tbuckley/cabot-search huggingface dataset:
Hepatoma Metastasis‐Inhibiting Supramolecular Nanoglycocalyx for Enhanced Type I Photodynamic Therapy
Authors: Yi‐Chen Liu, Gai‐Li Feng, Jia‐Long Jie, Wei Zhou, Guang‐Jian Liu, Yuan Zhang, Hong‐Mei Su, Guo‐Wen Xing
Journal: Advanced Healthcare Materials (2025)

Type I photodynamic therapy (PDT) is well demonstrated to have low oxygen dependency. However, fully suppressing the risk of hypoxia-induced tumor metastasis during PDT remains a great challenge. In this study, a tetra-lactosylated amphiphilic Aza-BODIPY glycocluster (TLBP) is reported that self-assembles into a supramolecular nanoglycocalyx on hepatoma cell membranes, serving as an artificial extracellular matrix (ECM) to inhibit hepatoma metastasis while facilitating efficient Type I PDT. Molecular engineering demonstrates that multi-glycosylation promotes the transition of nanostructures from disordered to ordered self-assembly by regulating intermolecular interactions. This modification enables the TLBP glycocalyx to exhibit significant intermolecular electron transfer, generating superoxide anion radicals (O2 -•) for Type I PDT. Moreover, the TLBP glycocalyx inhibits the PI3K-Akt signaling pathway by reducing Na+/K+-ATPase activity, leading to decreased migration and invasion of HepG2 cells. The synergistic antitumor effect of TLBP glycocalyx is further verified in a HepG2-bearing mouse model. This work innovatively utilizes glycosylation to regulate microelectronic properties and macroscopic nanoscale self-assembly characteristics, providing a novel concept for developing efficient synergistic anti-hepatoma strategies.
Remibrutinib in Chronic Spontaneous Urticaria
Authors: Martin Metz, Ana Giménez-Arnau, Michihiro Hide, Mark Lebwohl, Giselle Mosnaim, Sarbjit Saini, Gordon Sussman, Robert Szalewski, Sibylle Haemmerle, Karine Lheritier, El-Djouher Martzloff, Noriko Seko, Pengpeng Wang, Artem Zharkov, Marcus Maurer
Journal: New England Journal of Medicine (2025)

Chronic spontaneous urticaria is an idiopathic syndrome defined by recurring itch, hives, or angioedema (or a combination of these symptoms) for more than 6 weeks. Remibrutinib, an oral, highly selective Bruton's tyrosine kinase inhibitor, showed efficacy and favorable safety in phase 2b trials. Data from phase 3 trials are needed. In the identical, multicenter, double-blind, randomized, placebo-controlled REMIX-1 and REMIX-2 trials, we evaluated the efficacy and safety of remibrutinib in patients with symptomatic chronic spontaneous urticaria after treatment with second-generation H1-antihistamines. Patients were randomly assigned in a 2:1 ratio to receive oral remibrutinib at a dose of 25 mg twice daily or placebo. The primary end point was the change from baseline to week 12 in the urticaria activity score during a 7-day period (UAS7), which comprises severity scores for itch and hives during 1 week (scores range from 0 to 42, with higher scores indicating greater severity). Key secondary end points included adverse events and a UAS7 of 6 or lower at weeks 2 and 12 and a UAS7 of 0 at week 12. A total of 470 patients in REMIX-1 and 455 in REMIX-2 were randomly assigned to receive either remibrutinib (313 and 300 patients, respectively) or placebo (157 and 155 patients, respectively). The remibrutinib group had a significantly greater decrease in the UAS7 at week 12 than the placebo group (least-squares mean [±SE] change, -20.0±0.7 vs. -13.8±1.0 [P<0.001] in REMIX-1 and -19.4±0.7 vs. -11.7±0.9 [P<0.001] in REMIX-2), which appeared to be sustained through week 24. At week 12, significantly more patients in the remibrutinib group than in the placebo group had a UAS7 of 6 or lower (REMIX-1, 49.8% vs. 24.8% [P<0.001]; REMIX-2, 46.8% vs. 19.6% [P<0.001]) and a UAS7 of 0 (REMIX-1, 31.1% vs. 10.5% [P<0.001]; REMIX-2, 27.9% vs. 6.5% [P<0.001]). The percentages of patients with any adverse event and with serious adverse events were similar in the remibrutinib group and the placebo group, although a higher percentage of patients in the remibrutinib group than in the placebo group had petechiae (3.8% vs. 0.3% in the combined groups). Treatment with oral remibrutinib resulted in a significant improvement in a composite measure of itching and hives at week 12. (Funded by Novartis Pharmaceuticals; REMIX-1 and REMIX-2 ClinicalTrials.gov numbers, NCT05030311 and NCT05032157, respectively.).
Implications of lymphocyte kinetics after chimeric antigen receptor T cell therapy for multiple myeloma
Authors: Sarah Dingli, Paul Rothweiler, Moritz Binder, Joselle Cook, Morie A Gertz, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Shaji K Kumar, Mustaqeem Siddiqui, Rahma Warsame, Yi Lin, Arthur G Erdman, David Dingli
Journal: Leukemia (2025)
pH‐Responsive Engineered Exosomes Enhance Endogenous Hyaluronan Production by Reprogramming Chondrocytes for Cartilage Repair
Authors: Xiaodan Wu, Weiyong Tao, Ziyang Lan, Yaping Tian, Zhenyu Zhong, Jianwei Wang, Jiaqi Li, Xulong Liu, Xin Zhang, Yifan Wang, Jianglin Wang, Bin Zhang, Yingying Du, Shengmin Zhang
Journal: Advanced Healthcare Materials (2025)

