tbuckley/cabot-search huggingface dataset:
Death doulas could lead end-of-life care
Authors: Marian Krawczyk
Journal: BMJ (2024)

Hospice and palliative care can only do so much. Doulas—non-medical, community based practitioners—could have a central role in demedicalising and deinstitutionalising dying to help people navigate the holistic care they need at the end of life, writes <b>Marian Krawczyk</b>
Impact of the CAPTURE COPD Screening Tool in US Primary Care: A Cluster Randomized Trial
Authors: Fernando J. Martinez, Barbara P Yawn, Daniela Angulo, Camden Lopez, Susan Murray, David Mannino, Stacey Anderson, Rowena Dolor, Nancy Elder, Min Joo, Irfan Khan, Lyndee M. Knox, Catherine Meldrum, Elizabeth Peters, Cathie Spino, Hazel Tapp, Byron Thomashow, Linda Zittleman, Randall Brown, Barry Make, MeiLan K. Han
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Rationale: The impact of COPD screening on US primary care clinician behavior and patient outcomes is unclear. Objectives: Assess the impact of receiving CAPTURE (COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk) screening scores on clinical and patient outcomes. Methods: Cluster randomized trial included 49 usual care (COPD education only) and 51 intervention (COPD and CAPTURE education plus screening scores) primary care practices. Twelve-month medical record and patient survey outcome data were collected in patients with elevated screening scores or study spirometric abnormalities. Measurements and Main Results: Among 387 CAPTURE+ patients, no significant difference was noted between usual care and intervention practices in the primary composite outcome of: 1) spirometry referral/completion, 2) new COPD diagnosis, 3) newly prescribed inhaled long-acting respiratory medication, 4) referral to a respiratory specialist, or 5) pulmonary rehabilitation referral/completion, 45.9% versus 41.9% (+4.0%, 95% CI -6.9, +15.0, p=0.47). Only spirometry referral/completion was higher in the intervention group (+10.4%, 95% CI +0.1, +20.7, p = 0.0465). No differences were noted for secondary outcomes, composite components, change in COPD Assessment Test scores, rates of respiratory illnesses, or hospitalizations. For the 1,028 screen-negative (CAPTURE-) patients, composite primary and all secondary outcomes were similar in the two arms. In secondary and post hoc analyses evaluating the potential impact of the pandemic, intervention group differences in clinician and patient outcomes were noted for CAPTURE+ and CAPTURE- patients in the pre-pandemic period that diminished during the pandemic. Conclusions: Within these US primary care practices, COPD and CAPTURE education plus receipt of CAPTURE screening scores did not change clinician COPD assessment or care or patient outcomes for CAPTURE+ patients. However, in the pre-pandemic period CAPTURE+ patients were more likely to undergo spirometry referral completion while for CAPTURE- patients clinicians were significantly less likely to assess for COPD suggesting that the intervention resulted in a more appropriate use of healthcare resources
Impaired Wnt/Planar Cell Polarity Signaling in Yellow Nail Syndrome
Authors: Alina Kurolap, Chofit Chai Gadot, Orly Eshach Adiv, Tova Hershkovitz, Emily Avitan-Hersh, Ludovic Martin, Helene Humeau, Ulrich A. Schatz, Dominik S. Westphal, Silvia Lobmaier, Efrat Sofrin-Drucker, Patrick Stafler, Joshua Bugis, Irit Chermesh, Emilia Hardak, Polina Geva, Yaniv Zohar, Dov Hershkovitz, Adi Mory, Sumit Chatterji, Shoshana Greenberger, Michal Shteinberg, Hagit Baris Feldman
Journal: Annals of Internal Medicine (2024)

