tbuckley/cabot-search huggingface dataset:
Effect of <scp>Anti‐S100A4</scp> Monoclonal Antibody Treatment on Experimental Skin Fibrosis and Systemic Sclerosis–Specific Transcriptional Signatures in Human Skin
Authors: Thuong Trinh‐Minh, Andrea‐Hermina Györfi, Michal Tomcik, Cuong Tran‐Manh, Xiang Zhou, Nicholas Dickel, Bilgesu Safak Tümerdem, Alexander Kreuter, Sven‐Niklas Burmann, Signe Vedel Borchert, Rizwan Iqbal Hussain, Jonas Hallén, Jörg Klingelhöfer, Meik Kunz, Jörg H. W. Distler
Journal: Arthritis & Rheumatology (2023)

Objective S100A4 is a DAMP protein. S100A4 is overexpressed in patients with systemic sclerosis (SSc), and levels correlate with organ involvement and disease activity. S100A4 −/− mice are protected from fibrosis. The aim of this study was to assess the antifibrotic effects of anti‐S100A4 monoclonal antibody (mAb) in murine models of SSc and in precision cut skin slices of patients with SSc. Methods The effects of anti‐S100A4 mAbs were evaluated in a bleomycin‐induced skin fibrosis model and in Tsk‐1 mice with a therapeutic dosing regimen. In addition, the effects of anti‐S100A4 mAbs on precision cut SSc skin slices were analyzed by RNA sequencing. Results Inhibition of S100A4 was effective in the treatment of pre‐established bleomycin‐induced skin fibrosis and in regression of pre‐established fibrosis with reduced dermal thickening, myofibroblast counts, and collagen accumulation. Transcriptional profiling demonstrated targeting of multiple profibrotic and proinflammatory processes relevant to the pathogenesis of SSc on targeted S100A4 inhibition in a bleomycin‐induced skin fibrosis model. Moreover, targeted S100A4 inhibition also modulated inflammation‐ and fibrosis‐relevant gene sets in precision cut SSc skin slices in an ex vivo trial approach. Selected downstream targets of S100A4, such as AMP‐activated protein kinase, calsequestrin‐1, and phosphorylated STAT3, were validated on the protein level, and STAT3 inhibition was shown to prevent the profibrotic effects of S100A4 on fibroblasts in human skin. Conclusion Inhibition of S100A4 confers dual targeting of inflammatory and fibrotic pathways in complementary mouse models of fibrosis and in SSc skin. These effects support the further development of anti‐S100A4 mAbs as disease‐modifying targeted therapies for SSc.
Opioid-induced dysbiosis of maternal gut microbiota during gestation alters offspring gut microbiota and pain sensitivity
Authors: Yaa F. Abu, Salma Singh, Junyi Tao, Irina Chupikova, Praveen Singh, Jingjing Meng, Sabita Roy
Journal: Gut Microbes (2023)

There has been a rapid increase in neonates born with a history of prenatal opioid exposure. How prenatal opioid exposure affects pain sensitivity in offspring is of interest, as this may perpetuate the opioid epidemic. While few studies have reported hypersensitivity to thermal pain, potential mechanisms have not been described. This study posits that alterations in the gut microbiome may underly hypersensitivity to pain in prenatally methadone-exposed 3-week-old male offspring, which were generated using a mouse model of prenatal methadone exposure. Fecal samples collected from dams and their offspring were subjected to 16s rRNA sequencing. Thermal and mechanical pain were assessed using the tail flick and Von Frey assays. Transcriptomic changes in whole brain samples of opioid or saline-exposed offspring were investigated using RNA-sequencing, and midbrain sections from these animals were subjected to qPCR profiling of genes related to neuropathic and inflammatory pain pathways. Prenatal methadone exposure increased sensitivity to thermal and mechanical pain and elevated serum levels of IL-17a. Taxonomical analysis revealed that prenatal methadone exposure resulted in significant alterations in fecal gut microbiota composition, including depletion of Lactobacillus, Bifidobacterium, and Lachnospiracea sp and increased relative abundance of Akkermansia, Clostridium sensu stricto 1, and Lachnoclostridium. Supplementation of the probiotic VSL#3 in dams rescued hypersensitivity to thermal and mechanical pain in prenatally methadone-exposed offspring. Similarly, cross-fostering prenatally methadone-exposed offspring to control dams also attenuated hypersensitivity to thermal pain in opioid-exposed offspring. Modulation of the maternal and neonatal gut microbiome with probiotics resulted in transcriptional changes in genes related to neuropathic and immune-related signaling in whole brain and midbrain samples of prenatally methadone-exposed offspring. Together, our work provides compelling evidence of the gut-brain-axis in mediating pain sensitivity in prenatally opioid-exposed offspring.
Clinical Images: Crowned dens syndrome detected on <scp><sup>18</sup>F</scp>‐fludeoxyglucose–positron emission tomography/computed tomography during investigation for giant cell arteritis
Authors: Miao Yunn Lim, Ivan Ho Shon, Anthony M. Sammel
Journal: Arthritis & Rheumatology (2023)