Trauma or inflammation-caused cartilage injury leads to joint dysfunction and pain. Exogenous hyaluronic acid (HA) injection is a well-established treatment, but it has a short duration in vivo and requires multiple injections. Here, a new strategy for in situ reprogramming chondrocytes to continuously produce endogenous high molecular weight HA is developed. This involves a pH-responsive engineered exosome decorated with vesicular stomatitis virus glycoprotein (VSV-G) and hyaluronan synthase type 2 (HAS2). Such engineered exosomes successfully deliver HAS2 to the chondrocyte membranes via VSV-G-mediated membrane fusion triggered by low pH, rather than being degraded in lysosomes. This results in the generation of HAS2-chondrocytes, which are characterized to produce high molecular weight HA in vitro and in vivo. With increased endogenous HA, the injected engineered exosomes enhance cartilage regeneration and inhibit osteoarthritis (OA) progression. Notably, one-shot administration of engineered exosomes drastically increases the intra-articular concentration of high molecular weight HA to 145% of the exogenous HA injection group. Importantly, such endogenous HA is sustained for 4 weeks, whereas the injected exogenous HA rapidly decreases within 2 weeks. The findings demonstrate that pH-responsive engineered exosomes capable of generating endogenous HA hold great potential to replace the treatment of multiple injections of exogenous HA for cartilage repair.
Camlipixant in Refractory Chronic Cough: A Phase 2b, Randomized, Placebo-controlled Trial (SOOTHE)
Authors: Jaclyn A Smith, Surinder S Birring, Michael S. Blaiss, Lorcan McGarvey, Alyn H. Morice, Mandel Sher, Kevin J. Carroll, Margaret Garin, Sylvain Lanouette, Joan Shaw, Ronghua Yang, Catherine M. Bonuccelli
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

