tbuckley/cabot-search huggingface dataset:
Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases
Authors: Mandy Hector, Thomas Langmann, Anne Wolf
Journal: Progress in Retinal and Eye Research (2024)

Translocator protein (18 kDa) (Tspo), formerly known as peripheral benzodiazepine receptor is a highly conserved transmembrane protein primarily located in the outer mitochondrial membrane. In the central nervous system (CNS), especially in glia cells, Tspo is upregulated upon inflammation. Consequently, Tspo was used as a tool for diagnostic in vivo imaging of neuroinflammation in the brain and as a potential therapeutic target. Several synthetic Tspo ligands have been explored as immunomodulatory and neuroprotective therapy approaches. Although the function of Tspo and how its ligands exert these beneficial effects is not fully clear, it became a research topic of interest, especially in ocular diseases in the past few years. This review summarizes state-of-the-art knowledge of Tspo expression and its proposed functions in different cells of the retina including microglia, retinal pigment epithelium and Müller cells. Tspo is involved in cytokine signaling, oxidative stress and reactive oxygen species production, calcium signaling, neurosteroid synthesis, energy metabolism, and cholesterol efflux. We also highlight recent developments in preclinical models targeting Tspo and summarize the relevance of Tspo biology for ocular and retinal diseases. We conclude that glial upregulation of Tspo in different ocular pathologies and the use of Tspo ligands as promising therapeutic approaches in preclinical studies underline the importance of Tspo as a potential disease-modifying protein.
Immune Activation in Alzheimer Disease
Authors: Arnaud Mary, Renzo Mancuso, Michael T. Heneka
Journal: Annual Review of Immunology (2024)

Alzheimer disease (AD) is the most common neurodegenerative disease, and with no efficient curative treatment available, its medical, social, and economic burdens are expected to dramatically increase. AD is historically characterized by amyloid β (Aβ) plaques and tau neurofibrillary tangles, but over the last 25 years chronic immune activation has been identified as an important factor contributing to AD pathogenesis. In this article, we review recent and important advances in our understanding of the significance of immune activation in the development of AD. We describe how brain-resident macrophages, the microglia, are able to detect Aβ species and be activated, as well as the consequences of activated microglia in AD pathogenesis. We discuss transcriptional changes of microglia in AD, their unique heterogeneity in humans, and emerging strategies to study human microglia. Finally, we expose, beyond Aβ and microglia, the role of peripheral signals and different cell types in immune activation.
Nr4a1 enhances Wnt4 transcription to promote mesenchymal stem cell osteogenesis and alleviates inflammation-inhibited bone regeneration
Authors: Yangshuai Gao, Yuming Zou, Dimitri Sokolowskei, Xin Xing, Robert J. Tower, Zejia Lai, Jiawei Shi, Liheng Zhu, Quan Zheng, Aaron W. James, Jiajia Xu, Zhongmin Zhang
Journal: Molecular Therapy (2024)
Circuit-Specific Deep Brain Stimulation Provides Insights into Movement Control
Authors: Aryn H. Gittis, Roy V. Sillitoe
Journal: Annual Review of Neuroscience (2024)

Deep brain stimulation (DBS), a method in which electrical stimulation is delivered to specific areas of the brain, is an effective treatment for managing symptoms of a number of neurological and neuropsychiatric disorders. Clinical access to neural circuits during DBS provides an opportunity to study the functional link between neural circuits and behavior. This review discusses how the use of DBS in Parkinson's disease and dystonia has provided insights into the brain networks and physiological mechanisms that underlie motor control. In parallel, insights from basic science about how patterns of electrical stimulation impact plasticity and communication within neural circuits are transforming DBS from a therapy for treating symptoms to a therapy for treating circuits, with the goal of training the brain out of its diseased state.
Non-sleep related outcomes of maxillomandibular advancement, a systematic review
Authors: Joshua Yang, Misha L. Tan, Jean-Pierre T.F. Ho, Boudewijn R.A.M. Rosenmöller, Faridi S. Jamaludin, Tom C.T. van Riet, Jan de Lange
Journal: Sleep Medicine Reviews (2024)

