tbuckley/cabot-search huggingface dataset:
Contemporary review of clinical features, multi-modality imaging and management of coronary artery aneurysms
Authors: Sharmeen Sorathia, Aro Daniela Arockiam, Ankit Agrawal, Elio Haroun, Rishabh Khurana, Abdelrahman Ahmed, Leslie Cho, Wael Jaber, Brian Griffin, Tom Kai Ming Wang
Journal:  (2025)

Abstract Coronary artery aneurysm (CAA) is a rare, dilated segment of the coronary artery. Phenotypically, it can have different morphologies, patterns, content, and affected vessels, making multimodality invasive and noninvasive imaging play a significant role in its evaluation. In this review article, we discuss in depth the contemporary perspectives in pathophysiology, epidemiology, clinical presentation, multimodality imaging evaluation, treatment strategies (medical, percutaneous and surgical) and outcomes of CAA. CAA is predominantly associated with coronary atherosclerotic diseases and/or autoimmune vasculitis conditions including Kawasaki disease. It can present with various clinical manifestations, from an incidental finding to myocardial infarction and life-threatening complications. While coronary angiography has been the gold standard to detect CAA, noninvasive modalities including coronary computed tomography have increasingly been utilized given its high resolution for anatomical depiction of the vessels and relations to surrounding structures. We suggest a stepwise approach to the assessment and clinical decision-making in the management of CAA. Pharmacological strategies include risk factor control and secondary prevention. For obstructive ischaemic presenting aneurysms, percutaneous is pursued, while larger or multi-vessel obstructive lesions are typically managed with coronary surgery.
The Roles of Natural Killer Cells in Breast Cancer Pathobiology and their Regulation by Estrogens
Authors: Jovita Byemerwa, Ching-Yi Chang, Donald P McDonnell
Journal: Endocrine Reviews (2025)

Abstract/Summary Breast cancer remains the most commonly diagnosed malignancy among women worldwide. While breast cancer treatment outcomes have improved in recent years there remains an unmet medical need for therapeutics that can be used with curative intent in the most aggressive breast cancer subtypes and for those cancers that have metastasized. In recent years, the success of T-cell-based therapies and other technologies that boost anti-tumor activities of immune cells have increased interest in using natural killer (NK) cell-based immunotherapies to treat solid tumors. These innate lymphoid cells can identify and eliminate tumor cells through their intrinsic cytotoxic activities and their ability to modulate the immune response through cytokine production. Owing to their lack of T-cell receptors, NK cells can also be used in the allogeneic setting and strategies to develop and establish NK cells as therapeutics in breast cancer are currently being explored. In this review, we will describe NK cell biology as it relates to breast cancer pathobiology and treatment outcomes and discuss how NK cell biology can be exploited and manipulated in the development of new therapeutics for breast cancer. Additionally, we review the role of estrogens in regulating NK cell activity and discuss how endocrine therapies targeting the estrogen receptor signaling axis could be employed as an approach to increase tumor immunity and the efficacy of NK-cell-directed immunotherapies.
Health Trade-offs of Boiling Drinking Water with Solid Fuels: A Modeling Study
Authors: Emily Floess, Ayse Ercumen, Angela R. Harris, Andrew P. Grieshop
Journal: Environmental Health Perspectives (2025)

