tbuckley/cabot-search huggingface dataset:
Recent advances and strategies for nanocarrier-mediated topical therapy and theranostic for posterior eye disease
Authors: Maria João Faria, José M. González-Méijome, M. Elisabete C.D. Real Oliveira, Gonzalo Carracedo, Marlene Lúcio
Journal: Advanced Drug Delivery Reviews (2024)

Posterior eye disorders, such as age-related macular degeneration, diabetic retinopathy, and glaucoma, have a significant impact on human quality of life and are the primary cause of age-related retinal diseases among adults. There is a pressing need for innovative topical approaches to treat posterior eye disorders, as current methods often rely on invasive procedures with inherent risks. Limited success was attained in the realm of topical ophthalmic delivery through non-invasive means. Additionally, there exists a dearth of literature that delves into the potential of this approach for drug delivery and theranostic purposes, or that offers comprehensive design strategies for nanocarrier developers to surmount the significant physiological ocular barriers. This review offers a thorough and up-to-date state-of-the-art overview of 40 studies on therapeutic loaded nanocarriers and theranostic devices that, to the best of our knowledge, represent all successful works that reached posterior eye segments through a topical non-invasive administration. Most importantly, based on the successful literature studies, this review provides a comprehensive summary of the potential design strategies that can be implemented during nanocarrier development to overcome each ocular barrier.
Excess Child Mortality Associated With Colombia’s Armed Conflict, 1998-2019
Authors: Caitlin A. Moe, Andrés Villaveces, Pablo Montoya, Ali Rowhani-Rahbar
Journal: JAMA Network Open (2024)

Armed conflicts are directly and indirectly associated with morbidity and mortality due to destruction of health infrastructure and diversion of resources, forced displacement, environmental damage, and erosion of social and economic security. Colombia's conflict began in the 1940s and has been uniquely long-lasting and geographically dynamic.
Cellular senescence in lung cancer: Molecular mechanisms and therapeutic interventions
Authors: Saurav Kumar Jha, Gabriele De Rubis, Shankar Raj Devkota, Yali Zhang, Radhika Adhikari, Laxmi Akhileshwar Jha, Kunal Bhattacharya, Samir Mehndiratta, Gaurav Gupta, Sachin Kumar Singh, Nisha Panth, Kamal Dua, Philip M. Hansbro, Keshav Raj Paudel
Journal: Ageing Research Reviews (2024)

Lung cancer stands as the primary contributor to cancer-related fatalities worldwide, affecting both genders. Two primary types exist where non-small cell lung cancer (NSCLC), accounts for 80–85% and SCLC accounts for 10-15% of cases. NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Smoking, second-hand smoke, radon gas, asbestos, and other pollutants, genetic predisposition, and COPD are lung cancer risk factors. On the other hand, stresses such as DNA damage, telomere shortening, and oncogene activation cause a prolonged cell cycle halt, known as senescence. Despite its initial role as a tumor-suppressing mechanism that slows cell growth, excessive or improper control of this process can cause age-related diseases, including cancer. Cellular senescence has two purposes in lung cancer. Researchers report that senescence slows tumor growth by constraining multiplication of impaired cells. However, senescent cells also demonstrate the pro-inflammatory senescence-associated secretory phenotype (SASP), which is widely reported to promote cancer. This review will look at the role of cellular senescence in lung cancer, describe its diagnostic markers, ask about current treatments to control it, look at case studies and clinical trials that show how senescence-targeting therapies can be used in lung cancer, and talk about problems currently being faced, and possible solutions for the same in the future.
Characteristics and Health Care Utilization of Patients With Housing Insecurity in the ED
Authors: Madeleine A. Z. Ball, Daniel E. Sack, Sophia A. Druffner, Ian Jones, Jesse O. Wrenn, Mitchell M. Sexton, Marybeth Shinn, Jennifer J. Hess
Journal: JAMA Network Open (2024)

Unstable housing and homelessness can exacerbate adverse health outcomes leading to increased risk of chronic disease, injury, and disability. However, emergency departments (EDs) have no universal method to identify those at risk of or currently experiencing homelessness.
Survival After Out-of-Hospital Cardiac Arrest Before and After Legislation for Bystander CPR
Authors: Siwen Li, Chongzhen Qin, Hongjuan Zhang, Mailikezhati Maimaitiming, Junyi Shi, YiKai Feng, Kepei Huang, Yanxin Bi, Minmin Wang, Qiang Zhou, Yinzi Jin, Zhi-Jie Zheng
Journal: JAMA Network Open (2024)

