tbuckley/cabot-search huggingface dataset:
Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease
Authors: Paola Caruso, Maria Ida Maiorino, Miriam Longo, Chiara Porcellini, Rita Matrone, Lucia Digitale Selvaggio, Maurizio Gicchino, Carla Carbone, Lorenzo Scappaticcio, Giuseppe Bellastella, Dario Giugliano, Katherine Esposito
Journal: JAMA Network Open (2024)

Importance Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcP o 2 ) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania “Luigi Vanvitelli,” Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcP o 2 between 30 and 49 mm Hg were included. Interventions Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcP o 2 from baseline in each group. Results Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A 1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcP o 2 of 40.3 (5.7) mm Hg. Transcutaneous P o 2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P &amp;amp;lt; .001). The 10% increase of TcP o 2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P &amp;amp;lt; .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (−0.4 mg/dL; 95% CI, −0.7 to −0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (−119.4 mg/g; 95% CI, −195.0 to −43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P &amp;amp;lt; .001). Conclusions and Relevance In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcP o 2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration ClinicalTrials.gov Identifier: NCT04881110
Allergic Rhinitis
Authors: Jonathan A. Bernstein, Joshua S. Bernstein, Richika Makol, Stephanie Ward
Journal: JAMA (2024)

Importance Allergic rhinitis affects an estimated 15% of the US population (approximately 50 million individuals) and is associated with the presence of asthma, eczema, chronic or recurrent sinusitis, cough, and both tension and migraine headaches. Observations Allergic rhinitis occurs when disruption of the epithelial barrier allows allergens to penetrate the mucosal epithelium of nasal passages, inducing a T-helper type 2 inflammatory response and production of allergen-specific IgE. Allergic rhinitis typically presents with symptoms of nasal congestion, rhinorrhea, postnasal drainage, sneezing, and itching of the eyes, nose, and throat. In an international study, the most common symptoms of allergic rhinitis were rhinorrhea (90.38%) and nasal congestion (94.23%). Patients with nonallergic rhinitis present primarily with nasal congestion and postnasal drainage frequently associated with sinus pressure, ear plugging, muffled sounds and pain, and eustachian tube dysfunction that is less responsive to nasal corticosteroids. Patients with seasonal allergic rhinitis typically have physical examination findings of edematous and pale turbinates. Patients with perennial allergic rhinitis typically have erythematous and inflamed turbinates with serous secretions that appear similar to other forms of chronic rhinitis at physical examination. Patients with nonallergic rhinitis have negative test results for specific IgE aeroallergens. Intermittent allergic rhinitis is defined as symptoms occurring less than 4 consecutive days/week or less than 4 consecutive weeks/year. Persistent allergic rhinitis is defined as symptoms occurring more often than 4 consecutive days/week and for more than 4 consecutive weeks/year. Patients with allergic rhinitis should avoid inciting allergens. In addition, first-line treatment for mild intermittent or mild persistent allergic rhinitis may include a second-generation H 1 antihistamine (eg, cetirizine, fexofenadine, desloratadine, loratadine) or an intranasal antihistamine (eg, azelastine, olopatadine), whereas patients with persistent moderate to severe allergic rhinitis should be treated initially with an intranasal corticosteroid (eg, fluticasone, triamcinolone, budesonide, mometasone) either alone or in combination with an intranasal antihistamine. In contrast, first-line therapy for patients with nonallergic rhinitis consists of an intranasal antihistamine as monotherapy or in combination with an intranasal corticosteroid. Conclusions and Relevance Allergic rhinitis is associated with symptoms of nasal congestion, sneezing, and itching of the eyes, nose, and throat. Patients with allergic rhinitis should be instructed to avoid inciting allergens. Therapies include second-generation H 1 antihistamines (eg, cetirizine, fexofenadine, desloratadine, loratadine), intranasal antihistamines (eg, azelastine, olopatadine), and intranasal corticosteroids (eg, fluticasone, triamcinolone, budesonide, mometasone) and should be selected based on the severity and frequency of symptoms and patient preference.
Aftermath
Authors: Stacy R. Nigliazzo
Journal: JAMA (2024)

