tbuckley/cabot-search huggingface dataset:
All-stage targeted nanodiscs for glioma treatment by inducing cuproptosis and apoptosis of cancer cells and cancer stem cells
Authors: Yuan Ding, Ruohan Chen, Jianfen Zhou, Yanning Bao, Nana Meng, Xudong Zheng, Shengmin Yang, Jiasheng Lu, Zhixuan Jiang, Yu Liu, Cao Xie, Linwei Lu, Weiyue Lu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

There remain several intractable challenges for chemotherapy in glioma treatment, including the blood-brain barrier (BBB), blood-brain tumor barrier (BBTB), and tumor heterogeneity caused by cancer stem cells (CSCs), which are resistant to conventional chemotherapy. Here, we established a nano strategy to kill glioma cells and CSCs, combining carfilzomib and bis(diethyldithiocarbamate)copper. The synergistic drug combination disturbed cell protein metabolism at different stages and induced apoptosis and cuproptosis. The Y-shaped targeting ligand pHA-VAP-modified nanodiscs were designed to help the chemotherapeutic agents cross the BBB/BBTB and finally accumulate in tumor site. This all-stage targeting and all-stage treatment nanomedicine significantly prolonged the survival in glioma-bearing mice and might inspire the rational design of advanced drug delivery platforms.
Circulating tumor DNA dynamics and clinical outcome in metastatic colorectal cancer patients undergoing front-line chemotherapy
Authors: Michele Ghidini, Jens C. Hahne, Chiara Senti, Timon Heide, Paula Z. Proszek, Ridwan Shaikh, Paul Carter, Michael Hubank, Francesco Trevisani, Ornella Garrone, Maria Rosa Cappelletti, Daniele Generali, Monica Cattaneo, Nicoletta Gnocchi, Gianvito Donati, Angela Gobbi, Giulia Grizzi, Andrea Lampis, Raghad Elghadi, Giulia Tanzi, Gianluca Tomasello, Margherita Ratti, David J. Pinato, Matteo Fassan, Georgios Vlachogiannis, Andrea Sottoriva, Rodolfo Passalacqua, Nicola Valeri
Journal: Clinical Cancer Research (2024)

Abstract Purpose: we tested whether ctDNA changes may be used to assess early response and clinical outcome in metastatic colorectal cancer (mCRC) patients undergoing front-line systemic anti-cancer therapy (SACT). Experimental Design: 862 plasma samples were collected 4-weekly from baseline (BL) until disease progression in mCRC patients receiving front line SACT. ctDNA normalization was defined as ≥99% clearance after 1 month of therapy (Mo1) in the 3 variants with the highest allele frequency in BL ctDNA. Results: 83 paired samples from 75 patients were available for analysis. 12 pairs (14.4%) showed no variants in either BL or Mo1. In the remaining 71 comparisons (65 patients), 37 (52.1%) showed ctDNA normalization at Mo1. Patients that cleared ctDNA had significantly longer overall (45.6 months) and progression-free survival (13.9 months) compared to non-normalized patients [OS= 22.6 months (Log-rank p = 0.01) and PFS= 10.7 months (Log-rank p = 0.036) respectively]. In addition, higher response rate was observed in patients with ctDNA clearance (72.9%) compared to non-normalized cases (38.2%). Longitudinal sequencing of at least four timepoints in pts with a PFS&amp;gt;10 months showed emerging variants in 47.8% of cases; in all these patients the trajectory of these new “outlier” variants appeared in stark contrast with the clinical-radiological course of disease and the trend in other mutations. Conclusions: ctDNA clearance represents an early indicator of benefit from SACT in mCRC patients; serial tracking of multiple variants is warranted to improve specificity and to avoid misleading information due to the emergence of mutations of unknown clinical significance.
Carvedilol vs. propranolol for the prevention of decompensation and mortality in patients with compensated and decompensated cirrhosis
Authors: Jose Ignacio Fortea, Edilmar Alvarado-Tapias, Benedikt Simbrunner, Iranzu Ezcurra, Virginia Hernández-Gea, Carles Aracil, Elba Llop, Angela Puente, Cristina Roig, Thomas Reiberger, Juan Carlos García-Pagan, José Luis Calleja, Andreu Ferrero-Gregori, Matthias Mandorfer, Candid Villanueva, Javier Crespo
Journal: Journal of Hepatology (2024)
Author correction to “Celastrol targets adenylyl cyclase-associated protein 1 to reduce macrophages-mediated inflammation and ameliorates high fat diet-induced metabolic syndrome in mice” [Acta Pharmaceutica Sinica B 11 (2021) 1200-1212]
Authors: Yuyu Zhu, Ning Wan, Xinni Shan, Guoliang Deng, Qiang Xu, Hui Ye, Yang Sun
Journal: Acta Pharmaceutica Sinica B (2024)

