tbuckley/cabot-search huggingface dataset:
Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer
Authors: Jia-Bin Wang, You-Xin Gao, Yin-Hua Ye, Qiao-Ling Zheng, Hua-You Luo, Shuan-Hu Wang, Tao Zhang, Qin-Wen Jin, Chao-Hui Zheng, Ping Li, Jian-Xian Lin, Qi-Yue Chen, Long-Long Cao, Ying-Hong Yang, Chang-Ming Huang, Jian-Wei Xie
Journal: Theranostics (2024)

Background: Pyroptosis plays a crucial role in immune responses.However, the effects of pyroptosis on tumor microenvironment remodeling and immunotherapy in gastric cancer (GC) remain unclear.Patients and Methods: Large-sample GEO data (GSE15459, GSE54129, and GSE62254) were used to explore the immunoregulatory roles of pyroptosis.TCGA cohort was used to elucidate multiple molecular events associated with pyroptosis, and a pyroptosis risk score (PRS) was constructed.The prognostic performance of the PRS was validated using postoperative GC samples from three public databases (n=925) and four independent Chinese medical cohorts (n=978).Single-cell sequencing and multiplex immunofluorescence were used to elucidate the immune cell infiltration landscape associated with PRS.Patients with GC who received neoadjuvant immunotherapy (n=48) and those with GC who received neoadjuvant chemotherapy (n=49) were enrolled to explore the value of PRS in neoadjuvant immunotherapy.Results: GC pyroptosis participates in immune activation in the tumor microenvironment and plays a powerful role in immune regulation.PRS, composed of four pyroptosis-related differentially expressed genes (BATF2, PTPRJ, RGS1, and VCAN), is a reliable and independent biomarker for GC.PRS low is associated with an activated pyroptosis pathway and greater infiltration of anti-tumor immune cells, including more effector and CD4+ T cells, and with the polarization of tumor-associated macrophages in the tumor center.Importantly, PRS low marks the effectiveness of neoadjuvant immunotherapy and enables screening of GC patients with combined positive score ≥1 who benefit from neoadjuvant immunotherapy.Conclusion: Our study demonstrated that pyroptosis activates immune processes in the tumor microenvironment.A low PRS correlates with enhanced infiltration of anti-tumor immune cells at the tumor site, increased pyroptotic activity, and improved patient outcomes.The constructed PRS can be used as an effective quantitative tool for pyroptosis analysis to guide more effective immunotherapeutic strategies for patients with GC.
<i>In situ</i> single-cell therapeutic response imaging facilitated by the TRIPODD fluorescence imaging platform
Authors: Nathan P. McMahon, Allison Solanki, Lei G. Wang, Antonio R. Montaño, Jocelyn A. Jones, Kimberley S. Samkoe, Kenneth M. Tichauer, Summer L. Gibbs
Journal: Theranostics (2024)

: Small molecule drugs such as tyrosine kinase inhibitors (TKIs) targeting tumoral molecular dependencies have become standard of care for numerous cancer types. Notably, epidermal growth factor receptor (EGFR) TKIs (e.g., erlotinib, afatinib, osimertinib) are the current first-line treatment for non-small cell lung cancer (NSCLC) due to their improved therapeutic outcomes for EGFR mutated and overexpressing disease over traditional platinum-based chemotherapy. However, many NSCLC tumors develop resistance to EGFR TKI therapy causing disease progression. Currently, the relationship between
Activation of the hypoxia-inducible factor pathway protects against acute ischemic stroke by reprogramming central carbon metabolism
Authors: Sarah Madai, Pinar Kilic, Rolf M. Schmidt, Carlos Bas-Orth, Thomas Korff, Michael Büttner, Glynis Klinke, Gernot Poschet, Hugo H. Marti, Reiner Kunze
Journal: Theranostics (2024)

Cell metabolism reprogramming to sustain energy production, while reducing oxygen and energy consuming processes is crucially important for the adaptation to hypoxia/ischemia. Adaptive metabolic rewiring is controlled by hypoxia-inducible factors (HIFs). Accumulating experimental evidence indicates that timely activation of HIF in brain-resident cells improves the outcome from acute ischemic stroke. However, the underlying molecular mechanisms are still incompletely understood. Thus, we investigated whether HIF-dependent metabolic reprogramming affects the vulnerability of brain-resident cells towards ischemic stress.
Salt Sensitivity of Blood Pressure
Authors: Jeremiah Afolabi, Cheryl L. Laffer, Heather K. Beasley, Antentor Hinton, Sepiso K. Masenga, Annet Kirabo
Journal: Circulation Research (2024)

