tbuckley/cabot-search huggingface dataset:
Antibiotic-loaded lactoferrin nanoparticles as a platform for enhanced infection therapy through targeted elimination of intracellular bacteria
Authors: Wei Wang, Wanying Mo, Xue Xiao, Manying Cai, Songfu Feng, Yupeng Wang, Dongfang Zhou
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Intracellular bacteria can multiply inside host cells and manipulate their biology, and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation. Fighting against these stealthy bacteria has been a long-standing challenge. Here, a system of stimuli-responsive lactoferrin (Lf) nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin (Rif) (Rif@Lf NPs) for enhanced infection therapy through targeted elimination of intracellular bacteria. Compared to Rif@BSA NPs, the Rif@Lf NPs can specifically target macrophages infected by bacteria, thus increasing the accumulation of Rif within macrophages. Subsequently, Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redox-responsive manner. Combined with the antibacterial activities of Lf and Rif, the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms. As a result, the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection, sepsis, and bacterial keratitis. Taken together, the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.
Multi-scale relational graph convolutional network for multiple instance learning in histopathology images
Authors: Roozbeh Bazargani, Ladan Fazli, Martin Gleave, Larry Goldenberg, Ali Bashashati, Septimiu Salcudean
Journal: Medical Image Analysis (2024)

Graph convolutional neural networks have shown significant potential in natural and histopathology images. However, their use has only been studied in a single magnification or multi-magnification with either homogeneous graphs or only different node types. In order to leverage the multi-magnification information and improve message passing with graph convolutional networks, we handle different embedding spaces at each magnification by introducing the Multi-Scale Relational Graph Convolutional Network (MS-RGCN) as a multiple instance learning method. We model histopathology image patches and their relation with neighboring patches and patches at other scales (i.e., magnifications) as a graph. We define separate message-passing neural networks based on node and edge types to pass the information between different magnification embedding spaces. We experiment on prostate cancer histopathology images to predict the grade groups based on the extracted features from patches. We also compare our MS-RGCN with multiple state-of-the-art methods with evaluations on several source and held-out datasets. Our method outperforms the state-of-the-art on all of the datasets and image types consisting of tissue microarrays, whole-mount slide regions, and whole-slide images. Through an ablation study, we test and show the value of the pertinent design features of the MS-RGCN.
Artificial intelligence coronary computed tomography, coronary computed tomography angiography using fractional flow reserve, and physician visual interpretation in the per-vessel prediction of abnormal invasive adenosine fractional flow reserve
Authors: Andrew Chiou, Melody Hermel, Rajbir Sidhu, Eric Hu, Alexander van Rosendael, Samantha Bagsic, Emem Udoh, Ricardo Kosturakis, Mohammad Aziz, Christina Rodriguez Ruiz, Shawn Newlander, Bahram Khadivi, Jason Parker Brown, Martin L Charlat, Paul S Teirstein, Curtiss T Stinis, Richard Schatz, Matthew J Price, Jeffrey Cavendish, Michael Salerno, Austin Robinson, Sanjeev Bhavnani, Jorge Gonzalez, George E Wesbey
Journal:  (2024)

Abstract Aims A comparison of diagnostic performance comparing AI-QCTISCHEMIA, coronary computed tomography angiography using fractional flow reserve (CT-FFR), and physician visual interpretation on the prediction of invasive adenosine FFR have not been evaluated. Furthermore, the coronary plaque characteristics impacting these tests have not been assessed. Methods and results In a single centre, 43-month retrospective review of 442 patients referred for coronary computed tomography angiography and CT-FFR, 44 patients with CT-FFR had 54 vessels assessed using intracoronary adenosine FFR within 60 days. A comparison of the diagnostic performance among these three techniques for the prediction of FFR ≤ 0.80 was reported. The mean age of the study population was 65 years, 76.9% were male, and the median coronary artery calcium was 654. When analysing the per-vessel ischaemia prediction, AI-QCTISCHEMIA had greater specificity, positive predictive value (PPV), diagnostic accuracy, and area under the curve (AUC) vs. CT-FFR and physician visual interpretation CAD-RADS. The AUC for AI-QCTISCHEMIA was 0.91 vs. 0.76 for CT-FFR and 0.62 for CAD-RADS ≥ 3. Plaque characteristics that were different in false positive vs. true positive cases for AI-QCTISCHEMIA were max stenosis diameter % (54% vs. 67%, P &amp;lt; 0.01); for CT-FFR were maximum stenosis diameter % (40% vs. 65%, P &amp;lt; 0.001), total non-calcified plaque (9% vs. 13%, P &amp;lt; 0.01); and for physician visual interpretation CAD-RADS ≥ 3 were total non-calcified plaque (8% vs. 12%, P &amp;lt; 0.01), lumen volume (681 vs. 510 mm3, P = 0.02), maximum stenosis diameter % (40% vs. 62%, P &amp;lt; 0.001), total plaque (19% vs. 33%, P = 0.002), and total calcified plaque (11% vs. 22%, P = 0.003). Conclusion Regarding per-vessel prediction of FFR ≤ 0.8, AI-QCTISCHEMIA revealed greater specificity, PPV, accuracy, and AUC vs. CT-FFR and physician visual interpretation CAD-RADS ≥ 3.
Effectiveness of Personalized Hippocampal Network–Targeted Stimulation in Alzheimer Disease
Authors: Young Hee Jung, Hyemin Jang, Sungbeen Park, Hee Jin Kim, Sang Won Seo, Guk Bae Kim, Young-Min Shon, Sungshin Kim, Duk L. Na
Journal: JAMA Network Open (2024)