Rationale: There is no broadly accessible treatment for patients with refractory chronic cough, a disease characterized by chronic cough that persists despite treatment for other cough-related etiologies or has no identified underlying cause. Objectives: SOOTHE (NCT04678206), a Phase 2b, randomized, placebo-controlled trial, evaluated the efficacy and safety of P2X3 antagonist camlipixant in adults with refractory chronic cough (cough duration ≥1 year; baseline awake cough frequency ≥25 coughs/hour). Methods: After a single-blind, 16-day placebo run-in, patients were randomized (1:1:1:1) to receive camlipixant 12.5, 50, or 200 mg twice-daily, or placebo for 4 weeks. The primary endpoint was change from baseline to Day 28 in objective 24-hour cough frequency. Secondary endpoints included cough severity and cough-related quality of life. Measurements and Main Results: Overall, 310 patients were randomized. A statistically significant reduction in placebo-adjusted 24-hour cough frequency was seen in the 50 mg (-34.4%; 95% confidence interval: -50.5 to -13.3; P=0.0033) and 200 mg (-34.2%; 95% confidence interval: -50.7 to -12.2; P=0.0047) camlipixant arms. All camlipixant arms showed a trend for greater improvement in Cough Severity Visual Analog Scale and Leicester Cough Questionnaire over placebo. Camlipixant was well tolerated with no serious treatment emergent adverse events reported. Taste alteration occurred in 4.8-6.5% of patients in camlipixant arms (vs. 0% with placebo); these were usually mild-moderate. Conclusions: Camlipixant treatment reduced cough frequency and improved patient reported outcomes in patients with refractory chronic cough, with an acceptable safety profile. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04678206.
Alopecia Areata–Specific Patient-Reported Outcome Measures
Authors: Emadodin Darchini-Maragheh, Anthony Moussa, Nicole Yoong, Laita Bokhari, Leslie Jones, Rodney Sinclair
Journal: JAMA Dermatology (2025)

Alopecia areata (AA) has a high prevalence worldwide and causes considerable morbidity in patients. Patient-reported outcomes (PROs) have become an important component of clinical outcome assessment. The quality of existing AA-specific PRO measures (PROMs) has not been evaluated to date. To identify and critically appraise the quality of the measurement properties of existing AA-specific PROMs and provide evidence-based recommendations on the most valid PROMs. Using the predefined eligibility criteria, a systematic search was undertaken using 3 databases to screen the literature for available AA-specific PROMs after 2000. Original developmental studies and related validation studies that reported at least 1 measurement property of the primary PROM were retrieved. The Consensus Based Standards for the Selection of Health Measurement Instruments guidelines were used to examine the quality of the psychometric properties of retrieved PROMs. The quality of evidence was graded using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were analyzed from April to July 2024. A total of 15 articles were identified, including 8 developmental studies (describing 11 PROMs) and 7 validation studies. Three PROMs (Scale of Alopecia Areata Distress, Alopecia Areata Quality of Life Index, and Alopecia Areata Patients' Quality of Life) were AA-specific health-related quality-of-life instruments. Five instruments were single-item symptom-based PROMs (PRO measures for eyebrow, eyelash, nail appearance, and eye irritation, and Scalp Hair Assessment PRO). Three PROMs (Alopecia Areata Patient Priority Outcomes [AAPPO], Alopecia Areata Severity Self-Assessment, and Alopecia Areata Symptom Impact Scale) were based on both constructs. All PROMs were developed based on adult individuals. Seven PROMs (Scale of Alopecia Areata Distress, AAPPO, and all 5 symptom-based PROMs) featured very good development design. Content validity was the most frequently reported measurement property, rated to be sufficient for 8 PROMs. Internal consistency was reported for 5 PROMs with sufficient quality. AAPPO was the only PROM with high-quality evidence of sufficient structural validity and internal consistency. AAPPO was also the only PROM assessed for test-retest reliability, which was judged to be sufficient. No study reported measurement error. This systematic review shows that there is still an unmet need for high-quality validation studies on the internal structure of AA-specific PROMs. Recommendations have been provided to help improve the rigor of the validation of AA-specific PROMs. Use of standards in psychometric testing of instruments could enhance the quality of instruments.
Intended Mismatch DNA Nanocomplexes for Ultrasensitive, Enzymatic Colorimetric Detection of MPOX Virus in Minutes Using a Paper‐Based Fast‐Flow Micromixing Device
Authors: Lalitphan Hongtanee, Sudkate Chaiyo, Hongkai Wu, Abdulhadee Yakoh
Journal: Advanced Healthcare Materials (2025)