[This corrects the article DOI: 10.1016/j.apsb.2020.12.008.].
Differences in mean age at diagnosis of invasive melanoma for men and women, by anatomic site, thickness, and subtype
Authors: David C Whiteman, Nirmala Pandeya, Catherine M Olsen
Journal: British Journal of Dermatology (2024)

Abstract Background Understanding the factors influencing age at melanoma diagnosis by sex and anatomic site is crucial for developing effective prevention and early detection strategies. While previous research has highlighted sex-based differences in melanoma incidence by age and anatomic distribution, the underlying mechanisms remain unclear. We aimed to investigate sex-specific patterns in melanoma age at diagnosis across different anatomic sites and thickness categories, considering the potential influence of disease progression and detection rates. Methods We conducted a registry-based study to examine mean age at diagnosis of invasive melanoma over two decades for men and women in the US (limited to white race), and Queensland, Australia. Mean age at diagnosis was calculated for men and women according to anatomic site (head/neck, trunk, upper limb, lower limb), and further by Breslow thickness (&amp;lt;1.00 mm, 1.01-2.00 mm, 2.01-4.00 mm, &amp;gt;4.00 mm) and histologic subtype (superficial spreading, nodular, lentigo maligna, ‘other’ subtypes, and subtype ‘not otherwise specified’). Case-listings of all invasive melanoma diagnoses between 1 January 1999 and 31 December 2018 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program (9 registries) and from the Queensland Cancer Registry. Sensitivity analyses were performed restricting the data to the most recent 5-year time period (2014-2018). All analyses were conducted between 15 July and 19 August 2024. Results On average, women were diagnosed with invasive melanoma 3-8 years younger than men. The sex-difference in mean age at diagnosis was observed at all body sites and across most thickness categories in the US White and Queensland populations, but was most marked for thinner melanomas (&amp;lt;1.00 mm) and melanoma of the trunk. Women were significantly younger than men at diagnosis of superficial spreading and nodular melanoma at all body sites in both populations, even within 0.1mm thickness strata. Conclusions Sex may be a factor that influences melanocytic progression. The consistently younger age of melanoma diagnosis in women compared with men suggests a need for tailored approaches to melanoma control.
Molecular classification predicts response to surgery and radiotherapy
Authors: Gelareh Zadeh, Farshad Nassiri
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Molecular classification predicts response to surgery and radiotherapy Get access Gelareh Zadeh, Gelareh Zadeh Princess Margaret Cancer Centre, University Health Network, Toronto, ON, CanadaDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, CanadaMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, CanadaDepartment of Neurosurgery, Mayo Clinic, Rochester, MN, United States Corresponding Author: Gelareh Zadeh, MD, PhD, Department of Neurosurgery, Mayo Clinic in Rochester, 55905 MN, United States ([email protected]). https://orcid.org/0000-0002-6637-4502 Search for other works by this author on: Oxford Academic PubMed Google Scholar Farshad Nassiri Farshad Nassiri Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, CanadaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, CanadaDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON, CanadaMacFeeters Hamilton Neuro-Oncology Program, Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, ON, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae230, https://doi.org/10.1093/neuonc/noae230 Published: 17 December 2024 Article history Corrected and typeset: 17 December 2024 Published: 17 December 2024
Indirect immunofluorescence testing for immunoglobulin (Ig)G4 and IgG increases test sensitivity over that of indirect immunofluorescence testing for IgG alone for pemphigoid and pemphigus diseases: A retrospective study of 278 cases
Authors: Julia S Lehman, Nessa Aghazadeh Mohandesi, Shruti Agrawal, Michael J Camilleri, Derek J Cervenka, Nneka I Comfere, Emma F Johnson, Amer N Kalaaji, Colleen R Lange, Carly J Shore, Peyton Smith, Carilyn N Wieland, Anatilde M Gonzalez Guerrico
Journal: Journal of the American Academy of Dermatology (2024)
SerpinB1 targeting safeguards against pathological cardiac hypertrophy and remodelling by suppressing cardiomyocyte pyroptosis and inflammation initiation
Authors: Cong Lan, Guangyao Fang, Xiuchuan Li, Xiao Chen, Yingmei Chen, Tao Hu, Xuenan Wang, Huiling Cai, Jiajin Hao, Haoran Li, Yan Zhang, Ke Peng, Zaicheng Xu, Dachun Yang, Xia Kang, Qian Xin, Yongjian Yang
Journal: Cardiovascular Research (2024)

