tbuckley/cabot-search huggingface dataset:
Applying Transgenerational Scientific Evidence to the Next Wave of Early Identification Strategies for Psychopathological Risk—Transdiagnostic, Developmental, and Personalized
Authors: Andrea Raballo, Michele Poletti, Antonio Preti
Journal: JAMA Psychiatry (2021)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 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 Psychiatry journal
Fine Particulate Matter and Dementia Incidence in the Adult Changes in Thought Study
Authors: Rachel M. Shaffer, Magali N. Blanco, Ge Li, Sara D. Adar, Marco Carone, Adam A. Szpiro, Joel D. Kaufman, Timothy V. Larson, Eric B. Larson, Paul K. Crane, Lianne Sheppard
Journal: Environmental Health Perspectives (2021)

Background: Air pollution may be associated with elevated dementia risk. Prior research has limitations that may affect reliability, and no studies have evaluated this question in a population-based cohort of men and women in the United States. Objectives: We evaluated the association between time-varying, 10-y average fine particulate matter (PM2.5) exposure and hazard of all-cause dementia. An additional goal was to understand how to adequately control for age and calendar-time-related confounding through choice of the time axis and covariate adjustment. Methods: Using the Adult Changes in Thought (ACT) population-based prospective cohort study in Seattle, we linked spatiotemporal model-based PM2.5 exposures to participant addresses from 1978 to 2018. Dementia diagnoses were made using high-quality, standardized, consensus-based protocols at biennial follow-ups. We conducted multivariable Cox proportional hazards regression to evaluate the association between time-varying, 10-y average PM2.5 exposure and time to event in a model with age as the time axis, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Alternative models used calendar time as the time axis. Results: We report 1,136 cases of incident dementia among 4,166 individuals with nonmissing APOE status. Mean [mean ± standard deviation (SD)] 10-y average PM2.5 was 10.1 (±2.9) μg/m3. Each 1-μg/m3 increase in the moving average of 10-y PM2.5 was associated with a 16% greater hazard of all-cause dementia [1.16 (95% confidence interval: 1.03, 1.31)]. Results using calendar time as the time axis were similar. Discussion: In this prospective cohort study with extensive exposure data and consensus-based outcome ascertainment, elevated long-term exposure to PM2.5 was associated with increased hazard of all-cause dementia. We found that optimal control of age and time confounding could be achieved through use of either age or calendar time as the time axis in our study. Our results strengthen evidence on the neurodegenerative effects of PM2.5. https://doi.org/10.1289/EHP9018
The Ongoing Debate of Arthroplasty or Fusion for Cervical Radiculopathy
Authors: Elie Massaad, Ali Kiapour, John H. Shin
Journal: JAMA Network Open (2021)

Tonje Okkenhaug Johansen, MD; Jarle Sundseth, MD, PhD; Oddrun Anita Fredriksli, MD; Hege Andresen, RN; John-Anker Zwart, MD, PhD; Frode Kolstad, MD, PhD; Are Hugo Pripp, PhD; Sasha Gulati, MD, PhD; Øystein Petter Nygaard, MD, PhD
Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
Authors: Bing Bai, David Vanderwall, Yuxin Li, Xusheng Wang, Suresh Poudel, Hong Wang, Kaushik Kumar Dey, Ping-Chung Chen, Ka Yang, Junmin Peng
Journal: Molecular Neurodegeneration (2021)