The patient, a 66-year-old woman, presented to the emergency department with severe occipital and temporal headache, shoulder and neck pain with restricted range of movement, and nonspecific binocular vision disturbance. Initial investigations revealed an elevated C-reactive protein level of 52 mg/L (reference <3 mg/L) and an erythrocyte sedimentation rate of 20 mm/hr (reference range 0–20 mm/hr). On examination, she had severely restricted range of motion of the neck and shoulders bilaterally, generalized scalp tenderness, and a right-sided axillary bruit. A provisional diagnosis of giant cell arteritis (GCA) was made, and she was treated with 500 mg of pulse intravenous methylprednisone. An 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) scan protocolized for GCA to assess cranial and large vessels1 did not reveal evidence of active vasculitis, but demonstrated moderate to intense FDG uptake (standardised uptake value max 4.9) surrounding the medial atlantoaxial articulation (B, C, and D). This correlated with a crownlike calcification on the posterior aspect of the dens on CT (A), thus confirming the diagnosis of crowned dens syndrome, a rare condition of calcium pyrophosphate deposition around the odontoid process that can provoke an acute inflammatory syndrome and mimic the presentation of meningitis, GCA, and polymyalgia rheumatica.2 She was subsequently treated with a short course of oral prednisone at 25 mg for five days and colchicine at 500 μg twice daily, which she responded well to before being discharged in a stable condition. Markers of inflammation were normal at six weeks' follow-up, at which she was maintained on colchicine as a single agent, and outpatient vascular studies revealed nonvasculitic luminal irregularity in the proximal brachial artery corresponding to the bruit heard on auscultation. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians. Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Adjuvant and neoadjuvant therapies for hepatocellular carcinoma
Authors: Arndt Vogel, Robert C. Grant, Tim Meyer, Gonzalo Sapisochin, Grainne M. O’Kane, Anna Saborowski
Journal: Hepatology (2023)

Immune-oncology–based regimens have shown efficacy in advanced HCC and have been implemented as standard of care as first-line therapy. Their efficacy, including high response rates, and safety justify their evaluation in earlier disease stages. Following negative results for adjuvant sorafenib in the global STORM trial in 2015, 4 global phase 3 trials, featuring different immune checkpoint inhibitor combinations, entered in parallel the race in the adjuvant setting. The IMbrave050 trial, comparing adjuvant atezolizumab in combination with bevacizumab to active surveillance following curative-intent resection or ablation, was the first to report, fast-tracking the results of the first interim analysis and demonstrating an improvement in recurrence-free survival. The trial has provoked a discussion on the horizon of expectations from adjuvant treatment and the clinical relevance of efficacy endpoints. Moreover, major pathological responses reported from early phase 2 data in the neoadjuvant setting provide a strong rationale for the evaluation of these concepts in phase 3 trials. In this review, we summarize current evidence and outline future directions for systemic therapies in early-stage HCC.
Preventing the Continuing Tragedy of Silicosis—Reply
Authors: Jeremy T. Hua, Cecile S. Rose, Carrie A. Redlich
Journal: JAMA Internal Medicine (2023)