Importance The lack of evidence-based implementation strategies is a major contributor to increasing mortality due to out-of-hospital cardiac arrest (OHCA) in developing countries with limited resources. Objective To evaluate whether the implementation of legislation is associated with increased bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use and improved clinical outcomes for patients experiencing OHCA and to provide policy implications for low-income and middle-income settings. Design, Setting, and Participants This observational cohort study analyzed a prospective city registry of patients with bystander-witnessed OHCA between January 1, 2010, and December 31, 2022. The Emergency Medical Aid Act was implemented in Shenzhen, China, on October 1, 2018. An interrupted time-series analysis was used to assess changes in outcomes before and after the law. Data analysis was performed from May to October 2023. Exposure The Emergency Medical Aid Act stipulated the use of AEDs and CPR training for the public and provided clear legal guidance for OHCA rescuing. Main Outcomes and Measures The primary outcomes were rates of bystander-initiated CPR and use of AEDs. Secondary outcomes were rates of prehospital return of spontaneous circulation (ROSC), survival to arrival at the hospital, and survival at discharge. Results A total of 13 751 patients with OHCA (median [IQR] age, 59 [43-76] years; 10 011 men [72.83%]) were included, with 7858 OHCAs occurring during the prelegislation period (January 1, 2010, to September 30, 2018) and 5893 OHCAs occurring during the postlegislation period (October 1, 2018, to December 31, 2022). The rates of bystander-initiated CPR (320 patients [4.10%] vs 1103 patients [18.73%]) and AED use (214 patients [4.12%] vs 182 patients [5.29%]) increased significantly after legislation implementation vs rates before the legislation. Rates of prehospital ROSC (72 patients [0.92%] vs 425 patients [7.21%]), survival to arrival at the hospital (68 patients [0.87%] vs 321 patients [5.45%]), and survival at discharge (44 patients [0.56%] vs 165 patients [2.80%]) were significantly increased during the postlegislation period. Interrupted time-series models demonstrated a significant slope change in the rates of all outcomes. Conclusions and Relevance These findings suggest that implementation of the Emergency Medical Aid Act in China was associated with increased rates of CPR and public AED use and improved survival of patients with OHCA. The use of a systemwide approach to enact resuscitation initiatives and provide legal support may reduce the burden of OHCA in low-income and middle-income settings.
CPR—Letters of the Law
Authors: Maxwell A. Hockstein
Journal: JAMA Network Open (2024)

Siwen Li, PhD; Chongzhen Qin, MD; Hongjuan Zhang, MD; Mailikezhati Maimaitiming, MD; Junyi Shi, MD; YiKai Feng, PhD; Kepei Huang, MD; Yanxin Bi, MD; Minmin Wang, PhD; Qiang Zhou, MD; Yinzi Jin, PhD; Zhi-Jie Zheng, MD, PhD
Cell-Free Human Papillomavirus DNA Is a Sensitive Biomarker for Prognosis and for Early Detection of Relapse in Locally Advanced Cervical Cancer
Authors: Lars Sivars, Cecilia Jylhä, Ylva Crona Guterstam, Mark Zupancic, Britta Lindqvist, Magnus Nordenskjöld, Emma Tham, Kristina Hellman
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Human papillomavirus (HPV) is the cause of the majority of cervical cancer cases and has been showed to be released as cell-free tumor DNA (ctHPV DNA) into the circulation. Here, we analyze if ctHPV DNA could be used as a prognostic biomarker and/or to detect relapse earlier than traditional methods in locally advanced cervical cancer (LACC). Experimental Design: A total of 74 patients with LACC were included; 66of 74 were positive for 13 high-risk HPV types on a bead-based assay of tumor biopsy samples. HPV-type–specific droplet digital PCR assays were developed. Longitudinal plasma samples were then analyzed for the biopsy-verified HPV type for each patient. In total, 418 plasma samples were analyzed. Patients were followed for a median of 37 months. Results were correlated to tumor and clinical characteristics. Results: Of the pretreatment plasma samples, 92.4% were positive for ctHPV DNA. Persistent ctHPV DNA in end-of-treatment, early follow-up (1–2 months after end-of-treatment), or tumor evaluation (3–4 months after end-of-treatment) plasma was correlated with worse progression-free survival (P &amp;lt; 0.001) compared with if ctHPV DNA was not found. The positive predictive value of ctHPV status at early follow-up for predicting disease progression was 87.5%, and the negative predictive value was 89.3%. ctHPV DNA was found in plasma before relapse was diagnosed using radiology in all patients (n = 10) who experienced relapse after complete clinical response to treatment with a median 315 days lead time. Conclusions: ctHPV DNA in follow-up plasma is a promising prognostic biomarker in patients with LACC, useful for analysis of response to therapy and for early detection of relapse.
Treg–tissue cell interactions in repair and regeneration
Authors: Lucas F. Loffredo, Thomas M. Savage, Olivia R. Ringham, Nicholas Arpaia
Journal: The Journal of Experimental Medicine (2024)

