tbuckley/cabot-search huggingface dataset:
Intentional wedge resection versus segmentectomy for ≤2 cm ground-glass-opacity-dominant non-small cell lung cancer: a real-world study using inverse probability of treatment weighting
Authors: Chengwu Liu, Zhenyu Yang, Yiming Li, Chenglin Guo, Liang Xia, Weiheng Zhang, Congjia Xiao, Jiandong Mei, Hu Liao, Yunke Zhu, Feng Lin, Lin Ma, Qiang Pu, Lunxu Liu
Journal: International Journal of Surgery (2024)

Background: Whether wedge resection is oncological suitable for ground glass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) ≤2 cm is still debatable. The aim of this study is to investigate the short-term and long-term outcomes of intentional wedge resection and segmentectomy for those patients. Materials and Methods: This was a real-world study from one of the largest thoracic surgery centers in XX. Patients who underwent intentional wedge resection or segmentectomy for ≤2 cm CTR(consolidation-to-tumor)≤0.5 NSCLC were consecutively included between December 2009 and December 2018. Data were prospectively collected and retrospectively reviewed. Inverse probability of treatment weighting (IPTW) was used to balance baseline characteristics. Long-term outcomes, including overall survival (OS), recurrence-free survival (RFS) and lung cancer-specific survival (LCSS), were analyzed using Cox proportional model. Results: A total of 1209 patients were included (497 in the wedge resection group, 712 in the segmentectomy group). Compared to segmentectomy, wedge resection had a significantly lower rate of complications (3.8% vs. 7.7%, P =0.008), a shorter operating time (65min vs. 114min, P &lt;0.001), and a shorter postoperative stay (3d vs. 4d, P &lt;0.001). The median follow-up was 70.1 months. The multivariate Cox model indicated that wedge resection had survival outcomes that were similar to segmentectomy in terms of 5-year OS (98.8% vs. 99.6%, HR=1.98, 95%CI: 0.59-6.68, P =0.270), 5-year RFS (98.8% vs. 99.5%, HR=1.88, 95%CI: 0.56-6.31, P =0.307) and 5-year LCSS (99.9% vs. 99.6%, HR=1.76, 95%CI: 0.24-13.15, P =0.581). Conclusion: Intentional wedge resection is an appropriate choice for ≤2 cm GGO-dominant NSCLC.
Intestinal tuft cell immune privilege enables norovirus persistence
Authors: Madison S. Strine, Eric Fagerberg, Patrick W. Darcy, Gabriel M. Barrón, Renata B. Filler, Mia Madel Alfajaro, Nicole D’Angelo-Gavrish, Fang Wang, Vincent R. Graziano, Bridget L. Menasché, Martina Damo, Ya-Ting Wang, Michael R. Howitt, Sanghyun Lee, Nikhil S. Joshi, Daniel Mucida, Craig B. Wilen
Journal: Science Immunology (2024)

The persistent murine norovirus strain MNVCR6 is a model for human norovirus and enteric viral persistence. MNVCR6 causes chronic infection by directly infecting intestinal tuft cells, rare chemosensory epithelial cells. Although MNVCR6 induces functional MNV-specific CD8+ T cells, these lymphocytes fail to clear infection. To examine how tuft cells promote immune escape, we interrogated tuft cell interactions with CD8+ T cells by adoptively transferring JEDI (just EGFP death inducing) CD8+ T cells into Gfi1b-GFP tuft cell reporter mice. Unexpectedly, some intestinal tuft cells partially resisted JEDI CD8+ T cell-mediated killing-unlike Lgr5+ intestinal stem cells and extraintestinal tuft cells-despite seemingly normal antigen presentation. When targeting intestinal tuft cells, JEDI CD8+ T cells predominantly adopted a T resident memory phenotype with decreased effector and cytotoxic capacity, enabling tuft cell survival. JEDI CD8+ T cells neither cleared nor prevented MNVCR6 infection in the colon, the site of viral persistence, despite targeting a virus-independent antigen. Ultimately, we show that intestinal tuft cells are relatively resistant to CD8+ T cells independent of norovirus infection, representing an immune-privileged niche that can be leveraged by enteric microbes.
C1q enables influenza hemagglutinin stem binding antibodies to block viral attachment and broadens the antibody escape repertoire
Authors: Ivan Kosik, Jefferson Da Silva Santos, Mathew Angel, Zhe Hu, Jaroslav Holly, James S. Gibbs, Tanner Gill, Martina Kosikova, Tiansheng Li, William Bakhache, Patrick T. Dolan, Hang Xie, Sarah F. Andrews, Rebecca A. Gillespie, Masaru Kanekiyo, Adrian B. McDermott, Theodore C. Pierson, Jonathan W. Yewdell
Journal: Science Immunology (2024)

Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs and enhances their fusion and neuraminidase inhibition. As a result, virus neutralization activity in vitro is boosted up to 30-fold, and in vivo protection from influenza PR8 infection in mice is enhanced. These effects reflect increased steric hindrance and not increased Ab avidity. C1q greatly expands the anti-stem Ab viral escape repertoire to include residues throughout the HA, some of which cause antigenic alterations in the globular region or modulate HA receptor avidity. We also show that C1q enhances the neutralization activity of non-receptor binding domain anti-SARS-CoV-2 spike Abs, an effect dependent on spike density on the virion surface. These findings demonstrate that C1q can greatly expand Ab function and thereby contribute to viral evolution and immune escape.
Racial and ethnic associations with comprehensive cancer center access and clinical trial enrollment for acute leukemia
Authors: Andrew Hantel, Andrew M Brunner, Jesse J Plascak, Hajime Uno, Juan C Varela, Marlise R Luskin, Timothy R Rebbeck, Richard M Stone, Christopher S Lathan, Daniel J DeAngelo, Gregory A Abel
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Clinical trial participation at Comprehensive Cancer Centers (CCC) is inequitable for minoritized racial and ethnic groups with acute leukemia. CCCs care for a high proportion of adults with acute leukemia. It is unclear if participation inequities are due to CCC access, post-access enrollment, or both. Methods We conducted a retrospective cohort study of adults with acute leukemia (2010-2019) residing within Massachusetts, the designated catchment area of the Dana-Farber/Harvard Cancer Center (DF/HCC). Individuals were categorized as non-Hispanic Asian (NHA), Black (NHB), White (NHW), Hispanic White (HW), or Other. Decomposition analyses assessed covariate contributions to disparities in (1) access to DF/HCC care and (2) post-access enrollment. Results Of 3698 individuals with acute leukemia, 85.9% were NHW, 4.5% HW, 4.3% NHB, 3.7% NHA, and 1.3% Other. Access was lower for HW (age- and sex-adjusted OR = 0.64, 95% CI = 0.45 to 0.90) and reduced post-access enrollment for HW (aOR = 0.54, 95% CI =0.34 to 0.86) and NHB (aOR = 0.60, 95% CI = 0.39 to 0.92) compared to NHW. Payor and socioeconomic status (SES) accounted for 25.2% and 21.2% of the +1.1% absolute difference in HW access. Marital status and SES accounted for 8.0% and 7.0% of the -8.8% absolute disparity in HW enrollment; 76.4% of the disparity was unexplained. SES and marital status accounted for 8.2% and 7.1% of the -9.1% absolute disparity in NHB enrollment; 73.0% of the disparity was unexplained. Conclusions A substantial proportion of racial and ethnic inequities in acute leukemia trial enrollment at CCCs are from post-access enrollment, the majority of which was not explained by sociodemographic factors.
Invasion of spontaneous germinal centers by naive B cells is rapid and persistent
Authors: Theo van den Broek, Kristine Oleinika, Siti Rahmayanti, Carlos Castrillon, Cees E. van der Poel, Michael C. Carroll
Journal: Science Immunology (2024)