Maxillomandibular advancement has been shown to be an effective treatment for obstructive sleep apnea; however, the literature focuses mainly on sleep-related parameters such as apnea-hypopnea index, respiratory disturbance index and Epworth sleepiness scale. Other factors that may be important to patients, such as esthetics, patient satisfaction, nasality, swallowing problems and so forth have been reported in the literature but have not been systematically studied. Together with an information specialist, an extensive search in Medline, Embase and Scopus yielded 1592 unique articles. Titles and abstracts were screened by two blinded reviewers. In total, 75 articles were deemed eligible for full-text screening and 38 articles were included for qualitative synthesis. The most common categories of non-sleep related outcomes found were surgical accuracy, facial esthetics, functional outcomes, quality of life, patient satisfaction, and emotional health. All categories were reported using heterogenous methods, such that meta-analysis could not be performed. There was lack of consistent methods to assess these outcomes. This work is the first to systematically review non-sleep related outcomes of maxillomandibular advancement. Despite growing interest in evaluating surgical outcomes through patient subjective experiences, this review points to the need of standardized, validated methods to report these outcomes.
Effects of oral roflumilast therapy on body weight and cardiometabolic parameters in patients with psoriasis – results from a randomized controlled trial (PSORRO)
Authors: Mette Gyldenløve, Jennifer Astrup Sørensen, Simon Fage, Howraman Meteran, Lone Skov, Claus Zachariae, Filip Krag Knop, Mia-Louise Nielsen, Alexander Egeberg
Journal: Journal of the American Academy of Dermatology (2024)

BackgroundWeight loss is reported with oral roflumilast, which is approved for chronic obstructive pulmonary disease (COPD). Recently, the drug has shown efficacy in psoriasis, a disease strongly linked to overweight/obesity.ObjectiveTo describe the effects of oral roflumilast on body weight and cardio-metabolic parameters in patients with psoriasis.MethodsPosthoc analyses from the PSORRO study, where patients with moderate-to-severe plaque psoriasis were randomized 1:1 to oral roflumilast 500 μg once-daily or placebo for 12 weeks, followed by active, open-label treatment through week 24 in both groups. Changes in body weight, blood pressure, gastrointestinal symptoms, and laboratory tests were registered. No lifestyle or dietary interventions were applied.ResultsForty-six patients were randomized. Baseline characteristics across groups were comparable; mean weight was 103.6 kg. In patients receiving roflumilast, median weight change was −2.6% and −4% at week 12 and 24, respectively. Corresponding numbers were 0.0% and 1.3% in patients initially allocated to placebo. Reduced appetite was more frequent with active therapy. No changes in blood pressure or laboratory tests were observed.LimitationsPosthoc analyses and low numbers.ConclusionOral roflumilast induced weight loss and reduced appetite, which support the growing evidence of roflumilast as an attractive treatment alternative for patients with psoriasis.
Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets
Authors: Ian R. Woodward, Catherine A. Fromen
Journal: Annual Review of Biomedical Engineering (2024)

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by the COVID-19 pandemic, pulmonary aerosol drug delivery has seen a flourish of activity, building on the prior decades of innovation in particle engineering, inhaler device technologies, and clinical understanding. As such, the field has expanded into new directions and is working toward the efficient delivery of increasingly complex cargos to address a wider range of respiratory diseases. This review seeks to highlight recent innovations in approaches to personalize inhalation drug delivery, deliver complex cargos, and diversify the targets treated and prevented through pulmonary drug delivery. We aim to inform readers of the emerging efforts within the field and predict where future breakthroughs are expected to impact the treatment of respiratory diseases.
On the pitfalls of Batch Normalization for end-to-end video learning: A study on surgical workflow analysis
Authors: Dominik Rivoir, Isabel Funke, Stefanie Speidel
Journal: Medical Image Analysis (2024)

