tbuckley/cabot-search huggingface dataset:
Low Molecular Weight Alginate Oligosaccharides as Alternatives to PEG for Enhancement of the Diffusion of Cationic Nanoparticles Through Cystic Fibrosis Mucus
Authors: Ruhina Maeshima, Aristides D. Tagalakis, Dafni Gyftaki‐Venieri, Stuart A. Jones, Philip D. Rye, Anne Tøndervik, O. Alexander H. Åstrand, Stephen L. Hart
Journal: Advanced Healthcare Materials (2024)

Abstract Airway mucus is a major barrier to the delivery of lipid‐based nanoparticles in chronic airway diseases such as cystic fibrosis (CF). Receptor‐Targeted Nanocomplexes (RTN), comprise mixtures of cationic lipids and bifunctional peptides with receptor‐targeting and nucleic acid packaging properties. The aim of this study is to improve the mucus‐penetrating properties of cationic siRNA and mRNA RTNs by combining them with low molecular weight alginate oligosaccharides, OligoG and OligoM. Cationic RTNs formulated with either alginate become strongly anionic, while PEGylated messenger RNA (mRNA) and short interfering RNA (siRNA) RTNs remain cationic. Both alginates enhance mucus diffusion rates of cationic siRNA and mRNA RTNs in a static mucus barrier diffusion model, with OligoG particularly effective. PEGylation also enhance mucus diffusion rates of siRNA RTNs but not mRNA RTNs. Electron microscopy shows that RTNs remained intact after mucosal transit. The transfection efficiency of OligoM‐coated mRNA RTNs is better than those coated with OligoG or PEG, and similar to cationic RTNs. In siRNA RTN transfections, OligoM is better than OligoG although 1% PEG is slightly better than both. The combination of cationic RTNs and alginate oligosaccharides represents a promising alternative to PEGylation for epithelial delivery of genetic therapies across the mucus barrier while retaining transfection efficiency.
Meningiomas: Sex-Specific Differences and Prognostic Implications of a Chromosome X Loss
Authors: Natalie Berghaus, Thomas Hielscher, Dilan Savran, Daniel Schrimpf, Sybren L N Maas, Matthias Preusser, Michael Weller, Till Acker, Christel Herold-Mende, Wolfgang Wick, Andreas von Deimling, Felix Sahm
Journal: Neuro-Oncology (2024)

Meningiomas are the most common primary intracranial tumours in adults. Several studies proposed new stratification systems with a more accurate risk prediction than the WHO grading, e.g. based on methylation and copy number variations (CNVs). Yet, common shortcomings in these analyses are either a lack of stratification by sex of patients or excluding the gonososmes from CNV assessment.
Results of the prospective EORTC Children Leukemia Group study 58081 in precursor B‐ and T‐cell acute lymphoblastic leukemia
Authors: Carine Domenech, Michal Kicinski, Barbara De Moerloose, Caroline Piette, Wadih A. Chahla, Laure Kornreich, Marlène Pasquet, Anne Uyttebroeck, Alexandre Theron, Marilyne Poirée, Chloé Arfeuille, Marleen Bakkus, Nathalie Grardel, Catherine Paillard, Claire Freycon, Frédéric Millot, Pauline Simon, Pierre Philippet, Claire Pluchart, Stefan Suciu, Pierre Rohrlich, Alina Ferster, Yves Bertrand, Hélène Cavé
Journal: HemaSphere (2024)

Here, we report the results of the prospective cohort study EORTC-CLG 58081 and compare them to the control arm of the randomized phase 3 trial EORTC-CLG 58951, on which treatment recommendations were built. In both studies, patients aged 1-18 years with BCR::ABL1 negative acute lymphoblastic leukemia of the B-lineage (B-ALL) or T-lineage (T-ALL) were treated using a BFM backbone without cranial irradiation. Similarly to the control arm of 58951, prednisolone (PRED) 60 mg/m2/day was used for induction therapy, but a few modifications were made. Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients. Between 2011 and 2017, 835 patients were prospectively enrolled in the 58081 study. Overall, the 5-year event-free survival (EFS) was 84.8% versus 83.6% (hazard ratio [HR], 0.96 [95% confidence interval [CI]: 0.76-1.21]) for 58081 versus 58951 considered as a control group, respectively, 84.3% versus 84.9% (HR, 1.06 [99% CI: 0.75-1.49]) in B-ALL but 87.3% versus 76.6% (HR, 0.59 [99% CI: 0.28-1.24]) in T-ALL. The comparison between the two studies regarding EFS differed by risk group (p = 0.012). The HR was 2.15 (99% CI: 0.67-6.85) for very low-risk but 0.34 (99% CI: 0.13-0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.
Voxel-Based Dosimetry Predicts Local Tumor Progression Post 90Y Radiation Segmentectomy of Colorectal Liver Metastases
Authors: Platon M. Dimopoulos, Vlasios S. Sotirchos, Cynthia Dunne-Jaffe, Elena N. Petre, Mithat Gonen, Ken Zhao, Assen S. Kirov, Christopher Crane, Michael D’Angelica, Louise C. Connell, Constantinos T. Sofocleous
Journal: Clinical Nuclear Medicine (2024)

