tbuckley/cabot-search huggingface dataset:
CRISPR-mediated detection of Pneumocystis transcripts in bronchoalveolar, oropharyngeal, and serum specimens for Pneumocystis pneumonia diagnosis
Authors: Brady M. Youngquist, Ayanda Trevor Mnguni, Dora Pungan, Rachel P.J. Lai, Guixiang Dai, Chun Fai Ng, Amy Samson, Yasmean Abdelgaliel, Christopher J. Lyon, Bo Ning, Shahid Husain, Sean Wasserman, Jay K. Kolls, Tony Y. Hu
Journal: Journal of Clinical Investigation (2025)

Pneumocystis jirovecii pneumonia (PCP) is a leading cause of fungal pneumonia, but its diagnosis primarily relies on invasive bronchoalveolar lavage (BAL) specimens that are difficult to obtain. Oropharyngeal swabs and serum could improve the PCP diagnostic workflow, and we hypothesized that CRISPR could enhance assay sensitivity to allow robust P. jirovecii diagnosis using swabs and serum. Herein we describe the development of an ultrasensitive RT-PCR-coupled CRISPR assay with high active-infection specificity in infant swabs and adult BAL and serum. Mouse analyses employed an RT-PCR CRISPR assay to analyze P. murina transcripts in wild-type and Rag2-/- mouse lung RNA, BAL, and serum at 2-, 4-, and 6-weeks post-infection. Human studies used an optimized RT-PCR CRISPR assay to detect P. jirovecii transcripts in infant oropharyngeal swab samples, adult serum, and adult BAL specimens from P. jirovecii-infected and P. jirovecii-non-infected patients. The P. murina assays sensitively detected Pneumocystis RNA in the serum of infected mice throughout infection. Oropharyngeal swab CRISPR assay results identified infants infected with P. jirovecii with greater sensitivity (96.3% vs. 66.7%) and specificity (100% vs. 90.6%) than RT-qPCR compared to mtLSU standard marker, and CRISPR results achieved higher sensitivity than RT-qPCR results (93.3% vs. 26.7%) in adult serum specimens. Since swabs are routinely collected in pediatric pneumonia patients and serum is easier to obtain than BAL, this assay approach could improve the accuracy and timing of pediatric and adult Pneumocystis diagnosis by achieving specificity for active infection and potentially avoiding the requirement for BAL specimens.
Two Distinct Hyperactive Thyrothymic Remnants in a Patient With Graves’ Disease
Authors: Malik E. Juweid, Marwah Abdulrahman, Omar Albtoush, Soud F. Al-Qasem
Journal: Clinical Nuclear Medicine (2025)

A 40-year-old woman with Graves' disease underwent a technetium-99m pertechnetate thyroid scan showing two distinct foci of increased uptake, one just inferior to the right thyroid lobe and another further down in the right supraclavicular region. The foci were subsequently identified by contrast-enhanced computed tomography and interpreted as grade 4 thyrothymic remnants, both separate from the genuine thyroid. Detection of such variants by thyroid scintigraphy and anatomic imaging in such patients is important to minimize the risk of persistent/recurrent hyperthyroidism after surgery.
Pulmonary Metastases From Early-stage Granulosa Cell Tumor 15 Years Later on 18F-NOTA-FAPI-04 and 18F-FDG PET/CT
Authors: Yan Cui, Xin Zhou, Xiangping Guan, Nan Li
Journal: Clinical Nuclear Medicine (2025)

This article reports a case of rare pulmonary metastases arising from an ovarian granulosa cell tumor using 18F-NOTA-FAPI-04 PET/CT. We discussed a patient who was diagnosed with ovarian granulosa cell tumor (stage IA) after surgery 15 years ago and developed pulmonary metastases. The metastatic lesions with solid and (or) cystic components displayed variable (none to mild) fluorodeoxyglucose (FDG) avidity and significantly higher uptake of FAPI. This case highlighted the utility of 18F-NOTA-FAPI-04 PET/CT, suggesting that it may serve as a promising novel tool for the diagnosis and staging of ovarian granulosa cell tumors.
18F-FDG PET/CT Findings Mimicking Gallbladder Metastasis From a Rectal Adenocarcinoma: Rare Synchronous Gallbladder and Rectal Cancer
Authors: Ahmet Ertuğrul Öztürk, Elife Akgün, Göksel Alçin, İlkay Gültürk, Saime Gül Barut, Esra Arslan
Journal: Clinical Nuclear Medicine (2025)

