue gas.展开更多
The fields of biomechanics and mechanobiology have long been predicated on the premise that mechanics governs cell behavior. However, over the past few years, a growing body of evidence has suggested that the mechanic...The fields of biomechanics and mechanobiology have long been predicated on the premise that mechanics governs cell behavior. However, over the past few years, a growing body of evidence has suggested that the mechanical environment very close to cells–the cell microenvironment–plays the most important role in determining what a cell feels and how it responds to tissue-level stimuli. To complicate matters further, cells can actively manipulate their microenvironments through pathways of recursive mechanobiological feedback. Harnessing this recursive behavior to understand and control cell physiology and pathophysiology is a critical frontier in the field of mechanobiology. Recent results suggest that the key to opening this scientific frontier to investigation and engineering application is understanding a different frontier: the physical frontier that cells face when probing their mechanical microenvironments.展开更多
Purpose:The coronavirus disease-2019(COVID-19)pandemic in the United States led to nationwide stay-at-home orders and school closures.Declines in energy expenditure resulting from canceled physical education classes a...Purpose:The coronavirus disease-2019(COVID-19)pandemic in the United States led to nationwide stay-at-home orders and school closures.Declines in energy expenditure resulting from canceled physical education classes and reduced physical activity may elevate childhood obesity risk.This study estimated the impact of COVID-19 on childhood obesity.Methods:A microsimulation model simulated the trajectory of a nationally representative kindergarten cohort’s body mass index z-scores and childhood obesity prevalence from April 2020 to March 2021 under the control scenario without COVID-19 and under the 4 alternative scenarios with COVID-19—Scenario 1:2-month nationwide school closure in April and May 2020;Scenario 2:Scenario 1 followed by a 10%reduction in daily physical activity in the summer from June to August;Scenario 3:Scenario 2 followed by 2-month school closure in September and October;and Scenario 4:Scenario 3 followed by an additional 2-month school closure in November and December.Results:Relative to the control scenario without COVID-19,Scenarios 1,2,3,and 4 were associated with an increase in the mean body mass index z-scores by 0.056(95%confidence interval(95%CI):0.0550.056),0.084(95%CI:0.0840.085),0.141(95%CI:0.1400.142),and 0.198(95%CI:0.1970.199),respectively,and an increase in childhood obesity prevalence by 0.640(95%CI:0.5150.765),0.972(95%CI:0.8191.126),1.676(95%CI:1.4751.877),and 2.373(95%CI:2.1352.612)percentage points,respectively.Compared to girls and non-Hispanic whites and Asians,the impact of COVID-19 on childhood obesity was modestly larger among boys and non-Hispanic blacks and Hispanics,respectively.Conclusion:Public health interventions are urgently called to promote an active lifestyle and engagement in physical activity among children to mitigate the adverse impact of COVID-19 on unhealthy weight gains and childhood obesity.展开更多
BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).I...BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.展开更多
The anthocyanin content in apple skin determines its red coloration,as seen in a Fuji apple mutant.Comparative RNA-seq analysis was performed to determine differentially expressed genes at different fruit development ...The anthocyanin content in apple skin determines its red coloration,as seen in a Fuji apple mutant.Comparative RNA-seq analysis was performed to determine differentially expressed genes at different fruit development stages between the wild-type and the skin color mutant.A novel R2R3-MYB transcription factor,MdMYB90-like,was uncovered as the key regulatory gene for enhanced coloration in the mutant.The expression of MdMYB90-like was 21.3 times higher in the mutant.MdMYB90-like regulates anthocyanin biosynthesis directly through the activation of anthocyanin biosynthesis genes and indirectly through the activation of other transcription factors that activate anthocyanin biosynthesis.MdMYB90-like bound to the promoters of both structural genes(MdCHS and MdUFGT)and other transcription factor genes(MdMYB1 and MdbHLH3)in the yeast one-hybrid system,electrophoretic mobility shift assay,and dual-luciferase assay.Transgenic analysis showed that MdMYB90-like was localized in the nucleus,and its overexpression induced the expression of other anthocyanin-related genes,including MdCHS,MdCHI,MdANS,MdUFGT,MdbHLH3,and MdMYB1.The mutant had reduced levels of DNA methylation in two regions(−1183 to−988 and−2018 to−1778)of the MdMYB90-like gene promoter,which might explain the enhanced expression of the gene and the increased anthocyanin content in the mutant apple skin.展开更多
Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body.The molecular mechanisms of OA are currently unknown.OA is a heterogeneous di...Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body.The molecular mechanisms of OA are currently unknown.OA is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA development.To better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA pathogenesis.In this review,we first focus on the epigenetic regulation of OA,with a particular focus on DNA methylation,histone modification,and microRNA regulation,followed by a summary of several key mediators in OA-associated pain.We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain,such as CRISPR,scRNA sequencing,and lineage tracing.Next,we discuss the timely updates concerning cell death regulation in OA pathology,including pyroptosis,ferroptosis,and autophagy,as well as their individual roles in OA and potential molecular targets in treating OA.Finally,our review highlights new directions on the role of the synovial lymphatic system in OA.An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.展开更多
BACKGROUND Pre-transplant nutrition is a key driver of outcomes following liver transplantation in children.Patients with biliary atresia(BA) may have difficulty achieving satisfactory weight gain with enteral nutriti...BACKGROUND Pre-transplant nutrition is a key driver of outcomes following liver transplantation in children.Patients with biliary atresia(BA) may have difficulty achieving satisfactory weight gain with enteral nutrition alone,and parenteral nutrition(PN) may be indicated.While PN has been shown to improve anthropometric parameters of children with BA listed for liver transplantation,less is known about the risks,particularly infectious,associated with this therapy among this specific group of patients.AIM To describe the incidence,microbiology,and risk factors of central line-associated bloodstream infection(CLABSI) among children with BA listed for liver transplantation.METHODS Retrospective review of children aged ≤ 2-years of age with BA who were listed for primary liver transplantation at Texas Children's Hospital from 2008 through2015(n = 96).Patients with a central line for administration of PN(n = 63) were identified and details of each CLABSI event were abstracted.We compared the group of patients who experienced CLABSI to the group who did not,to determine whether demographic,clinical,or laboratory factors correlated with development of CLABSI.RESULTS Nineteen of 63 patients(30%,95%CI:19,43) experienced 29 episodes of CLABSI during 4800 line days(6.04 CLABSI per 1000 line days).CLABSI was predominantly associated with Gram-negative organisms(14/29 episodes,48%)including Klebsiella spp.,Enterobacter spp.,and Escherichia coli.The sole polymicrobial infection grew Enterobacter cloacae and Klebsiella pneumoniae.Grampositive organisms(all Staphylococcus spp.) and fungus(all Candida spp.)comprised 9/29(31%) and 6/29(21%) episodes,respectively.No demographic,clinical,or laboratory factors were significantly associated with an increased risk for the first CLABSI event in Cox proportional hazards regression analysis CONCLUSION There is substantial risk for CLABSI among children with BA listed for liver transplantation.No clinical,demographic,or laboratory factor we tested emerged as an independent predictor of CLABSI.While our data did not show an impact of CLABSI on the short-term clinical outcome,it would seem prudent to implement CLABSI reduction strategies in this population to the extent that each CLABSI event represents potentially preventable hospitalization,unnecessary healthcare dollar expenditures,and may exact an opportunity cost,in terms of missed allograft offers.展开更多
The gastrointestinal track is inhabited by tens of trillions of microorganisms. The gut microbiota is involved in gut motility, nutrient absorption and synthesis of metabolites that influence hmeostasis, metabolism an...The gastrointestinal track is inhabited by tens of trillions of microorganisms. The gut microbiota is involved in gut motility, nutrient absorption and synthesis of metabolites that influence hmeostasis, metabolism and immunefunction. Given the influence gut microbiota has on health, there is a growing body of literature describing the gut microbiota's impact on brain and behavior.展开更多
BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are f...BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.展开更多
Physical activity(PA)has strong relevance for limiting the harms to human health and well-being due to the coronavirus disease-2019(COVID-19)pandemic.1 Active muscles produce chemicals that improve immune functioning,...Physical activity(PA)has strong relevance for limiting the harms to human health and well-being due to the coronavirus disease-2019(COVID-19)pandemic.1 Active muscles produce chemicals that improve immune functioning,which in turn reduces the extent of infections,and decreases inflammation,and these are the main causes of the lung damage from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.PA is a powerful preventive and therapeutic intervention for the most common pre-existing chronic conditions that increase risk of severe COVID-19 infections and mortality.展开更多
Pain sensation may appear under long-lasting mechanical stimulation. Although people have the experience that pain sensation generally decreases with time while the stimulation remains, the underlying mechanism remain...Pain sensation may appear under long-lasting mechanical stimulation. Although people have the experience that pain sensation generally decreases with time while the stimulation remains, the underlying mechanism remains elusive. We experimentally studied the thermal and strain ratedependent viscoelastic behavior of skin in uniaxial stretch and numerically investigated the effects of temperature and strain rate on pain sensation. The results indicate that the viscosity of skin tissue decreases with increasing temperature and reducing strain rate, which subsequently decreases the discharge frequency of skin nociceptor and thus relieves the pain sensation. The results would contribute to the understanding of pain relief mechanism and optimizing for mechanical treatment.展开更多
文摘In recent decades,Haiti has been subject to man-made and natural disasters that have left its citizens vulnerable to a range of shocks.With a weak state unable to protect its populace,Haitians are exposed to some of the highest levels of poverty and violence in the Western Hemisphere.In recent years,Haitians have experienced two crises that this study analyzes:the instability and political violence of“peyi lòk”as well as the global pandemic of COVID-19.This community-based assessment explores the impact of these two crises on the mental health and psychological well-being of 38 Haitian university students in the understudied northern part of the country.Results indicate that both crises had similarities related to their psychological effects on young people,most notably in terms of traumatic experiences related to threats or violence,forced confinement,and large increases in population-wide uncertainty.Additionally,the extreme violence of“peyi lòk”and the widespread unpredictability of COVID-19 and its effects in the early days of the pandemic resulted in high levels of stress and fear.Both crises also resulted in extreme economic hardship for students,with many reporting difficulties accessing basic needs such as food and water.This study highlights how converging population-level crises in“complex emergencies”can heighten trauma and compromise mental health.
文摘Acute care management of traumatic brain injury is focused on the prevention and reduction of secondary insults such as hypotension,hypoxia,intracranial hypertension,and detrimental inflammation.However,the imperative to balance multiple clinical concerns simultaneously often results in therapeutic strategies targeted to address one clinical concern causing unintended effects in other remote organ systems.Recently the bidirectional communication between the gastrointestinal tract and the brain has been shown to influence both the central nervous system and gastrointestinal tract homeostasis in health and disease.A critical component of this axis is the microorganisms of the gut known as the gut microbiome.Changes in gut microbial populations in the setting of central nervous system disease,including traumatic brain injury,have been reported in both humans and experimental animal models and can be further disrupted by off-target effects of patient care.In this review article,we will explore the important role gut microbial populations play in regulating brain-resident and peripheral immune cell responses after traumatic brain injury.We will discuss the role of bacterial metabolites in gut microbial regulation of neuroinflammation and their potential as an avenue for therapeutic intervention in the setting of traumatic brain injury.
