tbuckley/cabot-search huggingface dataset:
The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates
Authors: Parham Ramezani-Rad, Ester Marina-Zárate, Laura Maiorino, Amber Myers, Katarzyna Kaczmarek Michaels, Ivan S. Pires, Nathaniel I. Bloom, Mariane B. Melo, Ashley A. Lemnios, Paul G. Lopez, Christopher A. Cottrell, Iszac Burton, Bettina Groschel, Arpan Pradhan, Gabriela Stiegler, Magdolna Budai, Daniel Kumar, Sam Pallerla, Eddy Sayeed, Sangeetha L. Sagar, Sudhir Pai Kasturi, Koen K.A. Van Rompay, Lars Hangartner, Andreas Wagner, Dennis R. Burton, William R. Schief, Shane Crotty, Darrell J. Irvine
Journal: Journal of Clinical Investigation (2025)

The induction of durable protective immune responses is the main goal of prophylactic vaccines, and adjuvants play a role as drivers of such responses. Despite advances in vaccine strategies, a safe and effective HIV vaccine remains a significant challenge. The use of an appropriate adjuvant is crucial to the success of HIV vaccines. Here we assessed the saponin/MPLA nanoparticle (SMNP) adjuvant with an HIV envelope (Env) trimer, evaluating the safety and impact of multiple variables including adjuvant dose (16-fold dose range), immunization route, and adjuvant composition on the establishment of Env-specific memory T and B cell responses (TMem and BMem) and long-lived plasma cells in non-human primates (NHPs). Robust BMem were detected in all groups, but a 6-fold increase was observed in the highest SMNP dose group vs. the lowest dose group. Similarly, stronger vaccine responses were induced in the highest SMNP dose for CD40L+OX40+ CD4 TMem (11-fold), IFN-γ+ CD4 TMem (15-fold), IL21+ CD4 TMem (9-fold), circulating TFH (3.6-fold), bone marrow plasma cells (7-fold), and binding IgG (1.3-fold). Substantial tier-2 neutralizing antibodies were only observed in the higher SMNP dose groups. These investigations highlight the dose-dependent potency of SMNP in NHPs, which are relevant for human use and next-generation vaccines.
Restoring mitochondrial function promotes hematopoietic reconstitution from cord blood following cryopreservation-related functional decline
Authors: Yaojin Huang, Xiaowei Xie, Mengyao Liu, Yawen Zhang, Junye Yang, Wenling Yang, Yu Hu, Saibing Qi, Yahui Feng, Guojun Liu, Shihong Lu, Xuemei Peng, Jinhui Ye, Shihui Ma, Jiali Sun, Lu Wang, Linping Hu, Lin Wang, Xiaofan Zhu, Hui Cheng, Zimin Sun, Junren Chen, Fang Dong, Yingchi Zhang, Tao Cheng
Journal: Journal of Clinical Investigation (2025)

Umbilical cord blood (UCB) showcases substantial roles in hematopoietic stem cells (HSCs) transplantation and regenerative medicine. UCB is usually cryopreserved for years before use. Whether and how cryopreservation affects its function remain unclear. We constructed single-cell transcriptomic profile of CD34+ hematopoietic stem and progenitor cells (HSPCs) and mononuclear cells (MNCs) from fresh and cryopreserved UCB stored for 1-, 5-, 10-, and 19- years. Compared to fresh UCB, cryopreserved HSCs and multipotent progenitors (MPPs) exhibited more active cell cycle and lower HSC/MPP signature gene expressions. Hematopoietic reconstitution of cryopreserved HSPCs gradually decreased during the first 5 years but stabilized thereafter, aligning with the negative correlation between clinical neutrophil engraftment and cryopreservation duration of UCB. Cryopreserved HSPCs also showed reduced megakaryocyte generation. In contrast, cryopreserved natural killer (NK) cells and T cells maintained cytokine production and cytotoxic ability comparable to fresh cells. Mechanistically, cryopreserved HSPCs exhibited elevated reactive oxygen species, reduced ATP synthesis, and abnormal mitochondrial distribution, which collectively led to attenuated hematopoietic reconstitution. These effects could be ameliorated by sulforaphane. Together, we elucidated the negative impact of cryopreservation on UCB HSPCs and provided sulforaphane as a mitigation strategy, broadening the temporal window and scope for clinical applications of cryopreserved UCB. .
Efficacy and safety of neoadjuvant SHR-A1811 with or without pyrotinib in women with locally advanced or early HER2-positive breast cancer: a randomized, open-label, phase 2 trial
Authors: J J Li, Z H Wang, L Chen, W J Zhang, L X X Ma, J Wu, G Y Liu, Y F Hou, K D Yu, G H Di, L Fan, Y Z Jiang, S H Jiang, Q N Liang, Y Shen, Z M Shao
Journal: Annals of Oncology (2025)