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Reconfiguration of Structural and Functional Connectivity Coupling in Patient Subgroups With Adolescent Depression
Authors: Ming Xu, Xuemei Li, Teng Teng, Yang Huang, Mengqi Liu, Yicheng Long, Fajin Lv, Dongmei Zhi, Xiang Li, Aichen Feng, Shan Yu, Vince Calhoun, Xinyu Zhou, Jing Sui
Journal: JAMA Network Open (2024)

Adolescent major depressive disorder (MDD) is associated with serious adverse implications for brain development and higher rates of self-injury and suicide, raising concerns about its neurobiological mechanisms in clinical neuroscience. However, most previous studies regarding the brain alterations in adolescent MDD focused on single-modal images or analyzed images of different modalities separately, ignoring the potential role of aberrant interactions between brain structure and function in the psychopathology.
Opioids in Hospitalized Infants—Managing Pain and Sedation While Avoiding Overuse
Authors: Scott E. Hadland, Davida M. Schiff
Journal: JAMA Network Open (2024)

Olivia A. Keane, MD; Shadassa Ourshalimian, MPH; Ashwini Lakshmanan, MD, MS, MPH; Henry C. Lee, MD; Susan R. Hintz, MD; Nam Nguyen, MD; Madeleine C. Ing, BA; Cynthia L. Gong, PhD, PharmD; Cameron Kaplan, PhD; Lorraine I. Kelley-Quon, MD, MSHS
Patient stratification using plasma cytokines and their regulators in sepsis: relationship to outcomes, treatment effect and leucocyte transcriptomic subphenotypes
Authors: David Benjamin Antcliffe, Yuxin Mi, Shalini Santhakumaran, Katie L Burnham, A Toby Prevost, Josie K Ward, Timothy J Marshall, Claire Bradley, Farah Al-Beidh, Paula Hutton, Stuart McKechnie, Emma E Davenport, Charles J Hinds, Cecilia M O'Kane, Daniel Francis McAuley, Manu Shankar-Hari, Anthony C Gordon, Julian C Knight
Journal: Thorax (2024)

Rationale Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported. Objectives We investigated whether inflammatory clusters based on cytokine protein abundance were seen in sepsis, and the relationships with previously described transcriptomic subphenotypes. Methods Hierarchical cluster and latent class analysis were applied to an observational study (UK Genomic Advances in Sepsis (GAinS)) (n=124 patients) and two clinical trial datasets (VANISH, n=155 and LeoPARDS, n=484) in which the plasma protein abundance of 65, 21, 11 circulating cytokines, cytokine receptors and regulators were quantified. Clinical features, outcomes, response to trial treatments and assignment to transcriptomic subphenotypes were compared between inflammatory clusters. Measurements and main results We identified two (UK GAinS, VANISH) or three (LeoPARDS) inflammatory clusters. A group with high levels of pro-inflammatory and anti-inflammatory cytokines was seen that was associated with worse organ dysfunction and survival. No interaction between inflammatory clusters and trial treatment response was found. We found variable overlap of inflammatory clusters and leucocyte transcriptomic subphenotypes. Conclusions These findings demonstrate that differences in response at the level of cytokine biology show clustering related to severity, but not treatment response, and may provide complementary information to transcriptomic sepsis subphenotypes. Trial registration number ISRCTN20769191 , ISRCTN12776039 .
Shared and Distinct Genomics of Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Embolism
Authors: James Liley, Michael Newnham, Marta Bleda, Katherine Bunclark, William Auger, Joan Albert Barbera, Harm Bogaard, Marion Delcroix, Timothy M. Fernandes, Luke Howard, David Jenkins, Irene Lang, Eckhard Mayer, Chris Rhodes, Michael Simpson, Laura Southgate, Richard Trembath, John Wharton, Martin R. Wilkins, Stefan Gräf, Nicholas Morrell, Joanna Pepke Zaba, Mark Toshner
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Chronic thromboembolic pulmonary hypertension involves the formation and nonresolution of thrombus, dysregulated inflammation, angiogenesis, and the development of a small-vessel vasculopathy.
Guidance on Use of Race, Ethnicity, and Geographic Origin as Proxies for Genetic Ancestry Groups in Biomedical Publications
Authors: W. Gregory Feero, Robert D. Steiner, Anne Slavotinek, Tiago Faial, Michael J. Bamshad, Jehannine Austin, Bruce R. Korf, Annette Flanagin, Kirsten Bibbins-Domingo
Journal: JAMA (2024)

