tbuckley/cabot-search huggingface dataset:
NIR‐Propelled Thermosensitive Bowl‐Shaped Nanomotors with High Penetration and Targeting for Photoacoustic Imaging Guided Thrombolysis Therapy
Authors: Yina Su, Linjie Huang, Guizhen Xu, Simin Chen, Jiaqiong Wu, Siyu Wang, Yichao Zhang, Xiahui Lin
Journal: Advanced Healthcare Materials (2025)

Traditional antithrombotic therapeutic strategies encounter challenges including heightened bleeding risks, short circulation times, low targeting ability, and inferior thrombus penetration. Therefore, a novel thrombolysis nanodrug (APBUL) is designed that incorporates urokinase (UK) loaded onto the surface of bowl-shaped nanomotors (APBs) encapsulated within fibrin peptide (CREKA)-modified thermosensitive liposomes, presenting an innovative therapeutic platform for thrombolysis. APBUL leverages CREKA's targeting ability for thrombus accumulation. Subsequently, under the irradiation of near-infrared light, the thermosensitive liposomal shell undergoes controlled disruption, releasing internal APBs and UK. Then, the APBs move directionally though thermophoresis effect, facilitating photothermal therapy and deep thrombus penetration, and synergistically enhancing UK release and diffusion to optimize thrombolysis. Moreover, the APBUL possesses a catalase-like activity, catalyzing hydrogen peroxide into oxygen to alleviate oxidative stress and inflammatory factors at the thrombus site, thereby lowering the recurrence risk. Combined with the ability of APBUL's photoacoustic imaging, this new strategy is expected to provide an inspiring idea for the integrated use of clinical thrombolytic therapy in diagnosis, imaging, and treatment.
Metronidazole response profiles of Gardnerella species are congruent with phylogenetic and comparative genomic analyses
Authors: Katherine A. Innamorati, Joshua P. Earl, Shirley C. Barrera, Rachel L. Ehrlich, Josephine Aiyeku, Ari Gordon, Evan Powell, Adam C. Retchless, Azad Ahmed, Bhaswati Sen, Sergey Balashov, Joshua Chang Mell, Sharon L. Hillier, Garth D. Ehrlich
Journal: Genome Medicine (2025)

Bacterial vaginosis (BV) affects 20–50% of reproductive-age female patients annually, arising when opportunistic pathogens outcompete healthy vaginal flora. Many patients fail to resolve symptoms with a course of metronidazole, the current first-line treatment for BV. Our study was designed to identify genomic variation associated with metronidazole resistance among strains of Gardnerella vaginalis spp. (GV), a genus of biogenic-amine-producing bacteria closely associated with BV pathogenesis, for the development of a companion molecular diagnostic. Whole-genome sequencing and comparative genomic metrics, including average nucleotide identity and GC content, were performed on a diverse set of 129 GV genomes to generate data for detailed taxonomic analyses. Pangenomic analyses were employed to construct a phylogenetic tree and cluster highly related strains within genospecies. G. vaginalis spp. clinical isolates within our collection were subjected to plate-based minimum inhibitory concentration (MIC) testing of metronidazole (n = 60) and clindamycin (n = 63). DECIPHER and MAFFT were used to identify genospecies-specific primers associated with antibiotic-resistance phenotypes. PCR-based analyses with these primers were used to confirm their specificity for the relevant genospecies. Eleven distinct genospecies based on standard ANI criteria were identified among the GV strains in our collection. Metronidazole MIC testing revealed six genospecies within a closely related phylogenetic clade contained only highly metronidazole-resistant strains (MIC ≥ 32 µg/mL) and suggested at least two mechanisms of metronidazole resistance within the eleven GV genospecies. All strains within the six highly metronidazole-resistant genospecies displayed susceptibility to clinically relevant clindamycin concentrations (MIC ≤ 2 µg/mL). A PCR-based molecular diagnostic assay was developed to distinguish between members of the metronidazole-resistant and mixed-response genospecies, which should be useful for determining the clade membership of various GV strains and could assist in the selection of appropriate antibiotic therapies for BV cases. This study provides comparative genomic and phylogenetic evidence for eleven distinct genospecies within the genus Gardnerella vaginalis spp., and identifies genospecies-specific responses to metronidazole, the first-line treatment for BV. A companion molecular diagnostic assay was developed that is capable of identifying essentially all highly metronidazole-resistant strains that phylogenetically cluster together within the GV genospecies, which is informative for antibiotic treatment options.
Questions and Answers about Measles
Authors: Susan Pasnick, Jonathan M Keller, Charles S. Dela Cruz, Jane E. Gross, W. Graham Carlos III, Ryan Maves, Shazia Jamil, Bridget Collins, Krishna Sundar
Journal: American Journal of Respiratory and Critical Care Medicine (2025)