The year 2024 marks the centennial of the initiation of the American Heart Association. Over the past 100 years, the American Heart Association has led groundbreaking discoveries in cardiovascular disease including salt sensitivity of blood pressure, which has been studied since the mid-1900s. Salt sensitivity of blood pressure is an important risk factor for cardiovascular events, but the phenotype remains unclear because of insufficient understanding of the underlying mechanisms and lack of feasible diagnostic tools. In honor of this centennial, we commemorate the initial discovery of salt sensitivity of blood pressure and chronicle the subsequent scientific discoveries and efforts to mitigate salt-induced cardiovascular disease with American Heart Association leading the way. We also highlight determinants of the pathophysiology of salt sensitivity of blood pressure in humans and recent developments in diagnostic methods and future prospects.
Hip and core exercise programme prevents running-related overuse injuries in adult novice recreational runners: a three-arm randomised controlled trial (Run RCT)
Authors: Mari Leppänen, Janne Viiala, Piia Kaikkonen, Kari Tokola, Tommi Vasankari, Benno M Nigg, Tron Krosshaug, Penny Werthner, Jari Parkkari, Kati Pasanen
Journal: British Journal of Sports Medicine (2024)

Objective This study aims to investigate the efficacy of two exercise interventions in reducing lower extremity (LE) injuries in novice recreational runners. Methods Novice runners (245 female, 80 male) were randomised into hip and core (n=108), ankle and foot (n=111) or control (n=106) groups. Interventions were completed before running and included exercise programmes focusing on either (1) hip and core or (2) ankle and foot muscles. The control group performed static stretching exercises. All groups were supervised by a physiotherapist and performed the same running programme. Injuries and running exposure were registered using weekly questionnaires during the 24-week study. Primary outcome was running-related LE injury. Results The incidence of LE injuries was lower in the hip and core group compared with the control group (HR 0.66; 95% CI 0.45 to 0.97). The average weekly prevalence of overuse injuries was 39% lower (prevalence rate ratio, PRR 0.61, 95% CI 0.39 to 0.96), and the prevalence of substantial overuse injuries was 52% lower (PRR 0.48, 95% CI 0.27 to 0.90) in the hip and core group compared with the control group. No significant difference was observed between the ankle and foot group and control group in the prevalence of overuse injuries. A higher incidence of acute injuries was observed in the ankle and foot group compared with the control group (HR 3.60, 95% CI 1.20 to 10.86). Conclusion A physiotherapist-guided hip and core-focused exercise programme was effective in preventing LE injuries in novice recreational runners. The ankle and foot programme did not reduce LE injuries and did not protect against acute LE injuries when compared with static stretching.
Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis
Authors: Sudha S Shankar, Samuel J Daniels, Darren Robertson, Janeli Sarv, José Sánchez, Debra Carter, Lutz Jermutus, Benjamin Challis, Arun J Sanyal
Journal: Clinical Gastroenterology and Hepatology (2024)

Cotadutide, a peptide co-agonist at the glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptors, has demonstrated robust improvements in body weight, glycemia, and hepatic fat fraction (HFF) in patients living with obesity and type 2 diabetes mellitus.
Peripherally targeted analgesia via AAV-mediated sensory neuron-specific inhibition of multiple pronociceptive sodium channels
Authors: Seung Min Shin, Brandon Itson-Zoske, Fan Fan, Yucheng Xiao, Chensheng Qiu, Theodore R. Cummins, Quinn H. Hogan, Hongwei Yu
Journal: Journal of Clinical Investigation (2024)

