tbuckley/cabot-search huggingface dataset:
Macrophage hitchhiking for systematic suppression in postablative multifocal HCC
Authors: Xuehan Li, Yan Zhang, Shun Li, Jiaqi Shi, Caiqi Liu, Xianjun Li, Yingjing Li, Shengnan Luo, Yuan Wang, Shihui Lai, Mingwei Li, Meng Zhang, Linlin Sun, Xiaoxue Du, Meng Zhou, Fan Xing, Qian Zhang, Zhiguang Wu, Tongsen Zheng
Journal: Hepatology (2024)

Background and Aims: HCC, particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. Approach and Results: Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation–guided macrophage hitchhiking for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. Microinvasive ablation–guided macrophage hitchhiking has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, ELISA, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. Conclusions: The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.
Mitochondrial dynamics, quality control, and mtDNA in alcohol-associated liver disease and liver cancer
Authors: Xiaowen Ma, Mengwei Niu, Hong-Min Ni, Wen-Xing Ding
Journal: Hepatology (2024)

Mitochondria are intracellular organelles responsible for energy production, glucose and lipid metabolism, cell death, cell proliferation, and innate immune response. Mitochondria are highly dynamic organelles that constantly undergo fission, fusion, and intracellular trafficking, as well as degradation and biogenesis. Mitochondrial dysfunction has been implicated in a variety of chronic liver diseases including alcohol-associated liver disease, metabolic dysfunction–associated steatohepatitis, and HCC. In this review, we provide a detailed overview of mitochondrial dynamics, mitophagy, and mitochondrial DNA–mediated innate immune response, and how dysregulation of these mitochondrial processes affects the pathogenesis of alcohol-associated liver disease and HCC. Mitochondrial dynamics and mitochondrial DNA–mediated innate immune response may thereby represent an attractive therapeutic target for ameliorating alcohol-associated liver disease and alcohol-associated HCC.
Letter to the Editor: Health warning for humble writers, distracted reviewers, and naive readers
Authors: Piero Amodio, Chien-Hao Huang, Sara Montagnese
Journal: Hepatology (2024)

1Department of Medicine (DIMED), University of Padova, Italy 2Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan Correspondence Piero Amodio, Università degli Studi di Padova, Department of Medicine. Email: [email protected]
Waitlisting and liver transplantation for MetALD in the United States: An analysis of the UNOS national registry
Authors: Pedro Ochoa-Allemant, Marina Serper, Roy X. Wang, Helen Tang, Bachir Ghandour, Sarem Khan, Nadim Mahmud
Journal: Hepatology (2024)

Background and Aims: The new steatotic liver disease (SLD) nomenclature introduced metabolic and alcohol-associated liver disease (MetALD), describing the intersection of metabolic dysfunction–associated steatotic liver disease and alcohol-associated liver disease. Waitlisting and liver transplantation for MetALD are not well defined. We aimed to develop and validate an algorithm for identifying SLD phenotypes and assessing trends in waitlisting and transplant outcomes. Approach and Results: We conducted a retrospective cohort study using the United Network for Organ Sharing registry, supplemented with detailed single-center data. We developed 5 candidate algorithms for SLD classification and calculated their diagnostic performance. Trends in waitlist registrations and transplants were estimated, and competing risk analyses and Cox regression models were conducted to assess waitlist removal and posttransplant outcomes among SLD phenotypes. The best-performing algorithm demonstrated substantial agreement (weighted kappa, 0.62) for SLD phenotypes, with acceptable sensitivity (73%) for MetALD. Between 2002 and 2022, waitlist registrations and transplants for MetALD increased 2.9-fold and 3.3-fold, respectively. Since 2013, there has been a significant increase in the absolute number of waitlist registrations (122 per year; 95% CI, 111–133) and transplants (107 per year; 95% CI, 94–120) for MetALD. Patients with MetALD experienced higher waitlist removal (adjusted subdistribution hazard ratio, 1.10; 95% CI, 1.03–1.17), all-cause mortality (adjusted hazard ratio, 1.13; 95% CI, 1.03–1.23), and graft failure (adjusted hazard ratio, 1.12; 95% CI, 1.03–1.21) than those with alcohol-associated liver disease. Conclusions: We developed and validated an algorithm for identifying SLD phenotypes in UNOS. MetALD is the third leading etiology among those waitlisted and underwent transplantation, exhibiting worse pretransplantation and posttransplantation outcomes compared to alcohol-associated liver disease. Identifying and addressing factors determining poor outcomes is crucial in this patient population.
Letter to the Editor: Tranexamic acid in upper gastrointestinal bleed in patients with cirrhosis - A randomized controlled trial
Authors: Shivani Y. Chopra, Vikramaditya L. Rawat, Meghraj A. Ingle, Saiprasad G. Lad, Vinay D. Borkar, Yatin H. Lunagariya, Deepak Sasikumar, Chintan S. Tailor, Mit B. Shah, Rohit S. Wagh
Journal: Hepatology (2024)

