tbuckley/cabot-search huggingface dataset:
Mobile Media Content Exposure and Toddlers’ Responses to Attention Prompts and Behavioral Requests
Authors: Sara Jane Webb, Waylon Howard, Michelle Garrison, Sarah Corrigan, Shayeleen Quinata, Lani Taylor, Dimitri A. Christakis
Journal: JAMA Network Open (2024)

Importance With personalized touch-screen tablets, young children can choose content and engage in play-like activities. However, tablets may also reduce shared engagement as the action of viewing or touching the screen is often not visible to nearby adults. This may impact communicative gazing and pointing, which is critical to the formation of shared awareness and in turn supports language development. Objective To assess the association of tablet media content with toddlers’ responses to joint attention prompts and behavioral requests. Design, Setting, and Participants This cohort study took place at a behavioral research laboratory and included toddlers who were aged 18 to 32 months with neurotypical development who were recruited from a volunteer and community sample. Toddlers engaged with a real toy or 3 different types of tablet content (ie, viewing video of toy play, playing with a digital toy, or playing a commercial game) while an experimenter delivered joint attention prompts. Data were acquired from June 2021 November XX 2022, and data analysis occurred from January 2023 to May 2024. Main Outcomes and Measures Main outcomes included child response to joint attention (number of prompts with joint attention response per number of prompts delivered) and child response to behavioral request (ie, the prompt on which the child responded to the behavioral request). Measures included crossed random effects, Wald tests, and likelihood ratio tests. Results In this study, 63 toddlers were enrolled, and data from 62 were included (31 female [49%]; mean [SD] age, 26.1 [3.4] months; median [IQR] age, 25.0 [18.6-32.6] months). When toddlers were playing a commercial game on a tablet, they responded to fewer joint attention prompts (crossed random effects model, −0.15; 95% CI, −0.24 to −0.06 prompts) and male toddlers took longer to acknowledge a behavioral request (interaction of content and sex, −0.75; 95% CI, −1.36 to −0.17). The negative impact of the tablet game was larger as child age increased (τ = −2.30; 95% CI, −0.05 to 0; P = . 03). Greater media use at home was associated with decreased responding to joint attention prompts during the tablet game ( ρ = −0.47; P &amp;amp;lt; .001), while better language skills were associated with more joint attention during play with a real toy ( ρ = 0.31; P = .02). Conclusions and Relevance In this cohort study, a touch-screen tablet game was associated with decreased joint attention among toddlers and they were less likely to respond to a behavioral request. In a laboratory setting, it was difficult for toddlers to engage in social-communicative interactions with adults when using a tablet media device.
Dupilumab in Adults With Moderate to Severe Atopic Dermatitis
Authors: Lisa A. Beck, Robert Bissonnette, Mette Deleuran, Takeshi Nakahara, Ryszard Galus, Anna Coleman, Guy Gherardi, Jing Xiao, Robert Dingman, Christine Xu, Elena Avetisova, Ariane Dubost-Brama, Arsalan Shabbir
Journal: JAMA Dermatology (2024)

Importance Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. Objective To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. Design, Setting, and Participants The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. Exposures At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. Main Outcomes and Measures The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. Results A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. Conclusions and Relevance In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.
Ushering in a New Paradigm of Substance Use Prevention—Low-Touch Personalized Interventions in Specialty Care
Authors: Emily Rider-Longmaid, J. Deanna Wilson
Journal: JAMA Network Open (2024)

Elissa R. Weitzman, ScD, MSc; Machiko Minegishi, MD, MPH, MSW; Fatma Dedeoglu, MD; Laurie N. Fishman, MD; Katharine C. Garvey, MD, MPH; Lauren E. Wisk, PhD; Sharon Levy, MD, MPH
Incidence of Panic Disorder Diagnoses After Celebrity Disclosures of Panic Disorder in South Korea
Authors: Ga Eun Kim, Min-Woo Jo, Young Eun Kim, Seok-Jun Yoon, Yong-Wook Shin
Journal: JAMA Network Open (2024)

The persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions.
Prehospital Partial Resuscitative Endovascular Balloon Occlusion of the Aorta for Exsanguinating Subdiaphragmatic Hemorrhage
Authors: Robbie A. Lendrum, Zane Perkins, Max Marsden, Claire Cochran, Ross Davenport, Frank Chege, Virginia Fitzpatrick-Swallow, Rob Greenhalgh, Jared M. Wohlgemut, Christine L. Henry, Ben Singer, Gareth Grier, Gareth Davies, Nick Bunker, Daniel Nevin, Mike Christian, Marion K. Campbell, Nigel Tai, Austin Johnson, Jan O. Jansen, Samy Sadek, Karim Brohi
Journal: JAMA Surgery (2024)

Hemorrhage is the most common cause of preventable death after injury. Most deaths occur early, in the prehospital phase of care.
Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure
Authors: Catherine Mezzacappa, Nicole J. Kim, Philip Vutien, David E. Kaplan, George N. Ioannou, Tamar H. Taddei
Journal: JAMA Network Open (2024)

The risk of hepatocellular carcinoma (HCC) declines over time after hepatitis C virus (HCV) cure by direct-acting antiviral (DAA) therapies. Liver society guidelines recommend continuing HCC screening for these patients, but data on screening outcomes are lacking.
Successful Treatment of Stimulator of Interferon Genes–Associated Vasculopathy of Infantile Onset SAVI Syndrome With Anifrolumab
Authors: Miguel Mansilla-Polo, Daniel Martín-Torregrosa, Begoña Escutia-Muñoz, Ignacio Torres-Navarro, Miguel Saro-Buendía, Rafael Botella-Estrada
Journal: JAMA Dermatology (2024)

This case report describes a woman in her 30s who presented with cutaneous lesions since age of 2 to 3 years with erythema and pain on her nose, both cheeks, and ears when exposed to cold temperatures that progressed to nasal and auricular cartilage necrosis and was diagnosed with stimulator of interferon genes–associated vasculopathy with onset in infancy (SAVI syndrome).
Accelerated Intermittent Theta-Burst Stimulation and Treatment-Refractory Bipolar Depression
Authors: Yvette I. Sheline, Walid Makhoul, Alexandra S. Batzdorf, Frederick J. Nitchie, Kevin G. Lynch, Robin Cash, Nicholas L. Balderston
Journal: JAMA Psychiatry (2024)

Importance Bipolar disorder (BD) is chronic and disabling, with depression accounting for the majority of time with illness. Recent research demonstrated a transformative advance in the clinical efficacy of transcranial magnetic stimulation for treatment-resistant major depressive disorder (MDD) using an accelerated schedule of intermittent theta-burst stimulation (aiTBS), but the effectiveness of this treatment for treatment-refractory BD is unknown. Objective To evaluate the effectiveness of aiTBS for treatment-refractory BD. Design, Setting, and Participants This randomized clinical trial, conducted from March 2022 to February 2024, included individuals with treatment-resistant BD with moderate to severe depressive episodes referred from the Penn Bipolar outpatient clinic. Included patients had 2 or more prior failed antidepressant trials by Antidepressant Treatment History Form criteria and no other primary psychiatric diagnosis, were receiving a mood stabilizer for 4 or more weeks, and had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or higher. Intervention Prior to treatment, resting-state functional magnetic resonance imaging was used to compute personalized left dorsolateral prefrontal cortex target by connectivity to subgenual anterior cingulate cortex. Patients were randomized 1:1 to 10 sessions per day of imaging-guided active or sham aiTBS for 5 days with 1 session per hour at 90% resting motor threshold for 90 000 pulses total. Main Outcome and Measures The main outcome was repeated MADRS scores before and after treatment. Results A total of 24 participants (12 [50%] female; 12 [50%] male; mean [SD] age, 43.3 [16.9] years) were randomized to active (n = 12) or sham (n = 12) aiTBS. All participants completed treatment and 1-month follow-up. MADRS scores were significantly lower in the active group (mean [SD], 30.4 [4.8] at baseline; 10.5 [6.7] after treatment) than in the sham group (28.0 [5.4] at baseline; 25.3 [6.7] after treatment) at treatment end (estimated difference, –14.75; 95% CI, –19.73 to –9.77; P &amp;amp;lt; .001; Cohen d , –2.19). Conclusion and Relevance In this randomized clinical trial, aiTBS was more effective than sham stimulation for depressive symptom reduction in patients with treatment-resistant BD. Further trials are needed to determine aiTBS durability and to compare with other treatments. Trial Registration ClinicalTrials.gov Identifier: NCT05228457
Disease-Tailored Brief Intervention for Alcohol Use Among Youths With Chronic Medical Conditions
Authors: Elissa R. Weitzman, Machiko Minegishi, Fatma Dedeoglu, Laurie N. Fishman, Katharine C. Garvey, Lauren E. Wisk, Sharon Levy
Journal: JAMA Network Open (2024)

