tbuckley/cabot-search huggingface dataset:
Annals Consult Guys - Reversals of Care Started After a Myocardial Infarction
Authors: Howard H. Weitz, Geno J. Merli
Journal: Annals of Internal Medicine (2024)

Web ExclusivesFebruary 2024Annals Consult Guys - Reversals of Care Started After a Myocardial InfarctionFREEHoward H. Weitz, MD, and Geno J. Merli, MDHoward H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.), and Geno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/W23-0013 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Annals Consult Guys discuss the modification of medication regimens initiated in the setting of an acute myocardial infarction.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Howard H. Weitz, MD; Geno J. Merli, MDAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Disclosures: Drs. Merli and Weitz report that they have no financial relationships or interests to disclose. All relevant financial relationships have been mitigated. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=W23-0013.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Current IssueFebruary 2024Volume 177, Issue 2 ePublished: 20 February 2024 Issue Published: February 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.Loading ...
Epigenetic regulation in cancer
Authors: Minzhi Gu, Bo Ren, Yuan Fang, Jie Ren, Xiaohong Liu, Xing Wang, Feihan Zhou, Ruiling Xiao, Xiyuan Luo, Lei You, Yupei Zhao
Journal: MedComm (2024)

Abstract Epigenetic modifications are defined as heritable changes in gene activity that do not involve changes in the underlying DNA sequence. The oncogenic process is driven by the accumulation of alterations that impact genome's structure and function. Genetic mutations, which directly disrupt the DNA sequence, are complemented by epigenetic modifications that modulate gene expression, thereby facilitating the acquisition of malignant characteristics. Principals among these epigenetic changes are shifts in DNA methylation and histone mark patterns, which promote tumor development and metastasis. Notably, the reversible nature of epigenetic alterations, as opposed to the permanence of genetic changes, positions the epigenetic machinery as a prime target in the discovery of novel therapeutics. Our review delves into the complexities of epigenetic regulation, exploring its profound effects on tumor initiation, metastatic behavior, metabolic pathways, and the tumor microenvironment. We place a particular emphasis on the dysregulation at each level of epigenetic modulation, including but not limited to, the aberrations in enzymes responsible for DNA methylation and histone modification, subunit loss or fusions in chromatin remodeling complexes, and the disturbances in higher‐order chromatin structure. Finally, we also evaluate therapeutic approaches that leverage the growing understanding of chromatin dysregulation, offering new avenues for cancer treatment.
at the end of a winter’s day
Authors: D.A. Frater
Journal: Annals of Internal Medicine (2024)

Ad LibitumFebruary 2024at the end of a winter’s dayD.A. Frater, MDD.A. Frater, MDE. Barrow Medical Group, Dallas, TexasAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-1751 Audio Reading - “at the end of a winter’s day” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “at the end of a winter’s day” by D.A. Frater Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail my father smiles and says my name when I come tovisit no longer complains when I turn off the talkingheads I retell stories he told me once and hopethey might unfurl his withered memories as water pouredon dry soil might find its way into parched taprootsHe could once launch a story at a name’s mere mention justone word releasing like magic the spill of capturedmoments long past I watch him now slopping soup intochild the sight puts ... Author, Article, and Disclosure InformationAuthors: D.A. Frater, MDAffiliations: E. Barrow Medical Group, Dallas, TexasCorresponding Author: D.A. Frater, MD, E. Barrow Medical Group, 8230 Walnut Hill Lane, Suite 620, Dallas, TX 75231; e-mail, dfratermd@ebarrowmedical.md. PreviousarticleNextarticle Advertisement Audio Reading - “at the end of a winter’s day” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “at the end of a winter’s day” by D.A. Frater Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current IssueFebruary 2024Volume 177, Issue 2Page: 258-259 ePublished: 20 February 2024 Issue Published: February 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Will It Ever Be Enough?
Authors: Sarah L. Becker
Journal: Annals of Internal Medicine (2024)