Yellow nail syndrome (YNS) is a rare disorder characterized by a triad of yellow dystrophic nails, lymphedema, and chronic lung disease. Most patients present in adulthood, with only a few congenital or familial cases described. The cause of YNS remains largely unknown, although defects in lymphatic vessel development are suggested to play a significant role.
Anticoagulation Among Patients Hospitalized for COVID-19
Authors: Claire L. Vale, Peter J. Godolphin, David J. Fisher, Julian P.T. Higgins, Alexandra McAleenan, Francesca Spiga, Tobias Tritschler, Pedro Gabriel Melo de Barros e Silva, David D. Berg, Jeffrey S. Berger, Lindsay R. Berry, Behnood Bikdeli, Marc Blondon, Erin A. Bohula, Marco Cattaneo, Riccardo Colombo, Valeria Coluccio, Maria T. DeSancho, Michael E. Farkouh, Valentin Fuster, Massimo Girardis, Judith S. Hochman, Thomas P. Jensen, Vivekanand Jha, Peter Jüni, Ajay J. Kirtane, Patrick Lawler, Grégoire Le Gal, Ramon Lecumberri, Steven R. Lentz, Renato D. Lopes, Elizabeth Lorenzi, Marco Marietta, Carlos Henrique Miranda, Nuccia Morici, Susan C. Morpeth, David A. Morrow, Zoe K. McQuilten, Nuria Muñoz-Rivas, Matthew D. Neal, Suman Pant, Sahil A. Parikh, Usha Perepu, Parham Sadeghipour, Sanjum Sethi, Michelle Sholzberg, Alex C. Spyropoulos, Gregg W. Stone, Azita Hajhossein Talasaz, Steven Tong, James Totterdell, Balasubramanian Venkatesh, Maddalena Alessandra Wu, Ryan Zarychanski, Stephane Zuily, Julie Viry, Jamie Rylance, Neill K.J. Adhikari, Janet V. Diaz, John C. Marshall, Jonathan A.C. Sterne, Srinivas Murthy
Journal: Annals of Internal Medicine (2024)

Reported results of clinical trials assessing higher-dose anticoagulation in patients hospitalized for COVID-19 have been inconsistent.
Cardiovascular Complications, Kidney Failure, and Mortality in Young-Onset Type 1 and 2 Diabetes: Data From the Korean National Health Insurance Service
Authors: Sung Eun Kim, Kyungdo Han, Won Kyoung Cho, Byung-Kyu Suh
Journal: Diabetes Care (2024)

OBJECTIVE To explore all-cause mortality and the incidence of cardiovascular and renal complications among patients with young-onset diabetes in South Korea using a nationwide registry database. RESEARCH DESIGN AND METHODS Data were collected from the Korean National Health Insurance Service–National Sample Cohort database from 2006 to 2019 for patients aged ≤30 years with type 1 diabetes (T1D) or type 2 diabetes (T2D). The incidence rates of cardiovascular complications (myocardial infarction [MI] and stroke) and kidney failure, as well as all-cause mortality, were compared with those in the general population. RESULTS This study included 513,633 participants, comprising 413 with T1D, 1,250 with T2D, and 511,970 control individuals. After adjusting for sex, age, family income, hypertension, and dyslipidemia, the hazard ratio (HR) for MI was 6.76 (95% CI 2.44–18.72) and 5.07 (95% CI 2.48–10.36) for T1D and T2D, respectively. The HR for stroke was 4.65 (95% CI 1.70–12.71) and 3.30 (95% CI 1.67–6.53) for T1D and T2D, respectively. The HR for kidney failure was 20.92 (95% CI 11.40–38.39) and 2.78 (95% CI 1.37–5.64) for T1D and T2D, respectively. The mortality risk was significantly higher in patients with T1D (3.69; 95% CI 1.95–6.98) and T2D (3.06; 95% CI 2.02–4.63) than in the control group. The mortality risk was highest in the T2D subgroup of participants aged &amp;lt;20 years at enrollment (10.70; 95% CI 4.41–25.94). CONCLUSIONS In South Korea, patients with young-onset diabetes are at high risk of cardiovascular complications, kidney failure, and death.
Ethical data acquisition for LLMs and AI algorithms in healthcare
Authors: Marta Williams, Wasie Karim, Justin Gelman, Marium Raza
Journal: npj Digital Medicine (2024)

Artificial intelligence (AI) algorithms will become increasingly integrated into our healthcare systems in the coming decades. These algorithms require large volumes of data for development and fine-tuning. Patient data is typically acquired for AI algorithms through an opt-out system in the United States, while others support an opt-in model. We argue that ethical principles around autonomy, patient ownership of data, and privacy should be prioritized in the data acquisition paradigm.
Endosomal traffic disorders: a driving force behind neurodegenerative diseases
Authors: Jianru Dong, Weiwei Tong, Mingyan Liu, Mengyu Liu, Jinyue Liu, Xin Jin, Ju Chen, Huachao Jia, Menglin Gao, Minjie Wei, Ying Duan, Xin Zhong
Journal: Translational Neurodegeneration (2024)