Billions of the world's poorest households are faced with the lack of access to both safe drinking water and clean cooking. One solution to microbiologically contaminated water is boiling, often promoted without acknowledging the additional risks incurred from indoor air degradation from using solid fuels. This modeling study explores the tradeoff of increased air pollution from boiling drinking water under multiple contamination and fuel use scenarios typical of low-income settings. We calculated the total change in disability-adjusted life years (DALYs) from household air pollution (HAP) and diarrhea from fecal contamination of drinking water for scenarios of different source water quality, boiling effectiveness, and stove type. We used Uganda and Vietnam, two countries with a high prevalence of water boiling and solid fuel use, as case studies. Boiling drinking water reduced the diarrhea disease burden by a mean of 1100 DALYs and 367 DALYs per 10,000 people for those under and over 5 years of age in Uganda, respectively, for high-risk water quality and the most efficient (lab-level) boiling scenario, with smaller reductions for less contaminated water and ineffective boiling. Similar results were found in Vietnam, though with fewer avoided DALYs in children under 5 due to different demographics. In both countries, for households with high baseline HAP from existing solid fuel use, adding water boiling to cooking on a given stove was associated with a limited increase in HAP DALYs due to the log-linear exposure-response curves. Boiling, even at low effectiveness, was associated with net DALY reductions for medium- and high-risk water, even with unclean stoves/fuels. Use of clean stoves coupled with effective boiling significantly reduced total DALYs. Boiling water generally resulted in net decreases in DALYs. Future efforts should empirically measure health outcomes from HAP vs. diarrhea associated with boiling drinking water using field studies with different boiling methods and stove types.. https://doi.org/10.1289/EHP15059.
Chimeric autoantibody receptor T cells clonally eliminate B cells producing autoantibodies against IFN-γ
Authors: Jhan-Jie Peng, Jing-Ya Ding, Yingxi Xu, Han-Po Shih, You-Ning Lin, Tsai-Yi Wu, Yu-Fang Lo, Chia-Chi Lo, Chu-Fu Yeh, Chen-Yen Kuo, Kun-Hua Tu, Shang-Yu Wang, Wei-Te Lei, Ting-Shu Wu, Huang-Shen Lin, Chen-Hsiang Lee, Wen-Chi Huang, Yi-Chun Chen, Yuag-Meng Liu, Zhi-Yuan Shi, Ya-Ting Chang, Ling-Shan Syue, Po-Lin Chen, Soon-Hian Teh, Chia-Huei Chou, Mao-Wang Ho, Chih-Yu Chi, Ping-Chih Ho, Cheng-Lung Ku
Journal: Science Immunology (2025)

Neutralizing anti–interferon-γ (IFN-γ) autoantibodies (nAIGAs) impair IFN-γ–mediated immunity, predisposing patients with nAIGAs to infection by nontuberculous mycobacteria, Talaromyces marneffei , and other intracellular pathogens. Current clinical management relies on continuous antimicrobial therapy, with no treatment offering sustained benefits. Here, we developed human chimeric autoantibody receptor (CAAR) T cells targeting autoreactive B cells expressing nAIGA B cell receptors (BCRs) using an IFN-γ receptor–irresponsive IFN-γ variant as bait. By exploiting a mouse model of nAIGA BCR-expressing B cell leukemia, we found that IFN-γ CAAR T cells lack off-target toxicity, including IFN-γ receptor cross-reactive toxicity and Fc-redirected toxicity. IFN-γ CAAR T cells substantially reduced circulating AIGAs secreted from target cells in vivo. Further, IFN-γ CAAR T cells effectively eliminated autoreactive B cells in ex vivo cultures of peripheral blood mononuclear cells from patients with nAIGAs. Together, these results demonstrate that IFN-γ CAAR T cells may be a promising strategy to ameliorate nAIGA-associated infections by eliminating autoreactive B cells.
Uptake of lipids from ascites drives NK cell metabolic dysfunction in ovarian cancer
Authors: Karen Slattery, Cong-Hui Yao, Eimear Mylod, John Scanlan, Barry Scott, Joseph Patrick Crowley, Orla McGowan, Gavin McManus, Martin Brennan, Katie O’Brien, Kate Glennon, Edward Corry, Ann Treacy, Rafael J. Argüello, Clair M. Gardiner, Marcia C. Haigis, Donal J. Brennan, Lydia Lynch
Journal: Science Immunology (2025)