文摘Purpose:Media exaggerations of health research may confuse readers’understanding,erode public trust in science and medicine,and cause disease mismanagement.This study built artificial intelligence(AI)models to automatically identify and correct news headlines exaggerating obesity-related research findings.Design/methodology/approach:We searched popular digital media outlets to collect 523 headlines exaggerating obesity-related research findings.The reasons for exaggerations include:inferring causality from observational studies,inferring human outcomes from animal research,inferring distant/end outcomes(e.g.,obesity)from immediate/intermediate outcomes(e.g.,calorie intake),and generalizing findings to the population from a subgroup or convenience sample.Each headline was paired with the title and abstract of the peer-reviewed journal publication covered by the news article.We drafted an exaggeration-free counterpart for each original headline and fined-tuned a BERT model to differentiate between them.We further fine-tuned three generative language models-BART,PEGASUS,and T5 to autogenerate exaggeration-free headlines based on a journal publication’s title and abstract.Model performance was evaluated using the ROUGE metrics by comparing model-generated headlines with journal publication titles.Findings:The fine-tuned BERT model achieved 92.5%accuracy in differentiating between exaggeration-free and original headlines.Baseline ROUGE scores averaged 0.311 for ROUGE-1,0.113 for ROUGE-2,0.253 for ROUGE-L,and 0.253 ROUGE-Lsum.PEGASUS,T5,and BART all outperformed the baseline.The best-performing BART model attained 0.447 for ROUGE-1,0.221 for ROUGE-2,0.402 for ROUGE-L,and 0.402 for ROUGE-Lsum.Originality/value:This study demonstrated the feasibility of leveraging AI to automatically identify and correct news headlines exaggerating obesity-related research findings.
文摘Background: Elevated Fontan pressure (FP) alone cannot fully predict clinical outcomes. We hypothesized thathemodynamic profiling using a cardiac index (CI)-systemic vascular resistance (SVR) plot could characterize clinicalfeatures and predict the prognosis of post-Fontan patients. Methods: We included post-Fontan patients whounderwent cardiac catheterization at age < 10 years. Patients were classified into four categories: A, CI ≥ 3, SVRindex (SVRI) ≥ 20;B, CI < 3, SVRI ≥ 20;C, CI ≥ 3, SVRI < 20;and D, CI < 3, SVRI < 20. The primary outcome wasfreedom from the combined endpoint: new onset of protein-losing enteropathy or plastic bronchitis, heart transplant,and death. Clinical and hemodynamic variables and freedom from the endpoint were compared betweenthe hemodynamic categories and outcome predictors were evaluated. Results: Eighty-three patients wereincluded. Median follow-up was 5.3 years. Category A/B/C/D consisted of 4/15/53/11 patients, respectively. Allthe patients in category A were New York Heart Association I/II and had a significantly lower pulmonary vascularresistance index (PVRI). Patients in category C had lower pulmonary/systemic blood flow. Patients in category Dhad a higher PVRI and had the poorest freedom from the endpoint (44% at 5 years). Elevated FP and category Dwere outcome predictors. Conclusions: CI-SVR plots was a novel adjunctive method for Fontan hemodynamicprofiling.
基金The U.S.Department of Agriculture National Institute of Food and Agriculture(USDA NIFA)grant:2015-68001-23242.The USDA was not involved in the design of the study and collection,analysis,and interpretation of data or writing of the manuscript.The authors wish to thank the School Wellness Teams(SWT)who participated in the intervention and led programming.The authors acknowledge the students and staff who helped facilitate data collection and analysis procedures:Andra Luth,Marisa Rosen,Laura C.Liechty,Ann Torbert,and Quinn M.Zuercher(Iowa State University Extension and Outreach),made contributions to the distribution,implementation,and evaluation of SWITCH.