In 2024, mpox (formerly "monkeypox") re-emerged as a global health threat due to the more severe Clade I strain, underscoring the need for rapid, accessible diagnostics. Traditional polymerase chain reaction (PCR) methods, while effective, demand complex laboratory infrastructure and extended processing times. To address these limitations, this study presents a fast-flow micromixer paper-based analytical device (fmPAD) designed for ultrasensitive, rapid mpox virus (MPXV) detection. The device employs a specially engineered sensing probe with a cytosine-cytosine (C─C) mismatch sequence that hybridizes with the MPXV target, reactivating urease previously inhibited by Ag+ ions and generating a color change in a pH-sensitive indicator. Enhanced fluid mixing and flow within the fmPAD allow efficient enzymatic reactivation, achieving a linear detection range from 1 to 1000 pm, with a limit of detection (LOD) down to 65 fM. Real viral particles in urine and saliva are also successfully detected at concentrations as low as 5 copies mL-1 without DNA amplification, using a portable colorimeter-representing the lowest LOD among current MPXV DNA sensors. The fmPAD, combined with portable readout technology, enables remote, real-time analysis, offering a practical tool for monitoring and containing the spread of Clade I mpox.
Camlipixant in Refractory Chronic Cough: A Phase 2a, Randomized, Controlled Trial (RELIEF)
Authors: Jaclyn A Smith, Alyn H. Morice, Surinder S Birring, Sean M. Parker, Paul A. Marsden, John R. Holcomb, Mandel Sher, Bruce M. Prenner, Gary Steven, Kevin J. Carroll, Sylvain Lanouette, Denis Garceau, Laurent Harvey, Catherine M. Bonuccelli
Journal: American Journal of Respiratory and Critical Care Medicine (2025)
Predicting Contrast-Associated Acute Kidney Injury
Authors: Yunlin Feng, Min Jun, Amanda Y. Wang, Song Ren, Steven D. Weisbord, Rinaldo Bellomo, Marlies Ostermann, Clare Arnott, Martin Gallagher
Journal: JAMA Network Open (2025)

This systematic review and meta-analysis updates a previous evaluation of the performance of risk-prediction models for contrast-associated acute kidney injury.
Margin thermal ablation eliminates size as a risk factor for recurrence after piecemeal endoscopic mucosal resection of large non-pedunculated colorectal polyps
Authors: Julia L Gauci, Francesco Vito Mandarino, Clarence Kerrison, Anthony M Whitfield, Timothy O'Sullivan, Sunil Gupta, Brian Lam, Varan Perananthan, Oliver Cronin, Eric Y Lee, Steven J Williams, Nicholas Burgess, Michael J Bourke
Journal: Gut (2025)

Lesion size is an independent risk factor for recurrence following endoscopic mucosal resection of large (≥20 mm) non-pedunculated colorectal polyps. Post-resection margin thermal ablation (MTA) reduces the risk of recurrence. Its impact on the uncommon larger (≥40 mm) lesions is unknown. We sought to analyse the impact of MTA on ≥40 mm lesions in a large, prospective cohort. A prospective cohort of patients with colorectal polyps ≥20 mm treated with piecemeal endoscopic mucosal resection in an expert tissue resection centre was divided into three phases: 'pre-MTA', July 2009-June 2012; 'MTA-adoption', July 2012-June 2017 and 'standardised-MTA', July 2017-July 2023. Recurrence was defined as adenomatous tissue endoscopically and/or histologically detected at the first surveillance colonoscopy. The primary outcome was the recurrence rate over the three time periods in three size groups: 20-39 mm, 40-59 mm and ≥60 mm. Over 14 years until July 2023, 1872 sporadic colorectal polyps ≥20 mm in 1872 patients underwent endoscopic mucosal resection (median lesion size 35 mm (IQR 25-45mm)). Of these, 1349 patients underwent surveillance colonoscopy at a median of 6 months (IQR 4-8 months). The overall rates of recurrence in the pre-MTA, MTA-adoption and standardised-MTA phases were 13.5% (n=42/310), 12.6% (n=72/560) and 2.1% (n=10/479), respectively, (p≤0.001). When MTA was applied in the standardised-MTA phase, the rate of recurrence was the same among 20-39 mm (1.5% (3/205)), 40-59 mm (1.6% (3/190)) and ≥60 mm polyps (1.4% (1/73)) (p=1.00). MTA negates the effect of size on the incidence of recurrence after piecemeal endoscopic mucosal resection of colorectal polyps ≥40 mm. Australian Colonic Endoscopic Resection cohort (NCT01368289; NCT02000141).
Effectiveness of Adalimumab Biosimilars and Originator for Psoriasis
Authors: Duc Binh Phan, Anthony P. Bewley, Philip Laws, Teena Mackenzie, Catherine H. Smith, Christopher E. M. Griffiths, Mark Lunt, Richard B. Warren, Zenas Z. N. Yiu
Journal: JAMA Dermatology (2025)