Abstract Endosomes are crucial sites for intracellular material sorting and transportation. Endosomal transport is a critical process involved in the selective uptake, processing, and intracellular transport of substances. The equilibrium between endocytosis and circulation mediated by the endosome-centered transport pathway plays a significant role in cell homeostasis, signal transduction, and immune response. In recent years, there have been hints linking endosomal transport abnormalities to neurodegenerative diseases, including Alzheimer's disease. Nonetheless, the related mechanisms remain unclear. Here, we provide an overview of endosomal-centered transport pathways and highlight potential physiological processes regulated by these pathways, with a particular focus on the correlation of endosomal trafficking disorders with common pathological features of neurodegenerative diseases. Additionally, we summarize potential therapeutic agents targeting endosomal trafficking for the treatment of neurodegenerative diseases. Graphical abstract
The α glycolipid rules the NKT cell TCR
Authors: Mitchell Kronenberg, Gabriel Ascui
Journal: The Journal of Experimental Medicine (2024)

In this issue of JEM, Hosono et al. (https://doi.org/10.1084/jem.20240728) characterize a putative self- glycolipid that engages the iNKT cell TCR when bound to CD1d. The expression and distribution of this compound helps to explain some of the unusual properties of invariant NKT cells.
Prospective Trial of Biomarker-Guided Surveillance for HPV-positive Oropharynx Cancer Using Plasma Tumor Tissue Modified Viral HPV DNA
Authors: Eleni M. Rettig, Jonathan D. Schoenfeld, Julianna Miller, Bethany Sargent, Evan Carey, Danielle N. Margalit, Kartik Sehgal, Rosh K.V. Sethi, Ravindra Uppaluri, Roy B. Tishler, Laura A. Goguen, Donald J. Annino, Edward S. Sim, Vickie Y. Jo, Kristine S. Wong, Jeffrey P. Guenette, Robert I. Haddad, Glenn J. Hanna
Journal: Clinical Cancer Research (2024)

Abstract Background: Observational studies suggest circulating tumor HPV DNA may facilitate early detection of recurrent HPV-positive oropharynx cancer (OPC). We prospectively investigated whether biomarker-guided surveillance detects recurrence sooner than standard-of-care. Patients and Methods: We enrolled patients evaluated for HPV-positive OPC at a single center 11/2020-4/2023 undergoing curative-intent treatment in a single-arm cohort study. Pretreatment plasma and/or tumor tissue were tested for tumor tissue modified viral HPV DNA (‘TTMV’) from HPV subtypes 16/18/31/33/35 using a ddPCR-based commercial assay. Post-treatment plasma TTMV was assessed periodically. Detectable/indeterminate tests prompted imaging. Primary outcome was proportion of recurrences first detected by TTMV. Results: Median follow-up was 23 months, with median 6 post-treatment TTMV tests for 155 subjects. Fifteen subjects (9%) recurred. Among these, 6 (40%, 95%CI=16%-68%) were ‘early true-positives’, for whom TTMV detection predated and prompted the imaging and clinical workup that diagnosed recurrence (median lead-time=132 days; range=47-280). Another 5 subjects (33%) were ‘confirmatory true-positives’, for whom detectable TTMV confirmed suspicious standard-of-care imaging findings. Finally, 4 subjects (27%) with recurrence had undetectable TTMV at diagnosis (‘false-negatives’). False-negatives had low or undetectable pretreatment TTMV, and 2/4 had non-HPV16 genotypes. Finally, 3 subjects had prolonged detectable TTMV without disease (‘false-positives’); all had immunologic comorbidities. Overall, sensitivity of TTMV for recurrence was 73% (95%CI=45-92%). Among 117 subjects with HPV16 and detectable pretreatment TTMV, sensitivity was higher (91%, 95%CI=59-100%) Conclusions: TTMV-guided surveillance facilitates early detection of many HPV-positive OPC recurrences, with highest sensitivity for HPV16 and detectable pretreatment TTMV. Clinical implementation should be carefully informed by the limitations described herein.
Longitudinal glioma monitoring via cerebrospinal fluid cell-free DNA
Authors: Cecile Riviere-Cazaux, Xiaoxi Dong, Wei Mo, Rahul Kumar, Chao Dai, Lucas P. Carlstrom, Amanda Munoz-Casabella, Keyvan Ghadimi, Cody L. Nesvick, Katherine M. Andersen, Matthew D. Hoplin, Nicholas Canaday, Ignacio Jusue-Torres, Noor Malik, Jian L. Campian, Michael W. Ruff, Joon H. Uhm, Jeanette E. Eckel-Passow, Timothy J. Kaufmann, David M. Routman, Sani H. Kizilbash, Ugur Sener, Arthur E. Warrington, Robert B. Jenkins, Pan Du, Shidong Jia, Terry C. Burns
Journal: Clinical Cancer Research (2024)