Standard neoadjuvant regimens for HER2-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-direted antibody-drug conjugate (ADC) remain to be elucidated. This open-label, randomized, phase 2 study enrolled patients aged 18 years or older with stage II-III Her2-positive breast cancer. Patients were randomly assigned (1:1:1) to receive neoadjuvant treatment either with SHR-A1811 monotherapy, SHR-A1811 with pyrotinib, or nab-paclitaxel combined with carboplatin, trastuzumab, and pertuzumab (PCbHP) for 24 weeks. The primary endpoint was pathological complete response (pCR). Safety was analysed in patients who received at least one dose of study medication. Between December 27, 2022, and February 11, 2024, 265 patients were randomly allocated to neoadjuvant, mono-SHR-A1811 (n=87), SHR-A1811 plus pyrotinib (n=88), or PCbHP (n=90). The baseline characteristics were well balanced; approximately 45% of the patients were hormone receptor (HR)-positive, and 70% of the patients were stage III. The pCR rate was 63.2% for mono-SHR-A1811 (50% for HR+ and 74.5% for HR-), 62.5% for SHR-A1811 plus pyrotinib (44.7% for HR+ and 76% for HR-) and 64.4% for PCbHP (54.1% for HR+ and 71.7% for HR-), with no significant difference between the groups. Grade 3 or higher treatment-related adverse events occurred in 44.8% of patients with mono-SHR-A1811, 71.6% with SHR-A1811 plus pyrotinib and 38.8% with PCbHP. One patient experienced grade 2 interstitial lung disease in SHR-A1811, 9.1% of patients experienced grade 3 diarrhea in SHR-A1811 plus pyrotinib, and no treatment-related deaths occurred. This is the first study to report the efficacy and safety of third-generation HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. SHR-A1811 showed robust activity, with a tolerable safety profile. (ClinicalTrials.gov, NCT05582499).
The Drug Allergy History Tool (DAHT): Validation of a Patient-Reported Survey Instrument
Authors: Kimberly G Blumenthal, Daniel A Gundersen, Liam R Smith, Brett Nava-Coulter, Andrew King, Elizabeth J Phillips, Alexei Gonzalez-Estrada, Iris M Otani, Allison Ramsey, Aleena Banerji, Timothy Chow, Cosby A Stone, Whitney A Salinas, David A Khan
Journal: Journal of Allergy and Clinical Immunology (2025)
Structural variants linked to Alzheimer’s disease and other common age-related clinical and neuropathologic traits
Authors: Ricardo A. Vialle, Katia de Paiva Lopes, Yan Li, Bernard Ng, Julie A. Schneider, Aron S. Buchman, Yanling Wang, Jose M. Farfel, Lisa L. Barnes, Aliza P. Wingo, Thomas S. Wingo, Nicholas T. Seyfried, Philip L. De Jager, Chris Gaiteri, Shinya Tasaki, David A. Bennett
Journal: Genome Medicine (2025)