High-grade serous ovarian cancer (HGSOC) remains an urgent unmet clinical need, with more than 70% of patients presenting with metastatic disease. Many patients develop large volumes of ascites, which promotes metastasis and is associated with poor therapeutic response and survival. Immunotherapy trials have shown limited success, highlighting the need to better understand HGSOC immunology. Here, we analyzed cytotoxic lymphocytes [natural killer (NK), T, and innate T cells] from patients with HGSOC and observed widespread dysfunction across primary and metastatic sites. Although nutrient rich, ascites was immunosuppressive for all lymphocyte subsets. NK cell dysfunction was driven by uptake of polar lipids, with associated dysregulation in lipid storage. Phosphatidylcholine was a key immunosuppressive metabolite, disrupting NK cell membrane order and cytotoxicity. Blocking lipid uptake through SR-B1 protected NK cell antitumor functions in ascites. These findings offer insights into immune suppression in HGSOC and have important implications for the design of future immunotherapies.
SARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy
Authors: Chen Ding, Papa S Ndiaye, Sydney R Campbell, Michelle Y Fry, Jincheng Gong, Sophia R Wienbar, Whitney Gibbs, Philippe Morquette, Luke H Chao, Michael Tri H Do, Thomas Schwarz
Journal: Journal of Clinical Investigation (2025)

Autosomal Dominant Optic Atrophy (ADOA), the most prevalent hereditary optic neuropathy, leads to retinal ganglion cell (RGC) degeneration and vision loss. ADOA is primarily caused by mutations in the OPA1 gene, which encodes a conserved GTPase important for mitochondrial inner membrane dynamics. To date, the disease mechanism remains unclear, and no therapies are available. We generated a mouse model carrying the pathogenic Opa1R290Q/+ allele that recapitulated key features of human ADOA, including mitochondrial defects, age-related RGC loss, optic nerve degeneration, and reduced RGC functions. We identified SARM1, a neurodegeneration switch, as a key driver of RGC degeneration in these mice. Sarm1 knockout nearly completely suppressed all the degeneration phenotypes without reversing mitochondrial fragmentation. Additionally, we showed that a portion of SARM1 localized within the mitochondrial intermembrane space (IMS). These findings indicated that SARM1 was activated downstream of mitochondrial dysfunction in ADOA, highlighting it as a promising therapeutic target.
Reversing the immunosuppressive tumor microenvironment via “Kynurenine starvation therapy” for postsurgical triple-negative breast cancer treatment
Authors: Zengguang Liu, Jiaxin Yin, Tianyuan Qiu, Aijiang Liu, Yanan Yu, Shengcai Yang, Ziling Liu, Quanshun Li
Journal: Journal of Controlled Release (2025)
Outcomes of elderly patients with relapsed refractory multiple myeloma (RRMM) treated with teclistamab: a multicenter study from the U.S. Multiple Myeloma Immunotherapy Consortium
Authors: Oren Pasvolsky, Danai Dima, Lei Feng, Wenli Dong, Tiffany Richards, James A Davis, Aimaz Afrough, Mariola Vazquez-Martinez, Aishwarya Sannareddy, Utkarsh Goel, Rahul Banerjee, Jack Khouri, Frances Cervoni, Mahmoud R Gaballa, Alex Lieberman-Cribbin, Masooma Shifa Rana, Kelley Julian, Christopher J Ferreri, Leyla Shune, Shaun DeJarnette, Evguenia Bhurtel, Sandra Susanibar Adaniya, Andrew Portuguese, Hitomi Hosoya, Lekha Mikkilineni, Gurbakhash Kaur, Adriana Rossi, Megan M Herr, Daniel Schrum, Chenyu Lin, Shahzad Raza, Yi Lin, Shonali Midha, Nadeem Omar, Shebli Atarsh, Joseph McGuirk, Douglas Sborov, Peter Voorhees, Faiz Anwer, Melissa Alsina, Ciara Freeman, Alfred L Garfall, Beatrice M Razzo, Surbhi Sidana, Andrew J Cowan, Larry D Anderson, Doris K Hansen, Shambavi Richard, Krina K Patel, Hans C Lee, Ariel Grajales-Cruz
Journal: Blood Cancer Journal (2025)
Hormone Therapy and Increased Risk of Psoriasis in Reproductive-age and Postmenopausal Women: A Nationwide Cohort Study and Target Trial Emulation
Authors: Hui-Wen Yang, Yi-Hsien Chen, Sheng-Yin To, Yuan-Liang Wen, Senyeong Kao, Liang-Hsuan Chen, Li-Ting Kao
Journal: British Journal of Dermatology (2025)