Abstract PURPOSE: Current methods for glioma response assessment are limited. This study aimed to assess the technical and clinical feasibility of molecular profiling using longitudinal intracranial CSF from patients with gliomas. EXPERIMENTAL DESIGN: Adults with gliomas underwent longitudinal intracranial CSF collection via Ommaya reservoirs or ventriculoperitoneal shunts. cfDNA was extracted and analyzed using PredicineCARE for cancer variant profiling and/or PredicineSCORE for low-pass whole genome sequencing (LP-WGS). RESULTS: Five patients (2 females, 3 males; median age: 40 years, range 32-64 years) underwent longitudinal intracranial CSF collection via Ommaya reservoirs (n=4) or ventriculoperitoneal shunts (n=1). In total, forty-seven CSF samples were obtained (median volume: 4.00 mL; 0.5-5 mL). Forty-one samples (87.2%) yielded sufficient cfDNA for testing. Patient-specific tumor-associated variant allelic frequencies (VAFs), and thus tumor fraction, decreased in pre-versus-post chemoradiation samples, including through pseudoprogression. These also increased with radiographic progression in three patients, although identifying the time of definitive disease progression from MRIs was a significant limitation. In two patients with isocitrate dehydrogenase (IDH) mutant gliomas, decreasing IDH1 VAF after resection and chemoradiation correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the first patient, and 0.01x and 0.07x for the other patient), although D-2-HG and IDH1 VAF were not concordant in one patient thereafter. Moreover, CNB decreased below the limit of quantification during treatment and increased above the limit at progression. CONCLUSION: Longitudinal intracranial CSF cfDNA can feasibly be obtained in patients with gliomas during their disease course. Numerous questions and challenges should be answered before deploying this technique.
MixtureFinder: Estimating DNA mixture models for phylogenetic analyses
Authors: Huaiyan Ren, Thomas K F Wong, Bui Quang Minh, Robert Lanfear
Journal: Molecular Biology and Evolution (2024)

Abstract In phylogenetic studies, both partitioned models and mixture models are used to account for heterogeneity in molecular evolution among the sites of DNA sequence alignments. Partitioned models require the user to specify the grouping of sites into subsets, and then assume that each subset of sites can be modelled by a single common process. Mixture models do not require users to pre-specify subsets of sites, and instead calculate the likelihood of every site under every model, while co-estimating the model weights and parameters. While much research has gone into the optimisation of partitioned models by merging user-specified subsets, there has been less attention paid to the optimisation of mixture models for DNA sequence alignments. In this study, we first ask whether a key assumption of partitioned models – that each user-specified subset can be modelled by a single common process – is supported by the data. Having shown that this is not the case, we then design, implement, test, and apply an algorithm, MixtureFinder, to select the optimum number of classes for a mixture model of Q matrices for the standard models of DNA sequence evolution. We show this algorithm performs well on simulated and empirical datasets and suggest that it may be useful for future empirical studies. MixtureFinder is available in IQ-TREE2, and a tutorial for using MixtureFinder can be found here: http://www.iqtree.org/doc/Complex-Models#mixture-models.
Buttonhole Sign in Anetoderma
Authors: Yu-Ting Tsai, Shang-Hung Lin
Journal: British Journal of Dermatology (2024)

A 29-year-old woman presented with a 6-month history of slack, circumscribed skin on her right neck, characterized by a soft, protuberant plaque and a positive ‘buttonhole’ sign. Histopathology revealed perivascular lymphocytic infiltration and loss of elastic fibres, leading to a diagnosis of anetoderma, an elastolytic disorder more common in young women. Although autoimmune factors like antiphospholipid antibodies can be implicated, her autoimmune profile was negative, and surgical excision was performed due to cosmetic concerns.
Systematic analysis of sugammadex-related adverse drug reaction signals using FAERS database
Authors: Hongtao Liu, Qianqian Yang, Zhaoyu Li, Su Yan, Shaopeng Ming
Journal: International Journal of Surgery (2024)