This study reports that targeting intrinsically disordered regions of NaV1.7 protein facilitates discovery of sodium channel inhibitory peptide aptamers (NaViPA) for adeno-associated virus (AAV)-mediated, sensory neuron-specific analgesia. A multipronged inhibition of INa1.7, INa1.6, INa1.3, and INa1.1. but not INa1.5 and INa1.8 was found for a prototype, named NaViPA1, which was derived from the NaV1.7 intracellular loop 1 and is conserved among the TTXs NaV subtypes. NaViPA1 expression in primary sensory neurons (PSNs) of dorsal root ganglia (DRG) produced significant inhibition of TTXs INa but not TTXr INa. DRG injection of AAV6-encoded NaViPA1 significantly attenuated evoked and spontaneous pain behaviors in both male and female rats with neuropathic pain induced by tibial nerve injury (TNI). Whole-cell current clamp of the PSNs showed that NaViPA1 expression normalized PSN excitability in TNI rats, suggesting that NaViPA1 attenuated pain by reversal of injury-induced neuronal hypersensitivity. Immunohistochemistry revealed efficient NaViPA1 expression restricted in PSNs and their central and peripheral terminals, indicating PSN-restricted AAV biodistribution. Inhibition of sodium channels by NaViPA1 was replicated in the human iPSC-derived sensory neurons. These results summate that NaViPA1 is a promising analgesic lead that, combined with AAV-mediated PSN-specific block of multiple TTXs NaVs, has potential as peripheral nerve-restricted analgesic therapeutics.
Comprehensive Bridging Radiotherapy for Limited Pre-CART Non-Hodgkin Lymphoma
Authors: Omran Saifi, William G. Breen, William G. Rule, Yi Lin, Javier Munoz, Mohamed A. Kharfan-Dabaja, Jennifer L. Peterson
Journal: JAMA Oncology (2024)

This cohort study examines the role of comprehensive bridging radiotherapy in the setting of chimeric antigen receptor T-cell therapy for non-Hodgkin lymphoma.
Bulevirtide monotherapy in patients with chronic HDV: Efficacy and safety results through week 96 from a phase III randomized trial
Authors: Heiner Wedemeyer, Soo Aleman, Maurizia Brunetto, Antje Blank, Pietro Andreone, Pavel Bogomolov, Vladimir Chulanov, Nina Mamonova, Natalia Geyvandova, Viacheslav Morozov, Olga Sagalova, Tatyana Stepanova, Annemarie Berger, Sandra Ciesek, Dmitry Manuilov, Renee-Claude Mercier, Ben L. Da, Grace M. Chee, Mingyang Li, John F. Flaherty, Audrey H. Lau, Anu Osinusi, Julian Schulze zur Wiesch, Markus Cornberg, Stefan Zeuzem, Pietro Lampertico
Journal: Journal of Hepatology (2024)

Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
Ponatinib vs Imatinib in Frontline Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia
Authors: Elias Jabbour, Hagop M. Kantarjian, Ibrahim Aldoss, Pau Montesinos, Jessica T. Leonard, David Gómez-Almaguer, Maria R. Baer, Carlo Gambacorti-Passerini, James McCloskey, Yosuke Minami, Cristina Papayannidis, Vanderson Rocha, Philippe Rousselot, Pankit Vachhani, Eunice S. Wang, Bingxia Wang, Meliessa Hennessy, Alexander Vorog, Niti Patel, Tammie Yeh, Jose-Maria Ribera
Journal: JAMA (2024)