The uncertainties about the real-world effectiveness of adalimumab biosimilars limit their widespread adoption for psoriasis. To compare the effectiveness of adalimumab biosimilars Amjevita and Imraldi with Humira for psoriasis. An emulation of 2 targeted pragmatic clinical trials was conducted using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective pharmacovigilance registry tracking individuals receiving biologic and conventional systemic treatments for psoriasis in the UK and the Republic of Ireland. Data from patients with psoriasis using adalimumab registered to BADBIR were included. Data were collected from September 2007 to January 2023, and data were analyzed from January to September 2023. The effectiveness of initiating Amjevita and Imraldi were compared with initiating Humira among adalimumab-naive patients, and the effectiveness of switching from Humira to either Amjevita or Imraldi were compared with continuing Humira among patients who had been using Humira consistently for more than 2 years. The study outcomes were absolute Psoriasis Area and Severity Index (PASI) score of 2 or less and PASI score of 4 or less at 12 months after the index date. Inverse propensity treatment weighting was used to analyze receiving either biosimilars or Humira to account for confounding. Multiple imputations were used to account for missing PASI data at 12 months and inverse probability of censoring weighting to account for censorship due to deviation from the treatments under investigation. Logistic regression models were fitted to compare the outcomes between study cohorts. Of 11 400 included patients, 6924 (60.7%) were male, and the mean (SD) age was 45.3 (12.5) years. A total of 6133 patients were identified in the new user analysis (5416 starting Humira, 382 starting Amjevita, and 335 starting Imraldi) and 5267 patients in the switcher analysis (3808 continuing Humira, 847 switching to Amjevita, and 612 switching to Imraldi). Amjevita and Imraldi new users had no significantly different probability of achieving a PASI score of 2 or less (Amjevita: adjusted odds ratio [aOR], 0.98; 95% CI, 0.78-1.25; Imraldi: aOR, 0.83; 95% CI, 0.64-1.07) and a PASI score of 4 or less (Amjevita: aOR, 1.07; 95% CI, 0.84-1.37; Imraldi: aOR, 0.91; 95% CI, 0.69-1.20) compared with Humira new users. Patients who switched to Amjevita and Imraldi also had no statistically significant differences in achieving a PASI score of 2 or less (Amjevita: aOR, 1.19; 95% CI, 0.94-1.51; Imraldi: aOR, 0.92; 95% CI, 0.72-1.18) and a PASI score of 4 or less (Amjevita: aOR, 1.32; 95% CI, 0.96-1.84; Imraldi: aOR, 1.00; 95% CI, 0.70-1.41) compared with those who continued Humira. In this study, Amjevita and Imraldi were as effective as Humira for both new starters and patients switching to biosimilars from Humira.
Boosting tumor homing of endogenous natural killer cells via therapeutic secretomes of chemically primed natural killer cells
Authors: Seohyun Cho, Seung Hee Choi, Eunchong Maeng, Hail Park, Ki Seo Ryu, Kyung-Soon Park
Journal: Journal for ImmunoTherapy of Cancer (2025)