Chopra, Shivani Y.; Rawat, Vikramaditya L.; Ingle, Meghraj A.; Lad, Saiprasad G.; Borkar, Vinay D.; Lunagariya, Yatin H.; Sasikumar, Deepak; Tailor, Chintan S.; Shah, Mit B.; Wagh, Rohit S. Author Information
Sex and gender in alcohol use disorder and alcohol-associated liver disease in the United States: A narrative review
Authors: Lauren E. Carlini, Anne C. Fernandez, Jessica L. Mellinger
Journal: Hepatology (2024)

Over the last 20 years, there has been an alarming increase in alcohol use and AUD prevalence among women, narrowing the historical gender gap. Concurrently, there has also been a significant rise in alcohol-associated liver disease (ALD) prevalence, severity, and mortality among women. Despite this, there are no recent reviews that have sought to evaluate both sex and gender differences at the intersection of AUD and ALD. In this narrative review, we address the escalating rates of ALD and AUD in the United States, with a specific focus on the disproportionate impact on women. Sex and gender play an important and well-known role in the pathogenesis and epidemiology of ALD. However, sex and gender are also implicated in the development and prevalence of AUD, as well as in the treatment of AUD, all of which have important consequences on the approach to the treatment of patients with ALD and AUD. A better understanding of sex and gender differences in AUD, ALD, and the intersection of the 2 is essential to enhance prevention, diagnosis, and management strategies. These data underscore the urgent need for awareness and preventive efforts to mitigate the potential long-term health consequences.
Liver cancer in young adults: Validity of global data sets
Authors: Carlo La Vecchia, Claudia Santucci
Journal: Hepatology (2024)

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Correspondence Carlo La Vecchia, Department of Clinical Sciences and Community Health, University of Milan, "La Statale" Via Celoria 22, 20133 Milan, Italy. Email: [email protected]
Ultrabright Dibenzofluoran‐Based Polymer Dots with NIR‐IIa Emission Maxima and Unusual Large Stokes Shifts for 3D Rotational Stereo Imaging
Authors: Partha Chowdhury, Zhao‐Yu Lu, Shih‐Po Su, Meng‐Huan Liu, Chun‐Yi Lin, Man‐Wen Wang, Yi‐Chi Luo, Yi‐Jang Lee, Huihua Kenny Chiang, Yang‐Hsiang Chan
Journal: Advanced Healthcare Materials (2024)

Emerging organic molecules with emissions in the second near-infrared (NIR-II) region are garnering significant attention. Unfortunately, achieving accountable organic emission intensity over the NIR-IIa (1300 nm) region faces challenges due to the intrinsic energy gap law. Up to the current stage, all reported organic NIR-IIa emitters belong to polymethine-based dyes with small Stokes shifts (<50 nm) and low quantum yield (QY; ≤0.015%). However, such polymethines have proved to cause self-absorption with constrained emission brightness, limiting advanced development in deep-tissue imaging. Here a new NIR-IIa scaffold based on rigid and highly conjugated dibenzofluoran core terminated by amino-containing moieties that reveal emission peaks of 1230-1305 nm is designed. The QY is at least 10 times higher than all synthesized or reported NIR-IIa polymethines with extraordinarily large Stokes shifts of 370-446 nm. DBF-BJ is further prepared as a polymer dot to demonstrate its in vivo 3D stereo imaging of mouse vasculature with a 1400 nm long-pass filter.
Author correction to ‘3-O-Acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma’ [Acta Pharm Sin B 10 (2020) 301–312]
Authors: Wan Li, Liwen Ren, Xiangjin Zheng, Jinyi Liu, Jinhua Wang, Tengfei Ji, Guanhua Du
Journal: Acta Pharmaceutica Sinica B (2024)