Nonhuman "Authors" and Implications for the Integrity of Scientific Publication and Medical Knowledge
Secukinumab in patients with moderate-to-severe hidradenitis suppurativa based on prior biologic exposure: an efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials
Authors: Christos C Zouboulis, Thierry Passeron, David Pariser, Magdalena B Wozniak, Xianjun Li, Lorenz Uhlmann, Iryna Lobach, Angela Llobet Martinez, Shoba Ravichandran, Ivette Alarcon, Annamaria Offidani, Maryam S Alam, Pedro Mendes-Bastos
Journal: British Journal of Dermatology (2024)

Lay Summary Hidradenitis suppurativa (HS) is a chronic skin disease that causes painful boils. HS is common and affects about 0.4% of the world’s population. Treating the condition is difficult, but drugs called ‘biologics’ can help to improve the symptoms. For example, secukinumab is a biologic drug that has been shown to be effective and well-tolerated for the treatment of HS. In this analysis, we investigated whether previous treatment with biologics could affect the effectiveness and tolerability of secukinumab. This analysis included data from two identical clinical trials (called SUNSHINE and SUNRISE) that recruited adult patients with HS who had moderate-to-severe disease. In these trials, patients took secukinumab 300 mg every 2 weeks or every 4 weeks for 1 year, or a placebo for 4 months and then switched to secukinumab until 1 year. At regular intervals, the effectiveness and tolerability of secukinumab were examined and the results were compared between patients who had previously used another biologic and patients who had never used a biologic before. After 16 weeks, patients who took secukinumab had better results than the patients who took a placebo, independent of previous biologic use. Secukinumab was still effective and had improved results over 1 year of treatment in both subgroups. Regardless of whether patients had previously been taking another biologic, secukinumab was just as tolerable as placebo and there were no new safety risks. Our analysis shows that secukinumab is effective and tolerable, regardless of whether patients have previously used another biologic drug.
Re: Marcin Miszczyk, Pawel Rajawa, Takafumi Yanagisawa, et al. The Efficacy and Safety of Metastasis-directed Therapy in Patients with Prostate Cancer: A Systematic Review and Meta-analysis of Prospective Studies. Eur Urol. In press. https://doi.org/10.1016/j.eururo.2023.10.012
Authors: Andrei Fodor, Chiara Brombin, Arturo Chiti, Nadia Di Muzio
Journal: European Urology (2024)
Impact of physical and sexual abuse on risk of hospitalisations for physical and mental illnesses: insights from two large prospective cohort studies
Authors: Philipp Frank, G. David Batty, Jaana Pentti, Markus Jokela, Jenni Ervasti, Andrew Steptoe, Glyn Lewis, Mika Kivimäki
Journal: The Lancet Regional Health - Europe (2024)

Physical abuse can lead to severe health consequences that extend beyond immediate harm. We explored the associations of physical abuse experienced during childhood and adulthood with a wide range of adult health conditions requiring hospital treatment.
Surveillance of Waterborne Disease Outbreaks Associated with Drinking Water — United States, 2015–2020
Authors: Jasen M. Kunz, Hannah Lawinger, Shanna Miko, Megan Gerdes, Muhammad Thuneibat, Elizabeth Hannapel, Virginia A. Roberts
Journal: MMWR Surveillance Summaries (2024)