Importance In newly diagnosed Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I. Objective To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL. Design, Setting, and Participants Global registrational, phase 3, open-label trial in adults aged 18 years or older with newly diagnosed Ph+ ALL. From January 2019 to May 2022, eligible patients at 77 sites were randomized 2:1 to ponatinib (30 mg/d) or imatinib (600 mg/d) with reduced-intensity chemotherapy, followed by single-agent ponatinib or imatinib after the cycle 20 phase of the trial. The last date of follow-up for this analysis was August 12, 2022. Intervention Patients received ponatinib, 30 mg/d, or imatinib, 600 mg/d, with reduced-intensity chemotherapy, followed by single-agent ponatinib or imatinib after cycle 20. The ponatinib dose was reduced to 15 mg on achievement of minimal residual disease–(MRD) negative complete remission. Main Outcomes and Measures The primary end point of this interim analysis was MRD-negative complete remission (≤0.01% BCR::ABL1 [MR4] centrally assessed by reverse transcriptase–quantitative polymerase chain reaction), with complete remission maintained for at least 4 weeks at the end of cycle 3. The key secondary end point was event-free survival. Results Of 245 patients randomized (median age, 54 years; 133 [54.3%] female), 232 (ponatinib, n = 154; imatinib, n = 78) who had p190 or p210 dominant isoforms verified by the central laboratory were analyzed for the primary end point. The MRD-negative complete remission rate (primary end point) was significantly higher with ponatinib (34.4% [53/154]) vs imatinib (16.7% [13/78]) (risk difference, 0.18 [95% CI, 0.06-0.29]; P = .002). At the data cutoff, event-free survival had not met the prespecified number of events. Median event-free survival was not reached in the ponatinib group and was 29 months in the imatinib group. The most common adverse events were similar between treatment groups. Arterial occlusive events were infrequent and comparable between groups (ponatinib, 2.5%; imatinib, 1.2%). Conclusions and Relevance Ponatinib demonstrated a superior rate of MRD-negative complete remission at the end of induction vs imatinib when combined with reduced-intensity chemotherapy in adults with newly diagnosed Ph+ ALL. The safety profile of ponatinib was comparable with imatinib. Trial Registration ClinicalTrials.gov Identifier: NCT03589326
Error in Results
Journal: JAMA Network Open (2024)

In the Original Investigation titled "Outcomes Following Extracorporeal Membrane Oxygenation for Severe COVID-19 in Pregnancy or Post Partum," 1 published May 22, 2023, there was a sentence in the Results section that should have read, "Among the 23 patients (23.0%) who delivered while receiving ECMO, the median (IQR) gestational age was 29.0 (26.9-29.6)weeks, and 8 (34.8%) had a postpartum hemorrhage."This article has been corrected. 1
PSMA-Avid Desmoid Tumor of the Abdominal Wall on 18F-Piflufolastat PET/CT
Authors: Siddharth Bommekal, Lesley Flynt, Sanjit Om Tewari, Devaki Shilpa Sudha Surasi
Journal: Clinical Nuclear Medicine (2024)

Abstract Prostate-specific membrane antigen (PSMA) PET/CT is widely used in the evaluation of suspected metastasis for initial definitive therapy and suspected recurrence of prostate cancer. We outline a case report of a 62-year-old man with history of prostate cancer treated with surgery, salvage radiation, and hormonal therapy presenting with rising PSA levels. There was incidental detection of a PSMA-avid subcutaneous abdominal wall mass on PSMA PET/CT study, which was consistent with desmoid fibromatosis on an ultrasound-guided biopsy.
Christensenella strain resources, genomic/metabolomic profiling, and association with host at species level
Authors: Xin-Wei Sun, Hao-Jie Huang, Xiao-Meng Wang, Rui-Qi Wei, Han-Yu Niu, Hao-Yu Chen, Man Luo, Rashidin Abdugheni, Yu-Lin Wang, Feng-Lan Liu, He Jiang, Chang Liu, Shuang-Jiang Liu
Journal: Gut Microbes (2024)

The gut commensal bacteria
Direct transposition of native DNA for sensitive multimodal single-molecule sequencing
Authors: Arjun S. Nanda, Ke Wu, Iryna Irkliyenko, Brian Woo, Megan S. Ostrowski, Andrew S. Clugston, Leanne C. Sayles, Lingru Xu, Ansuman T. Satpathy, Hao G. Nguyen, E. Alejandro Sweet-Cordero, Hani Goodarzi, Sivakanthan Kasinathan, Vijay Ramani
Journal: Nature Genetics (2024)

Concurrent readout of sequence and base modifications from long unamplified DNA templates by Pacific Biosciences of California (PacBio) single-molecule sequencing requires large amounts of input material. Here we adapt Tn5 transposition to introduce hairpin oligonucleotides and fragment (tagment) limiting quantities of DNA for generating PacBio-compatible circular molecules. We developed two methods that implement tagmentation and use 90-99% less input than current protocols: (1) single-molecule real-time sequencing by tagmentation (SMRT-Tag), which allows detection of genetic variation and CpG methylation; and (2) single-molecule adenine-methylated oligonucleosome sequencing assay by tagmentation (SAMOSA-Tag), which uses exogenous adenine methylation to add a third channel for probing chromatin accessibility. SMRT-Tag of 40 ng or more human DNA (approximately 7,000 cell equivalents) yielded data comparable to gold standard whole-genome and bisulfite sequencing. SAMOSA-Tag of 30,000-50,000 nuclei resolved single-fiber chromatin structure, CTCF binding and DNA methylation in patient-derived prostate cancer xenografts and uncovered metastasis-associated global epigenome disorganization. Tagmentation thus promises to enable sensitive, scalable and multimodal single-molecule genomics for diverse basic and clinical applications.
Aging clocks based on accumulating stochastic variation
Authors: David H. Meyer, Björn Schumacher
Journal: Nature Aging (2024)

