tbuckley/cabot-search huggingface dataset:
Phase 2 study of epigenetic priming with decitabine followed by cytarabine for acute myeloid leukemia in older patients
Authors: Annie Im, Kevin Quann, Mounzer Agha, Anastasios Raptis, Robert L. Redner, Jing‐Zhou Hou, Rafic Farah, Kathleen A. Dorritie, Alison R. Sehgal, Daniel Normolle, Dana H. Bovbjerg, Nidhi Aggarwal, James Herman, Konstantinos Lontos, Michael Boyiadzis
Journal: American Journal of Hematology (2024)

Abstract Acute myeloid leukemia (AML) in older patients has a poor prognosis, low complete remission (CR) rates, and poor overall survival (OS). Preclinical studies have shown synergistic effects of epigenetic priming with hypomethylating agents followed by cytarabine. Based on these data, we hypothesized that an induction regimen using epigenetic priming with decitabine, followed by cytarabine would be effective and safe in older patients with previously untreated AML. Here, we conducted a phase 2 trial in which older patients with previously untreated AML received an induction regimen consisting of 1 or 2 courses of decitabine 20 mg/m 2 intravenously (IV) for 5 days followed by cytarabine 100 mg/m 2 continuous IV infusion for 5 days. Forty‐four patients (median age 76 years) were enrolled, and CR/CRi was achieved by 26 patients (59% of all patients, 66.7% of evaluable patients). Fourteen of 21 (66.7%) patients with adverse cytogenetics achieved CR including six out of seven evaluable patients with TP53 mutations. The 4‐ and 8‐week mortality rates were 2.3% and 9.1%, respectively, with median OS of 10.7 months. These results suggest epigenetic priming with decitabine followed by cytarabine should be considered as an option for first‐line therapy in older patients with AML. This trial was registered at www.clinicaltrials.gov as # NCT01829503.
Nano oxygen chamber by cascade reaction for hypoxia mitigation and reactive oxygen species scavenging in wound healing
Authors: Xiaoxue Han, Leah Ju, Chai Saengow, Wen Ren, Randy Ewoldt, Timothy Fan, Joseph Irudayaraj
Journal: Bioactive Materials (2024)

Hypoxia, excessive reactive oxygen species (ROS), and impaired angiogenesis are prominent obstacles to wound healing following trauma and surgical procedures, often leading to the development of keloids and hypertrophic scars. To address these challenges, a novel approach has been proposed, involving the development of a cascade enzymatic reaction-based nanocarriers-laden wound dressing. This advanced technology incorporates superoxide dismutase modified oxygen nanobubbles and catalase modified oxygen nanobubbles within an alginate hydrogel matrix. The oxygen nano chamber functions through a cascade reaction between superoxide dismutase and catalase, wherein excessive superoxide in the wound environment is enzymatically decomposed into hydrogen peroxide, and this hydrogen peroxide is subsequently converted into oxygen by catalase. This enzymatic cascade effectively controls wound inflammation and hypoxia, mitigating the risk of keloid formation. Concurrently, the oxygen nanobubbles release oxygen continuously, thus providing a sustained supply of oxygen to the wound site. The oxygen release from this dynamic system stimulates fibroblast proliferation, fosters the formation of new blood vessels, and contributes to the overall wound healing process. In the rat full-thickness wound model, the cascade reaction-based nano oxygen chamber displayed a notable capacity to expedite wound healing without scarring. Furthermore, in the pilot study of porcine full-thickness wound healing, a notable acceleration of tissue repair was observed in the conceived cascade reaction-based gel treated group within the 3 days post-surgery, which represents the proliferation stage of healing process. These achievements hold significant importance in ensuring the complete functional recovery of tissues, thereby highlighting its potential as a promising approach for enhancing wound healing outcomes.
Role of Age and Competing Risk of Death in the Racial Disparity of Kidney Failure Incidence after Onset of CKD
Authors: Guofen Yan, Robert Nee, Julia J. Scialla, Tom Greene, Wei Yu, Fei Heng, Alfred K. Cheung, Keith C. Norris
Journal: Journal of the American Society of Nephrology (2024)