In the US, 25% of youths have a chronic medical condition (CMC). Alcohol use is prevalent among youths with a CMC and is associated with treatment nonadherence, simultaneous exposure to contraindicated medications, poor self-care, and elevated rates of progression to heavy and problem use by young adulthood. Preventive interventions targeting these youths are scarce and lack evidence about longer-term risk-stratified effects.
Heterogeneity in Antidepressant Treatment and Major Depressive Disorder Outcomes Among Clinicians
Authors: Sarah Rathnam, Kamber L. Hart, Abhishek Sharma, Pilar F. Verhaak, Thomas H. McCoy, Finale Doshi-Velez, Roy H. Perlis
Journal: JAMA Psychiatry (2024)

While abundant work has examined patient-level differences in antidepressant treatment outcomes, little is known about the extent of clinician-level differences. Understanding these differences may be important in the development of risk models, precision treatment strategies, and more efficient systems of care.
Exploration-Exploitation and Suicidal Behavior in Borderline Personality Disorder and Depression
Authors: Aliona Tsypes, Michael N. Hallquist, Angela Ianni, Aleksandra Kaurin, Aidan G. C. Wright, Alexandre Y. Dombrovski
Journal: JAMA Psychiatry (2024)

Clinical theory and behavioral studies suggest that people experiencing suicidal crisis are often unable to find constructive solutions or incorporate useful information into their decisions, resulting in premature convergence on suicide and neglect of better alternatives. However, prior studies of suicidal behavior have not formally examined how individuals resolve the tradeoffs between exploiting familiar options and exploring potentially superior alternatives.
Relationship between Airway Microbiome and the Immune Response to Diesel Exhaust: A Randomized Crossover Controlled Exposure Study
Authors: Min Hyung Ryu, Illiassou Hamidou Soumana, Denise J. Wooding, Fernando Sergio Leitao Filho, Julia Yang, Corey Nislow, Christopher F. Rider, Janice M. Leung, Chris Carlsten
Journal: Environmental Health Perspectives (2024)
Effectiveness of behavioural interventions with motivational interviewing on physical activity outcomes in adults: systematic review and meta-analysis
Authors: SuFen Zhu, Deepra Sinha, Megan Kirk, Moscho Michalopoulou, Anisa Hajizadeh, Gina Wren, Paul Doody, Lucy Mackillop, Ralph Smith, Susan A Jebb, Nerys M Astbury
Journal: BMJ (2024)