Abstract Aims While the pivotal role of inflammation in pathological cardiac hypertrophy and remodelling is widely acknowledged, the mechanisms triggering inflammation initiation remain largely obscure. This study aims to elucidate the role and mechanism of serpin family B member 1 (SerpinB1) in pro-inflammatory cardiomyocyte pyroptosis, heart inflammation, and cardiac remodelling. Methods and results C57BL/6J wild-type, inducible cardiac-specific SerpinB1 overexpression or knockout mice underwent transverse aortic constriction (TAC) surgery. Cardiac hypertrophy and remodelling were assessed through echocardiography and histology. Cardiomyocyte pyroptosis and heart inflammation were monitored. Adeno-associated virus 9 -mediated gene manipulations and molecular assays were employed to explore the mechanisms through which SerpinB1 regulates cardiomyocyte pyroptosis and heart inflammation. Finally, recombinant mouse SerpinB1 protein (rSerpinB1) was administrated both in vivo through osmotic minipump delivery and in vitro to investigate the therapeutic potential of SerpinB1 in cardiac remodelling. Myocardial SerpinB1 overexpression was up-regulated shortly upon TAC or phenylephrine challenge, with no further elevation during prolonged hypertrophic stimuli. It is important to note that cardiac-specific overexpression of SerpinB1 markedly attenuated TAC-induced cardiac remodelling, while deletion of SerpinB1 exacerbated it. At the mechanistic level, SerpinB1 gain-of-function inhibited cardiomyocyte pyroptosis and inflammation in hypertrophic hearts; the protective effect was nullified by overexpression of either cleaved N-terminal gasdermin D or cleaved caspase-1. Co-immunoprecipitation and confocal assays confirmed that SerpinB1 directly interacts with caspase-1 in cardiomyocytes. Remarkably, rSerpinB1 replicated the cardioprotective effect against cardiac hypertrophy and remodelling. Conclusion SerpinB1 safeguards against pathological cardiac hypertrophy and remodelling by impeding cardiomyocyte pyroptosis to suppress inflammation initiation, achieved through interaction with caspase-1 to inhibit its activation. Targeting SerpinB1 could represent a novel therapeutic strategy for treating pathological cardiac hypertrophy and remodelling.
Cannabis Use and Trajectories of Depression and Stress Across the Prenatal Period
Authors: Anna Constantino-Pettit, Rebecca Tillman, Jillian Wilson, Nicole Lashley-Simms, Naazanene Vatan, Azaria Atkinson, Shelby D. Leverett, Shannon Lenze, Christopher D. Smyser, Ryan Bogdan, Cynthia Rogers, Arpana Agrawal
Journal: JAMA Network Open (2024)