[This corrects the article DOI: 10.1016/j.apsb.2019.12.012.].
Postpartum Emergency Department Use Following Midwifery-Model vs Obstetrics-Model Care
Authors: Carla Sorbara, Joel G. Ray, Elizabeth K. Darling, Hannah Chung, Sho Podolsky, Therese A. Stukel
Journal: JAMA Network Open (2024)

Importance Emergency department (ED) use postpartum is a common and often-preventable event. Unlike traditional obstetrics models, the Ontario midwifery model offers early care postpartum. Objective To assess whether postpartum ED use differs between women who received perinatal care in midwifery-model care vs in traditional obstetrics-model care. Design, Setting, and Participants This retrospective population-based cohort study took place in Ontario, Canada, where public health care is universally funded. Participants included women who were low risk and primiparous and gave birth to a live baby in an Ontario hospital between 2012 and 2018. Data were collected from April 2012 to March 2018 and analyzed from June 2022 to April 2023. Exposures Perinatal care clinician, namely, a midwife or obstetrician. Main Outcome and Measures : Any unscheduled ED visit 42 days postpartum or less. Poisson regression models compared ED use between women with midwifery-model care vs obstetrics-model care, weighting by propensity score-based overlap weights. Results Among 104 995 primiparous women aged 11 to 50 years, those in midwifery-model care received a median (IQR) of 7 (6-8) postpartum visits, compared with 0 (0-1) visits among those receiving obstetrics-model care. Unscheduled ED visits 42 days or less postpartum occurred for 1549 of 23 124 women (6.7%) with midwifery-model care compared with 6902 of 81 871 women (8.4%) with traditional obstetrics-model care (adjusted relative risks [aRR], 0.78; 95% CI, 0.73-0.83). Similar aRRs were seen in women with a spontaneous vaginal birth (aRR, 0.71; 95% CI, 0.65-0.78) or assisted vaginal birth (aRR, 0.70; 95% CI, 0.59-0.82) but not those with a cesarean birth (aRR, 0.94; 95% CI, 0.86-1.03) or those with intrapartum transfer of care between a midwife and obstetrician (aRR, 0.94; 95% CI, 0.87-1.04). ED use 7 days or less postpartum was also lower among women receiving midwifery model care (aRR, 0.70; 95% CI, 0.65-0.77). Conclusions and Relevance In this cohort study, midwifery-model care was associated with less postpartum ED use than traditional obstetrics-model care among women who had low risk and were primiparous, which may be due to early access to postpartum care provided by Ontario midwives.
Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients
Authors: Darine Daher, Karim Seif El Dahan, Nicole E. Rich, Nabihah Tayob, Vincent Merrill, Daniel Q. Huang, Ju Dong Yang, Anand V. Kulkarni, Fasiha Kanwal, Jorge Marrero, Neehar Parikh, Amit G. Singal
Journal: JAMA Network Open (2024)

Importance Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. Objective To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. Design, Setting, and Participants This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023. Main Outcomes and Measures The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 months before diagnosis. Cox regression analysis was used to characterize differences in overall survival between patients with screen-detected and non–screen-detected HCC; lead-time and length-time adjustments were calculated using the Duffy parametric formula. Results Among 1313 patients with HCC (mean [SD] age, 61.7 [9.6] years; 993 male [75.6%]; 739 [56.3%] with Barcelona Clinic Liver Cancer stage 0/A disease), HCC was screen-detected in 556 (42.3%) and non–screen detected in 757 (57.7%). Patients with screen-detected HCC had higher proportions of early-stage HCC (393 patients [70.7%] vs 346 patients [45.7%]; risk ratio [RR], 1.54; 95% CI, 1.41-1.70) and curative treatment receipt (283 patients [51.1%] vs 252 patients [33.5%]; RR, 1.52; 95% CI, 1.34-1.74) compared with patients with non–screen-detected HCC. The screen-detected group had significantly lower mortality, which persisted after correcting for lead-time bias (hazard ratio, 0.75; 95% CI, 0.65-0.87) in fully adjusted models. Both groups had similar tumor doubling times (median [IQR], 3.8 [2.2-10.7] vs 5.6 [1.7-11.4] months) and proportions of indolent tumors (28 patients [35.4%] vs 24 patients [38.1%]; RR, 0.93; 95% CI, 0.60-1.43). Adjustment for length-time bias decreased survival estimates, although 3-year and 5-year survival for patients with screen-detected HCC remained longer than that for patients with non–screen-detected HCC. Conclusions and Relevance The findings of this cohort study suggest that HCC screening is associated with reduced mortality even after accounting for lead-time and length-time biases. However, these biases should be considered in future studies.
Caring Letters Sent by a Clinician or Peer to At-Risk Veterans
Authors: Mark A. Reger, Aaron Legler, MaryGrace Lauver, Kertu Tenso, Caitlin Manchester, Cameron Griffin, Kiersten L. Strombotne, Sara J. Landes, Shelan Porter, Jolie E. Bourgeois, Melissa M. Garrido
Journal: JAMA Network Open (2024)