Importance Repetitive transcranial magnetic stimulation (rTMS) has emerged as a safe and promising intervention for Alzheimer disease (AD). Objective To investigate the effect of a 4-week personalized hippocampal network–targeted rTMS on cognitive and functional performance, as well as functional connectivity in AD. Design, Setting, and Participants This randomized clinical trial, which was sham-controlled and masked to participants and evaluators, was conducted between May 2020 and April 2022 at a single Korean memory clinic. Eligible participants were between ages 55 and 90 years and had confirmed early AD with evidence of an amyloid biomarker. Participants who met the inclusion criteria were randomly assigned to receive hippocampal network–targeted rTMS or sham stimulation. Participants received 4-week rTMS treatment, with assessment conducted at weeks 4 and 8. Data were analyzed between April 2022 and January 2024. Interventions Each patient received 20 sessions of personalized rTMS targeting the left parietal area, functionally connected to the hippocampus, based on fMRI connectivity analysis over 4 weeks. The sham group underwent the same procedure, excluding actual magnetic stimulation. A personalized 3-dimensional printed frame to fix the TMS coil to the optimal target site was produced. Main Outcomes and Measures The primary outcome was the change in the AD Assessment Scale-Cognitive Subscale test (ADAS-Cog) after 8 weeks from baseline. Secondary outcomes included changes in the Clinical Dementia Rating-Sum of Boxes (CDR-SOB) and Seoul-Instrumental Activity Daily Living (S-IADL) scales, as well as resting-state fMRI connectivity between the hippocampus and cortical areas. Results Among 30 participants (18 in the rTMS group; 12 in the sham group) who completed the 8-week trial, the mean (SD) age was 69.8 (9.1) years; 18 (60%) were female. As the primary outcome, the change in ADAS-Cog at the eighth week was significantly different between the rTMS and sham groups (coefficient [SE], −5.2 [1.6]; P = .002). The change in CDR-SOB (−4.5 [1.4]; P = .007) and S-IADL (1.7 [0.7]; P = .004) were significantly different between the groups favoring rTMS groups. The fMRI connectivity analysis revealed that rTMS increased the functional connectivity between the hippocampus and precuneus, with its changes associated with improvements in ADAS-Cog ( r = −0.57; P = .005). Conclusions and Relevance This randomized clinical trial demonstrated the positive effects of rTMS on cognitive and functional performance, and the plastic changes in the hippocampal-cortical network. Our results support the consideration of rTMS as a potential treatment for AD. Trial Registration ClinicalTrials.gov Identifier: NCT04260724
PEGylated liposomes for diagnosis of polyethylene glycol allergy
Authors: Griffith B Perkins, Matthew J Tunbridge, Plinio R Hurtado, James Zuiani, Shweta Mhatre, Kwok Ho Yip, Thanh-Thao Adriana Le, Carlo Yuson, Frank Kette, Pravin Hissaria
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundPolyethylene glycol (PEG) is a nonprotein polymer that is present in its native (unbound) form as an excipient in a range of products. It is increasingly being utilized clinically in the form of PEGylated liposomal medications and vaccines. PEG is the cause of anaphylaxis in a small percentage of drug reactions; however, diagnosis of PEG allergy is complicated by the variable and poor diagnostic performance of current skin testing protocols.ObjectiveWe assessed the diagnostic performance of PEGylated lipid medications as an alternative to currently described tests that use medications containing PEG excipients.MethodsNine patients with a strong history of PEG allergy were evaluated by skin testing with a panel of PEG-containing medications and with a PEGylated lipid nanoparticle vaccine (BNT162b2). Reactivity of basophils to unbound and liposomal PEG was assessed ex vivo, and specificity of basophil responses to PEGylated liposomes was investigated with a competitive inhibition assay. More detailed information is provided in this article's Methods section in the Online Repository available at www.jacionline.org.ResultsDespite compelling histories of anaphylaxis to PEG-containing medications, only 2 (22%) of 9 patients were skin test positive for purified PEG or their index reaction-indicated PEG-containing compound. Conversely, all 9 patients were skin test positive or basophil activation test positive to PEGylated liposomal BNT162b2 vaccine. Concordantly, PEGylated liposomal drugs (BNT162b2 vaccine and PEGylated liposomal doxorubicin), but not purified PEG2000, consistently induced basophil activation ex vivo in patients with PEG allergy but not in nonallergic controls. Basophil reactivity to PEGylated nanoparticles competitively inhibited by preincubation of basophils with native PEG2000.ConclusionPresentation of PEG on the surface of a lipid nanoparticle increases its in vivo and ex vivo allergenicity, and improves diagnosis of PEG allergy.
IL-22 is increased in hospitalized patients with COVID-19 and associates with cardiac involvement
Authors: Bente Halvorsen, Hans-Kittil Viermyr, Thor Ueland, Ellen L Sagen, Annika E Michelsen, Vigdis Bjerkeli, Anders A Tveita, Katerina N Henriksen, Trine Kåsine, Anne Ma Dyrhol-Riise, Marius Trøseid, Tuva B Dahl, Pål Aukrust, Ida Gregersen
Journal: Journal of Infection (2024)
Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries
Authors: Kamika R. Reynolds, Farzin Khosrow-Khavar, Chintan V. Dave
Journal: JAMA Network Open (2024)