Radiation segmentectomy (RS) is an alternative potential local curative treatment for selected colorectal liver metastases (CLMs) not amenable to ablation or limited resection.
Risk of Infertility in Reproductive-Age Patients With Thyroid Cancer Receiving or Not Receiving 131I Treatment
Authors: Chun-Yi Lin, Cheng-Li Lin, Chia-Hung Kao
Journal: Clinical Nuclear Medicine (2024)

Fertility is the crucial concern for many survivors of cancer diagnosed as children, adolescents, and young adults. The objective of this study was to determine the risk of infertility in reproductive-age patients with thyroid cancer receiving or not receiving radioiodine treatment in Taiwan. This nationwide population-based cohort study was conducted using data obtained from the Taiwan National Health Insurance Database from 2009 to 2019. A total of 20,259 thyroid cancer patients aged from 15 to 50 years (8037 did not receive 131I treatment, and 12,222 received 131I treatment) and 20,259 controls were enrolled. A Cox proportional hazards model was applied to estimate the risk of infertility in thyroid cancer patients receiving or not receiving 131I treatment in terms of hazard ratios and 95% confidence intervals. The incidence rates of infertility in thyroid cancer receiving 131I therapy, those not receiving 131I therapy, and controls were 5.55, 5.07, and 3.61 per 1000 person-years, respectively. Compared with thyroid cancer patients treated with a cumulative 131I dose of 4.44 GBq or less, the risk of infertility was not significantly increased in those treated with a cumulative 131I dose of more than 4.44 GBq (adjusted hazard ratio, 1.13; 95% confidence interval, 0.95-1.36). The greatest increased risk of infertility in reproductive-age patients with thyroid cancer is associated with the fact that the patient has thyroid cancer regardless of 131I administration. 131I treatment or cumulative dose of 131I greater than 4.44 GBq did not further increase the risk of infertility.
Evaluation and prediction of relapse risk in stable systemic lupus erythematosus patients after glucocorticoid withdrawal (PRESS): an open-label, multicentre, non-inferiority, randomised controlled study in China
Authors: Yunyun Fei, Lidan Zhao, Lijun Wu, Xiaoxia Zuo, Rongli Li, Jiaomei Cheng, Hui Luo, Xue Wu, Li Sun, Jingjing Xu, Yingxuan Zhu, Yang Wang, Zhu Chen, Xiaomei Li, Xiaofei Wang, Xuan Zhang, Yunyun Fei, Lidan Zhao, Lijun Wu, Xiaoxia Zuo, Rongli Li, Jiaomei Cheng, Hui Luo, Xue Wu, Li Sun, Jingjing Xu, Yingxuan Zhu, Yang Wang, Zhu Chen, Xiaomei Li, Xiaofei Wang, Xuan Zhang
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Objectives</h3> To explore the relapse rate after glucocorticoid (GC) withdrawal with or without hydroxychloroquine (HCQ) maintenance in sustained clinically inactive systemic lupus erythematosus (SLE). <h3>Methods</h3> The PRESS trial is a multicentre, 33-week, open-label, three-arm, non-inferiority designed, randomised controlled trial. SLE patients with sustained clinically inactive disease who were maintained on low-dose GC plus HCQ therapy were screened and qualified patients were randomly assigned to three groups: drug-free group (both GC and HCQ withdrawal); HCQ group (discontinued GC but maintained HCQ); dual maintenance group (both GC and HCQ continued). The primary endpoint was to compare the proportion of patients experiencing a relapse as defined by the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index flare index by 33 weeks. Two parallel non-inferiority analyses were performed (drug-free group vs dual maintenance group and HCQ group vs dual maintenance group). <h3>Results</h3> From 3 November 2016 to 13 August 2021, 333 participants complied with the protocol after randomisation were analysed. The relapse rates in the three groups were 26.1%, 11.2% and 4.7%, respectively. Compared with dual maintenance group, drug-free group failed to achieve non-inferiority significance (relapse rate difference 21.4%; 95% CI 12.3% to 30.5%; P<sub>non-inferiority</sub>=0.238), whereas HCQ group achieved non-inferiority (relapse rate difference 6.5%; 95% CI −0.5% to 13.5%; P<sub>non-inferiority</sub>=0.034). HCQ group also exhibited fewer relapses than drug-free group (p=0.006). Adverse events were similar among all three groups. <h3>Conclusions</h3> GC withdrawal may be feasible in sustained clinically inactive SLE patients. HCQ maintenance can exert a protective role in preventing disease relapse after GC withdrawal. <h3>Trial registration number</h3> NCT02842814.
Papillary Tumor of the Pineal Gland With Discordant FDG and FAPi Uptake
Authors: Komal Preet, Priyavrat Purohit, Bhagwant Rai Mittal, Rajender Kumar, Harmandeep Singh, Jaya Shukla, Amanjit Bal, Renu Madan
Journal: Clinical Nuclear Medicine (2024)

