tbuckley/cabot-search huggingface dataset:
The cochlear dose and the age at radiotherapy predict severe hearing loss after passive scattering proton therapy and cisplatin in children with medulloblastoma
Authors: Mohammad H Abu-Arja, Austin L Brown, Jack M Su, M Fatih Okcu, Holly B Lindsay, Susan L McGovern, Mary Frances McAleer, David R Grosshans, Murali M Chintagumpala, Arnold C Paulino
Journal: Neuro-Oncology (2024)

Hearing loss (HL) is associated with worse neurocognitive outcomes among patients with medulloblastoma. We aimed to identify risk factors associated with severe HL and to evaluate the generalizability of a published HL calculator among patients treated with passive scattering proton therapy (PSPT) and cisplatin. We identified patients aged 3-21 years who were treated at our centers between 2007 and 2022. Audiograms were graded using the International Society of Pediatric Oncology (SIOP) Boston scale. Time to grades 3-4 HL was evaluated using Kaplan-Meier and multivariable Cox models to estimate hazard ratios and 95% confidence intervals (CI). Seventy-nine patients were treated with PSPT at a median age of 7.5 years (range: 3.1-21.1). The mean cochlear dose (Dmc) (±SD) was 31.5 ± 8.5 Gy, and the cumulative cisplatin dose was 295 ± 50 mg/m2. Fifty-nine patients (75%) received amifostine. Patients completed a median of 9 audiograms (range: 4-22) with a median audiogram follow-up of 49 months (range: 6-177). Twenty-seven patients (34%) had grades 3-4 HL. In adjusted Cox models, only higher Dmc (HR = 1.12, 95% CI:1.06-1.18) was associated with grades 3-4 HL. The predicted 3-year incidence of grades 3-4 HL was 40.0% (95% CI: 21.3-66.3) and 66.7% (95% CI: 35.4-93.7) for children with Dmc ≥36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .042). It was 8.9% (95% CI: 2.3-31.6) and 15.6% (95% CI: 5.3-41.1) for children with Dmc <36 Gy and age at radiotherapy ≥7 and <7 years, respectively (P = .78). Children <7 years at radiotherapy with a Dmc ≥36 Gy are at higher risk for HL.
Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study
Authors: Rebecca Dent, Javier Cortés, Lajos Pusztai, Heather McArthur, Sherko Kümmel, Jonas Bergh, Carsten Denkert, Yeon Hee Park, Rina Hui, Nadia Harbeck, Masato Takahashi, Michael Untch, Peter A Fasching, Fatima Cardoso, Amin Haiderali, Liyi Jia, Allison Martin Nguyen, Wilbur Pan, Joyce O’Shaughnessy, Peter Schmid
Journal: JNCI Journal of the National Cancer Institute (2024)

In KEYNOTE-522 (NCT03036488), neoadjuvant pembrolizumab plus chemotherapy and then adjuvant pembrolizumab significantly improved pathological complete response and event-free survival vs neoadjuvant chemotherapy in early-stage triple-negative breast cancer (TNBC). We report patient-reported outcomes (PROs) from KEYNOTE-522. Patients were randomized 2:1 to neoadjuvant pembrolizumab 200 mg or placebo every 3 weeks, plus 4 cycles of paclitaxel plus carboplatin and then 4 cycles of doxorubicin (or epirubicin) plus cyclophosphamide. After surgery, patients received adjuvant pembrolizumab or placebo for up to 9 cycles. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EORTC Breast Cancer-Specific Quality of Life Questionnaire (EORTC QLQ-BR23) were prespecified secondary objectives. Between-group differences in least squares (LS) mean change from baseline (day 1 of cycle 1 in both neoadjuvant and adjuvant phases) to the prespecified latest time point with at least 60% completion and at least 80% compliance were assessed using a longitudinal model (no alpha error assigned). Week 21 (neoadjuvant phase) and week 24 (adjuvant phase) were the latest time points at which completion/compliance rates were ≥60%/80%. In the neoadjuvant phase, between-group differences (pembrolizumab plus chemotherapy [n = 762] vs placebo plus chemotherapy [n = 383]) in LS mean change from baseline to week 21 in QLQ-C30 global health status/quality of life (GHS/QoL), emotional functioning, and physical functioning were -1.04 (95% confidence interval = -3.46 to 1.38), -0.69 (95% CI = -3.13 to 1.75), and -2.85 (95% CI = -5.11 to -0.60), respectively. In the adjuvant phase, between-group differences (pembrolizumab [n = 539] vs placebo [n = 308]) in LS mean change from baseline to week 24 were -0.41 (95% CI = -2.60 to 1.77), -0.60 (95% CI = -2.99 to 1.79), and -1.57 (95% CI = -3.36 to 0.21). No substantial differences in PRO assessments were observed between neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab vs neoadjuvant placebo plus chemotherapy in early-stage TNBC. ClinicalTrials.gov, NCT03036488.
Histopathological Evidence for a Non-Inflammatory Mechanism in Osimertinib-Induced Myopathy: A Case Report
Authors: Simone Rossi, Roberta Costa, Alessandro di Federico, Francesca Lo Bianco, Roberto D'Angelo, Gian Maria Asioli, Andrea De Giglio, Francesca Sperandi, Maria Guarino, Rita Rinaldi, Andrea Ardizzoni, Giovanna Cenacchi, Francesco Gelsomino
Journal: Journal of Thoracic Oncology (2024)
Minimally invasive nasal infusion (MINI) approach for CNS delivery of protein therapeutics: A case study with ovalbumin
Authors: Valentina Di Francesco, Andy J Chua, Elham Davoudi, Jonghan Kim, Benjamin S Bleier, Mansoor M Amiji
Journal: Journal of Controlled Release (2024)