文摘Background:The School Wellness Integration Targeting Child Health(SWITCH)intervention has demonstrated feasibility as an implementation approach to help schools facilitate changes in students’physical activity(PA),sedentary screen time(SST),and dietary intake(DI).This study evaluated the comparative effectiveness of enhanced(individualized)implementation and standard(group-based)implementation.Methods:Twenty-two Iowa elementary schools participated,with each receiving standardized training(wellness conference and webinars).Schools were matched within region and randomized to receive either individualized or group implementation support.The PA,SST,and DI outcomes of 1097 students were assessed at pre-and post-intervention periods using the Youth Activity Profile.Linear mixed models evaluated differential change in outcomes by condition,for comparative effectiveness,and by gender.Results:Both implementation conditions led to significant improvements in PA and SST over time(p<0.01),but DI did not improve commensurately(p value range:0.02‒0.05).There were no differential changes between the group and individualized conditions for PA(p=0.51),SST(p=0.19),or DI(p=0.73).There were no differential effects by gender(i.e.,non-significant condition-by-gender interactions)for PA(p_(for interaction)=0.86),SST(p_(for interaction)=0.46),or DI(p_(for interaction)=0.15).Effect sizes for both conditions equated to approximately 6 min more PA per day and approximately 3 min less sedentary time.Conclusion:The observed lack of difference in outcomes suggests that group implementation of SWITCH is equally effective as individualized implementation for building capacity in school wellness programming.Similarly,the lack of interaction by gender suggests that SWITCH can be beneficial for both boys and girls.Additional research is needed to understand the school-level factors that influence implementation(and outcomes)of SWITCH.
基金Supported by grants from the National Institutes of Health(R01 AR050211P30 AR057235)
文摘Bone is a highly vascularized tissue,although this aspect of bone is often overlooked.In this article,the importance of blood flow in bone repair and regeneration will be reviewed.First,the skeletal vascular anatomy,with an emphasis on long bones,the distinct mechanisms for vascularizing bone tissue,and methods for remodeling existing vasculature are discussed.Next,techniques for quantifying bone blood flow are briefly summarized.Finally,the body of experimental work that demonstrates the role of bone blood flow in fracture healing,distraction osteogenesis,osteoporosis,disuse osteopenia,and bone grafting is examined.These results illustrate that adequate bone blood flow is an important clinical consideration,particularly during bone regeneration and in at-risk patient groups.
文摘Ovarian cystic masses include a spectrum of benign, borderline and high grade malignant neoplasms. Imaging plays a crucial role in characterization and pretreatment planning of incidentally detected or suspected adnexal masses, as diagnosis of ovarian malignancy at an early stage is correlated with a better prognosis. Knowledge of differential diagnosis, imaging features, management trends and an algorithmic approach of such lesions is important for optimal clinical management. This article illustrates a multi-modality approach in the diagnosis of a spectrum of ovarian cystic masses and also proposes an algorithmic approach for the diagnosis of these lesions.
基金supported by Zhejiang Provincial Natural Science Foundation of China(Grant No.LZ12E08002)
文摘Industrial grade multi-walled carbon nanotubes(IG-MWCNTs) are a low-cost substitute for commercially purified multi-walled carbon nanotubes(P-MWCNTs). In this work, IG-MWCNTs were functionalized with tetraethylenepentamine(TEPA) for CO2capture. The TEPA impregnated IG-MWCNTs were characterized with various experimental methods including N2adsorption/desorption isotherms, elemental analysis, X-ray diffraction, Fourier transform infrared spectroscopy and thermogravimetric analysis. Both the adsorption isotherms of IGMWCNTs-n and the isosteric heats of different adsorption capacities were obtained from experiments. TEPA impregnated IG-MWCNTs were also shown to have high CO2adsorption capacity comparable to that of TEPA impregnated P-MWCNTs. The adsorption capacity of IG-MWCNTs based adsorbents was in the range of 2.145 to 3.088 mmol/g, depending on adsorption temperatures. Having the advantages of low-cost and high adsorption capacity, TEPA impregnated IG-MWCNTs seem to be a promising adsorbent for CO2capture from flue gas.