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer's disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in "amyloidome" (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies.
MONARCH 2: Subgroup Analysis of Patients Receiving Abemaciclib Plus Fulvestrant as First-Line and Second-Line Therapy for HR+, HER2−-Advanced Breast Cancer
Authors: Patrick Neven, Stephen R.D. Johnston, Masakazu Toi, Joohyuk Sohn, Kenichi Inoue, Xavier Pivot, Olga Burdaeva, Meena Okera, Norikazu Masuda, Peter A. Kaufman, Han Koh, Eva-Maria Grischke, PierFranco Conte, Yi Lu, Nadine Haddad, Karla C. Hurt, Antonio Llombart-Cussac, George W. Sledge
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In MONARCH 2, abemaciclib plus fulvestrant significantly prolonged progression-free survival (PFS) and overall survival (OS) versus placebo plus fulvestrant in patients with hormone receptor positive (HR+), HER2− advanced breast cancer. This exploratory analysis assessed the efficacy of abemaciclib plus fulvestrant across subgroups of patients receiving study therapy as first- or second-line treatment for metastatic disease. Patients and Methods: Improvements were estimated using Cox models, and a test of interactions of subgroups with treatment was performed. Results: The benefit in PFS [first-line, HR, 0.57; 95% confidence interval (CI), 0.45–0.73; second-line, HR, 0.48; 95% CI, 0.36–0.64] and OS (first-line, HR, 0.85; 95% CI, 0.64–1.14; second-line, HR, 0.66; 95% CI, 0.46–0.94) was observed across both subgroups, consistent with the intent-to-treat (ITT) population. In first-line patients (abemaciclib arm, n = 265; placebo arm, n = 133), the numerically largest effect on PFS and OS was observed in patients with primary resistance to endocrine therapy (ET; PFS, HR, 0.40; 95% CI, 0.26–0.63; OS, HR, 0.58; 95% CI, 0.35–0.97) and visceral disease (PFS, HR, 0.54; 95% CI, 0.39–0.73; OS, HR, 0.82; 95% CI, 0.58–1.20). In second-line patients (abemaciclib arm, n = 170; placebo arm, n = 86), a numerical benefit in PFS and OS was observed across primary and secondary ET resistance, with numerically more pronounced effects observed in patients with visceral disease (PFS, HR, 0.39; 95% CI, 0.27–0.57; OS, HR, 0.51; 95% CI, 0.33–0.81). Prolongation of time to second disease progression, time to chemotherapy, and chemotherapy-free survival was observed in both subgroups. Conclusions: Consistent with the ITT population, a benefit in PFS and OS was observed across the first- and second-line subgroups in MONARCH 2.
Impact of Post-Transplant High-Dose Cyclophosphamide on Reconstitution in Bone Marrow Recipients
Authors: Ekaterina Mikhaltsova, Mikhail Yu. Drokov, Julia O. Davydova, Larisa A. Kuzmina, Natalia Popova, Daria Dubnyak, Vera Vasilyeva, Olga Koroleva, Zoya Konova, Nikolay M. Kapranov, Irina V. Galtseva, Elena N. Parovichnikova, Valery Savchenko
Journal: Blood (2017)
Clinical risk factors and prognostic model for idiopathic inflammatory demyelinating diseases after haploidentical hematopoietic stem cell transplantation in patients with hematological malignancies
Authors: Rui‐Xin Deng, Ye‐Jun Wu, Lan‐Ping Xu, Kai‐Yan Liu, Xiao‐Jun Huang, Xiao‐Hui Zhang
Journal: American Journal of Hematology (2021)

Idiopathic inflammatory demyelinating diseases (IIDDs) of the central nervous system (CNS) are rare but serious neurological complications of haploidentical hematopoietic stem cell transplantation (haplo-HSCT). However, the risk factors and a method to predict the prognosis of post-transplantation CNS IIDDs are not available. This retrospective study first reviewed data from 4532 patients who received haplo-HSCT during 2008-2019 in our center, and 184 patients (4.1%) with IIDDs after haplo-HSCT were identified. Grades II to IV acute graft-versus-host disease (aGVHD) (p < 0.001) and chronic GVHD (cGVHD) (p = 0.009) were identified as risk factors for developing IIDDs after haplo-HSCT. We then divided the 184 IIDD patients into a derivation cohort and validation cohort due to transplantation time to develop and validate a model for predicting the prognosis of IIDDs. In the multivariate analysis of the derivation cohort, four candidate predictors were entered into the final prognostic model: cytomegalovirus (CMV) infection, Epstein-Barr virus (EBV) infection, IgG synthesis (IgG-syn) and spinal cord lesions. The prognostic model had an area under the receiver operating characteristic curve of 0.864 (95% CI: 0.803-0.925) in the internal validation cohort and 0.871 (95% CI: 0.806-0.931) in the external validation cohort. The calibration plots showed a high agreement between the predicted and observed outcomes. Decision curve analysis indicated that IIDD patients could benefit from the clinical application of the prognostic model. The identification of IIDD patients after allo-HSCT who have a poor prognosis might allow timely treatment and improve patient survival and outcomes.
Granulocyte Transfusions for Neutropenic Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Shuntaro Ikegawa, Nobuharu Fujii, Keiko Fujii, Yusuke Meguri, Kyosuke Saeki, Noboru Asada, Hisakazu Nishimori, Ken-ichi Matsuoka, Yoshinobu Maeda
Journal: Blood (2017)
Michael David Cameron
Authors: Anthony Kenney
Journal: BMJ (2021)