Regulatory T (Treg) cells are classically known for their critical immunosuppressive functions that support peripheral tolerance. More recent work has demonstrated that Treg cells produce pro-repair mediators independent of their immunosuppressive function, a process that is critical to repair and regeneration in response to numerous tissue insults. These factors act on resident parenchymal and structural cells to initiate repair in a tissue-specific context. This review examines interactions between Treg cells and tissue-resident non-immune cells—in the context of tissue repair, fibrosis, and cancer—and discusses areas for future exploration.
Cardiovascular Risk Associated With Social Determinants of Health at Individual and Area Levels
Authors: Mengying Xia, Jaejin An, Monika M. Safford, Lisandro D. Colantonio, Mario Sims, Kristi Reynolds, Andrew E. Moran, Yiyi Zhang
Journal: JAMA Network Open (2024)

The benefit of adding social determinants of health (SDOH) when estimating atherosclerotic cardiovascular disease (ASCVD) risk is unclear.
Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022
Authors: Marc C Shamier, Luca M Zaeck, Hannelore M Götz, Bruno Vieyra, Babs E Verstrepen, Koen Wijnans, Matthijs RA Welkers, Elske Hoornenborg, Brigitte AGL van Cleef, Martin E van Royen, Kai J Jonas, Marion PG Koopmans, Rory D de Vries, David AMC van de Vijver, Corine H GeurtsvanKessel
Journal: Eurosurveillance (2024)

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.
Materials Strategies to Overcome the Foreign Body Response
Authors: Xianchi Zhou, Youxiang Wang, Jian Ji, Peng Zhang
Journal: Advanced Healthcare Materials (2024)

The foreign body response (FBR) is an immune-mediated reaction that can occur with most biomaterials and biomedical devices. The FBR initiates a deterioration in the performance of implantable devices, representing a longstanding challenge that consistently hampers their optimal utilization. Over the last decade, significant strides are achieved based on either hydrogel design or surface modifications to mitigate the FBR. This review delves into recent material strategies aimed at mitigating the FBR. Further, the authors look forward to future novel anti-FBR materials from the perspective of clinical translation needs. Such prospective materials hold the potential to attenuate local immune responses, thereby significantly enhancing the overall performance of implantable devices.
Bacterial membrane vesicles in the pathogenesis and treatment of inflammatory bowel disease
Authors: Chinasa Valerie Olovo, Dickson Kofi Wiredu Ocansey, Ying Ji, Xinxiang Huang, Min Xu
Journal: Gut Microbes (2024)

Inflammatory bowel disease (IBD) is a chronic and debilitating condition of relapsing and remitting inflammation in the gastrointestinal tract. Conventional therapeutic approaches for IBD have shown limited efficacy and detrimental side effects, leading to the quest for novel and effective treatment options for the disease. Bacterial membrane vesicles (MVs) are nanosized lipid particles secreted by lysis or blebbing processes from both Gram-negative and Gram-positive bacteria. These vesicles, known to carry bioactive components, are facsimiles of the parent bacterium and have been implicated in the onset and progression, as well as in the amelioration of IBD. This review discusses the overview of MVs and their impact in the pathogenesis, diagnosis, and treatment of IBD. We further discuss the technical challenges facing this research area and possible research questions addressing these challenges. We summarize recent advances in the diverse relationship between IBD and MVs, and the application of this knowledge as a viable and potent therapeutic strategy for IBD.
Availability of drugs for the treatment of multidrug-resistant/rifampicin-resistant tuberculosis in the World Health Organization European Region, October 2023
Authors: Ralf Otto-Knapp, Suzanne Edwards, Giorgi Kuchukhidze, Stefan Kröger, Brit Häcker, Stela Bivol, Askar Yedilbayev
Journal: Eurosurveillance (2024)