Background: With the clinical integration of sugammadex, a selective relaxant-binding agent, the approach to reversing neuromuscular blockade is revolutionized. Despite its efficacy, sugammadex’s adverse reactions range from mild symptoms to severe cases, including anaphylaxis and coagulopathy. Assessing the nature of these reactions using the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database is vital for safe anesthetic practice. This study aimed to analyze and categorize the adverse drug events (ADEs) related to sugammadex reported in the FAERS database and evaluate the potential safety signals since its market entry. Materials and Methods: This systematic analysis study extracted and filtered FAERS data pertinent to sugammadex from its introduction in 2008 to the last quarter of 2023 and employed standardized MedDRA terminologies for ADE re-encoding. The Reporting Odds Ratio (ROR) method analyzed ADE signal strength, identifying significant cardiovascular, allergic, and neurological signals. Results: From 1,505 patient reports totaling 3,562 ADEs, prominent adverse reaction signals were detected for respiratory and cardiovascular systems and severe allergic and neurological effects. Specific signals, including laryngospasm, bronchospasm, and Disseminated Intravascular Coagulation (DIC), among others, were highlighted and necessitated urgent clinical attention. Conclusions: Sugammadex is associated with a spectrum of adverse reactions, some of which demand increased clinical surveillance, particularly in older and pediatric populations. The significance of allergic reactions, airway spasms, and coagulation events indicates the need for precise risk assessment and vigilant monitoring during clinical use.
Lip-split Mandibulectomy Versus Lip-mandible Preservation Technique for Oral and Oropharyngeal Cancer: a Systematic Review and Meta-analysis of Comparative Studies
Authors: Bincan Sun, Chengwen Gan, Yan Tang, Feiya Zhu
Journal: International Journal of Surgery (2024)

Background: Many studies have compared lip-splitting mandibulotomy (LSM) and lip-mandible preservation (LMP) techniques in oral and oropharyngeal cancer (OOPC) patients with inconsistent conclusions. Evidence-based recommendations for the optimal surgical approach for treating OOPC are lacking. Methods: The Cochrane Library, Pubmed, Embase, Web of Science, WAN-FANG, CQVIP, and China National Knowledge Infrastructure were systematically searched to identify studies that compared LSM versus LMP for OOPC. An additional search of the gray literature was performed using Google Scholar, OpenGrey and ProQuest Dissertations &amp; Theses Global. Survival rate, recurrence rate, surgical margin, perioperative outcomes, postoperative complications and functional status were assessed. The standard mean difference (SMD) and odds ratio (OR) with a 95% CI were pooled using fixed-effect or random-effect models. Results: Four randomized controlled trials, five case-control studies and twenty cohort studies including a total of 2622 patients were identified. The LSM approach significantly increased postoperative complications such as mandibular osteomyelitis/osteoradionecrosis (OR = 4.57; 95% CI = 1.20 ~ 17.39; p = 0.026), fistula (OR = 1.5; 95% CI = 1.05 ~ 2.15; p = 0.027), and flap infection (OR = 2.96; 95% CI = 1.49 ~ 5.87; p = 0.002), while LMP improved facial appearance (SMD = -0.65; 95% CI = -1.05 ~-0.25; p = 0.002). Meta-analyses showed no significant difference in survival rate (OR = 1.07; 95% CI = 0.83 ~ 1.38; p = 0.59), total recurrence (OR = 1.15; 95% CI = 0.87 ~ 1.52; p = 0.325), local recurrence (OR = 1.39; 95% CI = 0.88 ~ 2.19; p = 0.163), operation duration (SMD = 0.19; 95% CI = -0.75 ~ 1.13; p = 0.688), length of hospital stay (SMD = 0.48; 95% CI = -0.27 ~ 1.22; p = 0.208), volume of blood loss (SMD = 0.43; 95% CI = -0.17 ~ 1.03; p = 0.156), surgical margin (OR = 1.01; 95% CI = 0.72 ~ 1.41; p = 0.947), hematoma/seroma (OR = 1.01; 95% CI = 0.46 ~ 2.25; p = 0.972), wound infection (OR = 1.28; 95% CI = 0.92 ~ 1.79; p = 0.145), swallowing (SMD = -0.33; 95% CI = -0.91 ~ 0.24; p = 0.428) and speech (SMD = -0.14; 95% CI = -0.44 ~ 0.17; p = 0.381) between the LSM and LMP groups. Conclusion: These findings suggest that LMP may be a safe and efficient alternative to LSM for treating OOPC patients with decreased mandibular osteomyelitis/osteoradionecrosis, fistula, flap infection, and a better aesthetic outcome.
Letter to the editor: Can plasma FSTL-1 levels serve as a reliable biomarker for advanced fibrosis?
Authors: Enzo Emanuele, Piercarlo Minoretti
Journal: Hepatology (2024)

12E Science, Via Monte Grappa, 13, I-27038 Robbio (PV), Italy 2Studio Minoretti, Oggiono (LC), Italy Correspondence Enzo Emanuele, Scientific Directorate, 2E Science, Via Monte Grappa, 13, I-27038 Robbio (PV), Italy. Email: [email protected]