Cannabis use among pregnant individuals has increased. Depression and stress are frequently reported motives for cannabis use that may prolong using cannabis during pregnancy.
Image reconstruction impacts haemodynamic parameters derived from 4D flow magnetic resonance imaging with compressed sensing
Authors: Pia Sjöberg, Tania Lala, Johan Wittgren, Ning Jin, Erik Hedström, Johannes Töger
Journal:  (2024)

Abstract Aims 4D blood flow measurements by cardiac magnetic resonance imaging (CMR) can be used to simplify blood flow assessment. Compressed sensing (CS) can provide better flow measurements than conventional parallel imaging (PI), but clinical validation is needed. This study aimed to validate stroke volume (SV) measurements by 4D-CS in healthy volunteers and patients while also investigating the influence of the CS image reconstruction parameter λ on haemodynamic parameters. Methods and results Healthy participants (n = 9; 20–62 years) underwent CMR with 2D, 4D-CS, and 4D-PI flow. Patients (n = 30, 17 with congenital heart defect; 2–75 years) had 4D-CS added to their clinical examination. Impact of λ was assessed by reconstructing 4D-CS data for six different λ values. In healthy volunteers, 4D-CS and 4D-PI SV differed by 0.4 ± 6.5 mL [0.6 ± 9.1%; intraclass correlation coefficient (ICC) 0.98], and 4D-CS and 2D flow by 0.9 ± 7.0 mL (0.9 ± 10.6%; ICC 0.98). In patients, 4D-CS and 2D flow differed by −1.3 ± 6.0 mL (−7.2 ± 20%; ICC 0.97). SV was not dependent on λ in patients (P = 0.75) but an increase in λ by 0.001 led to increased differences between 4D-CS and 4D-PI of −0.4% (P = 0.0021) in healthy participants. There were significant differences for ventricular kinetic energy (systole: P &amp;lt; 0.0001; diastole: P &amp;lt; 0.0001) and haemodynamic forces (systole: P &amp;lt; 0.0001; diastole: P &amp;lt; 0.0001), where error increased with increasing λ values in both healthy participants and patients. Conclusion 4D flow CMR with CS can be used clinically to assess SV in paediatric and adult patients. Ventricular kinetic energy and haemodynamic forces are however sensitive to the change in reconstruction parameter λ, and it is therefore important to validate advanced blood flow measurements before comparing data between scanners and centres.
Physical Activity Engagement After Tai Ji Quan Intervention Among Older Adults With Mild Cognitive Impairment or Memory Concerns
Authors: Fuzhong Li, Peter Harmer, Elizabeth Eckstrom, Kerri Winters-Stone
Journal: JAMA Network Open (2024)

The effect of exercise interventions on increasing and sustaining moderate to vigorous physical activity (MVPA) among older adults with mild cognitive impairment (MCI), who are at heightened risk of dementia, remains unclear.
Building a Culture of Quality and Safety in Health Care—The Importance of Respect for Patients
Authors: Somnath Saha, Mary Catherine Beach
Journal: JAMA Network Open (2024)

Austin Wesevich, MD, MPH, MS; Erica Langan, BS; Ilona Fridman, PhD; Sonya Patel-Nguyen, MD; Monica E. Peek, MD, MPH, MSc; Victoria Parente, MD, MPH
Nicotine Pouch Use Among US Military Personnel
Authors: Melissa A. Little, Kathryn M. Polaskey, Asal Pilehvari, Rebecca A. Krukowski, Kurt M. Ribisl, Teresa D. Pearce
Journal: JAMA Network Open (2024)