Public health agencies in U.S. states, territories, and freely associated states investigate and voluntarily report waterborne disease outbreaks to CDC through the National Outbreak Reporting System (NORS). This report summarizes NORS drinking water outbreak epidemiologic, laboratory, and environmental data, including data for both public and private drinking water systems. The report presents outbreak-contributing factors (i.e., practices and factors that lead to outbreaks) and, for the first time, categorizes outbreaks as biofilm pathogen or enteric illness associated.
The influence of the severity of gender dysphoria on anxiety, depression, suicidal ideation, and non-suicidal self-injury in Chinese transgender, nonbinary, and gender-diverse youth
Authors: Jiaqi Li, Yu Jin, Shicun Xu, Amanda Wilson, Chang Chen, Yuanyuan Wang
Journal: International Journal of Transgender Health (2024)

Background: Gender dysphoria (GD) is frequently reported among transgender, nonbinary, and gender-diverse (TNG) populations, and is closely related to anxiety, depression, suicidal ideation, and non-suicidal self-injury (NSSI). This study aimed to understand how GD influences the four mental health disparities among TNG youth, and to compare these outcomes depending on the severity of GD.Methods: 96,218 College students participated in the survey, of which the analysis was run on an extracted sub-set data of 2,315 (2.40%) TNG youth, with a mean age of 19.46 (SD = 1.52). Self-reported inventories measured sociodemographic factors, the severity of GD (Utrecht Gender Dysphoria Scale-Gender Spectrum), anxiety (seven-item Generalized Anxiety Disorder Questionnaire), depression (nine-item Patient Health Questionnaire), suicidal ideation (Suicidal Behaviors Questionnaire-Revised), and NSSI (Clinician-Rated Severity of Non-Suicidal Self-Injury Scale). Binary logistic regression assessed the association between significant GD and the four psychiatric disorders. Adjusted multiple logistic regression, and directed acyclic graph (DAG) analyses were conducted to explore the activating relationship among GD, sociodemographic factors, and psychiatric disorders.Results: 1,582 (68.30%) TNG youth who experienced significant levels of GD (total scores cutoff >= 46) were entered into the analyses. Binary logistic regression displayed significantly positive associations between significant GD and anxiety, depression, suicidal ideation, and NSSI. Multiple regression models showed risk factors included poor relationship with one's father/mother, tobacco smoking, alcohol consumption, and having a lower subjective social status. While family harmony, a higher father's educational level, and partaking in exercise were protective factors that exerted distinct impacts on these four psychiatric disorders. DAG findings showed a poor relationship with one's father with significant GD via other socio-demographic characteristics, activated psychiatric disorders.Conclusions: TNG youth with higher levels of GD also exhibited more severe anxiety, depression, suicidal ideation, and NSSI. Tailored interventions should be provided to prioritize relieving those with severe GD to protect TNG youth from psychiatric outcomes further.
Identification of clinical disease trajectories in neurodegenerative disorders with natural language processing
Authors: Nienke J. Mekkes, Minke Groot, Eric Hoekstra, Alyse de Boer, Ekaterina Dagkesamanskaia, Sander Bouwman, Sophie M. T. Wehrens, Megan K. Herbert, Dennis D. Wever, Annemieke Rozemuller, Bart J. L. Eggen, Inge Huitinga, Inge R. Holtman
Journal: Nature Medicine (2024)