Metastasis from rectal adenocarcinoma (RAC) to the gallbladder (GB) is rare. Differentiating GB metastasis from primary gallbladder cancer (GBC) is important for treatment planning. A patient diagnosed RAC with 18F-FDG PET/CT found suspicious findings of GB metastasis. However, after surgery was found to be primary GBC. The incidence of multiple primary tumors (MPTs) varies 2.4%-8%. In this case report, we would like to present 18F-FDG PET/CT findings of rare synchronous coexistence of GBC and RAC, and also that, although rare, metastasis from the RAC to the GB should definitely be kept in mind.
Feasibility and Safety of Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE for Neuroendocrine Tumor in a Patient With Sickle Cell Anemia
Authors: Ismaheel O. Lawal, Olumide B. Gbolahan, Charles Marcus, Aaron T. Jones, Walid L. Shaib, Saima Muzahir
Journal: Clinical Nuclear Medicine (2025)

A 56-year-old woman with sickle cell anemia (SCA) and metastatic neuroendocrine tumor refractory to somatostatin analog received 4 cycles of peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE. The treatment schedule was delayed by multiple episodes of hospitalizations related to underlying SCA. PRRT was well-tolerated with stable renal, hematologic, and liver lab parameters. After PRRT, the disease remained stable for up to 13 months, and serum chromogranin levels declined by 45%. PRRT with 177Lu-DOTATATE can be safely administered for metastatic neuroendocrine tumors in patients with SCA with good anti-tumor effect. Disruption to the therapy schedule should be anticipated, given the potential for recurrent hospitalization for illnesses related to the underlying SCA.
Oromandibular Dyskinesia: Diagnostic Insights From 18F-FDG PET/CT Imaging
Authors: Anjali Jain, Sharjeel Usmani, Khulood Al Riyami, Asiya Al Busaidi, Sofiullah Abubakar, Subhash Kheruka, Rashid Al Sukaiti
Journal: Clinical Nuclear Medicine (2025)

Oromandibular dyskinesia is an abnormal, repetitive, involuntary movement of the jaw, tongue, and lips. We report an interesting image of a 72-year-old woman, who underwent 18F- FDG PET/CT for restaging of treated colon cancer. PET/CT scan shows diffuse uptake in orbicularis oris, muscles of the lips, muscles around the mandible and in the oral cavity, and anterior tongue muscles with no abnormality seen on corresponding CT images. A thorough search into patient history revealed the diagnosis of oromandibular dyskinesia.
Reply to Letter to the Editor: ‘A phase III randomised trial on the addition of a contact x-ray brachytherapy boost to standard neoadjuvant chemo-radiotherapy for organ preservation in early rectal adenocarcinoma: 5 years results of the OPERA trial’ by J. Meyer, T. Koessler
Authors: D Baron, S Ben Dhia, J-P Gerard, J Doyen
Journal: Annals of Oncology (2025)
Neural Circuits Underlying Sexually Dimorphic Innate Behaviors
Authors: Meital Oren-Suissa, Troy R. Shirangi
Journal: Annual Review of Neuroscience (2025)

Sexually dimorphic instinctual behaviors that set females and males apart are found across animal clades. Recent studies in a variety of animal systems have provided deep insights into the neural circuits that guide sexually dimorphic behaviors, such as mating practices and social responses, and how sex differences in these circuits develop. Here, we discuss the neural circuits of several sexually dimorphic instinctual behaviors in rodents, flies, and worms-from mate attraction and aggression to pain perception and empathy. We highlight several salient similarities and differences between these circuits and reveal general principles that underlie the function and development of neural circuits for dimorphic behaviors.
HER2-Selective Tyrosine Kinase Inhibitor, Zongertinib (BI 1810631), in Patients With Advanced/Metastatic Solid Tumors With <i>HER2</i> Alterations: A Phase Ia Dose-Escalation Study
Authors: John V. Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, David Berz, Lukas Schröter, Yanick Botilde, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2025)