One of the primary obstacles in treating central nervous system (CNS) disorders lies in the limited ability of disease-modifying drugs to cross the blood-brain barrier (BBB). Our previously described Minimally Invasive Nasal Depot (MIND) technique has proven successful in delivering various drugs to the brain in rat models via a trans-olfactory mucosal approach. In this study, we introduce a novel Minimally Invasive Nasal Infusion (MINI) delivery approach for administering ovalbumin, a model protein, utilizing a programmable infusion pump (iPRECIO SMP-310R) in a mouse model. This research highlights the significant role of olfactory mucosa in nose-to-brain delivery, with an efficacy of nearly 45% compared to intracerebroventricular (ICV) administration. This demonstrates its potential as an alternative procedure for treating CNS diseases, offering a greater safety profile relative to the highly invasive clinical routes traditionally adopted for CNS drug delivery.
Manganese-induced Photothermal-Ferroptosis for synergistic tumor therapy
Authors: Kun Chen, Rui Sun, Yudong Guan, Tao Fang, Jun Tao, Zhijie Li, Bingchen Zhang, Zhiqiang Yu, Jiahang Tian, Zhaogang Teng, Jigang Wang
Journal: Journal of Controlled Release (2024)
Analgesia efficacy of erector spinae plane block in laparoscopic Abdominal surgeries: A systemic review and meta-analysis
Authors: Crystal Jin-Yang Sia, Shei-La Wee, Phui-Sze Au-Yong, Sui-An Lie, Winson J. Tan, Fung-Joon Foo, Jiunn-Haur Kam, Daniel JK Lee, Frederick H. Koh
Journal: International Journal of Surgery (2024)

Background Multimodal analgesia is now widely practised to minimise postoperative opioid consumption while optimising pain control. The aim of this meta-analysis was to assess the analgesic efficacy of erector spinae plane block (ESPB) in patients undergoing laparoscopic abdominal surgeries. This will be determined by perioperative opioid consumption, subjective pain scores and incidences of postoperative nausea and vomiting. Methods We systemically searched electronic databases for randomised controlled trials (RCTs) published up to February 2023 comparing ESPB with other adjuvant analgesic techniques in laparoscopic abdominal surgeries. Nine randomised controlled trials encompassing 666 subjects were included in our study. Results ESPB was shown to reduce postoperative opioid consumption [mean difference (MD) of -5.95mg (95% CI: -8.86 to -3.04; P &lt; 0.0001); I 2 =89%], intraoperative opioid consumption [mean difference (MD) of -102.4mcg (95% CI: -145.58 to -59.21; P &lt; 0.00001); I 2 =39%] and incidence of nausea [RR 0.38 (95% CI: 0.25 to 0.60; P &lt; 0.0001); I 2 =0%] and vomiting [RR 0.32 (95% CI: 0.17 to 0.63; P =0.0009); I 2 =0%] in laparoscopic abdominal surgeries. Subgroup analysis on laparoscopic colorectal surgeries further showed reduction in postoperative pain scores [mean difference (MD) of -0.68 (95% CI: -0.94 to -0.41); P &lt; 0.00001; I 2 =0%]. Conclusions This study concludes that ESPB is a valuable technique with proven efficacy to potentially promote faster postoperative recovery through optimising pain control while minimising opioid requirements.
Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction
Authors: Morten Schou, Mark C. Petrie, Barry A. Borlaug, Javed Butler, Melanie J. Davies, Dalane W. Kitzman, Sanjiv J. Shah, Subodh Verma, Shachi Patel, Khaja M. Chinnakondepalli, Signe Harring, Steen Z. Abildstrøm, Karoline Liisberg, Mikhail N. Kosiborod
Journal: Journal of the American College of Cardiology (2024)