Abstract In recent years, 68 Ga-FAP inhibitor has emerged as a possible substitute radiotracer to FDG for imaging of most of the tumors. Here, we report a 7-year-old girl diagnosed with recurrent papillary tumor of the pineal gland, presenting with complaints of headache and vomiting. 18 F-FDG PET/CT revealed an FDG-avid enhancing lesion in the posterior part of the third ventricle. Negligible FAPI uptake was noted on the corresponding 68 Ga-FAPI-46 PET/CT images, highlighting the scope of 18 F-FDG PET/CT in this realm.
Has the Time Come to Switch From Extensive Lymph Node Dissection to Sentinel Lymph Node Biopsy in Prostate Cancer Patients Treated With Radical Laparoscopic Prostatectomy?
Authors: Roberto C. Delgado Bolton, Adriana K. Calapaquí Terán, Francesco Giammarile
Journal: Clinical Nuclear Medicine (2024)

Abstract The efficacy of the available procedures currently recommended for staging and prognostic evaluation of prostate cancer patients treated with radical laparoscopic prostatectomy is discussed, taking into account the available evidence and potential implications in patient management.
Using a Pre-Radiation Window to Identify Potentially Active Cytotoxic Agents in Adults with Newly Diagnosed Glioblastoma
Authors: Danielle A Bazer, Antonio C Wolff, Stuart A Grossman
Journal: Neuro-Oncology (2024)

Therapies shown to improve outcomes in patients with recurrent cancers are commonly used in the neoadjuvant setting to optimize surgery, reduce radiation fields, and treat micro-metastatic disease. While pre-radiation chemotherapy (PRC) use has flourished in systemic cancers, it has not in glioblastomas. This review documents these trajectories and highlights the potential of PRC to rapidly and safely screen cytotoxic drugs for efficacy in patients with newly diagnosed glioblastoma.
Correction: A novel reopenable clip with sharp claw for complete closure of mucosal defects after colorectal endoscopic submucosal dissection
Authors: Naohisa Yoshida, Ryohei Hirose, Osamu Dohi, Yoshikazu Inagaki, Takaaki Murakami, Yutaka Inada, Yasutaka Morimoto, Reo Kobayashi, Ken Inoue, Elsayed Ghoneem, Yoshito Itoh
Journal: Endoscopy (2024)

Correction to: A novel reopenable clip with sharp claw for complete closure of mucosal defects after colorectal endoscopic submucosal dissectionEndoscopy eFirstDOI: 10.1055/a-2421-9767
Update on Diagnosis and Management of Kawasaki Disease: A Scientific Statement From the American Heart Association
Authors: Pei-Ni Jone, Adriana Tremoulet, Nadine Choueiter, Samuel R. Dominguez, Ashraf S. Harahsheh, Yoshihide Mitani, Meghan Zimmerman, Ming-Tai Lin, Kevin G. Friedman
Journal: Circulation (2024)