Human epidermal growth factor receptor 2 (HER2) alterations occur in many solid cancers, including non-small cell lung cancer (NSCLC). Beamion LUNG-1 (ClinicalTrials.gov identifier: NCT04886804) is assessing the safety/efficacy of zongertinib (BI 1810631), a novel HER2-selective tyrosine kinase inhibitor that spares epidermal growth factor receptor, in patients with HER2-altered solid tumors. Beamion LUNG-1 is an ongoing multicenter, multicohort phase Ia/Ib trial. Phase Ia assessed zongertinib administered twice a day (15-150 mg) or once daily (60-360 mg) in pretreated patients with various tumors, including NSCLC. Primary end points were maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs); tumor response was a secondary end point. As of May 23, 2024, 105 patients were treated. Two DLTs occurred during the MTD evaluation period; MTD was not reached (NR). The recommended doses for expansion were 120 mg once daily and 240 mg once daily. Treatment-related adverse events (TRAEs; any/grade ≥3) occurred in 82%/10% of patients. The most common TRAEs (any/grade ≥3) included diarrhea (50%/1%), rash (16%/2%), anemia (10%/0%), decreased appetite (10%/1%), and increased alanine transaminase (10%/4%). The confirmed investigator-assessed overall response rate (ORR) across all doses/tumors was 30% (95% CI, 23 to 40); median duration of response was 12.7 months (95% CI, 6.9 to NR). In 54 patients with NSCLC, confirmed ORR was 35% (95% CI, 24 to 49). Activity was observed in patients with A775_G776insYVMA (ORR, 38%) and those who had received previous HER2-directed therapy (ORR, 28%). In patients with NSCLC receiving zongertinib once daily, median progression-free survival was 17.2 months (95% CI, 8.3 to NR). Zongertinib had a manageable safety profile and demonstrated preliminary antitumor activity in patients with HER2-altered tumors, including those with HER2-mutant NSCLC.
Leveraging Preclinical Modeling for Clinical Advancements in Single Ventricle Physiology: Spotlight on the Fontan Circulation
Authors: Andreas Escher, Carlos Aguilar Vega, Markus A. Horvath, Caglar Ozturk, Ellen T. Roche
Journal: Annual Review of Biomedical Engineering (2025)

Preclinical modeling of human circulation has been instrumental in advancing cardiovascular medicine. Alongside clinical research, the armamentarium of computational (e.g., lumped parameter or computational fluid dynamics) and experimental (e.g., benchtop or animal) models have substantially enhanced our understanding of risk factors and root causes for circulatory diseases. Recent innovations are further disrupting the boundaries of these preclinical models toward patient-specific simulations, surgical planning, and postoperative outcome prediction. This fast-paced progress empowers preclinical modeling to increasingly delve into the intricacies of single ventricle physiology, a rare and heterogeneous congenital heart disease that remains inadequately understood. Here, we review the current landscape of preclinical modeling (computational and experimental) proposed to advance clinical management of a prominent yet complex subset of single ventricle physiology: patients who have undergone Fontan-type surgical corrections. Further, we explore recent innovations and emerging technologies that are poised to bridge the gap between preclinical Fontan modeling and clinical implementation.
Biocompatibility and Therapeutic Efficacy of Crosslinked Hydrogel Filled 3D-Printed Nerve Conduit for Sacral Nerve Injury Repair
Authors: Jiajia Lu, Yongchuan Li, Jiao Cai, Xingwei Jin, Guangxin Chu, Hai Jin, Lei Zhu, Aimin Chen
Journal: Biomaterials (2025)
Prior SARS-Cov-2 infection affects adaptive immune responses to Omicron BA.4/BA.5 mRNA booster.
Authors: Brianna T Wachter, Qin Xu, Lihong Shi, Peter D Burbelo, Kathy Myint-Hpu, Pamela L Schwartzberg, Muhammad Tauseef Rehman, Robin L Dewar, Kristin L Boswell, Richard A Koup, Cihan Oguz, Luisa Imberti, Lorenza Bellusci, Sara Pourhashemi, Surender Khurana, Kalpana Manthiram, Luigi D Notarangelo, Ottavia M Delmonte
Journal: Journal of Allergy and Clinical Immunology (2025)
Identification of Candidate Alterations Mediating <i>KRAS</i>G12C Inhibitor Resistance in Advanced Colorectal and Pancreatic Cancers
Authors: Khalid Jazieh, Jill Tsai, Sheila Solomon, Mojun Zhu, Frank A. Sinicrope, Katrina S. Pedersen, Martin E. Fernandez-Zapico, Hao Xie
Journal: Clinical Cancer Research (2025)