Alzheimer's disease (AD) is a complex neurodegenerative disorder with substantial genetic influence. While genome-wide association studies (GWAS) have identified numerous risk loci for late-onset AD (LOAD), the functional mechanisms underlying most of these associations remain unresolved. Large genomic rearrangements, known as structural variants (SVs), represent a promising avenue for elucidating such mechanisms within some of these loci. By leveraging data from two ongoing cohort studies of aging and dementia, the Religious Orders Study and Rush Memory and Aging Project (ROS/MAP), we performed genome-wide association analysis testing 20,205 common SVs from 1088 participants with whole genome sequencing (WGS) data. A range of Alzheimer's disease and other common age-related clinical and neuropathologic traits were examined. First, we mapped SVs across 81 AD risk loci and discovered 22 SVs in linkage disequilibrium (LD) with GWAS lead variants and directly associated with the phenotypes tested. The strongest association was a deletion of an Alu element in the 3'UTR of the TMEM106B gene, in high LD with the respective AD GWAS locus and associated with multiple AD and AD-related disorders (ADRD) phenotypes, including tangles density, TDP-43, and cognitive resilience. The deletion of this element was also linked to lower TMEM106B protein abundance. We also found a 22-kb deletion associated with depression in ROS/MAP and bearing similar association patterns as GWAS SNPs at the IQCK locus. In addition, we leveraged our catalog of SV-GWAS to replicate and characterize independent findings in SV-based GWAS for AD and five other neurodegenerative diseases. Among these findings, we highlight the replication of genome-wide significant SVs for progressive supranuclear palsy (PSP), including markers for the 17q21.31 MAPT locus inversion and a 1483-bp deletion at the CYP2A13 locus, along with other suggestive associations, such as a 994-bp duplication in the LMNTD1 locus, suggestively linked to AD and a 3958-bp deletion at the DOCK5 locus linked to Lewy body disease (LBD) (P = 3.36 × 10-4). While still limited in sample size, this study highlights the utility of including analysis of SVs for elucidating mechanisms underlying GWAS loci and provides a valuable resource for the characterization of the effects of SVs in neurodegenerative disease pathogenesis.
Intrawound vancomycin powder for prevention of surgical site infections in primary joint arthroplasty: an umbrella review of systematic reviews and meta-analyses
Authors: Zhong Zhu, Tao-Hsin Tung, Yongwei Su, Yimin Li, Hua Luo
Journal: International Journal of Surgery (2025)