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
Public Benefit Programs and Differential Associations With Child Maltreatment by Race and Ethnicity
Authors: Henry T. Puls, Matthew Hall, Reiko Boyd, Paul J. Chung
Journal: JAMA Pediatrics (2023)

Importance Public benefit programs, including state spending on local, state, and federal-state partnership programs, have consistently been associated with overall reductions in child protective services (CPS) involvement. Inequities in eligibility and access to benefit programs may contribute to varying associations by race and ethnicity. Objective To determine whether associations between state spending on benefit programs and rates of CPS investigations differ by race and ethnicity. Design, Setting, and Participants This cross-sectional ecological study used repeated state-level measures of child maltreatment from the National Child Abuse and Neglect Data System and population estimates from the US Census Bureau for all Black, Hispanic, and White children. All 50 US states from October 1, 2009, through September 30, 2019 (fiscal years 2010-2019), were included. Data were collected and analyzed from May 13, 2022, to March 2, 2023. Exposures Annual state spending on benefit programs per person living below the federal poverty limit, total and by the following subcategories: (1) cash, housing, and in-kind; (2) housing infrastructure; (3) child care assistance; (4) refundable earned income tax credit; and (5) medical assistance programs. Main Outcomes and Measures Race- and ethnicity-specific rates of CPS investigations. Generalized estimating equations, with repeated measures of states, an interaction between race and spending, and estimated incidence rate ratios (IRRs) and 95% CIs for incremental changes in spending of US $1000 per person living below the federal poverty limit were calculated after adjustment for federal spending, race- and ethnicity-specific child poverty rate, and year. Results A total of 493 state-year observations were included in the analysis. The association between total spending and CPS investigations differed significantly by race and ethnicity: there was an inverse association between total state spending and CPS investigations for White children (IRR, 0.94 [95% CI, 0.91-0.98]) but not for Black children (IRR, 0.98 [95% CI, 0.94-1.02]) or Hispanic children (IRR, 0.99 [95% CI, 0.95-1.03]) ( P = .02 for interaction). Likewise, inverse associations were present for only White children with respect to all subcategories of state spending and differed significantly from Black and Hispanic children for all subcategories except the refundable earned income tax credit (eg, IRR for medical assistance programs for White children, 0.89 [95% CI, 0.82-0.96]; P = .005 for race and spending interaction term). Conclusions and Relevance These results raise concerns that benefit programs may add relative advantages for White children compared with Black and Hispanic children and contribute to racial and ethnic disparities in CPS investigations. States’ eligibility criteria and distribution practices should be examined to promote equitable effects on adverse child outcomes.
Local Treatment and Treatment-Related Adverse Effects Among Patients With Advanced Prostate Cancer
Authors: Saira Khan, Su-Hsin Chang, Mei Wang, Eric H. Kim, Martin W. Schoen, Carleena Rocuskie-Marker, Bettina F. Drake
Journal: JAMA Network Open (2023)