In autoreactive germinal centers (GC) initiated by a single rogue B cell clone, wild-type B cells expand and give rise to clones that target other autoantigens, known as epitope spreading. The chronic, progressive nature of epitope spreading calls for early interventions to limit autoimmune pathologies, but the kinetics and molecular requirements for wild-type B cell invasion and participation in GC remain largely unknown. With parabiosis and adoptive transfer approaches in a murine model of systemic lupus erythematosus, we demonstrate that wild-type B cells join existing GCs rapidly, clonally expand, persist, and contribute to autoantibody production and diversification. The invasion of autoreactive GCs by wild-type B cells required TLR7, B cell receptor specificity, antigen presentation, and type I interferon signaling. The adoptive transfer model provides a tool for identifying early events in the breaking of B cell tolerance in autoimmunity.
Multi-step strategies for synergistic treatment of urinary tract infections based on D-xylose-decorated antimicrobial peptide carbon dots
Authors: Chunhui Miao, Yajie Zhang, Guowen Liu, Jianming Yang, Kaiyuan Yu, Junqiang Lv, Ran Liu, Zhi Yao, Yuanjie Niu, Xiaojuan Wang, Quan Wang
Journal: Biomaterials (2024)
Targeted protein degradation in hematologic malignancies: latest updates from the 2023 ASH annual meeting
Authors: Guangcai Zhong, Ran Kong, Shi Feng, Cong Wang, Qingbo Hao, Weilin Xie, Xiangxiang Zhou
Journal: Journal of Hematology & Oncology (2024)

Abstract Protein degraders, emerging as a novel class of therapeutic agents, have gained widespread attention due to their advantages. They have several advantages over traditional small molecule inhibitors, including high target selectivity and ability to target “undruggable” targets and overcome inhibitor drug resistance. Tremendous research and development efforts and massive investment have resulted in rapid advancement of protein degrader drug discovery in recent years. Here, we overview the latest clinical and preclinical updates on protein degraders presented at the 2023 ASH Annual Meeting.
Correction: Blood–brain barrier-associated pericytes internalize and clear aggregated amyloid-β42 by LRP1-dependent apolipoprotein E isoform-specific mechanism
Authors: Qingyi Ma, Zhen Zhao, Abhay P. Sagare, Yingxi Wu, Min Wang, Nelly Chuqui Owens, Philip B. Verghese, Joachim Herz, David M. Holtzman, Berislav V. Zlokovic
Journal: Molecular Neurodegeneration (2024)
Measurable residual disease quantification in adult patients with KMT2A-rearranged acute lymphoblastic leukemia
Authors: Thomas Burmeister, Aeint-Steffen Ströh, Britta Kehden, Heiko Trautmann, Claus Meyer, Rolf Marschalek, Patrizia Larghero, Stefan Schwartz, Björn Steffen, Bernd Spriewald, Thomas Heinicke, Nadja Jäkel, Jörg Westermann, Kathrin Nachtkamp, Andreas Viardot, Max S. Topp, Martin Neumann, Claudia D. Baldus, Nicola Gökbuget, Monika Brüggemann
Journal: Leukemia (2024)