Abstract Neurodegenerative disorders exhibit considerable clinical heterogeneity and are frequently misdiagnosed. This heterogeneity is often neglected and difficult to study. Therefore, innovative data-driven approaches utilizing substantial autopsy cohorts are needed to address this complexity and improve diagnosis, prognosis and fundamental research. We present clinical disease trajectories from 3,042 Netherlands Brain Bank donors, encompassing 84 neuropsychiatric signs and symptoms identified through natural language processing. This unique resource provides valuable new insights into neurodegenerative disorder symptomatology. To illustrate, we identified signs and symptoms that differed between frequently misdiagnosed disorders. In addition, we performed predictive modeling and identified clinical subtypes of various brain disorders, indicative of neural substructures being differently affected. Finally, integrating clinical diagnosis information revealed a substantial proportion of inaccurately diagnosed donors that masquerade as another disorder. The unique datasets allow researchers to study the clinical manifestation of signs and symptoms across neurodegenerative disorders, and identify associated molecular and cellular features.
Age-dependent loss of HAPLN1 erodes vascular integrity via indirect upregulation of endothelial ICAM1 in melanoma
Authors: Gloria E. Marino-Bravante, Alexis E. Carey, Laura Hüser, Agrani Dixit, Vania Wang, Amanpreet Kaur, Ying Liu, Supeng Ding, Rahel Schnellmann, Sharon Gerecht, Luo Gu, T. S. Karin Eisinger-Mathason, Yash Chhabra, Ashani T. Weeraratna
Journal: Nature Aging (2024)
Liprin-α proteins are master regulators of human presynapse assembly
Authors: Berta Marcó de la Cruz, Joaquín Campos, Angela Molinaro, Xingqiao Xie, Gaowei Jin, Zhiyi Wei, Claudio Acuna, Fredrik H Sterky
Journal: Nature Neuroscience (2024)

ABSTRACT The formation of mammalian synapses entails the precise alignment of presynaptic release sites with postsynaptic receptors but how nascent cell–cell contacts translate into assembly of presynaptic specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that in mammalian synapses, liprin-α proteins directly link trans -synaptic initial contacts to downstream steps. Here we show that, in human neurons lacking all four liprin-α isoforms, nascent synaptic contacts are formed but recruitment of active zone components and accumulation of synaptic vesicles is blocked, resulting in ‘empty’ boutons and loss of synaptic transmission. Interactions with presynaptic cell adhesion molecules of either the LAR-RPTP family or neurexins via CASK are required to localize liprin-α to nascent synaptic sites. Liprin-α subsequently recruits presynaptic components via a direct interaction with ELKS proteins. Thus, assembly of human presynaptic terminals is governed by a hierarchical sequence of events in which the recruitment of liprin-α proteins by presynaptic cell adhesion molecules is a critical initial step.
Inverse‐Vaccines for Rheumatoid Arthritis Re‐establish Metabolic and Immunological Homeostasis in Joint Tissues
Authors: Abhirami Thumsi, Diego Martínez, Srivatsan J. Swaminathan, Arezoo Esrafili, Abhirami P. Suresh, Madhan Mohan Chandrasekhar Jaggarapu, Kelly Lintecum, Michelle Halim, Shivani V. Mantri, Yasmine Sleiman, Nicole Appel, Haiwei Gu, Marion Curtis, Cristal Zuniga, Abhinav P. Acharya
Journal: Advanced Healthcare Materials (2024)

Abstract Rheumatoid arthritis (RA) causes immunological and metabolic imbalances in tissue, exacerbating inflammation in affected joints. Changes in immunological and metabolic tissue homeostasis at different stages of RA are not well understood. Herein, the changes in the immunological and metabolic profiles in different stages in collagen induced arthritis (CIA), namely, early, intermediate, and late stage is examined. Moreover, the efficacy of the inverse‐vaccine, paKG(PFK15+bc2) microparticle, to restore tissue homeostasis at different stages is also investigated. Immunological analyses of inverse‐vaccine‐treated group revealed a significant decrease in the activation of pro‐inflammatory immune cells and remarkable increase in regulatory T‐cell populations in the intermediate and late stages compared to no treatment. Also, glycolysis in the spleen is normalized in the late stages of CIA in inverse‐vaccine‐treated mice, which is similar to no‐disease tissues. Metabolomics analyses revealed that metabolites UDP‐glucuronic acid and L‐Glutathione oxidized are significantly altered between treatment groups, and thus might provide new druggable targets for RA treatment. Flux metabolic modeling identified amino acid and carnitine pathways as the central pathways affected in arthritic tissue with CIA progression. Overall, this study shows that the inverse‐vaccines initiate early re‐establishment of homeostasis, which persists through the disease span.