During the second world war, Michael David Cameron (“Mike”) was evacuated from his preparatory school in Rottingdean, Sussex, to South Africa and spent the war away from his parents, who were in India. He attended Michaelhouse in Natal. This was a very difficult time for him.

After the war he returned to England and began his medical studies at Pembroke College, Cambridge. He decided on a career in medicine although his first choice would have been archaeology, particularly of Egypt, which remained a lifetime interest.

There was then a shocking incident in India, when his father was in a motor car with a driver at the time of partition and independence. They came across an angry mob and the driver, who was of the wrong religion, was dragged from the car together with Mike Cameron’s father. Both were killed. Mike did his clinical studies at the Middlesex Hospital …
A single-cell transcriptome of mesenchymal stromal cells to fabricate bioactive hydroxyapatite materials for bone regeneration
Authors: Peng Guo, Xizhe Liu, Penghui Zhang, Zhongyuan He, Zhen Li, Mauro Alini, R. Geoff Richards, Sibylle Grad, Martin J. Stoddart, Guangqian Zhou, Xuenong Zou, Danny Chan, Wei Tian, Dafu Chen, Manman Gao, Zhiyu Zhou, Shaoyu Liu
Journal: Bioactive Materials (2021)

The osteogenic microenvironment of bone-repairing materials plays a key role in accelerating bone regeneration but remains incompletely defined, which significantly limits the application of such bioactive materials. Here, the transcriptional landscapes of different osteogenic microenvironments, including three-dimensional (3D) hydroxyapatite (HA) scaffolds and osteogenic medium (OM), for mesenchymal stromal cells (MSCs) in vitro were mapped at single-cell resolution. Our findings suggested that an osteogenic process reminiscent of endochondral ossification occurred in HA scaffolds through sequential activation of osteogenic-related signaling pathways, along with inflammation and angiogenesis, but inhibition of adipogenesis and fibrosis. Moreover, we revealed the mechanism during OM-mediated osteogenesis involves the ZBTB16 and WNT signaling pathways. Heterogeneity of MSCs was also demonstrated. In vitro ossification of LRRC75A+ MSCs was shown to have better utilization of WNT-related ossification process, and PCDH10+ MSCs with superiority in hydroxyapatite-related osteogenic process. These findings provided further understanding of the cellular activity modulated by OM conditions and HA scaffolds, providing new insights for the improvement of osteogenic biomaterials. This atlas provides a blueprint for research on MSC heterogeneity and the osteogenic microenvironment of HA scaffolds and a database reference for the application of bioactive materials for bone regeneration.
Covid-19: Junior doctors write to young people to acknowledge vaccine concerns
Authors: Gareth Iacobucci
Journal: BMJ (2021)

A group of junior doctors from Scotland have written to young people in their age group to try to ease concerns they may have about receiving the covid-19 vaccine.

In an open letter sent on Friday 6 August the doctors, all in their 20s and 30s, acknowledged the pandemic’s effects on the lives of young people and that some were reluctant to be vaccinated.1

“Young people have had to put parts of their lives on hold—which is frustrating. Sometimes it feels like we are just being left out. As young medics, we share that frustration. We want to get our lives back to normal as quickly as possible too,” they wrote.