"Questions and Answers about Measles." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Long-term exposure to traffic-related air pollution and noise and dynamic brain connectivity across adolescence
Authors: Mónica López-Vicente, Michelle Kusters, Anne-Claire Binter, Sami Petricola, Henning Tiemeier, Ryan Muetzel, Mònica Guxens
Journal: Environmental Health Perspectives (2025)

Traffic-related exposures, such as air pollution and noise, show long-term associations with brain alterations in children and adolescents. The associations with functional connectivity have been studied using static approaches of resting-state functional magnetic resonance imaging (rs-fMRI) (i.e., average connectivity between regions across the scanning session).
mTOR inhibition modulates vaccine-induced immune responses to generate memory T cells in patients with solid tumors
Authors: Henry G Withers, Junko Matsuzaki, Mark Long, Spencer R Rosario, Thinle Chodon, Takemasa Tsuji, Richard Koya, Li Yan, Jianming Wang, Tibor Keler, Shashikant B Lele, Emese Zsiros, Amit Lugade, Alan Hutson, Stephanie Blank, Nina Bhardwaj, Protul Shrikant, Song Liu, Kunle Odunsi
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Perturbation of the mechanistic target of rapamycin (mTOR) pathway can instruct effector versus memory cell fate of tumor antigen-specific T cells in preclinical models. In this study, we sought to understand the impact of rapamycin (sirolimus), an mTOR inhibitor, on reprogramming vaccine-induced T cells to enhance memory responses in patients with solid tumors following completion of their standard therapy. Methods We conducted three phase I clinical trials employing New York esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccination approaches, with or without schedule-varied rapamycin. T cell phenotypes, functions, and Vβ usage in peripheral blood were analyzed to ask whether rapamycin influenced the generation of vaccine-induced T cells with memory attributes. Results The addition of rapamycin to all vaccination approaches was safe and well tolerated. Immediate (days 1–14 postvaccination) or delayed (days 15–28 postvaccination) administration of rapamycin led to a significant increase in the generation of vaccine-induced NY-ESO-1-specific T cells exhibiting central memory phenotypes (CD45RO + CD45RA − CCR7 + ). Moreover, delayed administration resulted in a greater than threefold (p=0.025) and eightfold (p=0.005) increase in the frequency of NY-ESO-1-specific CD4 + T and CD8 + T cells respectively at the time of long-term follow-up, compared with its immediate usage. Conclusion Our novel finding is that delayed administration of rapamycin to patients during the contraction phase of vaccine-induced antitumor immune responses was particularly effective in increasing the frequency of memory T cells up to 1 year postvaccination in patients with solid tumors. Further studies are warranted to identify the impact of this approach on the durability of clinical remission. Trial registration number NCT00803569 , NCT01536054 , NCT01522820 .
Patient Complexity and Bile Duct Injury After Robotic-Assisted vs Laparoscopic Cholecystectomy
Authors: Cody Lendon Mullens, Sarah Sheskey, Jyothi R. Thumma, Justin B. Dimick, Edward C. Norton, Kyle H. Sheetz
Journal: JAMA Network Open (2025)