Abstract Objective To evaluate the effectiveness of behavioural interventions that include motivational interviewing on physical activity outcomes in adults. Design Systematic review and meta-analysis. Study selection A search of seven databases for randomised controlled trials published from inception to 1 March 2023 comparing a behavioural intervention including motivational interviewing with a comparator without motivational interviewing on physical activity outcomes in adults. Outcomes of interest were differences in change in quantitative measures of total physical activity, moderate to vigorous physical activity (MVPA), and sedentary time. Data extraction and synthesis Two reviewers extracted data and assessed risk of bias. Population characteristics, intervention components, comparison groups, and outcomes of studies were summarised. For overall main effects, random effects meta-analyses were used to report standardised mean differences (SMDs) and 95% confidence intervals (CIs). Differential effects based on duration of follow-up, comparator type, intervention duration, and disease or health condition of participants were also examined. Results 129 papers reporting 97 randomised controlled trials totalling 27 811 participants and 105 comparisons were included. Interventions including motivational interviewing were superior to comparators for increases in total physical activity (SMD 0.45, 95% CI 0.33 to 0.65, equivalent to 1323 extra steps/day; low certainty evidence) and MVPA (0.45, 0.19 to 0.71, equivalent to 95 extra min/week; very low certainty evidence) and for reductions in sedentary time (−0.58, −1.03 to −0.14, equivalent to −51 min/day; very low certainty evidence). Evidence for a difference in any outcome compared with comparators of similar intensity was lacking. The magnitude of effect diminished over time, and evidence of an effect of motivational interviewing beyond one year was lacking. Most interventions involved patients with a specific health condition, and evidence of an effect of motivational interviewing to increase MVPA or decrease sedentary time was lacking in general population samples. Conclusions Certainty of the evidence using motivational interviewing as part of complex behavioural interventions for promoting total physical activity in adults was low, and for MVPA and sedentary time was very low. The totality of evidence suggests that although interventions with motivational interviewing increase physical activity and decrease sedentary behaviour, no difference was found in studies where the effect of motivational interviewing could be isolated. Effectiveness waned over time, with no evidence of a benefit of motivational interviewing to increase physical activity beyond one year. Systematic review registration PROSPERO CRD42020219881.
Aerosolized Antibiotic Therapy in Mechanically Ventilated Patients
Authors: Stephan Ehrmann, François Barbier, Jie Li
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Delivering antibiotics directly to the respiratory tract through inhalation to address lung infections has garnered clinical and scientific interest for decades, given the potential favorable pharmacokinetic profile of this administration route. Among critically ill patients, the burden of healthcare-associated pulmonary infections particularly drove continued interest in delivering inhaled antibiotics to intubated patients. We present a concise overview of the existing rationale and evidence and provide guidance for implementing inhaled antibiotics among ventilated critically ill patients, emphasizing insights from recent literature.
Contemporary Treatment of Pulmonary Arterial Hypertension: A US Perspective
Authors: Sandeep Sahay, Murali M. Chakinala, Nick H. Kim, Ioana R. Preston, Thenappan Thenappan, Vallerie V. Mclaughlin
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Pulmonary arterial hypertension (PAH) is a complex fatal condition that requires aggressive treatment with close monitoring. Significant progress has been made over the last three decades in the treatment of PAH, but, despite this progress, survival has remained unacceptably low. In the quest to improve survival, therapeutic interventions play a central role. In the last few years, there have been remarkable attempts to identify novel treatments. Finally, we have had a breakthrough with the discovery of the fourth treatment pathway in PAH. Activin signaling inhibition distinguishes itself as a potential antiproliferative intervention as opposed to the traditional therapies, which mediate their effect primarily by vasodilatation. With this novel treatment pathway, we stand at an important milestone with an exciting future ahead and the natural question of when to use an activin signaling inhibitor for the treatment of PAH. In this state-of-the-art review, we focus on the placement of this novel agent in the PAH treatment paradigm, based on the available evidence, with special focus on the U.S. patient population. This review also provides an expert opinion of the current treatment algorithm in important subgroups of patients with comorbidities from the U.S. perspective.
Characterization and Mortality Risk of Impaired Left Ventricular Filling in COPD
Authors: Mustafa Abdo, Henrik Watz, Peter Alter, Kathrin Kahnert, Franziska Trudzinski, Espen E. Groth, Martin Claussen, Anne-Marie Kirsten, Tobias Welte, Rudolf A Jörres, Claus F Vogelmeier, Robert Bals, Klaus F. Rabe, Benjamin Waschki
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