They recognised that young people might be fed up with being told what to …
Firearm Practices, Perceptions of Safety, and Opinions on Injury Prevention Strategies Among California Adults With vs Without Children
Authors: Rocco Pallin, Garen J. Wintemute, Nicole Kravitz-Wirtz
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Safe firearm storage and other interventions may reduce pediatric firearm deaths and injuries. <h3>Objective</h3> To compare firearm ownership and storage practices, opinions on firearm injury prevention strategies, and perceptions of safety among adults in California households with and without children and/or adolescents. <h3>Design, Setting, and Participants</h3> This survey study used data from the 2018 California Safety and Well-being Survey, a California-representative, probability-based internet survey. Respondents were part of the Ipsos KnowledgePanel, an online research panel that uses address-based sampling and provides survey weights to produce estimates representative of the adult population of California. <h3>Main Outcomes and Measures</h3> Topics included firearm storage practices, opinions on interventions to reduce pediatric firearm injury, and perceptions of household safety related to firearm ownership. Respondents were stratified by firearm ownership and household presence or absence of children and/or adolescents. Weighted percentages and 95% CIs are presented. <h3>Results</h3> Of 5232 invited panel members, 2558 (48.9%) completed the survey. Among respondents, 52.5% (95% CI, 49.3%-55.7%) were women, 42.9% (95% CI, 39.9%-45.9%) were White, 30.0% (95% CI, 26.8%-32.9%) lived in homes with children, and the mean (SD) age was 48.0 (17.1) years. Among those in homes with children, more than two-thirds of individuals who owned firearms (70.6% [95% CI, 50.1%-85.2%]) and more than half of individuals who did not own firearms but lived in homes with guns (54.9% [95% CI, 37.9%-70.8%]) reported that they believed a firearm in the home made it safer. Half of those who owned firearms (52.3% [95% CI, 34.9%-69.2%]) and more than three-quarters of individuals who did not own firearms but lived in homes with guns (78.4% [95% CI, 57.5%-90.7%]) reported it was always appropriate for parents to inquire about unlocked guns in homes where their children play. Among those who had previously owned at least 1 gun but no longer did, 13.3% (95% CI, 7.1%-23.8%) reported getting rid of guns at least in part due to concern for the safety of a child in the home. Nearly two-thirds of those who owned firearms living with children and/or adolescents (64.5% [95% CI, 46.5%-79.2%]) did not store all firearms in the most secure manner (ie, unloaded and locked up), compared with 36.4% (95% CI, 29.4%-44.1%) of individuals who owned firearms but did not live with children. <h3>Conclusions and Relevance</h3> In this study, although a substantial percentage of individuals who owned guns and lived with children did not store all firearms as recommended, parents and caregivers who owned firearms reported being amenable to interventions that reduce young people's risk of firearm-related harm. Future work should investigate acceptable risk reduction and safe storage interventions.
脂肪組織由来PDGFRβ+細胞を頸動脈内注入すると虚血脳を救済し,神経血管形成の可能性がある
Authors: Chu Kon, Jung Keun-Hwa, Lee Soon-Tae, Lee Sang Kun, Roh Jae-Kyu
Journal: Molecular Therapy (2011)
Rivaroxaban in Patients With Recent Peripheral Artery Revascularization and Renal Impairment
Authors: Judith Hsia, Michael Szarek, Sonia Anand, Manesh R. Patel, Sebastian Debus, Scott D. Berkowitz, Eva Muehlhofer, Lloyd P. Haskell, Rupert M. Bauersachs, Marc P. Bonaca
Journal: Journal of the American College of Cardiology (2021)
Mice with muscle-specific deletion of Bin1 recapitulate centronuclear myopathy and acute downregulation of dynamin 2 improves their phenotypes
Authors: Roberto Silva-Rojas, Vasugi Nattarayan, Francisco Jaque-Fernandez, Raquel Gomez-Oca, Alexia Menuet, David Reiss, Marie Goret, Nadia Messaddeq, Valentina M. Lionello, Christine Kretz, Belinda S. Cowling, Vincent Jacquemond, Jocelyn Laporte
Journal: Molecular Therapy (2021)