The BPaLM regimen (bedaquiline, pretomanid, linezolid and moxifloxacin) recently recommended by the World Health Organization offers short, safe, and effective treatment for multidrug-resistant/rifampicin-resistant tuberculosis (TB). In a survey with national TB focal points in 18 central and western European countries to explore barriers for the implementation of BPaLM, only three reported full availability of pretomanid, a necessary component of this regimen. Implementation barriers included financing and procurement. Solutions on national and supranational level are needed to guarantee universal access.
Apolipoprotein E controls Dectin-1-dependent development of monocyte-derived alveolar macrophages upon pulmonary β-glucan-induced inflammatory adaptation
Authors: H. Theobald, D. A. Bejarano, N. Katzmarski, J. Haub, J. Schulte-Schrepping, J. Yu, K. Bassler, A. L. Ament, C. Osei-Sarpong, F. Piattini, L. Vornholz, W. T’Jonck, A. H. Györfi, H. Hayer, X. Yu, S. Sheoran, A. Al Jawazneh, S. Chakarov, K. Haendler, G. D. Brown, D. L. Williams, L. Bosurgi, J. H. W. Distler, F. Ginhoux, J. Ruland, M. D. Beyer, M. Greter, C. C. Bain, A. I. Vazquez-Armendariz, M. Kopf, J. L. Schultze, A. Schlitzer
Journal: Nature Immunology (2024)