Abstract Purpose: KRAS G12C inhibitors can treat KRASG12C-mutant advanced colorectal cancers and pancreatic ductal adenocarcinomas (PDAC), but alterations in Kirsten rat sarcoma (KRAS), EGFR, BRAF, MAP2K1, and other genes bypass KRAS inhibition and reduce therapy efficacy. Our study evaluates the genetic landscape of candidate primary resistance alterations relevant to KRAS targeting in KRASG12C-mutant colorectal cancer and PDAC. Experimental Design: We analyzed two cohorts (national database and Mayo) of patients with advanced colorectal cancer or PDAC tested with next-generation sequencing of ctDNA via Guardant360. Cohorts were divided into three groups: KRASG12C alone (KRASG12C without a resistance gene), KRASG12C with resistance (KRASG12C and ≥1 candidate resistance gene), and KRAS not detected. Candidate resistance mutations were inferred from the reported literature. Results: Among the national (13,603 colorectal cancer and 5,016 PDAC cases) and Mayo (741 colorectal cancer and 422 PDAC cases) cohorts, resistance alterations were identified in a considerable number of KRASG12C cases (46.5% of national colorectal cancer, 16.4% of national PDAC, 53.8% of Mayo colorectal cancer, and 36.4% of Mayo PDAC). The presence of resistance alterations was associated with a trend toward worse overall survival in KRASG12C colorectal cancer (P = 0.05). Conclusions: Putative resistance alterations are prevalent in PDAC and colorectal cancer and may limit monotherapy efficacy. Identifying these alterations has potential implications in optimal patient selection for targeted therapies and the development of combination therapy strategies to overcome primary resistance.
Unlocking the Role of Senescent Cell–Derived Extracellular Vesicles in Immune-Mediated Tumor Suppression
Authors: Sofia Almeida, Sonia A. Melo
Journal: Cancer Research (2025)

Senescence, a state of stable cell-cycle arrest, plays a dual role in cancer by suppressing tumor growth while potentially promoting relapse through its secretome, including senescence-associated secretory phenotype factors and senescent cell–derived extracellular vesicles (senEV). In this issue of Cancer Research, Ziglari and colleagues elucidate the role of senEVs in immune-mediated tumor suppression using an in vivo model that preserves immune integrity. Their findings demonstrate that senEVs are distinct from extracellular vesicles of proliferating cells, enriched with molecules that recruit and activate antigen-presenting cells and orchestrate TH17-driven antitumor immunity. Notably, the absence of senEVs accelerated tumor relapse, highlighting their necessity in senescence surveillance. Despite these advancements, further work is required to identify the specific senEV cargo driving antigen-presenting cell activation and to define the long-term dynamics of tumor relapse. This study underscores the potential of senEVs as biomarkers and therapeutic targets to enhance immune clearance of senescent cells and prevent cancer recurrence. The findings in this study pave the way for innovative strategies to modulate senescence and its secretome in cancer therapy. See related article by Ziglari et al., p. 859
Editor’s Note: <i>PTEN</i> Loss Contributes to Erlotinib Resistance in EGFR-Mutant Lung Cancer by Activation of Akt and EGFR
Authors: Martin L. Sos, Mirjam Koker, Barbara A. Weir, Stefanie Heynck, Rosalia Rabinovsky, Thomas Zander, Jens M. Seeger, Jonathan Weiss, Florian Fischer, Peter Frommolt, Kathrin Michel, Martin Peifer, Craig Mermel, Luc Girard, Michael Peyton, Adi F. Gazdar, John D. Minna, Levi A. Garraway, Hamid Kashkar, William Pao, Matthew Meyerson, Roman K. Thomas
Journal: Cancer Research (2025)
Correction: Targeting Translation Initiation Bypasses Signaling Crosstalk Mechanisms That Maintain High MYC Levels in Colorectal Cancer
Authors: Armin Wiegering, Friedrich W. Uthe, Thomas Jamieson, Yvonne Ruoss, Melanie Hüttenrauch, Maritta Küspert, Christina Pfann, Colin Nixon, Steffi Herold, Susanne Walz, Lyudmyla Taranets, Christoph-Thomas Germer, Andreas Rosenwald, Owen J. Sansom, Martin Eilers
Journal: Cancer Discovery (2025)
Correction: Clinical Efficacy of ONC201 in H3K27M-Mutant Diffuse Midline Gliomas Is Driven by Disruption of Integrated Metabolic and Epigenetic Pathways
Authors: Sriram Venneti, Abed Rahman Kawakibi, Sunjong Ji, Sebastian M. Waszak, Stefan R. Sweha, Mateus Mota, Matthew Pun, Akash Deogharkar, Chan Chung, Rohinton S. Tarapore, Samuel Ramage, Andrew Chi, Patrick Y. Wen, Isabel Arrillaga-Romany, Tracy T. Batchelor, Nicholas A. Butowski, Ashley Sumrall, Nicole Shonka, Rebecca A. Harrison, John de Groot, Minesh Mehta, Matthew D. Hall, Doured Daghistani, Timothy F. Cloughesy, Benjamin M. Ellingson, Kevin Beccaria, Pascale Varlet, Michelle M. Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Rajan Jain, Maureen Kachman, Heidi Baum, Charles F. Burant, Sophie L. Mottl, Rodrigo T. Cartaxo, Vishal John, Dana Messinger, Tingting Qin, Erik Peterson, Peter Sajjakulnukit, Karthik Ravi, Alyssa Waugh, Dustin Walling, Yujie Ding, Ziyun Xia, Anna Schwendeman, Debra Hawes, Fusheng Yang, Alexander R. Judkins, Daniel Wahl, Costas A. Lyssiotis, Daniel de la Nava, Marta M. Alonso, Augustine Eze, Jasper Spitzer, Susanne V. Schmidt, Ryan J. Duchatel, Matthew D. Dun, Jason E. Cain, Li Jiang, Sylwia A. Stopka, Gerard Baquer, Michael S. Regan, Mariella G. Filbin, Nathalie Y.R. Agar, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Viveka N. Yadav, Jacques Grill, Cassie Kline, Sabine Mueller, Adam Resnick, Javad Nazarian, Joshua E. Allen, Yazmin Odia, Sharon L. Gardner, Carl Koschmann
Journal: Cancer Discovery (2025)
The Study of the Parameters of Diffusion Tensor MRI of Brachial Plexuses and Parameters Correlations with Demographic and Anthropometric Data
Authors: V. V. Sin’kova, S. N. Morozova, D. A. Grishina, T. А. Tumilovich, N. А. Suponeva
Journal: Radiology - Practice (2025)