Kawasaki disease (KD), an acute self-limited febrile illness that primarily affects children <5 years old, is the leading cause of acquired heart disease in developed countries, with the potential of leading to coronary artery dilation and coronary artery aneurysms in 25% of untreated patients. This update summarizes relevant clinical data published since the 2017 American Heart Association scientific statement on KD related to diagnosis, cardiac imaging in acute KD treatment, and long-term management. Criteria defining North American patients at high risk for developing coronary artery aneurysms who may benefit from more intensive initial treatment have been published. Advances in cardiovascular imaging have improved the ability to identify coronary artery stenosis in patients with KD, yet knowledge gaps remain regarding optimal frequency of serial imaging and the best imaging modality to identify those at risk for inducible myocardial ischemia. Recent data have advanced the understanding of safety and dosing for several anti-inflammatory therapies in KD. New anticoagulation medication, myocardial infarction management, transition of health care for patients with KD, and future directions in research are discussed.
JAK/STAT signaling maintains an intermediate cell population during prostate basal cell fate determination
Authors: Wangxin Guo, Xiaoyu Zhang, Lin Li, Pengfei Shao, Chao Liang, Hongjiong Zhang, Kuo Liu, Shuoming Wang, Yunyi Peng, Jun Luo, Yi Ju, Angelo M De Marzo, Chen Yu, Luonan Chen, Bin Zhou, Dong Gao
Journal: Nature Genetics (2024)
Clearance of p21 highly expressing senescent cells accelerates cutaneous wound healing
Authors: Nathan S Gasek, Pengyi Yan, Junyu Zhu, K-Raman Purushothaman, Taewan Kim, Lichao Wang, Binsheng Wang, William F Flynn, Mingda Sun, Chun Guo, Billy Huggins, Roshanak Sharafieh, Yueying Zhou, Vojtech Parizek, Tamar Tchkonia, James L Kirkland, Saranya P Wyles, Ming Xu
Journal: Nature Aging (2024)
Understanding human-commensalism through an ecological and evolutionary framework
Authors: Ruth Fawthrop, José Cerca, George Pacheco, Glenn-Peter Sætre, Elizabeth S C Scordato, Mark Ravinet, Melissah Rowe
Journal: Trends in Ecology & Evolution (2024)

Human-commensalism has been intuitively characterised as an interspecific interaction whereby non-human individuals benefit from tight associations with anthropogenic environments. However, a clear definition of human-commensalism, rooted within an ecological and evolutionary framework, has yet to be proposed. Here, we define human-commensalism as a population-level dependence on anthropogenic resources, associated with genetic differentiation from the ancestral, non-commensal form. Such a definition helps us to understand the origins of human-commensalism and the pace and form of adaptation to anthropogenic niches, and may enable the prediction of future evolution in an increasingly human-modified world. Our discussion encourages greater consideration of the spatial and temporal complexity in anthropogenic niches, promoting a nuanced consideration of human-commensal populations when formulating research questions.
TRIM21-mediated ubiquitination and phosphorylation of ERK1/2 promotes cell proliferation and drug resistance in pituitary adenomas
Authors: Yanting Liu, Fang Liu, Chuanbao Li, Tao Zhang, Tianyi Han, Yuting Dai, Ning Huang, Hao Tang, Xiaobin Wang, Shaojian Lin, Li Xue, Zhe Bao Wu
Journal: Neuro-Oncology (2024)

Pituitary adenomas (PAs) are common intracranial tumors and TRIM family plays a crucial role in cell proliferation, and therapeutic resistance of tumors. However, the role of the TRIM family in PAs is not well recognized.
Correction: Aberrant BCAT1 expression augments MTOR activity and accelerates disease progression in chronic lymphocytic leukemia
Authors: Qiangqiang Shao, Jedrzej Wykretowicz, Nan Hu, Karan Bedi, Mohamed Rizk, Isabella A Malek, Surinder Kumar, David B Lombard, Kerby Shedden, David Scott, Sami N Malek
Journal: Leukemia (2024)
Food Swamps and Food Deserts Impact on Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Mortality in US Counties
Authors: Annette Paik, Linda Henry, Leyla De Avila, Saleh AlQahtani, Fatema Nader, James M Paik, Zobair M Younossi
Journal: Clinical Gastroenterology and Hepatology (2024)
The applications and advances of artificial intelligence in drug regulation: A global perspective
Authors: Lixia Fu, Guoshu Jia, Zhenming Liu, Xiaocong Pang, Yimin Cui
Journal: Acta Pharmaceutica Sinica B (2024)