In the Semaglutide Treatment Effect in People with obesity and HFpEF (STEP-HFpEF) program, semaglutide improved heart failure (HF)-related symptoms, physical limitations, and exercise function, and reduced bodyweight in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Whether semaglutide improves functional status, as assessed by NYHA functional class, is unknown.
Consensus Guidance for Monitoring Individuals With Islet Autoantibody–Positive Pre-Stage 3 Type 1 Diabetes
Authors: Moshe Phillip, Peter Achenbach, Ananta Addala, Anastasia Albanese-O’Neill, Tadej Battelino, Kirstine J. Bell, Rachel E.J. Besser, Ezio Bonifacio, Helen M. Colhoun, Jennifer J. Couper, Maria E. Craig, Thomas Danne, Carine de Beaufort, Klemen Dovc, Kimberly A. Driscoll, Sanjoy Dutta, Osagie Ebekozien, Helena Elding Larsson, Daniel J. Feiten, Brigitte I. Frohnert, Robert A. Gabbay, Mary P. Gallagher, Carla J. Greenbaum, Kurt J. Griffin, William Hagopian, Michael J. Haller, Christel Hendrieckx, Emile Hendriks, Richard I.G. Holt, Lucille Hughes, Heba M. Ismail, Laura M. Jacobsen, Suzanne B. Johnson, Leslie E. Kolb, Olga Kordonouri, Karin Lange, Robert W. Lash, Åke Lernmark, Ingrid Libman, Markus Lundgren, David M. Maahs, M. Loredana Marcovecchio, Chantal Mathieu, Kellee M. Miller, Holly K. O’Donnell, Tal Oron, Shivajirao P. Patil, Rodica Pop-Busui, Marian J. Rewers, Stephen S. Rich, Desmond A. Schatz, Rifka Schulman-Rosenbaum, Kimber M. Simmons, Emily K. Sims, Jay S. Skyler, Laura B. Smith, Cate Speake, Andrea K. Steck, Nicholas P.B. Thomas, Ksenia N. Tonyushkina, Riitta Veijola, John M. Wentworth, Diane K. Wherrett, Jamie R. Wood, Anette-Gabriele Ziegler, Linda A. DiMeglio
Journal: Diabetes Care (2024)

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.
Nanoparticle-mediated thermal Cancer therapies: Strategies to improve clinical translatability
Authors: M Bravo, B Fortuni, P Mulvaney, J Hofkens, H Uji-I, S Rocha, J A Hutchison
Journal: Journal of Controlled Release (2024)

Despite significant advances, cancer remains a leading global cause of death. Current therapies often fail due to incomplete tumor removal and nonspecific targeting, spurring interest in alternative treatments. Hyperthermia, which uses elevated temperatures to kill cancer cells or boost their sensitivity to radio/chemotherapy, has emerged as a promising alternative. Recent advancements employ nanoparticles (NPs) as heat mediators for selective cancer cell destruction, minimizing damage to healthy tissues. This approach, known as NP hyperthermia, falls into two categories: photothermal therapies (PTT) and magnetothermal therapies (MTT). PTT utilizes NPs that convert light to heat, while MTT uses magnetic NPs activated by alternating magnetic fields (AMF), both achieving localized tumor damage. These methods offer advantages like precise targeting, minimal invasiveness, and reduced systemic toxicity. However, the efficacy of NP hyperthermia depends on many factors, in particular, the NP properties, the tumor microenvironment (TME), and TME-NP interactions. Optimizing this treatment requires accurate heat monitoring strategies, such as nanothermometry and biologically relevant screening models that can better mimic the physiological features of the tumor in the human body. This review explores the state-of-the-art in NP-mediated cancer hyperthermia, discussing available nanomaterials, their strengths and weaknesses, characterization methods, and future directions. Our particular focus lies in preclinical NP screening techniques, providing an updated perspective on their efficacy and relevance in the journey towards clinical trials.
Opportunities for nanomaterials in enzyme therapy
Authors: Beatriz Torres-Herrero, Ilaria Armenia, Cecilia Ortiz, Jesús Martinez de la Fuente, Lorena Betancor, Valeria Grazú
Journal: Journal of Controlled Release (2024)