Importance Caring letters is an evidence-based suicide prevention intervention in acute care settings, but its outcomes among individuals who contact a national crisis line have not previously been evaluated. Objective To examine the outcomes of the Veterans Crisis Line (VCL) caring letters intervention and determine whether there are differences in outcomes by signatory. Design, Setting, and Participants This parallel randomized clinical trial compared signatories of caring letters and used an observational design to compare no receipt of caring letters with any caring letters receipt. Participants included veterans who contacted the VCL. Enrollment occurred between June 11, 2020, and June 10, 2021, with 1 year of follow-up. Analyses were completed between July 2022 and August 2023. Intervention Veterans were randomized to receive 9 caring letters for 1 year from either a clinician or peer veteran signatory. Main Outcomes and Measures The primary outcome measure was suicide attempt incidence in the 12 months following the index VCL contact. Incidence of Veterans Health Administration (VHA) inpatient, outpatient, and emergency health care use were secondary outcomes. All-cause mortality was an exploratory outcome. Wilcoxon rank-sum tests and χ 2 tests were used to assess the differences in outcomes among the treatment and comparison groups. Results A total of 102 709 veterans (86 942 males [84.65%]; 15 737 females [15.32%]; mean [SD] age, 53.82 [17.35] years) contacted the VCL and were randomized. No association was found among signatory and suicide attempts, secondary outcomes, or all-cause mortality. In the analysis of any receipt of caring letters, there was no evidence of an association between caring letters receipt and suicide attempt incidence. Caring letters receipt was associated with increased VHA health care use (any outpatient: hazard ratio [HR], 1.10; 95% CI, 1.08-1.13; outpatient mental health: HR, 1.19; 95% CI, 1.17-1.22; any inpatient: HR, 1.13; 95% CI, 1.08-1.18; inpatient mental health: HR, 1.14; 95% CI, 1.07-1.21). Caring letters receipt was not associated with all-cause mortality. Conclusions and Relevance Among VHA patients who contacted the VCL, caring letters were not associated with suicide attempts, but were associated with a higher probability of health care use. No differences in outcomes were identified by signatory. Trial Registration isrctn.org Identifier: ISRCTN27551361
Association of New-Onset Seizures With SARS-CoV-2 Vaccines
Authors: Ali Rafati, Melika Jameie, Mobina Amanollahi, Yeganeh Pasebani, Mana Jameie, Ali Kabiri, Sara Montazeri Namin, Delaram Sakhaei, Fateme Feizollahi, Mohammad Yazdan Pasebani, Hossein Mohebbi, Saba Ilkhani, Mohammadreza Azadi, Mehran Rahimlou, Churl-Su Kwon
Journal: JAMA Neurology (2024)