On Being a DoctorFebruary 2024Will It Ever Be Enough?Sarah L. Becker, BASarah L. Becker, BAOregon Health & Science University, Portland, OregonAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-3024 Audio Reading - “Will It Ever Be Enough?” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Will It Ever Be Enough?” by Sarah L. Becker, BA. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When I walked into the OR, the patient was essentially dead on the table. We had done every lifesaving operation except inserting a surgical airway to keep her alive. Her chest cavity had been completely cut open to allow access to her internal organs, and two surgeons were elbows-deep in her abdominal cavity desperately trying to identify the source of her bleeding as a third applied compressions directly to her heart. Empty bags of donor blood were piled near the side of the operating table as three anesthesiologists all fought with blood products, fluids, and medicines to help normalize her ... Author, Article, and Disclosure InformationAuthors: Sarah L. Becker, BAAffiliations: Oregon Health & Science University, Portland, OregonNote: Some information has been changed to protect patient privacy.Corresponding Author: Sarah L. Becker, BA, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239; e-mail, beckersa@ohsu.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Will It Ever Be Enough?” Supplement. Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Will It Ever Be Enough?” by Sarah L. Becker, BA. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Current IssueFebruary 2024Volume 177, Issue 2Page: 257 ePublished: 20 February 2024 Issue Published: February 2024 Copyright & PermissionsCopyright © 2024 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Fusion genes in pancreatic tumors
Authors: Anastasios Gkountakos, Aatur D. Singhi, C. Benedikt Westphalen, Aldo Scarpa, Claudio Luchini
Journal: Trends in cancer (2024)

Gene fusions and rearrangements play a crucial role in tumor biology. They are rare events typically detected in KRAS wild-type (WT) pancreatic tumors. Their identification can inform clinical management by enabling precision oncology, as fusions involving BRAF, FGFR2, RET, NTRK, NRG1, and ALK represent actionable targets in KRAS-WT cancers, and serve diagnostic purposes since fusions involving PRKACA/B represent the diagnostic hallmark of intraductal oncocytic papillary neoplasms (IOPNs). Although they are rare, the therapeutic and diagnostic importance of these genomic events should not be underestimated, highlighting the need for quality-ensured molecular diagnostics in the management of cancer. Herein we review the existing literature on the role of fusion genes in pancreatic tumors and their clinical potential as effective biomarkers and therapeutic targets.
Urchin-like multiscale structured fluorinated hydroxyapatite as versatile filler for caries restoration dental resin composites
Authors: Shuning Zhang, Xiao Wang, Shi Yin, Junjun Wang, Hongyan Chen, Xinquan Jiang
Journal: Bioactive Materials (2024)

Caries is one of the most prevalent human diseases, resulting from demineralization of tooth hard tissue caused by acids produced from bacteria, and can progress to pulpal inflammation. Filling restoration with dental resin composites (DRCs) is currently the most common treatment for caries. However, existing DRCs suffer from low fracture strength and lack comprehensive anti-caries bioactivity including remineralization, pulp protection, and anti-cariogenic bacteria effects. In this study, inspired by plant roots' ability to stabilize and improve soil, fluorinated urchin-like hydroxyapatite (FUHA) with a three-dimensional whisker structure and bioactive components of calcium, phosphorus, and fluorine was designed and synthesized by a dynamic self-assembly method. Furthermore, versatile FUHA particles with different loading fractions were used as functional fillers to fabricate methacrylate-based DRCs, where the urchin-like hydroxyapatite (UHA) filled DRCs and commercial DRCs (Z350XT and BEAUTIFIL II) served as the control groups. The results demonstrated that FUHA with 50 wt% loading in resin matrix endowed DRC (F5) with excellent physicochemical properties, dentin remineralization property, cell viability, promotion of dental pulp stem cells mineralization, and antibacterial properties. Meanwhile, F5 also presented good clinical handling and aesthetic characteristics. Therefore, structure/functional-integrated FUHA filled DRCs have potential as a promising strategy for tooth restoration and anti-caries bioactivity.
JAK inhibitors—Friend or Foe?
Authors: None The Lancet Rheumatology
Journal: The Lancet Rheumatology (2024)