In recent years, enzyme therapy strategies have rapidly evolved to catalyze essential biochemical reactions with therapeutic potential. These approaches hold particular promise in addressing rare genetic disorders, cancer treatment, neurodegenerative conditions, wound healing, inflammation management, and infectious disease control, among others. There are several primary reasons for the utilization of enzymes as therapeutics: their substrate specificity, their biological compatibility, and their ability to generate a high number of product molecules per enzyme unit. These features have encouraged their application in enzyme replacement therapy where the enzyme serves as the therapeutic agent to rectify abnormal metabolic and physiological processes, enzyme prodrug therapy where the enzyme initiates a clinical effect by activating prodrugs, and enzyme dynamic or starving therapy where the enzyme acts upon host substrate molecules. Currently, there are >20 commercialized products based on therapeutic enzymes, but approval rates are considerably lower than other biologicals. This has stimulated nanobiotechnology in the last years to develop nanoparticle-based solutions that integrate therapeutic enzymes. This approach aims to enhance stability, prevent rapid clearance, reduce immunogenicity, and even enable spatio-temporal activation of the therapeutic catalyst. This comprehensive review delves into emerging trends in the application of therapeutic enzymes, with a particular emphasis on the synergistic opportunities presented by incorporating enzymes into nanomaterials. Such integration holds the promise of enhancing existing therapies or even paving the way for innovative nanotherapeutic approaches.
Resiquimod-loaded cationic liposomes cure mice with peritoneal carcinomatosis and induce specific anti-tumor immunity
Authors: Po-Han Chao, Vanessa Chan, Jiamin Wu, Lucas J Andrew, Shyh-Dar Li
Journal: Journal of Controlled Release (2024)

Peritoneal carcinomatosis (PC) is characterized by a high recurrence rate and mortality following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), primarily due to incomplete cancer elimination. To enhance the standard of care for PC, we developed two cationic liposomal formulations aimed at localizing a toll-like receptor agonist, resiquimod (R848), in the peritoneal cavity to activate the immune system locally to specifically eradicate residual tumor cells. These formulations effectively extended R848 retention in the peritoneum by >10-fold, resulting in up to a 2-fold increase in interferon α (IFN-α) induction in the peritoneal fluid, without increasing the plasma levels. In a CT26 colon cancer model with peritoneal metastases, these liposomal R848 formulations, when combined with oxaliplatin (OXA)-an agent used in HIPEC that induces immunogenic cell death-increased tumor infiltration of effector immune cells, including DCs, CD4, and CD8 T cells. This led to the complete elimination of PC in 60-70% of the mice, while the control mice reached humane endpoints by 30 days. The cured mice developed specific antitumor immunity, as re-challenging them with the same tumor cells did not result in tumor establishment. However, inoculation with a different tumor line led to tumor development. Additionally, exposing CT26 tumor antigens to the splenocytes isolated from the cured mice induced the expansion of CD4 and CD8 T cells and the release of IFN-γ, demonstrating long-term immune memory to the specific tumor. The anti-tumor efficacy of these liposomal R848 formulations was mediated via CD8 T cells with different levels of involvement of CD4 and B cells, and the combination with an anti-PD-1 antibody achieved a cure rate of 90%.
Machine learning in drug delivery
Authors: Adam J Gormley
Journal: Journal of Controlled Release (2024)