Natural killer (NK) cells play a critical role in modulating immune responses by secreting soluble factors, including chemotactic cytokines. Our previous study demonstrated the potent antitumor activity of Chem_NK, referring to NK cells chemically primed with 25 kDa branched polyethyleneimine. However, the potential of Chem_NK secretomes to educate other NK cells and enhance their tumor-homing ability remains unexplored. The effects of Chem_NK conditioned media (Chem CM) on NK cells were evaluated in vitro by examining chemokine receptor expression and migration toward cancer cells. In vivo, the impact of Chem_NK and Chem CM on endogenous NK cell populations was assessed using xenograft and syngeneic mouse tumor models. Cytokine array and signaling analyses were performed to identify factors secreted by Chem_NK and their role in activating recipient NK cells. Chem CM effectively educated NK cells in vitro, enhancing chemokine receptor expression and improving their migration toward cancer cells. In vivo, adoptively transferred Chem_NK increased endogenous NK cell populations within xenograft tumors. Furthermore, direct injection of Chem CM into a syngeneic mouse tumor model significantly promoted endogenous NK cell infiltration into tumors and suppressed lung metastasis. Cytokine analysis revealed that Chem_NK secreted high levels of cytokines, which activated ERK1/2 signaling in recipient NK cells, leading to upregulation of chemokine receptors. Chem_NK secretomes effectively enhance the tumor-homing ability of NK cells and amplify antitumor efficacy by educating other NK cells. These findings offer novel insights into activated NK cell-mediated immune communication and highlight the therapeutic potential of NK cell-derived secretomes in cancer therapy.
Male-Partner Treatment to Prevent Recurrence of Bacterial Vaginosis
Authors: Lenka A Vodstrcil, Erica L Plummer, Christopher K Fairley, Jane S Hocking, Matthew G Law, Kathy Petoumenos, Deborah Bateson, Gerald L Murray, Basil Donovan, Eric P F Chow, Marcus Y Chen, John Kaldor, Catriona S Bradshaw
Journal: New England Journal of Medicine (2025)

Bacterial vaginosis affects one third of reproductive-aged women, and recurrence is common. Evidence of sexual exchange of bacterial vaginosis-associated organisms between partners suggests that male-partner treatment may increase the likelihood of cure. This open-label, randomized, controlled trial involved couples in which a woman had bacterial vaginosis and was in a monogamous relationship with a male partner. In the partner-treatment group, the woman received first-line recommended antimicrobial agents and the male partner received oral and topical antimicrobial treatment (metronidazole 400-mg tablets and 2% clindamycin cream applied to penile skin, both twice daily for 7 days). In the control group, the woman received first-line treatment and the male partner received no treatment (standard care). The primary outcome was recurrence of bacterial vaginosis within 12 weeks. A total of 81 couples were assigned to the partner-treatment group, and 83 couples were assigned to the control group. The trial was stopped by the data and safety monitoring board after 150 couples had completed the 12-week follow-up period because treatment of the woman only was inferior to treatment of both the woman and her male partner. In the modified intention-to-treat population, recurrence occurred in 24 of 69 women (35%) in the partner-treatment group (recurrence rate, 1.6 per person-year; 95% confidence interval [CI], 1.1 to 2.4) and in 43 of 68 women (63%) in the control group (recurrence rate, 4.2 per person-year; 95% CI, 3.2 to 5.7), which corresponded to an absolute risk difference of -2.6 recurrences per person-year (95% CI, -4.0 to -1.2; P<0.001). Adverse events in treated men included nausea, headache, and metallic taste. The addition of combined oral and topical antimicrobial therapy for male partners to treatment of women for bacterial vaginosis resulted in a lower rate of recurrence of bacterial vaginosis within 12 weeks than standard care. (Funded by the National Health and Medical Research Council of Australia; StepUp Australian New Zealand Clinical Trials Registry number, ACTRN12619000196145.).
Expanding the Phenotype of <scp>DNA</scp> Ligase 1 Deficiency: First Report of Macrocytic Sideroblastic Anemia
Authors: Debbie Jiang, Emily Vistica Sampino, Kira Rosenlind, Dean R. Campagna, Stephanie DiTroia, Mark D. Fleming, Siobán B. Keel
Journal: American Journal of Hematology (2025)