Abstract Background Hormonal therapy (HT) is widely administered for contraception and menopausal symptom management. However, its impact on psoriasis risk remains unclear, requiring an evaluation across diverse age groups to inform clinical practice and optimize treatment strategies. Objective To investigate the association between HT and the risk of psoriasis in reproductive-age and postmenopausal women. Methods This study utilized both nationwide cohort design and target trial emulation, analyzing data from Taiwan's National Health Insurance Database (2001–2021). Women over 20 years old without a prior history of psoriasis, ovarian cancer, or breast cancer were included, segmented into reproductive-age (≤50 years) and postmenopausal (&amp;gt;50 years) groups. Women who initiated HT were assigned as the exposed group, while women without HT formed the comparison group. The primary outcome was the incidence of psoriasis over a five-year period. The study applied inverse probability of treatment weighting (IPTW) and Cox proportional hazards models to estimate hazard ratios (HRs). Both intention-to-treat (ITT) and per-protocol (PP) analyses were performed to enhance the robustness of the findings. Results In the postmenopausal cohort, comprising 1,482,302 HT users and 1,313,799 nonusers, the IPTW-adjusted HR for psoriasis in the ITT analysis was 1.48 (95% CI 1.44–1.52). The PP analysis indicated a more pronounced risk, with an HR of 5.93 (95% CI 5.66–6.22). Among the reproductive-age cohort, which included 3,849,721 HT users and 1,585,461 nonusers, the IPTW-adjusted HR in the ITT analysis was 1.93 (95% CI 1.90–1.99). In the PP analysis, the risk increased, showing an HR of 7.85 (95% CI 7.56–8.15). These findings highlight the significantly elevated psoriasis risk associated with HT, especially in younger women. Conclusion This study establishes an association between HT and an increased risk of psoriasis in both reproductive-age and postmenopausal women using a nationwide cohort design and target trial emulation. These findings further highlight the potential influence of hormonal factors on psoriasis development. Clinicians should remain attentive to early signs of psoriasis in women receiving HT to ensure timely recognition and management.
Restoring AIBP expression in the retina provides neuroprotection in glaucoma
Authors: Won-Kyu Ju, Keun-Young Kim, Tonking Bastola, Ziyao Shen, Seunghwan Choi, Guy A Perkins, Sinwoo Hwang, Jungsu Kim, Jin-Woo Kwon, Muna Poudel, Sébastien Phan, Fan Xia, Shuizhen Shi, Hyunkyung Cho, Hua Liu, Wenbo Zhang, Robert N Weinreb, Mark H Ellisman, Yury I Miller, Soo-Ho Choi
Journal: Molecular Therapy (2025)
A plague like no other Beyond the buboes in Thucydides’ account of the plague of Athens
Authors: Pere Domingo, Paula Prieto, Lluis Pons
Journal: Clinical Microbiology and Infection (2025)