Importance Recent evidence suggests higher bile duct injury rates for patients undergoing robotic-assisted cholecystectomy compared with laparoscopic cholecystectomy. Proponents of the robotic-assisted approach contend that this may be due to selection of higher-risk and more complex patients being offered robotic-assisted cholecystectomy. Objective To evaluate the comparative safety of robotic-assisted cholecystectomy and laparoscopic cholecystectomy among patients with varying levels of risk for adverse postoperative outcomes. Design, Setting, and Participants This retrospective cohort study assessed fee-for-service Medicare beneficiaries aged 66 to 99 years who underwent cholecystectomy between January 1, 2010, and December 31, 2021. Data analysis was performed between June and August 2024. Medicare beneficiaries were separated into model training and experimental cohorts (60% and 40%, respectively). Random forest modeling and least absolute shrinkage and selection operator techniques were then used in a risk model training cohort to stratify beneficiaries based on their risk of a composite outcome of postoperative adverse events consisting of 90-day postoperative complications, serious complications, reoperations, and rehospitalization in an independent experimental cohort. Exposures Robotic-assisted vs laparoscopic cholecystectomy. Main Outcomes and Measures The primary outcome of interest was bile duct injury requiring operative intervention after cholecystectomy. Secondary outcomes were composite outcomes from cholecystectomy composed of any complications, serious complications, reoperations, and readmissions. Results A total of 737 908 individuals (mean [SD] age, 74.7 [9.9] years; 387 563 [52.5%] female) were included, with 295 807 in an experimental cohort and 442 101 in a training cohort. Bile duct injury was higher among patients undergoing robotic-assisted compared with laparoscopic cholecystectomy in each subgroup (low-risk group: relative risk [RR], 3.14; 95% CI, 2.35-3.94; medium-risk group: RR, 3.13; 95% CI, 2.35-3.92; and high-risk group: RR, 3.11; 95% CI, 2.34-3.88). Overall, composite outcomes between the 2 groups were similar for robotic-assisted cholecystectomy compared with laparoscopic cholecystectomy (RR, 1.09; 95% CI, 1.07-1.12), aside from reoperation, which was overall higher in the robotic-assisted group compared with the laparoscopic group (RR, 1.47; 95% CI, 1.35-1.59). Conclusions and Relevance In this cohort study of Medicare beneficiaries, bile duct injury rates were higher among low-, medium-, and high-risk surgical candidates after robotic-assisted cholecystectomy. These findings suggest that patient selection may not be the cause of differences in bile duct injury rates among patients undergoing robotic-assisted vs laparoscopic cholecystectomy.
LGBTQ+ Inclusive Policies, Nurse Job Outcomes, and Quality of Care in Hospitals
Authors: Hyunmin Yu, Matthew D. McHugh, José A. Bauermeister, Tari Hanneman, Karen B. Lasater
Journal: JAMA Network Open (2025)

Importance Despite emphasis on the establishment of inclusive hospital policies, the impact of these policies on employees and organizations remains unknown. Objective To evaluate the association between inclusive policies for lesbian, gay, bisexual, transgender, queer or questioning, and other sexual and gender minority (LGBTQ+) and nurse job outcomes as well as nurse-reported quality of care. Design, Setting, and Participants This cross-sectional study analyzed 4 survey datasets from 2021: the RN4CAST-NY/IL, including registered nurses from New York and Illinois, and the Healthcare Equality Index (HEI) data. The HEI evaluates and scores US health care facilities that voluntarily participate based on their LGBTQ+ inclusivity in policies, such as nondiscrimination policies and LGBTQ+ inclusive clinical services. The study used American Hospital Association Annual Survey data for hospital characteristics and Magnet organization data to classify hospitals by Magnet status. Data analyses were performed in December 2024. Main Outcomes and Measures Nurse job outcomes included burnout and job dissatisfaction. Quality of care outcomes included nurses’ perceptions of care quality and their likelihood of recommending their hospital. The independent variable was LGBTQ+ Healthcare Equality Leader (HEI Leader) status, which signified hospitals with the highest levels of LGBTQ+ inclusion. Multilevel logistic regression models included nurse-level (age, race and ethnicity, gender, and years of experience at the current hospital) and hospital-level (Magnet status, size, teaching status, specialized service capability, and ownership) covariates. Results A total of 7343 nurses (mean [SD] age, 44.9 [13.4] years; 6584 [89.6%] women) from 111 hospitals were included in the study. Nurses in hospitals with HEI Leader status had lower odds of high burnout (adjusted odds ratio [AOR], 0.69; 95% CI, 0.52-0.92) and lower odds of job dissatisfaction (AOR, 0.62; 95% CI, 0.45-0.86) compared with those in hospitals without the status. They also had higher odds of reporting excellent or good quality of care (AOR, 1.83; 95% CI, 1.23-2.73) and higher odds of recommending their hospital (AOR, 1.72; 95% CI, 1.19-2.50). Conclusions and Relevance In this cross-sectional study, nurses in hospitals with high LGBTQ+ inclusion reported more favorable job outcomes and care quality. Hospitals should understand that implementing LGBTQ+ inclusive policies goes beyond compliance or diversity; it is essential for improving the work climate, enhancing staff well-being, and optimizing care delivery.
Diagnostic Utility of Trio–Exome Sequencing for Children With Neurodevelopmental Disorders
Authors: Xiaoping Lan, Xiaojun Tang, Wenhao Weng, Wuhen Xu, Xiaozhen Song, Yongchen Yang, Hong Sun, Haiyun Ye, Hong Zhang, Guangjun Yu, Shengnan Wu
Journal: JAMA Network Open (2025)