Importance The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.
Fritz Kahn and the Centenary of <i>The Doctor of the Future</i>
Authors: Conrad-Amadeus Voltin, Lionel S. Zuckier
Journal: JAMA (2024)

This JAMA Arts and Medicine feature describes ways in which Fritz Kahn shared a prescient and nuanced vision of technology’s role in the patient-physician interaction, a topic of continued interest and relevance today, through his illustrations.
Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia
Authors: Alexander Makhnevich, Alexandra Perrin, Dristi Talukder, Yan Liu, Stephanie Izard, Codruta Chiuzan, Stefani D’Angelo, Rebecca Affoo, Nicole Rogus-Pulia, Liron Sinvani
Journal: JAMA Internal Medicine (2024)

Oropharyngeal dysphagia is common in hospitalized patients with Alzheimer disease and related dementias (ADRD). Although the use of thick liquids in patients with dysphagia has been shown to reduce aspiration on direct visualization, there is no clear evidence that this practice translates into improved clinical outcomes.
100% Fruit Juice and Body Weight
Authors: Tim Cassettari, Carlene Starck, Emma Beckett
Journal: JAMA Pediatrics (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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Relaxation Therapy and Human Milk Feeding Outcomes
Authors: Ilana Levene, Nurul Husna Mohd Shukri, Frances O’Brien, Maria A. Quigley, Mary Fewtrell
Journal: JAMA Pediatrics (2024)