The Athens Plague (430-427 BCE) was a devastating outbreak during the Peloponnesian War, described in detail by Thucydides. Although there is ongoing discussion, the specific cause of the epidemic remains undetermined. This review reexamines the Athenian plague through historical and microbiological lenses, reassessing diagnostic hypotheses and proposing the plausibility of an ancient pneumonic strain ofYersinia pestis. We analyzed Thucydides' original account alongside interdisciplinary literature from classical studies, paleopathology, epidemiology, and microbiology. We gathered sources from PubMed, JSTOR, Google Scholar, and the Perseus Digital Library, covering works from 1634 to 2024. The clinical progression described by Thucydides-fever, conjunctivitis, bloody cough, gastrointestinal symptoms, rash, and high mortality-is compared to the presentations of typhoid fever, smallpox, epidemic typhus, measles, and plague. This review considers archaeological and paleogenomic findings, including controversial evidence of Salmonella enterica and the evolutionary history of Y. pestis. Special emphasis is placed on early strains of Y. pestis that lacked flea-borne virulence factors but may have caused pneumonic forms transmitted between humans. The epidemic's significant demographic, political, and social impacts highlight the broader consequences of infectious diseases in ancient history. This review emphasizes the necessity of employing a multidisciplinary approach in historical epidemiology and advocates for reassessing pneumonic plague as a likely contributor to the outbreak that occurred in Athens.
Intracerebral delivery of the ionic liquid form of edaravone via nose-to-brain delivery route for treating cerebral ischemia/reperfusion injury
Authors: Tatsuya Fukuta, Kotone Yoshimura, Rikuto Ihara, Katsuhiko Minoura, Mayumi Ikeda-Imafuku, Kazunori Kadota
Journal: Journal of Controlled Release (2025)
Lazertinib for patients with NSCLC harboring uncommon EGFR mutations: A phase II multi-center trial
Authors: Sehhoon Park, Hee Kyung Ahn, Seoyoung Lee, Young Joo Min, Jinyong Kim, Hyun Ae Jung, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Myung-Ju Ahn, Jii Bum Lee, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho, Min Hee Hong
Journal: Journal of Thoracic Oncology (2025)

Uncommon EGFR mutations comprise 10-20% of all EGFR mutations in non-small cell lung cancer (NSCLC) and generally show reduced responsiveness to EGFR tyrosine kinase inhibitors (TKIs). Lazertinib, a third-generation EGFR-TKI, has demonstrated efficacy in common EGFR mutations, but its potential in uncommon mutations remains unexplored. This study investigated the efficacy and safety of lazertinib in NSCLC patients with uncommon EGFR mutations. This single-arm, multicenter phase II trial enrolled patients with advanced NSCLC harboring uncommon EGFR mutations excluding exon 20 insertions. Patients received lazertinib 240 mg daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Among 36 enrolled patients, the ORR was 50.0% (95% CI: 34.5-65.5%), with 18 partial responses, meeting the primary endpoint. Disease control rate was 88.9% (95% CI: 74.1-96.2%). Patients with major uncommon mutations (G719X, L861Q, S768I) showed an ORR of 54.8% (17/31). Median PFS was 10.8 months (95% CI: 4.4-19.2) and median DoR was 15.1 months. G719X mutations showed the highest response (ORR 61%, median PFS 20.3 months), followed by S768I (ORR 60%) and L861Q (ORR 58%, median PFS 9.5 months). Treatment-emergent adverse events occurred in all patients, with grade ≥3 events in 33.3%; most common were rash (47.2%), pruritus (36.1%), and muscle spasms (33.3%). Lazertinib demonstrated promising efficacy and a manageable safety profile in NSCLC patients with uncommon EGFR mutations, particularly for G719X, S768I, and L861Q subtypes. These results suggest lazertinib could be an effective treatment option for this heterogeneous patient population with limited therapeutic alternatives.
Herpes Simplex Virus and Drug Resistance - Comprehensive Update on Resistance Mutations and Implications for Clinical Management: A Narrative Review
Authors: Theo Dähne, Lena Jaki, Rainer Gosert, Jonas Fuchs, Andi Krumbholz, Klaudia Nägele, Mathias W Pletz, Nina Khanna, Karoline Leuzinger, Marcus Panning
Journal: Clinical Microbiology and Infection (2025)