In adult ALL, 5-10% of patients show KMT2A translocations (KMT2A rearrangements) with only a few secondary alterations, implicating it as a leukemia-initiating factor [1,2].Approximately 95% of all fusions in adult ALL are KMT2A::AFF1 or KMT2A::MLLT1 [3].KMT2A-rearranged adult ALL patients are generally considered high-risk and are treated with intensified therapy, including allogeneic hematopoietic stem cell transplantation (SCT) [4].Current ALL treatment protocols are often guided by measurable residual disease (MRD)-based risk stratification [4-8], however, limited data are available regarding the prognostic value of MRD in adult ALL with KMT2A rearrangement.In infant KMT2Arearranged ALL, more reliable MRD data were obtained using the individual KMT2A breakpoints as molecular MRD target as compared to IG/TR [6, 9-11], but no such comparisons have been made in adult ALL.We evaluated the impact of MRD on diseasefree survival (DFS) and overall survival (OS) in a cohort of 156 KMT2A-rearranged adult patients and compared IG/TR-and KMT2A-based MRD levels in 46 patients.In total, 769 bone marrow and/or peripheral blood samples from 193 adult ALL patients with KMT2A rearrangement (175 KMT2A::AFF1, 13 KMT2A::MLLT1, 1 KMT2A::MLLT3, 4 KMT2A+ unspecified) obtained between 2001 and 2021 were available for longitudinal MRD measurements.All patients were treated according to different protocols of the German Multicenter ALL (GMALL) study group and gave their informed consent to further scientific investigations on residual material.Patients with KMT2A::AFF1 aged up to 55 years were assigned to the high-risk group and were candidates for SCT in first CR after consolidation I. Immunophenotyping and MRD measurement with real-time PCR based on KMT2A fusion genes
Antibiotic Use in Late Preterm and Full-Term Newborns
Authors: Johan Gyllensvärd, Marie Studahl, Lars Gustavsson, Elisabet Hentz, Karin Åkesson, Huiqi Li, Mikael Norman, Anders Elfvin, Stellan Håkansson
Journal: JAMA Network Open (2024)

Importance Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies. Objective To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns. Design, Setting, and Participants The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks’ gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023. Exposure Admission for neonatal intensive care during the first week of life. Main Outcomes and Measures The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS. Results A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed. Conclusions and Relevance This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.
Caring is the invisible piece of the stroke recovery puzzle
Authors: Chandrika Kaviraj
Journal: BMJ (2024)

Caring is the invisible piece of the stroke recovery puzzle Chandrika describes the impact of becoming a carer for her mum after she had a stroke Chandrika KavirajIn early 2008 my mum had a severe stroke.She was left with hemiparesis and her life-and ours-changed forever.Part of my mum's personality went with the cells that would never return.She lost her mobility and experienced changes in cognition, dysarthria, needing emergency dental care, changes in her sight, and emotionalism.I spent every day in hospital with her, and I became the sole carer for a person who had gone from fully independent to needing a great deal of assistance.I felt like I had been pushed off a cliff.Navigating health and social care support systems was not (and is not) easy.Health professionals felt my mum would do better recovering in her own home, but that meant I had to establish new contacts with pharmacies, spend time making GP calls and seeking referrals, administering medications, maintaining physiotherapy exercises, making meals, running a household, and coping psychologically, while helping my dad come to terms with the upheaval.
Digital Avatars and Personalized Voices—How AI Is Helping to Restore Speech to Patients
Authors: Samantha Anderer, Yulin Hswen
Journal: JAMA (2024)

In this Medical News article, Edward Chang, MD, chair of the department of neurological surgery at the University of California, San Francisco Weill Institute for Neurosciences joins JAMA Editor in Chief Kirsten Bibbins-Domingo, PhD, MD, MAS, to discuss the potential for AI to revolutionize communication for those unable to speak due to aphasia.
Patient Characteristics and Telemedicine Use in the US, 2022
Authors: Eva Chang, Robert B. Penfold, Nancy D. Berkman
Journal: JAMA Network Open (2024)