For decades, drug delivery scientists have been performing trial-and-error experimentation to manually sample parameter spaces and optimize release profiles through rational design. To enable this approach, scientists spend much of their career learning nuanced drug-material interactions that drive system behavior. In relatively simple systems, rational design criteria allow us to fine tune release profiles and enable efficacious therapies. However, as materials and drugs become increasingly sophisticated and their interactions have non-linear and compounding effects, the field is suffering the Curse of Dimensionality which prevents us from comprehending complex structure-function relationships. In the past, we have embraced this complexity by implementing high-throughput screens to increase the probability of finding ideal compositions. However, this brute force method was inefficient and led many to abandon these fishing expeditions. Fortunately, methods in data science including artificial intelligence / machine learning (AI/ML) are providing ideal analytical tools to model this complex data and ascertain quantitative structure-function relationships. In this Oration, I speak to the potential value of data science in drug delivery with particular focus on polymeric delivery systems. Here, I do not suggest that AI/ML will simply replace mechanistic understanding of complex systems. Rather, I propose that AI/ML should be yet another useful tool in the lab to navigate complex parameter spaces. The recent hype around AI/ML is breathtaking and potentially over inflated, but the value of these methods is poised to revolutionize how we perform science. Therefore, I encourage readers to consider adopting these skills and applying data science methods to their own problems. If done successfully, I believe we will all realize a paradigm shift in our approach to drug delivery.
The aging lipidome: exercise is medicine
Authors: Abel Plaza-Florido, Inmaculada Pérez-Prieto, Alejandro Lucia
Journal: Trends in Molecular Medicine (2024)

The molecular mechanisms behind the potential 'anti-aging' effects of exercise remain to be elucidated. Janssens et al. studied the lipidome of different mouse tissues and human skeletal muscle. They identified an evolutionary conserved 'lipid aging' signature, characterized by bis(monoacylglycero)phosphate accumulation, which, at the muscle level, can be attenuated by exercise.
Curcumin-loaded polymeric nanomaterials as a novel therapeutic strategy for Alzheimer's disease: A comprehensive review
Authors: JinJin Pei, Chella Perumal Palanisamy, Prabhu Manickam Natarajan, Vidhya Rekha Umapathy, Jeane Rebecca Roy, Guru Prasad Srinivasan, Mani Panagal, Selvaraj Jayaraman
Journal: Ageing Research Reviews (2024)
Histological predictors of aggressive recurrence of hepatocellular carcinoma after liver resection
Authors: Carla Fuster-Anglada, Ezequiel Mauro, Joana Ferrer-Fàbrega, Berta Caballol, Marco Sanduzzi-Zamparelli, Jordi Bruix, Josep Fuster, María Reig, Alba Díaz, Alejandro Forner
Journal: Journal of Hepatology (2024)
Factors associated with acceleration of clinical development for infectious diseases: a cross-sectional analysis of 10-year EMA registration data
Authors: Hanna K de Jong, Sabine M Hermans, Sophie M Schuitenmaker, Maya Oli, Mariëtte A van den Hoven, Martin P Grobusch
Journal: The Lancet Regional Health - Europe (2024)

Clinical trials feature centrally in the development of drugs and vaccines to determine safety and efficacy. Clinical development can be slow and may have a duration of more than ten years. Global public health threats such as Ebola virus disease (EVD) and COVID-19 have demonstrated that it is possible to accelerate clinical trials while maintaining safety and efficacy. We investigated acceleration in clinical trials over the past decade and identified factors associated with acceleration for drugs targeting infectious diseases.
Prevalence of radicular neuropathic pain in idiopathic Parkinson’s disease: A systematic review and meta-analysis
Authors: Leonardo Gomes Pereira, Patrícia Rodrigues, Fernanda Tibolla Viero, Sabrina Qader Kudsi, Julia Maria Frare, Chaiane Tais Rech, Gabriela Graiczicki, Gabriela Trevisan
Journal: Ageing Research Reviews (2024)
Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment
Authors: Antonino Glaviano, Seth A. Wander, Richard D. Baird, Kenneth C.-H. Yap, Hiu Yan Lam, Masakazu Toi, Daniela Carbone, Birgit Geoerger, Violeta Serra, Robert H. Jones, Joanne Ngeow, Eneda Toska, Justin Stebbing, Karen Crasta, Richard S. Finn, Patrizia Diana, Karla Vuina, Robertus A.M. de Bruin, Uttam Surana, Aditya Bardia, Alan Prem Kumar
Journal: Drug Resistance Updates (2024)

Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase. Three CDK4/6i are approved for the first-line treatment of patients with advanced/metastatic hormone receptor-positive (HR