Importance Copy number variants (CNVs) and single-nucleotide variations (SNVs) or insertions and deletions are key genetic contributors to neurodevelopmental disorders (NDDs). Traditionally, chromosome microarray and exome sequencing (ES) have been used to detect CNVs and single gene variants, respectively. Objective To identify genetic variants causing NDDs and evaluate the diagnostic yield and clinical utility of ES by simultaneously analyzing CNVs and SNVs in patients with NDDs and their biologic parents (trios). Design, Setting, and Participants This retrospective cohort study included pediatric patients with suspected NDDs who visited Shanghai Children’s Hospital between January 1, 2018, and December 31, 2023. ES was used to investigate trios (trio-ES) including patients with NDDs who remained undiagnosed after phenotype identification and underwent gene panel testing, multiplex ligation-dependent probe amplification, or karyotyping. Comprehensive clinical and laboratory data were collected. Data were analyzed from July 2022 to December 2023. Exposure NDDs, characterized by global developmental delay or intellectual disability. Main Outcomes and Measures The study measured the overall diagnostic yield of SNVs and CNVs in the NDD cohort as well as within NDD syndromic subtypes. Results Of the 1106 patients with NDDs, 731 (66.1%) were male. The mean (SD) age of patients at diagnosis was 3.80 (2.82) years. The overall diagnostic yield of trio-ES was 46.1% (510 diagnoses among 1106 patients), with 149 CNVs (13.5%), 355 SNVs (32.1%), and 4 cases of uniparental disomy (0.4%). Codiagnosis of SNVs and CNVs occurred in 2 cases (0.2%). Among the trios, 812 candidate germline variants were identified, including 634 SNVs (78.1%), 174 CNVs (21.4%), and 4 cases of uniparental disomy (0.5%). Of these, 423 SNVs (66.7%) and 157 CNVs (90.2%) were diagnostic variants, while 211 SNVs (33.3%) and 17 CNVs (9.8%) were variants of uncertain significance. Sixteen CNVs smaller than 20 kilobase were detected using ES. Conclusions and Relevance In this cohort study, trio-ES, by simultaneously detecting SNVs and CNVs, achieved a diagnostic yield of 46.1%. Trio-ES may be particularly applicable for identifying small CNVs and recessive genetic diseases involving both SNVs and CNVs. These findings suggest that in clinical practice, simultaneously analyzing SNVs and CNVs using trio-ES data has a favorable genetic diagnostic yield for children with NDDs.
Successful biliary decompression for multiple biliary obstructions by bridging stenting using the partial stent-in-stent method via endoscopic ultrasound-guided hepaticogastrostomy
Authors: Masaki Miyazawa, Masaki Nishitani, Noriaki Orita, Tomoyuki Hayashi, Shinya Yamada, Hajime Takatori, Taro Yamashita
Journal: Endoscopy (2025)

Recently, the usefulness of endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for malignant hilar biliary obstruction (MHBO) has been reported, offering a feasible alternative approach in cases where transpapillary stenting is impossible [1] [2] [3] [4]. Herein, we present a case in which bridging stenting using the partial stent-in-stent method via the EUS-HGS route was performed to treat multiple right intrahepatic bile duct (IHBD) obstructions ([Video 1]).
Diagnosis of massive obscure gastrointestinal bleeding from a Dieulafoy lesion identified by intraoperative enteroscopy
Authors: Jiaqi Gao, Tianyu He, Liping Duan, Rongli Cui, Zhijie Xu
Journal: Endoscopy (2025)

A 32-year-old woman was admitted to the emergency department with syncope, shock, and persistent hematochezia. Her hemoglobin had drastically declined from 14.1 g/dL to 5.5 g/dL within 4 hours. Prompt, although challenging, central venous catheterization coupled with rapid intravenous fluid resuscitation elevated her systolic blood pressure from 60 mmHg to approximately 90 mmHg. Computed tomographic angiography (CTA) revealed a dense shadow in the bowel lumen in the left upper abdomen ([Fig. 1]). Consequently, a multidisciplinary team collaborated to perform an open laparotomy, complemented by intraoperative endoscopy.
Transpapillary stenting by the rendezvous technique using a novel device delivery guide sheath via percutaneous transhepatic biliary drainage route for hilar biliary obstruction
Authors: Masaki Miyazawa, Kazuki Nagai, Masaki Nishitani, Tomoyuki Hayashi, Shinya Yamada, Hajime Takatori, Taro Yamashita
Journal: Endoscopy (2025)