In COPD, impaired left ventricular (LV) filling might be associated with coexisting HFpEF or due to reduced pulmonary venous return indicated by small LV size. We investigate the all-cause mortality associated with small LV or HFpEF and clinical features discriminating between both patterns of impaired LV filling.
Nanomedicine regulating PSC-mediated intercellular crosstalk: Mechanisms and therapeutic strategies
Authors: Hui Wang, Liang Qi, Han Han, Xuena Li, Mengmeng Han, Lei Xing, Ling Li, Hulin Jiang
Journal: Acta Pharmaceutica Sinica B (2024)

Pancreatic fibrosis (PF) is primarily distinguished by the stimulation of pancreatic stellate cells (PSCs) and excessive extracellular matrix deposition, which is the main barrier impeding drug delivery and distribution. Recently, nanomedicine, with efficient, targeted, and controllable drug release characteristics, has demonstrated enormous advantages in the regression of pancreas fibrotic diseases. Notably, paracrine signals from parenchymal and immune cells such as pancreatic acinar cells, islet cells, pancreatic cancer cells, and immune cells can directly or indirectly modulate PSC differentiation and activation. The intercellular crosstalk between PSCs and these cells has been a critical event involved in fibrogenesis. However, the connections between PSCs and other pancreatic cells during the progression of diseases have yet to be discussed. Herein, we summarize intercellular crosstalk in the activation of PSCs and its contribution to the development of common pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes. Then, we also examine the latest treatment strategies of nanomedicine and potential targets for PSCs crosstalk in fibrosis, thereby offering innovative insights for the design of antifibrotic nanomedicine. Ultimately, the enhanced understanding of PF will facilitate the development of more precise intervention strategies and foster individually tailored therapeutic approaches for pancreatic diseases.
Targeted degradation of LRG1 to attenuate renal fibrosis
Authors: Linyao Fan, Yingqiu Qi, Xi Yang, Yarui Xu, Yana Zhang, Longdi Wang, Anying Zhu, Lirong Zhang, Jian Song, Shengnan Du, Guangjun Nie, Huan Min
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Leucine-rich α-2 glycoprotein 1 (LRG1), a secreted glycoprotein, has been identified as significantly upregulated in renal fibrosis, potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways. Herein, utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement, we developed an advanced proteolysis targeting chimera,
Controlling tumor progression and recurrence in mice through combined treatment with a PD-L1 inhibitor and a designer Salmonella strain that delivers GM-CSF
Authors: Heung Jin Jeon, Daejin Lim, EunA So, Solbi Kim, Jae-Ho Jeong, Miryoung Song, Hyo-Jin Lee
Journal: Acta Pharmaceutica Sinica B (2024)

Combination therapy with checkpoint inhibitors blocks inhibitory immune cell signaling and improves clinical responses to anticancer treatments. However, continued development of innovative and controllable delivery systems for immune-stimulating agents is necessary to optimize clinical responses. Herein, we engineered Salmonella to deliver recombinant granulocyte macrophage colony stimulating factor (GM-CSF) in a controllable manner for combination treatment with a programmed death-ligand 1 (PD-L1) inhibitor. The engineered Salmonella enabled delivery of recombinant GM-CSF into mouse tumors, activating recruitment of immune cells, such as M1-polarized macrophages, dendritic cells, and CD8+ T cells. Combination treatment with the PD-L1 inhibitor and engineered Salmonella increased the survival rate of tumor-bearing mice by 25%. New tumor growth was strongly suppressed, and visible tumors disappeared at 120 days post-infection (dpi) in mice rechallenged with additional tumor implantation at 100 dpi. The number of memory T cells increased >2-fold in tumor-rechallenged mice. Our findings demonstrate superiority of the engineered Salmonella as a cancer therapeutic agent with precise targeting ability, immune-boosting activity, and ease of combination with other therapeutics.