Abstract Aging clocks have provided one of the most important recent breakthroughs in the biology of aging, and may provide indicators for the effectiveness of interventions in the aging process and preventive treatments for age-related diseases. The reproducibility of accurate aging clocks has reinvigorated the debate on whether a programmed process underlies aging. Here we show that accumulating stochastic variation in purely simulated data is sufficient to build aging clocks, and that first-generation and second-generation aging clocks are compatible with the accumulation of stochastic variation in DNA methylation or transcriptomic data. We find that accumulating stochastic variation is sufficient to predict chronological and biological age, indicated by significant prediction differences in smoking, calorie restriction, heterochronic parabiosis and partial reprogramming. Although our simulations may not explicitly rule out a programmed aging process, our results suggest that stochastically accumulating changes in any set of data that have a ground state at age zero are sufficient for generating aging clocks.
Strategies of functionalized GelMA-based bioinks for bone regeneration: Recent advances and future perspectives
Authors: Yaru Zhu, Xingge Yu, Hao Liu, Junjun Li, Mazaher Gholipourmalekabadi, Kaili Lin, Changyong Yuan, Penglai Wang
Journal: Bioactive Materials (2024)

Gelatin methacryloyl (GelMA) hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties, which has been widely used in a variety of tissue engineering and tissue regeneration. However, pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment, which is difficult to meet the needs of bone repair. Moreover, GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments. This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration. The synthesis process of GelMA hydrogel was described in details, and various functional methods to meet the requirements of bone regeneration, including mechanical strength, porosity, vascularization, osteogenic differentiation, and immunoregulation for patient specific repair, etc. In addition, the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation, as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases (such as inflammation, infection, tumor) are also briefly reviewed. Finally, we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.
Shikonin and chitosan-silver nanoparticles synergize against triple-negative breast cancer through RIPK3-triggered necroptotic immunogenic cell death
Authors: Jiahao Liang, Xiangge Tian, Meirong Zhou, Fei Yan, Jialong Fan, Yan Qin, Binlong Chen, Xiaokui Huo, Zhenlong Yu, Yan Tian, Sa Deng, Yulin Peng, Yan Wang, Bin Liu, Xiaochi Ma
Journal: Biomaterials (2024)
The concept of Sfrp1<sup>+</sup>transitional fibroblasts: the key to dissociating lineage heterogeneity and fate of invasive fibroblasts in pulmonary fibrosis?
Authors: Xue Liu, Xuexi Zhang, Jiurong Liang, Paul W. Noble, Dianhua Jiang
Journal: European Respiratory Journal (2024)

<h3>Shareable abstract</h3> <b>The novel concept of Sfrp1<sup>+</sup> transitional fibroblasts has sparked novel points of interest: the mechanisms under which the Sfrp1<sup>+</sup> transitional fibroblasts emerge and the <i>in vivo</i> functions of Sfrp1 and Sfrp1<sup>+</sup> transitional fibroblasts in pulmonary fibrosis</b> https://bit.ly/4aq6iAI
Prevalence of anal cytology screening among persons with HIV and lack of access to high-resolution anoscopy at HIV care facilities
Authors: Sun Hee Rim, Linda Beer, Mona Saraiya, Yunfeng Tie, Xin Yuan, John Weiser
Journal: JNCI Journal of the National Cancer Institute (2024)

People with HIV at highest risk of anal cancer include gay, bisexual, and other men who have sex with men and transgender women aged 35 years or older as well as other people with HIV aged 45 years or older. Identifying and treating precancerous lesions can reduce anal cancer incidence in these groups. We assessed the prevalence of anal cytology and access to high-resolution anoscopy among people with HIV overall and in those individuals at highest risk.