Importance Recent data suggest that local treatment with radical prostatectomy or radiation may improve survival outcomes in men with advanced prostate cancer. However, evidence is lacking on treatment-related adverse effects among men with advanced prostate cancer. Objective To assess the association of local treatment on treatment-related adverse effects among men diagnosed with advanced prostate cancer. Design, Setting, and Participants This cohort study assessed men diagnosed with advanced prostate cancer (defined as T4, N1, and/or M1 prostate cancer) between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2021, who were treated at Veterans Health Administration medical centers. Exposure Local treatment with radical prostatectomy or radiation. Main Outcomes and Measures Main outcomes were treatment-related adverse effects, including constitutional, gastrointestinal, pain, sexual function, and urinary function conditions, at 3 intervals after initial treatment (≤1 year, &amp;amp;gt;1 to ≤2 years, and &amp;amp;gt;2 to ≤5 years) after initial treatment. Results This cohort study consisted of 5502 men (mean [SD] age, 68.7 [10.3] years) diagnosed with advanced prostate cancer. Of the cohort, 1705 men (31.0%) received local treatment. There was a high prevalence of adverse conditions in men receiving both local and nonlocal treatment, and these adverse conditions persisted for more than 2 years to 5 years or less after initial treatment. A total of 916 men (75.2%) with initial local treatment and 897 men (67.1%) with initial nonlocal treatment reported the presence of at least 1 adverse condition for more than 2 years to 5 years or less after initial treatment. In the first year, local treatment (vs nonlocal) was associated with adverse gastrointestinal (multivariable-adjusted odds ratio [AOR], 4.08; 95% CI, 3.06-5.45), pain (AOR, 1.57; 95% CI, 1.35-1.83), sexual (AOR, 2.96; 95% CI, 2.42-3.62), and urinary (AOR, 2.25; 95% CI, 1.90-2.66) conditions. Local treatment (without secondary treatment) remained significantly associated with adverse gastrointestinal (AOR, 2.39; 95% CI, 1.52-3.77), sexual (AOR, 3.36; 95% CI, 2.56-4.41), and urinary (AOR, 1.39; 95% CI, 1.09-1.78) conditions at more than 2 years to 5 years or less after treatment. Conclusions and Relevance In this cohort study of men with advanced prostate cancer, local treatment was associated with persistent treatment-related adverse effects across multiple domains. These results suggest that patients and clinicians should consider the adverse effects of local treatment when making treatment decisions in the setting of advanced prostate cancer.
Daily Toothbrushing to Prevent Hospital-Acquired Pneumonia—Brushing Away the Risk
Authors: Rupak Datta
Journal: JAMA Internal Medicine (2023)

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
Selective homing of brain-derived reconstituted lipid nanoparticles to cerebral ischemic area enables improved ischemic stroke treatment
Authors: Dan Han, Meihua Wang, Ningyu Dong, Jiaxing Zhang, Dingran Li, Xiaoling Ma, Ying Ma, Siliang Wang, Yun Zhu, Cheng Wang
Journal: Journal of Controlled Release (2023)

Lipid nanoparticles (LNPs) hold great promise as carriers for developing drug delivery systems (DDSs) aimed at managing ischemic stroke (IS). Previous research has highlighted the vital role played by the lipid composition and biophysical characteristics of LNPs, influencing their interactions with cells and tissues. This understanding presents an opportunity to engineer LNPs tailored specifically for enhanced IS treatment. We previously introduced the innovative concept of reconstituted lipid nanoparticles (rLNPs), which not only retain the advantages of conventional LNPs but also incorporate lipids from the originating cell or tissue. Brain-derived rLNPs (B-rLNPs) exhibit significantly superior accumulation within the cerebral ischemic region when compared to liver-derived rLNPs (L-rLNPs). The homing effect of B-rLNPs was then employed to construct 3-n-butylphthalide (NBP) loaded DDS (B-rLNPs/NBP) for the treatment of IS. Our results demonstrated that compared with free NBP, B-rLNPs/NBP can significantly reduce infarct volume, neurological deficits, blood-brain barrier (BBB) leakage rate, brain water content, neutrophil infiltration, alleviate pathological structures, and improve the motor function in MCAO/R model. We also proved that B-rLNPs/NBP showed further reinforced protective effects on the same model than free NBP through the regulation of TLR4/MyD88/NF-κB (anti-inflammation) and Bax/Bcl-2 (anti-apoptosis) pathways. This study offers a promising tool towards improved IS treatment.
Trends by Acuity for Emergency Department Visits and Hospital Admissions in California, 2012 to 2022
Authors: Talia Ruxin, Madeline Feldmeier, Newton Addo, Renee Y. Hsia
Journal: JAMA Network Open (2023)