The licensing of Janus kinase (JAK) inhibitors for patients with rheumatic disease marked a pivotal moment in the pursuit of new groundbreaking therapies for patients. However, as safety concerns surrounding these drugs continue to mount, do the benefits of JAK inhibitors outweigh the risks for patients?
Gout and incidence of 12 cardiovascular diseases: a case–control study including 152 663 individuals with gout and 709 981 matched controls
Authors: Lyn D Ferguson, Geert Molenberghs, Geert Verbeke, Kazem Rahimi, Shishir Rao, Iain B McInnes, John J V McMurray, Naveed Sattar, Nathalie Conrad
Journal: The Lancet Rheumatology (2024)
Miniaturized Capsule System Toward Real‐Time Electrochemical Detection of H<sub>2</sub>S in the Gastrointestinal Tract (Adv. Healthcare Mater. 5/2024)
Authors: Justin M. Stine, Katie L. Ruland, Luke A. Beardslee, Joshua A. Levy, Hossein Abianeh, Santiago Botasini, Pankaj J. Pasricha, Reza Ghodssi
Journal: Advanced Healthcare Materials (2024)
Pitfalls of Cuff Size and Blood Pressure Measurement
Authors: Benjamin D. Gallagher, Kelsey B. Bryant, Jennifer L. Cluett
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Closing Gaps in Public Services for US Residents With Intellectual and Developmental Disabilities
Authors: Kenton J. Johnston, Michelle A. Hendricks, Harold A. Pollack
Journal: JAMA Pediatrics (2024)

This Viewpoint describes existing public health and social service systems for persons with intellectual and developmental disabilities as they transition to adult care, barriers and opportunities faced in service access, and potential actions to narrow these gaps and enhance equity.
Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial
Authors: Hyung-Don Kim, Seyoung Jung, Ho Yeong Lim, Baek-Yeol Ryoo, Min-Hee Ryu, Samuel Chuah, Hong Jae Chon, Beodeul Kang, Jung Yong Hong, Han Chu Lee, Deok-Bog Moon, Ki-Hun Kim, Tae Won Kim, David Tai, Valerie Chew, Jeong Seok Lee, Richard S. Finn, June-Young Koh, Changhoon Yoo
Journal: Nature Medicine (2024)

Abstract Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib–nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67 + proliferating CD8 + T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib–nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709 .
Immunotherapy targeting the obese white adipose tissue microenvironment: Focus on non-communicable diseases
Authors: Lia Priscilla, Chaerim Yoo, Seonmi Jang, Sewon Park, Gayoung Lim, Taekyun Kim, Dong Yun Lee
Journal: Bioactive Materials (2024)

Obesity triggers inflammatory responses in the microenvironment of white adipose tissue, resulting in chronic systemic inflammation and the subsequent development of non-communicable diseases, including type 2 diabetes, coronary heart disease, and breast cancer. Current therapy approaches for obesity-induced non-communicable diseases persist in prioritizing symptom remission while frequently overlooking the criticality of targeting and alleviating inflammation at its source. Accordingly, this review highlights the importance of the microenvironment of obese white adipose tissue and the promising potential of employing immunotherapy to target it as an effective therapeutic approach for non-communicable diseases induced by obesity. Additionally, this review discusses the challenges and offers perspective about the immunotherapy targeting the microenvironment of obese white adipose tissue.
A Multilayered Post–<scp>Genome‐Wide</scp> Association Study Analysis Pipeline Defines Functional Variants and Target Genes for Systemic Lupus Erythematosus
Authors: Mehdi Fazel‐Najafabadi, Loren L. Looger, Harikrishna Reddy Rallabandi, Swapan K. Nath
Journal: Arthritis & Rheumatology (2024)