Mutations in the BIN1 (Bridging Interactor 1) gene, encoding the membrane remodeling protein amphiphysin 2, cause centronuclear myopathy (CNM) associated with severe muscle weakness and myofiber disorganization and hypotrophy. There is no available therapy, and the validation of therapeutic proof of concept is impaired by the lack of a faithful and easy-to-handle mammalian model. Here, we generated and characterized the Bin1mck-/- mouse through Bin1 knockout in skeletal muscle. Bin1mck-/- mice were viable, unlike the constitutive Bin1 knockout, and displayed decreased muscle force and most histological hallmarks of CNM, including myofiber hypotrophy and intracellular disorganization. Notably, Bin1mck-/- myofibers presented strong defects in mitochondria and T-tubule networks associated with deficient calcium homeostasis and excitation-contraction coupling at the triads, potentially representing the main pathomechanisms. Systemic injection of antisense oligonucleotides (ASOs) targeting Dnm2 (Dynamin 2), which codes for dynamin 2, a BIN1 binding partner regulating membrane fission and mutated in other forms of CNM, improved muscle force and normalized the histological Bin1mck-/- phenotypes within 5 weeks. Overall, we generated a faithful mammalian model for CNM linked to BIN1 defects and validated Dnm2 ASOs as a first translatable approach to efficiently treat BIN1-CNM.
Derivation of a prototype asthma attack risk scale centred on blood eosinophils and exhaled nitric oxide
Authors: Simon Couillard, Annette Laugerud, Maisha Jabeen, Sanjay Ramakrishnan, James Melhorn, Timothy Hinks, Ian Pavord
Journal: Thorax (2021)

Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1-2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.
Covid-19 laboratory leak hypothesis: how a few kept the many from considering alternative possibilities
Authors: Gee Yen Shin, Rohini Manuel
Journal: BMJ (2021)

s comprehensive review of the Wuhan laboratory leak hypothesis makes for uncomfortable reading. 1 That a small group of scientists, with (apparently) hitherto undeclared links to the Wuhan Institute of Virology, were able to prevent open minded, critical analysis of the origins of SARS-CoV-2 for much of 2020 is regrettable.
The Dawn of Myeloid-Derived Suppressor Cells: Identification of Arginase I as the Mechanism of Immune Suppression
Authors: Dmitry I. Gabrilovich
Journal: Cancer Research (2021)

Abstract A study published in Cancer Research in 2004 by Rodriguez and colleagues identified the existence of arginase-producing myeloid cells in tumors distinct from macrophages. They demonstrated the role of arginase in negative regulation of T-cell function in vivo. This was one of the first reports implicating cells, which later were named myeloid-derived suppressor cells (MDSC), in T-cell suppression in vivo and linking this effect with arginase activity and expression. This work was important in advancing the field of MDSC research and helped to bring these cells to the forefront of cancer immunology. See related article by Rodriguez et al., Cancer Res 2004;64:5839–49
Nanozyme with Robust Catalase Activity by Multiple Mechanisms and Its Application for Hypoxic Tumor Treatment
Authors: Chongchong Wang, Yanqing Li, Weijie Yang, Lin Zhou, Shaohua Wei
Journal: Advanced Healthcare Materials (2021)

Abstract Utilizing catalase‐mimicking nanozymes to produce O 2 is an effective method to overcome tumor hypoxia. However, it is challenging to fabricate nanozymes with ultrahigh catalytic activity. Palladium nanosheet (Pd NS), a photothermal agent for photothermal therapy (PTT), has superior catalase‐mimicking activity. Here, titanium dioxide (TiO 2 ) is used to modify Pd NS (denoted Pd@TiO 2 ) by a simple one‐step method to improve its catalytic activity about 8 times. The enhancement mechanism's fundamental insights are discussed through experiments and density functional theory calculations. Next, zinc phthalocyanine is loaded on Pd@TiO 2 to form a nanomotor (denoted PTZCs) with the synergistic activities of photodynamic therapy and PTT. PTZCs inherit the catalase activity of Pd@TiO 2 to facilitate the decomposition of endogenous H 2 O 2 to O 2 , which can relieve tumor hypoxia and propel PTZC migration to expand the reach of PTZCs, further enhancing its synergistic treatment outcome both in vitro and in vivo. It is proposed that this work can provide a simple and effective strategy for catalytic activity enhancement and bring a critical new perspective to studying and guiding the nanozyme design.