文摘The fields of biomechanics and mechanobiology have long been predicated on the premise that mechanics governs cell behavior. However, over the past few years, a growing body of evidence has suggested that the mechanical environment very close to cells–the cell microenvironment–plays the most important role in determining what a cell feels and how it responds to tissue-level stimuli. To complicate matters further, cells can actively manipulate their microenvironments through pathways of recursive mechanobiological feedback. Harnessing this recursive behavior to understand and control cell physiology and pathophysiology is a critical frontier in the field of mechanobiology. Recent results suggest that the key to opening this scientific frontier to investigation and engineering application is understanding a different frontier: the physical frontier that cells face when probing their mechanical microenvironments.
文摘Purpose:The coronavirus disease-2019(COVID-19)pandemic in the United States led to nationwide stay-at-home orders and school closures.Declines in energy expenditure resulting from canceled physical education classes and reduced physical activity may elevate childhood obesity risk.This study estimated the impact of COVID-19 on childhood obesity.Methods:A microsimulation model simulated the trajectory of a nationally representative kindergarten cohort’s body mass index z-scores and childhood obesity prevalence from April 2020 to March 2021 under the control scenario without COVID-19 and under the 4 alternative scenarios with COVID-19—Scenario 1:2-month nationwide school closure in April and May 2020;Scenario 2:Scenario 1 followed by a 10%reduction in daily physical activity in the summer from June to August;Scenario 3:Scenario 2 followed by 2-month school closure in September and October;and Scenario 4:Scenario 3 followed by an additional 2-month school closure in November and December.Results:Relative to the control scenario without COVID-19,Scenarios 1,2,3,and 4 were associated with an increase in the mean body mass index z-scores by 0.056(95%confidence interval(95%CI):0.0550.056),0.084(95%CI:0.0840.085),0.141(95%CI:0.1400.142),and 0.198(95%CI:0.1970.199),respectively,and an increase in childhood obesity prevalence by 0.640(95%CI:0.5150.765),0.972(95%CI:0.8191.126),1.676(95%CI:1.4751.877),and 2.373(95%CI:2.1352.612)percentage points,respectively.Compared to girls and non-Hispanic whites and Asians,the impact of COVID-19 on childhood obesity was modestly larger among boys and non-Hispanic blacks and Hispanics,respectively.Conclusion:Public health interventions are urgently called to promote an active lifestyle and engagement in physical activity among children to mitigate the adverse impact of COVID-19 on unhealthy weight gains and childhood obesity.
文摘BACKGROUND Primary sclerosing cholangitis(PSC)associated inflammatory bowel disease(IBD)is a unique form of IBD(PSC-IBD)with distinct clinical and histologic features from ulcerative colitis(UC)and Crohn disease(CD).In patients with PSC and IBD,the severity of the two disease processes may depend on each other.AIM To study the histologic and clinical features of PSC patients with and without IBD.METHODS We assessed specimens from patients with UC(n=28),CD(n=10),PSC and UC(PSC-UC;n=26);PSC and CD(PSC-CD;n=6);and PSC and no IBD(PSC-no IBD;n=4)between years 1999-2013.PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration.Clinical data including age,gender,age at IBD and PSC diagnoses,IBD duration,treatment,follow-up,orthotopic liver transplantation(OLT)were noted.RESULTS PSC-UC patients had more isolated right-sided disease(P=0.03),and less active inflammation in left colon,rectum(P=0.03 and P=0.0006),and overall(P=0.0005)compared to UC.They required less steroids(P=0.01)and fewer colectomies(P=0.03)than UC patients.The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD.No PSC-CD patients required OLT compared to 38%of PSC-UC(P=0.1).PSC-IBD(PSC-UC and PSCCD)patients with OLT had severe disease in the left colon and rectum(P=0.04).CONCLUSION PSC-UC represents a distinct form of IBD.The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction,however warrants clinical attention and further research.
基金This work was supported by National Key R&D Program of China(2019YFD1000100)the Fundamental Research Funds for the Central Universities(KYZZ2021002)+3 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions to S.C.Q.the National Natural Science Foundation of China(31671766)the Guangdong Innovation Research Team Fund(No.2014ZT05S078)the Shenzhen Commission of Science and Technology Innovation Project(JCYJ20190808143207457,JCYJ20180305124101630,and JCYJ20170818094958663)to W.Y.