This cross-sectional study evaluates the prevalence of and factors associated with use of nicotine pouches among active US military personnel.
Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance
Authors: Marc Duque, Alex B Chen, Eric Hsu, Sujatha Narayan, Altyn Rymbek, Shahinoor Begum, Gesine Saher, Adam E Cohen, David E Olson, Yulong Li, David A Prober, Dwight E Bergles, Mark C Fishman, Florian Engert, Misha B Ahrens
Journal: Neuron (2024)
Baseline Prevalence of Oral Human Papillomavirus in Mother-Child Pairs With and Without HIV Infection
Authors: Modupe O. Coker, Nicolas F. Schlecht, Esosa Osagie, Paul Akhigbe, Ozoemene N. Obuekwe, Yana Bromberg, Nosayaba Osazuwa-Peters
Journal: JAMA Network Open (2024)

This cohort study measures the prevalence of oral human papillomavirus (HPV) in women and their children in sub-Saharan African by HIV status.
Carbohydrates-Last Food Order Improves Time in Range and Reduces Glycemic Variability
Authors: Samir Touhamy, Kathyayini Palepu, Ampadi Karan, Katie C. Hootman, Jessica Riad, Sriharsha Sripadrao, Alice S. Zhao, Ashley Giannita, Debra D’Angelo, Laura C. Alonso, Louis J. Aronne, Alpana P. Shukla
Journal: Diabetes Care (2024)

Advancements in continuous glucose monitoring technology allow nuanced assessment of glycemic control.Glycemic variability (GV) and time spent with glucose in target range time-in-range (TIR) are now recognized risk predictors for diabetes-related complications and are associated with cardiovascular risk, even for patients with well-controlled HbA 1c (1,2).Prior research by our group and others demonstrates that besides carbohydrate amount and type, the timing of carbohydrate consumption during a meal significantly impacts regulation of postprandial glucose levels (3-5).In acute crossover studies, consuming fibrous vegetables and protein 10 min before carbohydrate (i.e., carbohydrates-last [CL] food order) reduced incremental postprandial glucose peaks and glycemic variability for up to 3 h in comparison with the reverse sequence (carbohydrates-first [CF] food order) in patients with type 2 diabetes (T2D) (4).Here, in this study (clinical trial reg.no.NCT04738799, clinicaltrials.gov)we examine the glycemic effects of nutrient sequencing without a rest interval between consumption of meal components-under
Biased Language in Simulated Handoffs and Clinician Recall and Attitudes
Authors: Austin Wesevich, Erica Langan, Ilona Fridman, Sonya Patel-Nguyen, Monica E. Peek, Victoria Parente
Journal: JAMA Network Open (2024)

Importance Poor-quality handoffs can lead to medical errors when transitioning patient care. Biased language within handoffs may contribute to errors and lead to disparities in health care delivery. Objective To compare clinical information recall accuracy and attitudes toward patients among trainees in paired cases of biased vs neutral language in simulated handoffs. Design, Setting, and Participants Surveys administered from April 29 to June 15 and from July 20 to October 10, 2023, included 3 simulated verbal handoffs, randomized between biased and neutral, and measured clinical information recall, attitudes toward patients, and key takeaways after each handoff. Participants included residents in internal medicine, pediatrics, and internal medicine–pediatrics and senior medical students at 2 academic medical centers in different geographic regions of the US. Data were analyzed from November 2023 to June 2024. Exposures Each participant received 3 handoffs that were based on real handoffs about Black patients at 1 academic center. These handoffs were each randomized to either a biased or neutral version. Biased handoffs had 1 of 3 types of bias: stereotype, blame, or doubt. The order of handoff presentation was also randomized. Internal medicine and pediatrics residents received slightly different surveys, tailored for their specialty. Internal medicine–pediatrics residents received the pediatric survey. Medical students were randomly assigned the survey type. Main Outcomes and Measures Each handoff was followed by a clinical information recall question, an adapted version of the Provider Attitudes Toward Sickle Cell Patients Scale (PASS), and 3 free-response takeaways. Results Of 748 trainees contacted, 169 participants (142 residents and 27 medical students) completed the survey (23% overall response rate), distributed across institutions, residency programs, and years of training (95 female [56%]; mean [SD] age, 28.6 [2.3] years). Participants who received handoffs with blame-based bias had less accurate information recall than those who received neutral handoffs (77% vs 93%; P = .005). Those who reported bias as a key takeaway of the handoff had lower clinical information recall accuracy than those who did not (85% vs 93%; P = .01). Participants had less positive attitudes toward patients per PASS scores after receiving biased compared with neutral handoffs (mean scores, 22.9 [3.3] vs 25.2 [2.7]; P &amp;amp;lt; .001). More positive attitudes toward patients were associated with higher clinical information recall accuracy (odds ratio, 1.12; 95% CI, 1.02-1.22). Conclusions and Relevance In this survey study of residents and medical students, biased handoffs impeded accurate transfer of key clinical information and decreased empathy, potentially endangering patients and worsening health disparities. Handoff standardization is critical to addressing racial bias and improving patient safety.
Daily Physical Activity, Sports Participation, and Executive Function in Children
Authors: Lu Yang, Eva Corpeleijn, Esther Hartman
Journal: JAMA Network Open (2024)