Importance Human milk feeding is a key public health goal to optimize infant and maternal/parental health, but global lactation outcomes do not meet recommended duration and exclusivity. There are connections between lactation and mental health. Objective To appraise all available evidence on whether the provision of relaxation interventions to lactating individuals improves lactation and well-being. Data Sources Embase, MEDLINE, CINAHL, Allied and Complementary Medicine Database, Web of Science, and the Cochrane Library were searched on September 30, 2023, and topic experts were consulted. Study Selection Two independent reviewers screened for eligibility. Inclusion criteria were full-text, peer-reviewed publications with a randomized clinical trial design. Techniques that were entirely physical (eg, massage) were excluded. A total of 7% of initially identified studies met selection criteria. Data Extraction and Synthesis Two independent reviewers extracted data and assessed risk of bias with the Cochrane Risk of Bias 2 tool. Fixed-effects meta-analysis and Grading of Recommendations, Assessment, Development, and Evaluations guidelines were used to synthesize and present evidence. Main Outcomes and Measures Prespecified primary outcomes were human milk quantity, length and exclusivity of human milk feeding, milk macronutrients/cortisol, and infant growth and behavior. Results A total of 16 studies were included with 1871 participants (pooled mean [SD] age for 1656 participants, 29.6 [6.1] years). Interventions were music, guided relaxation, mindfulness, and breathing exercises/muscle relaxation. Provision of relaxation was not associated with a change in human milk protein (mean difference [MD], 0 g/100 mL; 95% CI, 0; 205 participants). Provision of relaxation was associated with an increase in human milk quantity (standardized mean difference [SMD], 0.73; 95% CI, 0.57-0.89; 464 participants), increased infant weight gain in breastfeeding infants (MD, z score change = 0.51; 95% CI, 0.30-0.72; 226 participants), and a slight reduction in stress and anxiety (SMD stress score, −0.49; 95% CI, −0.70 to −0.27; 355 participants; SMD anxiety score, −0.45; 95% CI, −0.67 to −0.22; 410 participants). Conclusions and Relevance Results of this systematic review and meta-analysis suggest that provision of relaxation was associated with an increase in human milk quantity and infant weight gain and a slight reduction in stress and anxiety. Relaxation interventions can be offered to lactating parents who would like to increase well-being and improve milk supply or, where directly breastfeeding, increase infant weight gain.
Modulation of ER-mitochondria tethering complex VAPB-PTPIP51: Novel therapeutic targets for aging-associated diseases
Authors: Tao Jiang, Nan Ruan, Pengcheng Luo, Qian Wang, Xiuxian Wei, Yi Li, Yue Dai, Li Lin, Jiagao Lv, Yu Liu, Cuntai Zhang
Journal: Ageing Research Reviews (2024)

Aging is a gradual and irreversible natural process. With aging, the body experiences a functional decline, and the effects amplify the vulnerability to a range of age-related diseases, including neurodegenerative, cardiovascular, and metabolic diseases. Within the aging process, the morphology and function of mitochondria and the endoplasmic reticulum (ER) undergo alterations, particularly in the structure connecting these organelles known as mitochondria-associated membranes (MAMs). MAMs serve as vital intracellular signaling hubs, facilitating communication between the ER and mitochondria when regulating various cellular events, including calcium homeostasis, lipid metabolism, mitochondrial function, and apoptosis. The formation of MAMs is partly dependent on the interaction between the vesicle-associated membrane protein-associated protein-B (VAPB) and protein tyrosine phosphatase-interacting protein-51 (PTPIP51). Accumulating evidence has begun to elucidate the pivotal role of the VAPB-PTPIP51 tether in the initiation and progression of age-related diseases. In this study, we delineate the intricate structure and multifunctional role of the VAPB-PTPIP51 tether and discuss its profound implications in aging-associated diseases. Moreover, we provide a comprehensive overview of potential therapeutic interventions and pharmacological agents targeting the VAPB-PTPIP51-mediated MAMs, thereby offering a glimmer of hope in mitigating aging processes and treating age-related disorders.
Advancing Pharmacoequity in Atrial Fibrillation—The Case for Direct Oral Anticoagulants
Authors: Brian C. Boursiquot, Larry R. Jackson, Utibe R. Essien
Journal: JAMA Network Open (2024)

Ischemic stroke is one of the most devastating consequences of atrial fibrillation (AF).Oral anticoagulation for stroke risk reduction in those at moderate to high risk is a cornerstone of AF management.Direct oral anticoagulants (DOACs) were first approved in the US in 2010 and have since supplanted warfarin as the first-line oral anticoagulant for AF in most cases. 1 A major advantage of DOAC therapy, beyond its improved effectiveness and safety over warfarin, is the ease of dosing without the need for laboratory monitoring as well as fewer drug and food interactions.However, among the initial barriers to effective uptake of DOACs were the higher costs of these newer drugs.[4][5] In this issue of JAMA Network Open, Reynolds et al 6 sought to extend this literature, examining racial and ethnic differences in the initiation of DOACs vs warfarin among Medicare beneficiaries with AF and no evidence of valvular heart disease.The authors identified 950 698 episodes of oral anticoagulant initiation in this cohort from 2010 to 2019.After adjustment for individual demographic and clinical covariates, as well as county-level social vulnerability, they found that Black Open Access.