文摘The anthocyanin content in apple skin determines its red coloration,as seen in a Fuji apple mutant.Comparative RNA-seq analysis was performed to determine differentially expressed genes at different fruit development stages between the wild-type and the skin color mutant.A novel R2R3-MYB transcription factor,MdMYB90-like,was uncovered as the key regulatory gene for enhanced coloration in the mutant.The expression of MdMYB90-like was 21.3 times higher in the mutant.MdMYB90-like regulates anthocyanin biosynthesis directly through the activation of anthocyanin biosynthesis genes and indirectly through the activation of other transcription factors that activate anthocyanin biosynthesis.MdMYB90-like bound to the promoters of both structural genes(MdCHS and MdUFGT)and other transcription factor genes(MdMYB1 and MdbHLH3)in the yeast one-hybrid system,electrophoretic mobility shift assay,and dual-luciferase assay.Transgenic analysis showed that MdMYB90-like was localized in the nucleus,and its overexpression induced the expression of other anthocyanin-related genes,including MdCHS,MdCHI,MdANS,MdUFGT,MdbHLH3,and MdMYB1.The mutant had reduced levels of DNA methylation in two regions(−1183 to−988 and−2018 to−1778)of the MdMYB90-like gene promoter,which might explain the enhanced expression of the gene and the increased anthocyanin content in the mutant apple skin.
基金supported by the National Natural Science Foundation of China(NSFC)grants(82030067,82161160342,and 82172397)to D.C.and L.T.a grant from the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2020353)to L.T.+1 种基金supported by the National Key Research and Development Program of China(2021YFB3800800 to L.T.and D.C)supported by the research grant NIH AG0599775.
文摘Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body.The molecular mechanisms of OA are currently unknown.OA is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA development.To better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA pathogenesis.In this review,we first focus on the epigenetic regulation of OA,with a particular focus on DNA methylation,histone modification,and microRNA regulation,followed by a summary of several key mediators in OA-associated pain.We then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain,such as CRISPR,scRNA sequencing,and lineage tracing.Next,we discuss the timely updates concerning cell death regulation in OA pathology,including pyroptosis,ferroptosis,and autophagy,as well as their individual roles in OA and potential molecular targets in treating OA.Finally,our review highlights new directions on the role of the synovial lymphatic system in OA.An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.
文摘BACKGROUND Pre-transplant nutrition is a key driver of outcomes following liver transplantation in children.Patients with biliary atresia(BA) may have difficulty achieving satisfactory weight gain with enteral nutrition alone,and parenteral nutrition(PN) may be indicated.While PN has been shown to improve anthropometric parameters of children with BA listed for liver transplantation,less is known about the risks,particularly infectious,associated with this therapy among this specific group of patients.AIM To describe the incidence,microbiology,and risk factors of central line-associated bloodstream infection(CLABSI) among children with BA listed for liver transplantation.METHODS Retrospective review of children aged ≤ 2-years of age with BA who were listed for primary liver transplantation at Texas Children's Hospital from 2008 through2015(n = 96).Patients with a central line for administration of PN(n = 63) were identified and details of each CLABSI event were abstracted.We compared the group of patients who experienced CLABSI to the group who did not,to determine whether demographic,clinical,or laboratory factors correlated with development of CLABSI.RESULTS Nineteen of 63 patients(30%,95%CI:19,43) experienced 29 episodes of CLABSI during 4800 line days(6.04 CLABSI per 1000 line days).CLABSI was predominantly associated with Gram-negative organisms(14/29 episodes,48%)including Klebsiella spp.,Enterobacter spp.,and Escherichia coli.The sole polymicrobial infection grew Enterobacter cloacae and Klebsiella pneumoniae.Grampositive organisms(all Staphylococcus spp.) and fungus(all Candida spp.)comprised 9/29(31%) and 6/29(21%) episodes,respectively.No demographic,clinical,or laboratory factors were significantly associated with an increased risk for the first CLABSI event in Cox proportional hazards regression analysis CONCLUSION There is substantial risk for CLABSI among children with BA listed for liver transplantation.No clinical,demographic,or laboratory factor we tested emerged as an independent predictor of CLABSI.While our data did not show an impact of CLABSI on the short-term clinical outcome,it would seem prudent to implement CLABSI reduction strategies in this population to the extent that each CLABSI event represents potentially preventable hospitalization,unnecessary healthcare dollar expenditures,and may exact an opportunity cost,in terms of missed allograft offers.