Significance Statement Black adults in the United States have 2–4 times higher incidence of kidney failure than White adults. Yet, the reasons underlying this disparity remain poorly understood. Among 547,188 US veterans with new-onset CKD, according to a new race-free GFR equation, Black veterans had a 2.5-fold higher cumulative incidence of kidney failure, compared with White veterans, in any follow-up period from CKD onset. This disparity resulted from a combination of higher hazards of progression to kidney failure and lower hazards of competing-risk death in Black veterans. Both, in turn, were largely explained by the younger age at CKD onset in Black veterans, underscoring an urgent need to prevent early onset and slow progression of CKD in younger Black adults. Background The Black adult population is well known to have higher incidence of kidney failure than their White counterpart in the United States, but the reasons underlying this disparity are unclear. We assessed the racial differences in kidney failure and death from onset of CKD on the basis of the race-free 2021 CKD Epidemiology Collaboration equation and examined the extent to which these differences could be explained by factors at the time of CKD onset. Methods We analyzed a national cohort consisting of 547,188 US veterans (103,821 non-Hispanic Black and 443,367 non-Hispanic White), aged 18–85 years, with new-onset CKD between 2005 and 2016 who were followed through 10 years or May 2018 for incident kidney failure with replacement therapy (KFRT) and pre-KFRT death. Results At CKD onset, Black veterans were, on average, 7.8 years younger than White veterans. In any time period from CKD onset, the cumulative incidence of KFRT was 2.5-fold higher for Black versus White veterans. Meanwhile, Black veterans had persistently &gt;2-fold higher hazards of KFRT throughout follow-up (overall hazard ratio [95% confidence interval], 2.38 [2.31 to 2.45]) and conversely had 17%–48% decreased hazards of pre-KFRT death. These differences were reduced after accounting for the racial difference in age at CKD onset. Conclusions The 2.5-fold higher cumulative incidence of kidney failure in Black adults resulted from a combination of higher hazards of progression to kidney failure and lower hazards of the competing risk of death, both of which can be largely explained by the younger age at CKD onset in Black compared with White adults.
Pkd2 Deficiency in Embryonic Aqp2+ Progenitor Cells Is Sufficient to Cause Severe Polycystic Kidney Disease
Authors: Akaki Tsilosani, Chao Gao, Enuo Chen, Andrea R. Lightle, Sana Shehzad, Madhulika Sharma, Pamela V. Tran, Carlton M. Bates, Darren P. Wallace, Wenzheng Zhang
Journal: Journal of the American Society of Nephrology (2024)

Autosomal dominant polycystic kidney disease (ADPKD) is a devastating disorder caused by mutations in polycystin 1 ( PKD1 ) and polycystin 2 ( PKD2 ). Currently, the mechanism for renal cyst formation remains unclear. Here, we provide convincing and conclusive data in mice demonstrating that Pkd2 deletion in embryonic Aqp2 + progenitor cells (AP), but not in neonate or adult Aqp2 + cells, is sufficient to cause severe polycystic kidney disease (PKD) with progressive loss of intercalated cells and complete elimination of α -intercalated cells, accurately recapitulating a newly identified cellular phenotype of patients with ADPKD. Hence, Pkd2 is a new potential regulator critical for balanced AP differentiation into, proliferation, and/or maintenance of various cell types, particularly α -intercalated cells. The Pkd2 conditional knockout mice developed in this study are valuable tools for further studies on collecting duct development and early steps in cyst formation. The finding that Pkd2 loss triggers the loss of intercalated cells is a suitable topic for further mechanistic studies.
E-Cigarettes and FDA Nicotine Cap
Authors: Eleanor L. S. Leavens, Theodore L. Wagener
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Leveraging external control data in the design and analysis of neuro-oncology trials: Pearls and perils
Authors: Mei-Yin C Polley, Daniel Schwartz, Theodore Karrison, James J Dignam
Journal: Neuro-Oncology (2024)