The rendezvous technique via percutaneous transhepatic biliary drainage (PTBD) or endoscopic ultrasonography-guided biliary drainage is a useful salvage procedure when transpapillary stenting is unsuccessful [1] [2]. The success of this procedure requires that the guidewire on the fistula side break through the bile duct stricture, which can sometimes be difficult. Herein, we report successful transpapillary stenting by the rendezvous technique using a novel device delivery guide sheath via the PTBD route to treat hilar biliary obstruction (HBO).
M1 receptor positive allosteric modulators discovery approaches
Authors: Takao Mandai, Arthur A Simen, Antonio Laurenza, Haruhide Kimura
Journal: Trends in Pharmacological Sciences (2025)

The development of M1 muscarinic acetylcholine-receptor-positive allosteric modulators has been hindered by their limited cognitive efficacy and cholinergic side effects. We discuss two unique approaches - low intrinsic agonism and low binding cooperativity - that were developed to address these issues and their therapeutic implications.
Endoscopic ultrasound-guided mucosal dissection to remove an entirely embedded esophageal fishbone
Authors: Hongna Lu, Xiaolin Chen, Xiaofeng Feng, Feng Xu
Journal: Endoscopy (2025)

A 56-year-old woman presented with swallowing pain after eating fish. She underwent laryngoscopy at a local hospital, which did not reveal the fishbone. Consequently, she was referred to our hospital for further investigation.
Ambulatory atrial fibrillation detection and quantification by wristworn AI device compared to standard holter monitoring
Authors: Mariska van Vliet, Jan J. J. Aalberts, Cora Hamelinck, Arnaud D. Hauer, Dieke Hoftijzer, Stefan H. J. Monnink, Jurjan C. Schipper, Jan C. Constandse, Nicholas S. Peters, Gregory Y. H. Lip, Steven R. Steinhubl, Eelko Ronner
Journal: npj Digital Medicine (2025)

Timely detection of atrial fibrillation (AF) is crucial for the prevention of serious consequences such as stroke and heart failure, yet it remains challenging due to its often asymptomatic or paroxysmal nature. Wearable devices with artificial intelligence algorithms offer promising solutions. AF detection by the CardioWatch 287-2 (CW2), a wrist-worn photoplethysmography (PPG) and single-lead ECG device, was compared to 24-h Holter. Patient compliance, AF prevalence and AF burden were evaluated for 27 additional days. Data from 150 participants (mean age 64 ± 12 SD; 41% female) were analysed. The CW2's PPG and single-lead ECG algorithms achieved a specificity ≥98% and sensitivity ≥95% for AF detection, and 99% correlation for AF burden, compared to 24-h Holter. AF prevalence increased from 14.7% (24-h Holter) to 26.7% (28-day CW2). Thus, the wrist-worn device showed promising performance in detecting AF and determining AF burden. The trial was registered on ClinicalTrials.gov (NCT05899959) on June 2, 2023.
Accuracy of online symptom assessment applications, large language models, and laypeople for self–triage decisions
Authors: Marvin Kopka, Niklas von Kalckreuth, Markus A. Feufel
Journal: npj Digital Medicine (2025)

Abstract Symptom-Assessment Application (SAAs, e.g., NHS 111 online) that assist laypeople in deciding if and where to seek care ( self-triage ) are gaining popularity and Large Language Models (LLMs) are increasingly used too. However, there is no evidence synthesis on the accuracy of LLMs, and no review has contextualized the accuracy of SAAs and LLMs. This systematic review evaluates the self-triage accuracy of both SAAs and LLMs and compares them to the accuracy of laypeople. A total of 1549 studies were screened and 19 included. The self-triage accuracy of SAAs was moderate but highly variable (11.5–90.0%), while the accuracy of LLMs (57.8–76.0%) and laypeople (47.3–62.4%) was moderate with low variability. Based on the available evidence, the use of SAAs or LLMs should neither be universally recommended nor discouraged; rather, we suggest that their utility should be assessed based on the specific use case and user group under consideration.