This cohort study investigates trends in emergency department (ED) visits and hospital admissions from EDs in California by visit acuity from 2012 to 2022.
Biomimetic Hydrogels as the Inductive Endochondral Ossification Template for Promoting bone Regeneration
Authors: Fujian Zhao, Yonghao Qiu, Wenjing Liu, Yanli Zhang, Jia Liu, Liming Bian, Longquan Shao
Journal: Advanced Healthcare Materials (2023)

Repairing critical size bone defects (CSBD) is a major clinical challenge and requires effective intervention by biomaterial scaffolds. Inspired by the fact that the cartilaginous template-based endochondral ossification (ECO) process is crucial to bone healing and development, developing biomimetic biomaterials to promote ECO is recognized as a promising approach for repairing CSBD. With the unique highly hydrated 3D polymeric network, hydrogels can be designed to closely emulate the physiochemical properties of cartilage matrix to facilitate ECO. In this review, the various preparation methods of hydrogels possessing the specific physiochemical properties required for promoting ECO are introduced. The materiobiological impacts of the physicochemical properties of hydrogels, such as mechanical properties, topographical structures and chemical compositions on ECO, and the associated molecular mechanisms related to the BMP, Wnt, TGF-β, HIF-1α, FGF, and RhoA signaling pathways are further summarized. This review provides a detailed coverage on the materiobiological insights required for the design and preparation of hydrogel-based biomaterials to facilitate bone regeneration.
Progressive Dyspnea on Exertion in an 82-Year-Old
Authors: Akshay Mathavan, Akash Mathavan, Ali Ataya
Journal: JAMA (2023)

An older patient with hereditary hemorrhagic telangiectasia and right lower lobe segmental pulmonary embolism presented with dyspnea that had worsened over 5 years; physical examination and laboratory testing showed jugular venous distension, a cardiac systolic murmur, right ventricular heave, bilateral lower extremity edema to the knees, and elevated brain-type natriuretic peptide level. What is the diagnosis and what would you do next?
Declining Incidence of Systemic Lupus Erythematosus in Norway 1999–2017: Data From a Population Cohort Identified by <i>International Classification of Diseases, 10th Revision</i> Code and Verified by Classification
Authors: Hilde Haukeland, Sigrid R. Moe, Cathrine Brunborg, Antonela Botea, Nenad Damjanic, Gro Å. Wivestad, Heidi K. Øvreås, Thea B. Bøe, Anniken Orre, Torhild Garen, Øyvind Molberg, Karoline Lerang
Journal: Arthritis & Rheumatology (2023)

Objective The goal of this study was to provide complete, robust data on annual systemic lupus erythematosus (SLE) incidence rates over nearly two decades from the Southeast Norway area (2.9 million inhabitants) and assess accuracy of SLE‐specific International Classification of Diseases (ICD) codes for SLE diagnosis. Methods From administrative databases, we identified all cases International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD‐10) coded as SLE during 1999 through 2017 in Southeast Norway. We manually reviewed the chart of every case ICD‐10 coded as SLE to either confirm or reject SLE diagnosis. Using SLE classification criteria, we classified all cases with confirmed SLE. We estimated annual incidence rates of classified SLE, and subsets, defined by age at diagnosis, sex, and parental country of birth. The chi‐square test was applied for linear time‐trend analyses of incidence. Results Among the 3,488 cases ICD‐10 coded as SLE, chart reviews confirmed SLE diagnosis in 1,558 (45%), of which 797 had new‐onset disease during 1999 through 2017. Annual SLE incidence rates fell during 1999 to 2017. The fall was most pronounced in female persons 50 to 59 years old at diagnosis, in whom incidence fell from 3.4 to 1.1 per 100,000 persons ( P trend &lt; 0.001). Concurrent ecological data from the study area showed a 74% reduction in prescriptions of menopausal hormone treatment. Accuracy of ICD‐10 codes for incident SLE diagnosis was acceptable in juveniles and young adults (up to 20 years) but otherwise low. Conclusion In a presumably complete population‐based cohort, we identified decreasing incidence of SLE, especially among female persons 50 to 59 years old. Although reasons for declining incidence are not clear, ecological data indicate a possible role of environmental factors, for example, menopausal hormone treatments. image