Abstract Background Randomized controlled trials have been the gold standard for evaluating medical treatments for many decades but they are often criticized for requiring large sample sizes. Given the urgent need for better therapies for glioblastoma, it has been argued that data collected from patients treated with the standard regimen can provide high-quality external control data to supplement or replace concurrent control arm in future glioblastoma trials. Methods In this article, we provide an in-depth appraisal of the use of external control data in the context of neuro-oncology trials. We describe several clinical trial designs with particular attention to how external information is utilized and address common fallacies that may lead to inappropriate adoptions of external control data. Results Using 2 completed glioblastoma trials, we illustrate the use of an assessment tool that lays out a blueprint for assembling a high-quality external control data set. Using statistical simulations, we draw caution from scenarios where these approaches can fall short on controlling the type I error rate. Conclusions While this approach may hold promise in generating informative data in certain settings, this sense of optimism should be tampered with a healthy dose of skepticism due to a myriad of design and analysis challenges articulated in this review. Importantly, careful planning is key to its successful implementation.
Sex Disparities in Longitudinal Use and Intensification of Guideline-Directed Medical Therapy Among Patients With Newly Diagnosed Heart Failure With Reduced Ejection Fraction
Authors: Andrew Sumarsono, Luyu Xie, Neil Keshvani, Chenguang Zhang, Lajjaben Patel, Windy W. Alonso, Jennifer T. Thibodeau, Gregg C. Fonarow, Harriette G.C. Van Spall, Sarah E. Messiah, Ambarish Pandey
Journal: Circulation (2024)

Guideline-directed medical therapies (GDMTs) are the mainstay of treatment for heart failure with reduced ejection fraction (HFrEF), but they are underused. Whether sex differences exist in the initiation and intensification of GDMT for newly diagnosed HFrEF is not well established.
The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing
Authors: Yuqing Liu, Yejun Tan, Zheyu Zhang, Min Yi, Lemei Zhu, Weijun Peng
Journal: Translational Neurodegeneration (2024)

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.
Generative AI in glioma: Ensuring diversity in training image phenotypes to improve diagnostic performance for IDH mutation prediction
Authors: Hye Hyeon Moon, Jiheon Jeong, Ji Eun Park, Namkug Kim, Changyong Choi, Young‑Hoon Kim, Sang Woo Song, Chang-Ki Hong, Jeong Hoon Kim, Ho Sung Kim
Journal: Neuro-Oncology (2024)

This study evaluated whether generative artificial intelligence (AI)-based augmentation (GAA) can provide diverse and realistic imaging phenotypes and improve deep learning-based classification of isocitrate dehydrogenase (IDH) type in glioma compared with neuroradiologists.
Options for Building a Diverse Health Care Workforce
Authors: Mark C. Henderson, Shadi Aminololama-Shakeri
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The DNA damage sensor ATM kinase interacts with the p53 mRNA and guides the DNA damage response pathway
Authors: Konstantinos Karakostis, Laurence Malbert-Colas, Aikaterini Thermou, Borek Vojtesek, Robin Fåhraeus
Journal: Molecular Cancer (2024)

Abstract Background The ATM kinase constitutes a master regulatory hub of DNA damage and activates the p53 response pathway by phosphorylating the MDM2 protein, which develops an affinity for the p53 mRNA secondary structure. Disruption of this interaction prevents the activation of the nascent p53. The link of the MDM2 protein— p53 mRNA interaction with the upstream DNA damage sensor ATM kinase and the role of the p53 mRNA in the DNA damage sensing mechanism, are still highly anticipated. Methods The proximity ligation assay (PLA) has been extensively used to reveal the sub-cellular localisation of the protein—mRNA and protein–protein interactions. ELISA and co-immunoprecipitation confirmed the interactions in vitro and in cells. Results This study provides a novel mechanism whereby the p53 mRNA interacts with the ATM kinase enzyme and shows that the L22L synonymous mutant, known to alter the secondary structure of the p53 mRNA, prevents the interaction. The relevant mechanistic roles in the DNA Damage Sensing pathway, which is linked to downstream DNA damage response, are explored. Following DNA damage (double-stranded DNA breaks activating ATM), activated MDMX protein competes the ATM— p53 mRNA interaction and prevents the association of the p53 mRNA with NBS1 (MRN complex). These data also reveal the binding domains and the phosphorylation events on ATM that regulate the interaction and the trafficking of the complex to the cytoplasm. Conclusion The presented model shows a novel interaction of ATM with the p53 mRNA and describes the link between DNA Damage Sensing with the downstream p53 activation pathways; supporting the rising functional implications of synonymous mutations altering secondary mRNA structures.
Association between Urinary Haloacetic Acid Concentrations and Liver Injury among Women: Results from the Tongji Reproductive and Environmental (TREE) Study
Authors: Yan-Ling Deng, Ting-Ting Lu, Hua Hao, Chong Liu, Xiao-Qiong Yuan, Yu Miao, Min Zhang, Jia-Yue Zeng, Yu-Feng Li, Wen-Qing Lu, Qiang Zeng
Journal: Environmental Health Perspectives (2024)