Importance Seizures have been reported as an adverse effect of the SARS-CoV-2 vaccine. However, no study has answered the question of whether there is any association between seizures in the general population and COVID-19 vaccination. Objective To evaluate the seizure incidence among SARS-CoV-2 vaccine recipients compared with those who received a placebo. Data Sources A systematic search of MEDLINE (via PubMed), Web of Science, Scopus, Cochrane Library, Google Scholar, review publications, editorials, letters to editors, and conference papers, along with the references of the included studies from December 2019 to July 7, 2023. Study Selection Randomized clinical trials (RCTs) reporting seizure incidence with SARS-CoV-2 vaccination were included. Data Extraction and Synthesis This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework and used the Mantel-Haenszel method with random- and common-effect models. The risk of bias of the studies was assessed using the Cochrane assessment tool for RCTs. Main Outcomes and Measures The outcome of interest was new-onset seizure incidence proportion compared among (1) SARS-CoV-2 vaccine recipients and (2) placebo recipients. Results Six RCTs were included in the study. Results of the pooled analysis comparing the incidence of new-onset seizure between the 63 521 vaccine and 54 919 placebo recipients in the 28-day follow-up after vaccine/placebo injection showed no statistically significant difference between the 2 groups (9 events [0.014%] in vaccine and 1 event [0.002%] in placebo recipients; odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12; I 2 = 0%, τ2 = 0, Cochran Q P = .74). Likewise, in the entire blinded-phase period after injection, with a median of more than 43 days, no significant difference was identified between the vaccine and placebo groups regarding incident new-onset seizure (13/43 724 events [0.03%] in vaccine and 5/40 612 [0.012%] in placebo recipients; OR, 2.31; 95% CI, 0.86-6.23, P = .10, I 2 = 0%, τ2 = 0, Cochran Q P = .95). Conclusions and Relevance According to this systematic review and meta-analysis, there was no statistically significant difference in the risk of new-onset seizure incidence between vaccinated individuals and placebo recipients.
National Breast, Cervical, and Colorectal Cancer Screening Use in Federally Qualified Health Centers
Authors: Trisha L. Amboree, Jane R. Montealegre, Susan L. Parker, Ashvita Garg, Haluk Damgacioglu, Kathleen M. Schmeler, Elizabeth Y. Chiao, Elizabeth G. Hill, Kalyani Sonawane, Ashish A. Deshmukh, Prajakta Adsul
Journal: JAMA Internal Medicine (2024)

Importance Federally qualified health centers (FQHCs) deliver health care to nearly 30 million underserved persons across the US, yet nationwide and state-level breast, cervical, and colorectal cancer screening use in FQHCs is not described. Furthermore, it is unknown how the underscreened FQHC population contributes to the total underscreened population at national and state levels. Objective To describe national- and state-level breast, cervical, and colorectal cancer screening use among individuals served by FQHCs in the US and to estimate the percentage of underscreened individuals in the general population served by FQHCs. Design, Setting, and Participants This cross-sectional analysis of cancer screening used data from January 1 through December 31, 2020, from the FQHC Uniform Data System, reported by 1364 FQHCs across the US, and self-reported estimates from the Behavioral Risk Factor Surveillance System. Participants were 16 696 692 US adults served by FQHCs who were eligible for breast (age, 50-74 years), cervical (age, 21-64 years), and colorectal (age, 50-75 years) cancer screening. Analyses were conducted between January 1 and June 30, 2023. Exposures Breast, cervical, and colorectal cancer screening. Main Outcomes and Measures Percentages of breast, cervical, and colorectal cancer screening-eligible individuals up to date on screening. Results A total of 3 162 882 breast, 7 444 465 cervical, and 6 089 345 colorectal screening–eligible individuals were served by FQHCs in 2020. Nationally, screening use in FQHCs was 45.4% (95% CI, 45.4%-45.5%) for breast cancer, 51.0% (95% CI, 51.0%-51.1%) for cervical cancer, and 40.2% (95% CI, 40.1%-40.2%) for colorectal cancer. Screening use among the US general population was 78.2% (95% CI, 77.6%-78.9%) for breast cancer, 82.9% (95% CI, 82.3%-83.4%) for cervical cancer, and 72.3% (95% CI, 71.7%-72.8%) for colorectal cancer. The contribution of the underscreened population served by FQHCs to the national underscreened general population was 16.9% (95% uncertainty interval [UI], 16.4%-17.4%) for breast cancer, 29.7% (95% UI, 28.8%-30.7%) for cervical cancer, and 14.7% (95% UI, 14.4%-15.0%) for colorectal cancer. Conclusions and Relevance Findings from this national cross-sectional study indicated major gaps in cancer screening use in FQHCs in the US. Improved prevention is urgently needed to address screening disparities.
Magnetic vs Electric Seizure Induction for the Treatment of Mania—Similar, But Not Yet the Same
Authors: Axel Nordenskjöld, Katarzyna Popiolek, Charles H. Kellner
Journal: JAMA Network Open (2024)

Shan Chen, MMed; Jianhua Sheng, MD; Fuzhong Yang, MD; Yi Qiao, MD; Wenzheng Wang, MD; Hui Wen, MMed; Qiao Yang, MMed; Xiaochen Chen, MD; Yingying Tang, PhD