Antiviral drug resistance in herpes simplex virus 1 and 2 (HSV-1 & 2) is a significant clinical challenge, particularly in immunocompromised patients. Drug susceptibility testing (DST) aids clinical management and can be conducted through genotypic (partial genome sequencing) or phenotypic (cell culture) methods. Both have inherent limitations: genotypic DST is limited by outdated datasets lacking information on new helicase-primase inhibitors and corresponding phenotypic data as well as sparse clinical correlations. Phenotypic DST is mainly hampered by a lack of standardization and timely results. To compile an up-to-date and comprehensive HSV drug resistance dataset encompassing all reported drug resistance-associated mutations (DRMs), polymorphisms, and viral phenotypes. To aggregate clinical conditions with available DST data. A PubMed search identified studies (January 2016-September 2024) on DRMs associated with resistance to aciclovir, penciclovir, brivudine, foscarnet, cidofovir, amenamevir, and pritelivir. Data from a previous HSV resistance dataset (pre-2016) were also included. In this review, we summarize novel mutations in the thymidine kinase, polymerase, and helicase-primase gene of HSV conferring resistance to antiviral drugs. Clinical information was available for 513 mutations. In 90% of these (461 cases), viral phenotype and clinical assessment were congruent. However, 10% of cases not responding to antiviral therapy showed phenotypically susceptible virus isolates. We present a framework for clinical and diagnostic management of cases with drug resistant HSV infection. This dataset paves the way to harmonize reporting of DRMs for diagnostic labs and to accelerate genotypic DST interpretation through aggregated data. Ongoing large-scale data collection of genotypic, phenotypic, and clinical data is crucial for evidence-based management of HSV antiviral resistance and clinical guidelines.
Inadequate imipenem dosing in patients with decreased kidney function: A clinical pharmacokinetic study
Authors: Anh Quan Truong, Tim J L Smeets, Jean Terrier, Letao Li, Xuan Co Dao, Jan Strojil, Tim Preijers, Birgit C P Koch, Angela Huttner, Sebastiaan D T Sassen
Journal: Clinical Microbiology and Infection (2025)

A number of population pharmacokinetic (popPK) models of imipenem in critically ill patients are available for dosing optimisation, but they represent only a narrow range of kidney functions. This study evaluates the target attainment of on-label regimens through popPK modelling and simulation in patients across different kidney functions. A popPK model was built based on two datasets from Switzerland (model development population, 151 patients, 322 concentrations) and externally validated on two datasets from the Czech Republic (19 patients, 111 concentrations) and Vietnam (43 patients, 85 concentrations). Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) from a minimum inhibitory concentration (MIC) of 0.125 to 32 mg/L. We estimated the cumulative fraction of response (CFR) against Pseudomonas aeruginosa (the epidemiological cut-off value was 4 mg/L) across a broad range of Cockcroft-Gault creatinine clearance values (CLCRCG 15-130 mL/min). Targets of 40% and 100%ƒT>MIC (percentage of dosing interval estimated free concentrations above MIC) were investigated. Decreased kidney function (eGFRCKD-EPI <90mL/min) was observed in 70/151 patients (46.4%) within the model development population, and in 11/19 (57.9%) and 24/43 (55.8%) patients in the Czech Republic and Vietnam, respectively. CLCRCG significantly influenced the imipenem clearance described by a two-compartment model. For PTA, all regimens achieved 40% ƒT>MIC2mg/L. With a 100%ƒT>MIC target, 500 mg q6h (CLCRCG 30-60 mL/min) could only cover a MIC of up to 1 mg/L, irrespective of infusion time. For CFR, no dosing regimen could cover susceptible P. aeruginosa for 100%ƒT>MIC. The highest on-label imipenem dosing regimens failed to attain 100% ƒT>MIC4mg/L in patients with decreased kidney function. Higher dosing may be necessary to cover MIC of 4mg/L. Future trials should explore their efficacy, toxicity, and the utility of model-informed precision dosing in this population.