It is crucial to know the numerical values of diffusion tensor magnetic resonance imaging (DTMRI) parameters in healthy subjects, as well as their correlation with demographic, biometric data and the key parameters of standard MRI, for the purpose of diagnosing pathological changes in brachial plexuses, especially when dealing with non-specific or unclear alterations according to standard magnetic resonance imaging finding. Aim . Assessing the potential of using diffusion tensor magnetic resonance imaging (DTMRI) to study brachial plexuses, developing an algorithm for data processing and evaluating the distribution of parameter values in normal conditions, as well as exploring whether they correlate with socio-demographic and anthropometric indicators. Materials and Methods . The study included 50 healthy volunteers without signs of damage to the peripheral nervous system. The diffusion tensor MRI parameters were recorded at a distance of 1–2 cm from the spinal ganglion on both sides using the Siemens workstation with manual setting of the area of interest. Parameters such as fractional anisotropy, mean diffusivity, axial and radial diffusion coefficients were recorded. In addition, the intensity coefficient was measured at the same point using a standard three-dimensional sequence STIR images. Results . The average values for each assessed parameter were obtained. A statistically significant difference in FA was found between the sides, with the right side being significantly higher than the left. Additionally, a negative correlation was observed between AD and the age of the subjects on both sides. When the subjects were categorized by gender, men exhibited significantly larger nerve diameter, subclavian artery diameter, height, and weight. Conclusion . The presence of a significant negative correlation between AD on both sides and age may indicate a gradual thinning of nerve fibers as one ages. The differences in measured parameters among subjects of different genders and their dependence on biometric indicators are consistent and should be taken into account when interpreting studies in patients with various pathological conditions. Furthermore, the substantial difference in the functional asymmetry between sides prevents the interpretation of the obtained data using a mixed model and necessitates the examination of numerical parameters for each side separately.
The Possibilities of Diagnostics Radiology Methods in the Complicated Course of the Intestine Tumor. Clinical Observation
Authors: T. G. Morozova, T. D. Gelt, A. V. Kovaljov
Journal: Radiology - Practice (2025)

Objective . Demonstration of the possibilities of diagnostics radiology methods in a hospital in the diagnosis of intestinal tumor with invading the bladder and uterus. Materials and Methods . A patient with pelvic mass underwent magnetic resonance imaging (MRI) and computed tomography (CT) with contrast enhancement to differentiate diagnosis. Results . Tumor of the distal ileum with invading the bladder and parauterine fat was revealed according to CT and MRI of the pelvis. Signs of liver metastases were noted according to CT of abdomen cavity with intravenous contrast enhancement Conclusion . The clinical observation presented the c possibilities of MRI and CT with contrast enhancement, performed according to the standard protocol, to diagnose the intestine tumors. The advantages of CT are shown, which made it possible to evaluate several areas (abdominal and pelvic cavities) in a single study in a minimum time and demonstrated better tolerability of the procedure compared to MRI.