Importance It is unclear whether daily physical activity and sports participation relate to executive function (EF) in children. Objective To explore associations between early-life physical activity, sports participation, and executive function in primary school children. Design, Setting, and Participants Data for this cohort study were collected from April 2006 to December 2017 from the Groningen Expert Center for Kids with Obesity (GECKO) Drenthe birth cohort, which includes Northern Dutch children. Preschool children aged 5 to 6 years and primary school children aged 10 to 11 years with valid EF, daily physical activity, and sports participation data were included in the analysis. Data were analyzed from May 2023 to February 2024. Exposures At ages 5 to 6 years, daily physical activity was measured with accelerometry. At ages 10 to 11 years, sports participation data were collected using the Short Questionnaire to Assess Health–Enhancing Physical Activity. Main Outcomes and Measures Executive function was assessed using the Behavior Rating Inventory of Executive Function at ages 10 to 11 years. Results A total of 880 children (470 female [53.4%]; mean [SD] age at EF measurement, 11.1 [0.4] years) were included. Moderate to vigorous physical activity at ages 5 to 6 years did not correlate with EF at ages 10 to 11 years (eg, Global Executive Composite [GEC]: β, 0.16; 95% CI, −0.21 to 0.53). Higher levels of light physical activity at ages 5 to 6 years were associated with poorer inhibitory control (β, 0.86; 95% CI, 0.24-1.47) and self-monitoring (β, 0.79; 95% CI, 0.09-1.48) at ages 10 to 11 years, while greater sedentary time was associated with better inhibitory control (β, −0.62; 95% CI, −1.08 to −0.16) and self-monitoring (β, −0.57; 95% CI, −1.09 to −0.06). Compared with children engaged in individual sports, team sports participants exhibited better overall EF (mean difference [SE], −3.03 [0.81]), behavior regulation (mean difference [SE], −3.39 [0.77]), and metacognition (mean difference [SE], −2.55 [0.81]). Children involved in both types of sports vs only individual sports had better EF (GEC: mean difference [SE], −2.66 [0.93]). Conclusions and Relevance In this cohort study of Dutch children, early-life moderate to vigorous physical activity was not associated with EF in middle childhood. Children participating in team sports at ages 10 to 11 years consistently exhibited superior EF compared with participants in individual sports.
Improved Neurodevelopment Following In Utero Sulfonylurea Exposure in a Patient With <i>KCNJ11</i> Permanent Neonatal Diabetes: Future Implications for Targeted Treatment During Pregnancy
Authors: Pamela Bowman, Maggie H. Shepherd, Sarah E. Flanagan, James Tonks, Maria Salguero-Bermonth, Lisa Letourneau-Freiberg, Siri A.W. Greeley, Andrew T. Hattersley
Journal: Diabetes Care (2024)