Batch Normalization's (BN) unique property of depending on other samples in a batch is known to cause problems in several tasks, including sequential modeling. Yet, BN-related issues are hardly studied for long video understanding, despite the ubiquitous use of BN in CNNs (Convolutional Neural Networks) for feature extraction. Especially in surgical workflow analysis, where the lack of pretrained feature extractors has led to complex, multi-stage training pipelines, limited awareness of BN issues may have hidden the benefits of training CNNs and temporal models end to end. In this paper, we analyze pitfalls of BN in video learning, including issues specific to online tasks such as a 'cheating' effect in anticipation. We observe that BN's properties create major obstacles for end-to-end learning. However, using BN-free backbones, even simple CNN-LSTMs beat the state of the art on three surgical workflow benchmarks by utilizing adequate end-to-end training strategies which maximize temporal context. We conclude that awareness of BN's pitfalls is crucial for effective end-to-end learning in surgical tasks. By reproducing results on natural-video datasets, we hope our insights will benefit other areas of video learning as well. Code is available at: https://gitlab.com/nct_tso_public/pitfalls_bn.
Predictive Processing: A Circuit Approach to Psychosis
Authors: Georg B. Keller, Philipp Sterzer
Journal: Annual Review of Neuroscience (2024)

Predictive processing is a computational framework that aims to explain how the brain processes sensory information by making predictions about the environment and minimizing prediction errors. It can also be used to explain some of the key symptoms of psychotic disorders such as schizophrenia. In recent years, substantial advances have been made in our understanding of the neuronal circuitry that underlies predictive processing in cortex. In this review, we summarize these findings and how they might relate to psychosis and to observed cell type–specific effects of antipsychotic drugs. We argue that quantifying the effects of antipsychotic drugs on specific neuronal circuit elements is a promising approach to understanding not only the mechanism of action of antipsychotic drugs but also psychosis. Finally, we outline some of the key experiments that should be done. The aims of this review are to provide an overview of the current circuit-based approaches to psychosis and to encourage further research in this direction.
Direct Electron Transfer–Type Oxidoreductases for Biomedical Applications
Authors: Keisei Sowa, Junko Okuda-Shimazaki, Eole Fukawa, Koji Sode
Journal: Annual Review of Biomedical Engineering (2024)

Among the various types of enzyme-based biosensors, sensors utilizing enzymes capable of direct electron transfer (DET) are recognized as the most ideal. However, only a limited number of redox enzymes are capable of DET with electrodes, that is, dehydrogenases harboring a subunit or domain that functions specifically to accept electrons from the redox cofactor of the catalytic site and transfer the electrons to the external electron acceptor. Such subunits or domains act as built-in mediators for electron transfer between enzymes and electrodes; consequently, such enzymes enable direct electron transfer to electrodes and are designated as DET-type enzymes. DET-type enzymes fall into several categories, including redox cofactors of catalytic reactions, built-in mediators for DET with electrodes and by their protein hierarchic structures, DET-type oxidoreductases with oligomeric structures harboring electron transfer subunits, and monomeric DET-type oxidoreductases harboring electron transfer domains. In this review, we cover the science of DET-type oxidoreductases and their biomedical applications. First, we introduce the structural biology and current understanding of DET-type enzyme reactions. Next, we describe recent technological developments based on DET-type enzymes for biomedical applications, such as biosensors and biochemical energy harvesting for self-powered medical devices. Finally, after discussing how to further engineer and create DET-type enzymes, we address the future prospects for DET-type enzymes in biomedical engineering.
A metatranscriptomics strategy for efficient characterization of the microbiome in human tissues with low microbial biomass
Authors: Joana Pereira-Marques, Rui M. Ferreira, Ceu Figueiredo
Journal: Gut Microbes (2024)

The high background of host RNA poses a major challenge to metatranscriptome analysis of human samples. Hence, metatranscriptomics has been mainly applied to microbe-rich samples, while its application in human tissues with low ratio of microbial to host cells has yet to be explored. Since there is no computational workflow specifically designed for the taxonomic and functional analysis of this type of samples, we propose an effective metatranscriptomics strategy to accurately characterize the microbiome in human tissues with a low ratio of microbial to host content. We experimentally generated synthetic samples with well-characterized bacterial and host cell compositions, and mimicking human samples with high and low microbial loads. These synthetic samples were used for optimizing and establishing the workflow in a controlled setting. Our results show that the integration of the taxonomic analysis of optimized Kraken 2/Bracken with the functional analysis of HUMAnN 3 in samples with low microbial content, enables the accurate identification of a large number of microbial species with a low false-positive rate, while improving the detection of microbial functions. The effectiveness of our metatranscriptomics workflow was demonstrated in synthetic samples, simulated datasets, and most importantly, human gastric tissue specimens, thus providing a proof of concept for its applicability on mucosal tissues of the gastrointestinal tract. The use of an accurate and reliable metatranscriptomics approach for human tissues with low microbial content will expand our understanding of the functional activity of the mucosal microbiome, uncovering critical interactions between the microbiome and the host in health and disease.
Heterogeneity of Distal Convoluted Tubule Cells
Authors: Adrián R. Murillo-de-Ozores, Lihe Chen
Journal: Journal of the American Society of Nephrology (2024)