Artificial intelligence (AI) has emerged as a transformative force in healthcare, with applications spanning diagnostics to drug development. However, its integration into drug regulation remains nascent, with varying degrees of adoption and implementation across different regulatory bodies worldwide. This review aims to provide a comprehensive overview of the current state of AI in drug regulation, encapsulating AI-related policies, initiatives, and its practical application in regulatory agencies globally. It further discusses the challenges and future prospects of AI in this field. The findings reveal that numerous agencies have launched action plans and initiatives to incorporate AI, aiming to streamline regulatory processes and enhance data-driven regulatory decision-making. Moreover, AI's deployment in safety surveillance, workflow optimization, and regulatory science research is expanding, highlighting its increasing impact on drug regulation. Nonetheless, key challenges persist, such as data quality and reliability, technical limitations, talent shortage and the absence of standards. The review concludes that interdisciplinary collaboration is crucial to harness AI's full potential in drug regulation and overcoming its current limitations. In the future, AI may become a pivotal catalyst in drug regulation, promising a new era of enhanced scrutiny, efficiency, and innovation that will benefit public health on a global scale.
Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review
Authors: Anna Maggiore, Valentina Latina, Maria D'Erme, Giuseppina Amadoro, Roberto Coccurello
Journal: Ageing Research Reviews (2024)

Alzheimer's Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points. Ageing, genetic and environmental risk factors, along with different clinical symptoms suggest that AD is a complex and heterogeneous disorder with multiple interconnected pathological pathways rather than a single disease entity. In the present review, we highlight and discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid and sugar signaling, and cerebrovascular damage that contribute to the onset and development of AD. We emphasize that challenging the traditional "amyloid cascade hypothesis" may improve our understanding of this age-related complex syndrome and help fight the progressive cognitive decline in AD.
Switch from Off-Label Swallowed Topical Corticosteroids to Budesonide Orodispersible Tablets in Eosinophilic Esophagitis patients
Authors: Gaia Pellegatta, Francesca Paola Giugliano, Elisabetta Mastrorocco, Baiardini Ilaria, Cesare Hassan, Alessandro Repici
Journal: Clinical Gastroenterology and Hepatology (2024)
Magnetic Resonance Imaging Versus Computed Tomography Guidance for Stereotactic Body Radiotherapy in Prostate Cancer: 2-year Outcomes from the MIRAGE Randomized Clinical Trial
Authors: Amar U Kishan, James M Lamb, Holly Wilhalme, Maria Casado, Natalie Chong, Lily Zello, Jesus E Juarez, Tommy Jiang, Beth K Neilsen, Daniel A Low, Yingli Yang, John Neylon, Vincent Basehart, Ting Martin Ma, Luca F Valle, Minsong Cao, Michael L Steinberg
Journal: European Urology (2024)

It has been shown that magnetic resonance imaging (MRI) guidance versus computed tomography (CT) guidance for aggressive margin-reduction (AMR) for stereotactic body radiotherapy (SBRT) in prostate cancer reduces acute toxicity, but the longer-term benefits are unknown. We performed a secondary analysis of MIRAGE, a phase 3 randomized clinical trial of MRI-guided SBRT for prostate cancer, to determine whether AMR with MRI guidance significantly reduced 2-yr physician-scored or patient-reported toxic effects in comparison to CT guidance. The cumulative incidence of 2-yr physician-scored toxicity, defined as grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxic effects according to Common Terminology Criteria for Adverse Events v4.03, were lower with MRI guidance. Cumulative incidence rates of late grade ≥2 toxicity at 2 yr with MRI-guided versus CT-guided SBRT were 27% (95% confidence interval [CI] 19-39%)] versus 51% (95% CI 41-63%) for GU toxicity (p = 0.004), and 1.4% (95% CI 0.2-9.6) versus 9.5% (95% CI 4.6-19) for GI toxicity (p = 0.025). Cumulative logistic regression revealed that MRI-guided SBRT was associated with significantly lower odds of a clinically relevant deterioration in bowel function according to the Expanded Prostate Cancer Index Composite-26 score (odds ratio 0.444, 95% CI 0.209-0.942; p = 0.035) and in the Sexual Health Inventory in Men score (odds ratio 0.366, 95% CI 0.148-0.906; p = 0.03). There were no significant differences in the odds of a deterioration for other quality-of-life metrics. These findings support the hypothesis that aggressive planning for margin reduction for prostate SBRT using MRI leads to continued reductions in toxic effects over 2-yr follow-up. This trial is registered on ClinicalTrials.gov Identifier as NCT04384770.