Background: Experimental studies have shown that disinfection byproducts (DBPs) including haloacetic acids (HAAs) can cause liver toxicity, but evidence linking this association in humans is sparse. Objectives: We aimed to explore the associations between HAA exposures and liver injury. Methods: We included 922 women between December 2018 and January 2020 from the Tongji Reproductive and Environmental (TREE) cohort study in Wuhan, China. Urinary HAA concentrations including trichloroacetic acid (TCAA) and dichloroacetic acid (DCAA) and serum indicators of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were measured. Liver injury was defined as if any of serum indicator levels were above the 90th percentile. Multivariate logistic and linear regression models were fitted to assess the associations of urinary HAA concentrations with the risk of liver injury and liver function indicators. Stratified analyses by age, body mass index (BMI), alcohol use, and passive smoking were also applied to evaluate the potential effect modifiers. Results: There is little evidence of associations of urinary TCAA concentrations with liver injury risk and liver function indicators. However, urinary DCAA concentrations were associated with a higher risk of liver injury [odds ratios (OR) for 1-interquartile range (IQR) increase in natural log (ln) transformed DCAA concentrations: 1.45; 95% confidence interval (CI): 1.07, 1.98]. This association was observed only among nondrinkers (pinteraction=0.058). We also found that a 1-IQR increase in ln-transformed DCAA concentrations was positively associated with ALT levels (percentage change=6.06%; 95% CI: 0.48%, 11.95%) and negatively associated with AST/ALT (percentage change=−4.48%; 95% CI: −7.80%, −1.04%). In addition, urinary DCAA concentrations in relation to higher GGT levels was observed only among passive smokers (pinteraction=0.040). Conclusion: Our findings suggest that exposure to DCAA but not TCAA is associated with liver injury among women undergoing assisted reproductive technology. https://doi.org/10.1289/EHP13386
Errors in the Figures and Results
Journal: JAMA Network Open (2024)

Karol M. Pencina, PhD; Thomas G. Travison, PhD; Andrew S. Artz, MD, MS; A. Michael Lincoff, MD; Steven E. Nissen, MD; Panagiotis Flevaris, MD, PhD; Anna Chan, PharmD; Xue Li, PhD; Scott A. Diegel, MS; Kathleen Wannemuehler, PhD; Shalender Bhasin, MB, BS
A commentary on ‘Prediction models of surgical site infection after gastrointestinal surgery: a nationwide prospective cohort study’
Authors: Siqin Wang, Wenyan Liu, Limei Zhan, Yongchao He, Jing Xu
Journal: International Journal of Surgery (2024)

aOperating Room,Yantai Yuhuangding Hospital,Yantai,Shandong,264000 ,China bDisinfection Supply Center,Yantai Yuhuangding Hospital,Yantai,Shandong,264000 ,China #Co-authors: Siqin Wang and Wenyan Liu equally contributed to the article. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Disinfection Supply Center, Yantai Yuhuangding Hospital, Yantai,Shandong, 264000, China. E-mail address: [email protected] (J. Xu) This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Platelet-rich plasma-derived exosomes boost mesenchymal stem cells to promote peripheral nerve regeneration
Authors: Yongyi Zhang, Dan Yi, Quan Hong, Jiangbei Cao, Xiaodong Geng, Jinwei Liu, Chuang Xu, Mengyu Cao, Chao Chen, Shuaixuan Xu, Zhen Zhang, Molin Li, Yaqiong Zhu, Nan Peng
Journal: Journal of Controlled Release (2024)
Screening for Speech and Language Delay and Disorders in Children 5 Years or Younger
Authors: Cynthia Feltner, Ina F. Wallace, Sallie W. Nowell, Colin J. Orr, Brittany Raffa, Jennifer Cook Middleton, Jessica Vaughan, Claire Baker, Roger Chou, Leila Kahwati
Journal: JAMA (2024)

Importance Children with speech and language difficulties are at risk for learning and behavioral problems. Objective To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.