Objectives: The aim of this umbrella review is to explore the effect of intrawound vancomycin on the incidence of infection and wound complications in patients undergoing primary joint arthroplasty. Methods: Two authors conducted a systematic search of PubMed, EMBASE, Medline, and the Cochrane Central Register of Controlled Trials from inception to 15 October 2023. All systematic reviews and meta-analyses examining the effect of intrawound vancomycin on the incidence of infection and wound complications in primary joint arthroplasty were included. Two authors independently screened and extracted the data from the studies, evaluated the methodological quality of the included studies using the Assessment of Multiple Systematic Reviews scale, and assessed the publication bias and small-sample effects. Results: Our umbrella review includes a total of five systematic reviews, comprising 16 retrospective studies. The pooled results indicate that intrawound vancomycin significantly reduces overall infection rates (OR: 0.41; 95% CI: 0.30-0.54, P &lt; 0.001), superficial infections (OR: 0.51; 95% CI: 0.26-0.97, P = 0.04), and periprosthetic joint infection (PJI) rates (OR: 0.38; 95% CI: 0.28-0.52, P &lt; 0.001) among patients undergoing primary joint arthroplasty. However, vancomycin did not increase the risk of aseptic wound complications (OR: 1.34; 95% CI: 0.88-2.04, P = 0.17) and prolong wound healing (OR: 1.40; 95% CI: 0.87-2.26, P = 0.17). Conclusions: Based on the available research, our umbrella review demonstrates that intrawound vancomycin significantly reduces infection rates in primary joint arthroplasty, including periprosthetic joint and superficial infections, without increasing wound complications. However, given the inclusion of studies with varying quality, these findings should be interpreted with caution. Further high-quality studies are needed to better confirm its long-term safety, cost-effectiveness, and overall clinical utility.
Multiomics reveal key inflammatory drivers of severe obesity: IL4R, LILRA5, and OSM
Authors: Hung-Hsin Chen, Heather M. Highland, Elizabeth G. Frankel, Alyssa C. Scartozzi, Xinruo Zhang, Rashedeh Roshani, Priya Sharma, Asha Kar, Victoria L. Buchanan, Hannah G. Polikowsky, Lauren E. Petty, Jungkyun Seo, Mohammad Yaser Anwar, Daeeun Kim, Mariaelisa Graff, Kristin L. Young, Wanying Zhu, Kalypso Karastergiou, Douglas M. Shaw, Anne E. Justice, Lindsay Fernández-Rhodes, Mohanraj Krishnan, Absalon Gutierrez, Peter J. McCormick, Carlos A. Aguilar-Salinas, Maria Teresa Tusié-Luna, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Miryoung Lee, Eric R. Gamazon, Nancy J. Cox, Päivi Pajukanta, Susan K. Fried, Penny Gordon-Larsen, Ravi V. Shah, Susan P. Fisher-Hoch, Joseph B. McCormick, Kari E. North, Jennifer E. Below
Journal: Cell Genomics (2025)

Polygenic severe obesity (body mass index [BMI] ≥40 kg/m2) has increased, especially in Hispanic/Latino populations, yet we know little about the underlying mechanistic pathways. We analyzed whole-blood multiomics data to identify genes differentially regulated in severe obesity in Mexican Americans from the Cameron County Hispanic Cohort. Our RNA sequencing analysis identified 124 genes significantly differentially expressed between severe obesity cases (BMI ≥40 kg/m2) and controls (BMI <25 kg/m2); 33% replicated in an independent sample from the same population. Our integrative approach identified inflammatory genes, including IL4R, ZNF438, and LILRA5. Several genes displayed transcriptomic effects on severe obesity in subcutaneous adipose tissue. We further showed that the genetic regulation of these genes is associated with several traits in a large biobank, including bone fractures, obstructive sleep apnea, and hyperaldosteronism, illuminating potential risk mechanisms. Our findings furnish a molecular architecture of the severe obesity phenotype across multiple molecular domains.
Shared HLA-Bound Neoepitopes Are New Targets for Pancreatic Cancer Immunotherapy
Authors: Hao Yuan, Qun Chen, Kuirong Jiang, Courtney W. Houchen, Yuqing Zhang, Min Li
Journal: Clinical Cancer Research (2025)

Abstract The shared HLA-bound neoepitopes in pancreatic ductal adenocarcinoma (PDAC) represent a novel class of non-canonical antigens with single amino acid substitutions, resulting from translational errors. These peptides, shared across PDAC patients, showed higher immunogenicity than wild-type counterparts, offering potential candidates for specific immunotherapy development in PDAC.
Germline variants and mosaic chromosomal alterations affect COVID-19 vaccine immunogenicity
Authors: Kyuto Sonehara, Yoshifumi Uwamino, Ryunosuke Saiki, Masaru Takeshita, Shinichi Namba, Shunsuke Uno, Tomoko Nakanishi, Tomoyasu Nishimura, Tatsuhiko Naito, Go Sato, Masahiro Kanai, Aoxing Liu, Sho Uchida, Toshinobu Kurafuji, Akiko Tanabe, Tomoko Arai, Akemi Ohno, Ayako Shibata, Shiho Tanaka, Masatoshi Wakui, Shoko Kashimura, Chiharu Tomi, Akemi Hara, Shiori Yoshikawa, Keiko Gotanda, Kana Misawa, Hiromu Tanaka, Shuhei Azekawa, Qingbo S. Wang, Ryuya Edahiro, Yuya Shirai, Kenichi Yamamoto, Genta Nagao, Takuo Suzuki, Masato Kiyoshi, Akiko Ishii-Watabe, Shinichi Higashiue, Shuzo Kobayashi, Hiroki Yamaguchi, Yasushi Okazaki, Naoyuki Matsumoto, Akihide Masumoto, Hidenobu Koga, Akinori Kanai, Yoshiya Oda, Yutaka Suzuki, Koichi Matsuda, Yuko Kitagawa, Ryuji Koike, Akinori Kimura, Atsushi Kumanogoh, Akihiko Yoshimura, Seiya Imoto, Satoru Miyano, Takanori Kanai, Koichi Fukunaga, Naoki Hasegawa, Mitsuru Murata, Hiromichi Matsushita, Seishi Ogawa, Yukinori Okada, Ho Namkoong
Journal: Cell Genomics (2025)