The lung is constantly exposed to the outside world and optimal adaptation of immune responses is crucial for efficient pathogen clearance. However, mechanisms that lead to lung-associated macrophages' functional and developmental adaptation remain elusive. To reveal such mechanisms, we developed a reductionist model of environmental intranasal β-glucan exposure, allowing for the detailed interrogation of molecular mechanisms of pulmonary macrophage adaptation. Employing single-cell transcriptomics, high-dimensional imaging and flow cytometric characterization paired with in vivo and ex vivo challenge models, we reveal that pulmonary low-grade inflammation results in the development of apolipoprotein E (ApoE)-dependent monocyte-derived alveolar macrophages (ApoE
Bispecific T cell engager therapy for refractory rheumatoid arthritis
Authors: Laura Bucci, Melanie Hagen, Tobias Rothe, Maria Gabriella Raimondo, Filippo Fagni, Carlo Tur, Andreas Wirsching, Jochen Wacker, Artur Wilhelm, Jean-Philippe Auger, Milena Pachowsky, Markus Eckstein, Stefano Alivernini, Angelo Zoli, Gerhard Krönke, Stefan Uderhardt, Aline Bozec, Maria-Antonietta D’Agostino, Georg Schett, Ricardo Grieshaber-Bouyer
Journal: Nature Medicine (2024)
Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions
Authors: Mark P Purdue, Diptavo Dutta, Mitchell J Machiela, Bryan R Gorman, Timothy Winter, Dayne Okuhara, Sara Cleland, Aida Ferreiro-Iglesias, Paul Scheet, Aoxing Liu, Chao Wu, Samuel O Antwi, James Larkin, Stênio C Zequi, Maxine Sun, Keiko Hikino, Ali Hajiran, Keith A Lawson, Flavio Cárcano, Odile Blanchet, Brian Shuch, Kenneth G Nepple, Gaëlle Margue, Debasish Sundi, W Ryan Diver, Maria A A K Folgueira, Adrie van Bokhoven, Florencia Neffa, Kevin M Brown, Jonathan N Hofmann, Jongeun Rhee, Meredith Yeager, Nathan R Cole, Belynda D Hicks, Michelle R Manning, Amy A Hutchinson, Nathaniel Rothman, Wen-Yi Huang, W Marston Linehan, Adriana Lori, Matthieu Ferragu, Merzouka Zidane-Marinnes, Sérgio V Serrano, Wesley J Magnabosco, Ana Vilas, Ricardo Decia, Florencia Carusso, Laura S Graham, Kyra Anderson, Mehmet A Bilen, Cletus Arciero, Isabelle Pellegrin, Solène Ricard, Ghislaine Scelo, Rosamonde E Banks, Naveen S Vasudev, Naeem Soomro, Grant D Stewart, Adebanji Adeyoju, Stephen Bromage, David Hrouda, Norma Gibbons, Poulam Patel, Mark Sullivan, Andrew Protheroe, Francesca I Nugent, Michelle J Fournier, Xiaoyu Zhang, Lisa J Martin, Maria Komisarenko, Timothy Eisen, Sonia A Cunningham, Denise C Connolly, Robert G Uzzo, David Zaridze, Anush Mukeria, Ivana Holcatova, Anna Hornakova, Lenka Foretova, Vladimir Janout, Dana Mates, Viorel Jinga, Stefan Rascu, Mirjana Mijuskovic, Slavisa Savic, Sasa Milosavljevic, Valérie Gaborieau, Behnoush Abedi-Ardekani, James McKay, Mattias Johansson, Larry Phouthavongsy, Lindsay Hayman, Jason Li, Ilinca Lungu, Stephania M Bezerra, Aline G Souza, Claudia T G Sares, Rodolfo B Reis, Fabio P Gallucci, Mauricio D Cordeiro, Mark Pomerantz, Gwo-Shu M Lee, Matthew L Freedman, Anhyo Jeong, Samantha E Greenberg, Alejandro Sanchez, R Houston Thompson, Vidit Sharma, David D Thiel, Colleen T Ball, Diego Abreu, Elaine T Lam, William C Nahas, Viraj A Master, Alpa V Patel, Jean-Christophe Bernhard, Neal D Freedman, Pierre Bigot, Rui M Reis, Leandro M Colli, Antonio Finelli, Brandon J Manley, Chikashi Terao, Toni K Choueiri, Dirce M Carraro, Richard Houlston, Jeanette E Eckel-Passow, Philip H Abbosh, Andrea Ganna, Paul Brennan, Jian Gu, Stephen J Chanock
Journal: Nature Genetics (2024)
“This Patient Needs a Doctor, Not a Guideline!” The Zone of Uncertainty in Pulmonary Arterial Wedge Pressure Measurement
Authors: Samuel G Rayner, Ryan J Tedford, Peter J Leary, Susanna Mak, Brian A Houston
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

""This Patient Needs a Doctor - Not a Guideline!" The Zone of Uncertainty in Pulmonary Arterial Wedge Pressure Measurement." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
hadge: a comprehensive pipeline for donor deconvolution in single-cell studies
Authors: Fabiola Curion, Xichen Wu, Lukas Heumos, Mylene Mariana Gonzales André, Lennard Halle, Matiss Ozols, Melissa Grant-Peters, Charlotte Rich-Griffin, Hing-Yuen Yeung, Calliope A. Dendrou, Herbert B. Schiller, Fabian J. Theis
Journal: Genome biology (2024)

Single-cell multiplexing techniques (cell hashing and genetic multiplexing) combine multiple samples, optimizing sample processing and reducing costs. Cell hashing conjugates antibody-tags or chemical-oligonucleotides to cell membranes, while genetic multiplexing allows to mix genetically diverse samples and relies on aggregation of RNA reads at known genomic coordinates. We develop hadge (hashing deconvolution combined with genotype information), a Nextflow pipeline that combines 12 methods to perform both hashing- and genotype-based deconvolution. We propose a joint deconvolution strategy combining best-performing methods and demonstrate how this approach leads to the recovery of previously discarded cells in a nuclei hashing of fresh-frozen brain tissue.
Reply to Geoffrey H. Rosen, Nicholas H. Chakiryan, and Katie S. Murray’s Letter to the Editor re: Jim C. Hu, Melissa Assel, Mohamad E. Allaf, et al. Transperineal Versus Transrectal Magnetic Resonance Imaging–targeted and Systematic Prostate Biopsy to Prevent Infectious Complications: The PREVENT Randomized Trial. Eur Urol. 2024;86:61–68
Authors: Jim C Hu, Andrew J Vickers, Edward M Schaeffer
Journal: European Urology (2024)