Importance Telemedicine use was common during the COVID-19 pandemic, expanding many patients’ approaches to accessing health care. Of concern is whether telemedicine access was poorer among higher-needs and disadvantaged populations. Objective To assess patient characteristics associated with telemedicine use and telemedicine mode and describe telemedicine visit experiences by telemedicine mode. Design, Setting, and Participants This cross-sectional study included data from the 2022 Health Information National Trends Survey and included US adults with a health care visit. Data were analyzed from May to September 2023. Exposure Patient characteristics. Main Outcomes and Measures Any telemedicine visits vs in-person visits only; telemedicine mode (video vs audio-only). Multivariable logistic models assessed patient characteristics associated with telemedicine visits and mode. Bivariate analyses compared telemedicine experiences by mode. Results The study included 5437 adult patients (mean [SE] age, 49.4 [0.23] years; 3136 females [53.4%]; 1928 males [46.6%]). In 2022, 2384 patients (43%) had a telemedicine visit; 1565 (70%) had a video visit while 819 (30%) had an audio-only visit. In multivariable models, older age (≥75 years: adjusted odds ratio [aOR], 0.63; 95% CI, 0.42-0.94), no internet use (aOR, 0.62; 95% CI, 0.48-0.81), and living in the Midwest (aOR, 0.50; 95% CI, 0.35-0.70) were negatively associated with having telemedicine visits. Female sex (aOR, 1.43; 95% CI, 1.12-1.83), having chronic conditions (aOR, 2.13; 95% CI, 1.66-2.73), and multiple health care visits (2-4 visits: aOR, 1.77; 95% CI, 1.23-2.54; ≥5 visits: aOR, 3.29; 95% CI, 2.20-4.92) were positively associated. Among individuals who used telemedicine, older age (65-74 years: aOR, 2.13; 95% CI, 1.09-4.14; ≥75 years: aOR, 3.58; 95% CI, 1.60-8.00), no health insurance (aOR, 2.84; 95% CI, 1.42-5.67), and no internet use (aOR, 2.11; 95% CI, 1.18-3.78) were positively associated with having audio-only visits. We observed no significant differences in telemedicine use or mode by education, race and ethnicity, or income. Patients’ experiences using telemedicine were generally similar for video and audio-only except more individuals who used audio-only had privacy concerns (20% vs 12%, P = .02). Conclusions and Relevance In this cross-sectional study of adults with health care visits, many patients, including those with the greatest care needs, chose telemedicine even after in-person visits were available. These findings support continuing this care delivery approach as an option valued by patients. Differences were not observed by most common measures of socioeconomic status. Continued monitoring of telemedicine use is needed to ensure equitable access to health care innovations.
Using a human colonoid-derived monolayer to study bacteriophage translocation
Authors: Huu Thanh Le, Alicia Fajardo Lubian, Bethany Bowring, David van der Poorten, Jonathan Iredell, Jacob George, Carola Venturini, Golo Ahlenstiel, Scott Read
Journal: Gut Microbes (2024)

Bacteriophages (phages) are estimated to be the most abundant microorganisms on Earth. Their presence in human blood suggests that they can translocate from non-sterile sites such as the gastrointestinal tract where they are concentrated. To examine phage translocation ex vivo, we adapted a primary colonoid monolayer model possessing cell diversity and architecture, and a thick layer of mucus akin to the colonic environment in vivo. We show that the colonoid monolayer is superior to the Caco-2 cell-line model, possessing intact and organized tight junctions and generating a physiologically relevant mucus layer. We showed, using two different phages, that translocation across the colonoid monolayer was largely absent in differentiated monolayers that express mucus, unlike Caco-2 cultures that expressed little to no mucus. By stimulating mucus production or removing mucus, we further demonstrated the importance of colonic mucus in preventing phage translocation. Finally, we used etiological drivers of gut permeability (alcohol, fat, and inflammatory cytokines) to measure their effects on phage translocation, demonstrating that all three stimuli have the capacity to amplify phage translocation. These findings suggest that phage translocation does occur in vivo but may be largely dependent on colonic mucus, an important insight to consider in future phage applications.
Affinity-independent plasma cell differentiation in germinal centers
Authors: Roser Tachó-Piñot, Carola G. Vinuesa
Journal: Trends in Immunology (2024)

The role of antibody affinity in plasma cell (PC) differentiation from germinal centers (GCs) remains contested. Parallel studies by Sprumont et al. and Sutton and Gao et al. show that PCs emerging from GCs produce antibodies with a diverse range of affinities and lack signatures of affinity-based selection. Therefore, commitment to the PC lineage is affinity independent.