Vaccine immunogenicity is influenced by the vaccinee's genetic background. Here, we perform a genome-wide association study of vaccine-induced SARS-CoV-2-specific immunoglobulin G (IgG) antibody titers and T cell immune responses in 1,559 mRNA-1273 and 537 BNT162b2 vaccinees of Japanese ancestry. SARS-CoV-2-specific antibody titers are associated with the immunoglobulin heavy chain (IGH) and major histocompatibility complex (MHC) locus, and T cell responses are associated with MHC. The lead variants at IGH contain a population-specific missense variant (rs1043109-C; p.Leu192Val) in the immunoglobulin heavy constant gamma 1 gene (IGHG1), with a strong decreasing effect (β = -0.54). Antibody-titer-associated variants modulate circulating immune regulatory proteins (e.g., LILRB4 and FCRL6). Age-related hematopoietic expanded mosaic chromosomal alterations (mCAs) affecting MHC and IGH also impair antibody production. MHC-/IGH-affecting mCAs confer infectious and immune disease risk, including sepsis and Graves' disease. Impacts of expanded mosaic loss of chromosomes X/Y on these phenotypes were examined. Altogether, both germline and somatic mutations contribute to adaptive immunity functions.
Cross-kingdom-mediated detection of intestinal protozoa through NLRP6
Authors: Nathaniel J Winsor, Giuliano Bayer, Ojas Singh, Jeremy K Chan, Lu Yi Li, Brandon Y Lieng, Elisabeth Foerster, Ana Popovic, Boyan K Tsankov, Heather Maughan, Paul Lemire, Elaine Tam, Catherine Streutker, Lina Chen, Stacey L Heaver, Ruth E Ley, John Parkinson, J Rafael Montenegro-Burke, George M H Birchenough, Dana J Philpott, Stephen E Girardin
Journal: Cell Host & Microbe (2025)
Assessments of lung nodules by an artificial intelligence chatbot using longitudinal CT images
Authors: Yuqiang Mao, Nan Xu, Yanan Wu, Lu Wang, Hongtao Wang, Qianqian He, Tianqi Zhao, Shuangchun Ma, Meihong Zhou, Hongjie Jin, Dongmei Pei, Lina Zhang, Jiangdian Song
Journal: Cell Reports Medicine (2025)

Large language models have shown efficacy across multiple medical tasks. However, their value in the assessment of longitudinal follow-up computed tomography (CT) images of patients with lung nodules is unclear. In this study, we evaluate the ability of the latest generative pre-trained transformer (GPT)-4o model to assess changes in malignancy probability, size, and features of lung nodules on longitudinal CT scans from 647 patients (547 from two local centers and 100 from a public dataset). GPT-4o achieves an average accuracy of 0.88 in predicting lung nodule malignancy compared to pathological results and an average intraclass correlation coefficient of 0.91 in measuring nodule size compared with manual measurements by radiologists. Six radiologists' evaluations demonstrate GPT-4o's ability to capture changes in nodule features with a median Likert score of 4.17 (out of 5.00). In summary, GPT-4o could capture dynamic changes in lung nodules across longitudinal follow-up CT images, thus providing high-quality radiological evidence to assist in clinical management.
Benchmarking single-cell cross-omics imputation methods for surface protein expression
Authors: Chen-Yang Li, Yong-Jia Hong, Bo Li, Xiao-Fei Zhang
Journal: Genome biology (2025)