Objective Systemic lupus erythematosus (SLE), an autoimmune disease with incompletely understood etiology, has a strong genetic component. Although genome‐wide association studies (GWASs) have revealed multiple SLE susceptibility loci and associated single‐nucleotide polymorphisms (SNPs), the precise causal variants, target genes, cell types, tissues, and mechanisms of action remain largely unknown. Methods Here, we report a comprehensive post‐GWAS analysis using extensive bioinformatics, molecular modeling, and integrative functional genomic and epigenomic analyses to optimize fine‐mapping. We compile and cross‐reference immune cell–specific expression quantitative trait loci (cis– and trans–expression quantitative trait loci) with promoter capture high‐throughput capture chromatin conformation (PCHi‐C), allele‐specific chromatin accessibility, and massively parallel reporter assay data to define predisposing variants and target genes. We experimentally validate a predicted locus using CRISPR/Cas9 genome editing, quantitative polymerase chain reaction, and Western blot. Results Anchoring on 452 index SNPs, we selected 9,931 high linkage disequilibrium ( r 2 &gt; 0.8) SNPs and defined 182 independent non‐human leukocyte antigen (HLA) SLE loci. The 3,746 SNPs from 143 loci were identified as regulating 564 unique genes. Target genes are enriched in lupus‐related tissues and associated with other autoimmune diseases. Of these, 329 SNPs (106 loci) showed significant allele‐specific chromatin accessibility and/or enhancer activity, indicating regulatory potential. Using CRISPR/Cas9, we validated reference SNP identifier 57668933 (rs57668933) as a functional variant regulating multiple targets, including SLE‐risk gene ELF1 in B cells. Conclusion We demonstrate and validate post‐GWAS strategies for using multidimensional data to prioritize likely causal variants with cognate gene targets underlying SLE pathogenesis. Our results provide a catalog of significantly SLE‐associated SNPs and loci, target genes, and likely biochemical mechanisms to guide experimental characterization.
Severe, Rebound Mpox in an Immunocompromised Man
Authors: Adam J. Neuhouser, Alisha Kamboj
Journal: Ophthalmology (2024)

A 35-year-old man with a history of untreated human immunodeficiency virus/AIDS and recent recovery from an mpox infection involving the genitalia and neck 2 months prior presented with new disseminated cutaneous lesions. Examination revealed multiple flesh-colored, indurated, and umbilicated plaques, along with necrotizing blepharoconjunctivitis of the left upper and lower eyelid (A). Cultures of the lesions confirmed a rebound mpox infection. Despite 1 month of intensive treatment with tecovirimat, immune globulin, antiretrovirals, and trifluridine eye drops, the lesions worsened (B-C), suggesting an immune reconstitution inflammatory syndrome. The last follow-up revealed healing pox lesions with hypopigmentation and granulation (D). (Magnified version of Figure A-D is available online at www.aaojournal.org).
Consumption responses to an unconditional child allowance in the United States
Authors: Zachary Parolin, Giulia Giupponi, Emma K. Lee, Sophie Collyer
Journal: Nature Human Behaviour (2024)

Abstract The COVID-19 pandemic put families in the United States under financial stress. The federal government’s largest response in 2021 was the American Rescue Plan Act, which temporarily expanded the Child Tax Credit (CTC) into a large, unconditional child allowance providing monthly payments to families with children. This study investigates consumption responses to the CTC expansion using anonymized mobile-location data and debit/credit card data that track visits and spending at 1.3 million establishments across US counties. For identification, we exploit variation in the size of households’ income gains due to the CTC across counties in a difference-in-differences framework spanning January 2021 to May 2022. Counties benefiting most from the CTC expansion experienced larger increases in visits to childcare centres and health- and personal-care establishments, and increased visits to and spending per transaction at grocery and general stores. These findings suggest that the CTC expansion increased household consumption and spending on children.
Impact of metronomic trabectedin combined with low-dose cyclophosphamide on sarcoma microenvironment and correlation with clinical outcome: results from the TARMIC study
Authors: Cheng-Ming Sun, Maud Toulmonde, Mariella Spalato-Ceruso, Florent Peyraud, Alban Bessede, Michèle Kind, Sophie Cousin, Xavier Buy, Jean Palussiere, Antoine Bougouin, Catherine Sautès-Fridman, Hervé Wolf Fridman, Marina Pulido, Antoine Italiano
Journal: Molecular Cancer (2024)

Abstract Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin’s antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas. 50 patients participated: 20 in phase I and 30 in phase II. Changes in the TME were assessed in 28 patients using sequential tumor samples at baseline and day two of the cycle. Treatment notably decreased CD68 + CD163 + macrophages in biopsies from tumor lesions compared to pre-treatment samples in 9 of the 28 patients after 4 weeks. Baseline CD8 + T cell presence increased in 11 of these patients. In summary, up to 57% of patients exhibited a positive immunological response marked by reduced M2 macrophages or increased CD8 + T cells post-treatment. This positive shift in the TME correlated with improved clinical benefit and progression-free survival. This study offers the first prospective evidence of trabectedin’s immunological effect in advanced STS patients, highlighting a relationship between TME modulation and patient outcomes. This study was registered with ClinicalTrial.gov, number NCT02406781.