文摘The gastrointestinal track is inhabited by tens of trillions of microorganisms. The gut microbiota is involved in gut motility, nutrient absorption and synthesis of metabolites that influence hmeostasis, metabolism and immunefunction. Given the influence gut microbiota has on health, there is a growing body of literature describing the gut microbiota's impact on brain and behavior.
基金Supported by TMH-IRG(account number-466/2012 and 164/2016)LTMT grant for project funding+1 种基金ACTREC-TMC for funding to Gupta labsupported by ACTREC fellowships
文摘BACKGROUND The prognosis of gastric cancer continues to remain poor,and epigenetic drugs like histone deacetylase inhibitors(HDACi)have been envisaged as potential therapeutic agents.Nevertheless,clinical trials are facing issues with toxicity and efficacy against solid tumors,which may be partly due to the lack of patient stratification for effective treatments.To study the need of patient stratification before HDACi treatment,and the efficacy of pre-treatment of HDACi as a chemotherapeutic drug sensitizer.METHODS The expression activity of class 1 HDACs and histone acetylation was examined in human gastric cancer cells and tissues.The potential combinatorial regime of HDACi and chemotherapy drugs was defined on the basis of observed drug binding assays,chromatin remodeling and cell death.RESULTS In the present study,the data suggest that the differential increase in HDAC activity and the expression of class 1 HDACs are associated with hypoacetylation of histone proteins in tumors compared to normal adjacent mucosa tissue samples of gastric cancer.The data highlights for the first time that pretreatment of HDACi results in an increased amount of DNA-bound drugs associated with enhanced histone acetylation,chromatin relaxation and cell cycle arrest.Fraction-affected plots and combination index-based analysis show that pre-HDACi chemo drug combinatorial regimes,including valproic acid with cisplatin or oxaliplatin and trichostatin A with epirubicin,exhibit synergism with maximum cytotoxic potential due to higher cell death at low combined doses in gastric cancer cell lines.CONCLUSION Expression or activity of class 1 HDACs among gastric cancer patients present an effective approach for patient stratification.Furthermore,HDACi therapy in pretreatment regimes is more effective with chemotherapy drugs,and may aid in predicting individual patient prognosis.
文摘Physical activity(PA)has strong relevance for limiting the harms to human health and well-being due to the coronavirus disease-2019(COVID-19)pandemic.1 Active muscles produce chemicals that improve immune functioning,which in turn reduces the extent of infections,and decreases inflammation,and these are the main causes of the lung damage from severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.PA is a powerful preventive and therapeutic intervention for the most common pre-existing chronic conditions that increase risk of severe COVID-19 infections and mortality.
基金supported by the National Natural Science Foundation of China (11372243, 11372243, 1152219)the International Science and Technology Cooperation Program of China (2013DFG02930)
文摘Pain sensation may appear under long-lasting mechanical stimulation. Although people have the experience that pain sensation generally decreases with time while the stimulation remains, the underlying mechanism remains elusive. We experimentally studied the thermal and strain ratedependent viscoelastic behavior of skin in uniaxial stretch and numerically investigated the effects of temperature and strain rate on pain sensation. The results indicate that the viscosity of skin tissue decreases with increasing temperature and reducing strain rate, which subsequently decreases the discharge frequency of skin nociceptor and thus relieves the pain sensation. The results would contribute to the understanding of pain relief mechanism and optimizing for mechanical treatment.