Recent advances in single-cell multimodal omics sequencing have facilitated the simultaneous profiling of transcriptomes and surface proteomes within individual cells, offering insights into cellular functions and heterogeneity. However, the high costs and technical complexity of protocols like CITE-seq and REAP-seq constrain large-scale dataset generation. To overcome this limitation, surface protein data imputation methods have emerged to predict protein abundances from scRNA-seq data. We present a comprehensive benchmark of twelve state-of-the-art imputation methods across eleven datasets and six scenarios. Our analysis evaluates the methods' accuracy, sensitivity to training data size, robustness across experiments, and usability in terms of running time, memory usage, popularity, and user-friendliness. With benchmark experiments in diverse scenarios and a comprehensive evaluation framework of the results, our study offers valuable insights into the performance and applicability of surface protein data imputation methods in single-cell omics research. Based on our results, Seurat v4 (PCA) and Seurat v3 (PCA) demonstrate exceptional performance, offering promising avenues for further research in single-cell omics.
Consistent Safety and Efficacy of Sotatercept for Pulmonary Arterial Hypertension in <i>BMPR2</i> Mutation Carriers and Noncarriers: A Planned Analysis of Phase 2, Double-Blind, Placebo-controlled Clinical Trial (PULSAR)
Authors: David Montani, Vallerie V. McLaughlin, J. Simon R Gibbs, Mardi Gomberg-Maitland, Marius M. Hoeper, Ioana R Preston, Rogerio Souza, Aaron B. Waxman, Pilar Escribano Subias, Jeremy Feldman, Gisela M Meyer, Karen M. Olsson, Florence Coulet, Solaiappan Manimaran, Yujie Zhao, Anna Lau, Janethe de Oliveira Pena, David B. Badesch, Marc Humbert
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

To evaluate the effect of genetic variant status on sotatercept efficacy and effect of sotatercept treatment on biomarkers in pulmonary arterial hypertension Methods: PULSAR (NCT03496207) was a phase 2, randomized, controlled study of sotatercept vs placebo added to background therapy for pulmonary arterial hypertension. Participants had DNA sequencing done at baseline to detect genetic variants in disease-associated genes (ACVRL1, BMPR2, CAV1, EIF2AK4, ENG, KCNA3, KCNK3, and SMAD9). Safety (adverse events) and efficacy (pulmonary vascular resistance, 6-minute walk distance) were assessed by variant status and treatment at 24 weeks. Serum levels of BMPR2 mRNA and N-terminal pro-hormone B-type natriuretic peptide were assessed at baseline and 24 weeks by treatment and variant status. Analysis of covariance was used to compare the change from baseline by treatment and variant status. Of 76 participants included, 25 had pathogenic variants detected (23 BMPR2; 2 other) and 51 had no variants or variants of uncertain significance. BMPR2 mutation carriers were younger and more frequently on triple therapy but had less severe clinical characteristics at baseline. Changes at 24 weeks in pulmonary vascular resistance and 6-minute walk distance did not differ by variant status. BMPR2 gene expression varied less than twofold from baseline over time, irrespective of treatment or variant status. The adverse events profile was generally consistent with that seen in the parent PULSAR study. These results suggest consistent safety and clinical efficacy of sotatercept for treatment of pulmonary arterial hypertension, irrespective of BMPR2 variant status. Clinical trial registration available at www. gov, ID: NCT03496207.