Epithelial Systems Biology Laboratory, Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland Correspondence: Dr. Lihe Chen, email: [email protected] See related article, "Enriched Single-Nucleus RNA-Sequencing Reveals Unique Attributes of Distal Convoluted Tubule Cells," on pages 426–440.
Author Correction: Tissue-resident macrophages exacerbate lung injury after remote sterile damage
Authors: Hanhui Zhong, Jingjing Ji, Jinling Zhuang, Ziying Xiong, Pengyun Xie, Xiaolei Liu, Jundi Zheng, Wangli Tian, Xiaoyang Hong, Jing Tang
Journal: Cellular and Molecular Immunology (2024)
Developments in predictive biomarker testing and targeted therapy in advanced stage non-small cell lung cancer and their application across European countries
Authors: Vincent D. de Jager, Wim Timens, Arnaud Bayle, Johan Botling, Luka Brcic, Reinhard Büttner, Maria Gabriela O. Fernandes, Libor Havel, Maximilian J. Hochmair, Paul Hofman, Annelies Janssens, Mikael Johansson, Léon van Kempen, Izidor Kern, Fernando Lopez-Rios, Margreet Lüchtenborg, José Carlos Machado, Katja Mohorcic, Luis Paz-Ares, Sanjay Popat, Aleš Ryška, Phillipe Taniere, Jürgen Wolf, Ed Schuuring, Anthonie J. van der Wekken
Journal: The Lancet Regional Health - Europe (2024)

In the past two decades, the treatment of metastatic non-small cell lung cancer (NSCLC), has undergone significant changes due to the introduction of targeted therapies and immunotherapy. These advancements have led to the need for predictive molecular tests to identify patients eligible for targeted therapy. This review provides an overview of the development and current application of targeted therapies and predictive biomarker testing in European patients with advanced stage NSCLC. Using data from eleven European countries, we conclude that recommendations for predictive testing are incorporated in national guidelines across Europe, although there are differences in their comprehensiveness. Moreover, the availability of recently EMA-approved targeted therapies varies between European countries. Unfortunately, routine assessment of national/regional molecular testing rates is limited. As a result, it remains uncertain which proportion of patients with metastatic NSCLC in Europe receive adequate predictive biomarker testing. Lastly, Molecular Tumor Boards (MTBs) for discussion of molecular test results are widely implemented, but national guidelines for their composition and functioning are lacking. The establishment of MTB guidelines can provide a framework for interpreting rare or complex mutations, facilitating appropriate treatment decision-making, and ensuring quality control.
Multilayered Immunity by Tissue-Resident Lymphocytes in Cancer
Authors: Ming O. Li, Jing Zhang, Zijian Xu, Xian Zhang, Peng Li, Andrew E. Cornish
Journal: Annual Review of Immunology (2024)

Lymphocytes spanning the entire innate-adaptive spectrum can stably reside in tissues and constitute an integral component of the local defense network against immunological challenges. In tight interactions with the epithelium and endothelium, tissue-resident lymphocytes sense antigens and alarmins elicited by infectious microbes and abiotic stresses at barrier sites and mount effector responses to restore tissue homeostasis. Of note, such a host cell–directed immune defense system has been recently demonstrated to surveil epithelial cell transformation and carcinoma development, as well as cancer cell metastasis at selected distant organs, and thus represents a primordial cancer immune defense module. Here we review how distinct lineages of tissue-resident innate lymphoid cells, innate-like T cells, and adaptive T cells participate in a form of multilayered cancer immunity in murine models and patients, and how their convergent effector programs may be targeted through both shared and private regulatory pathways for cancer immunotherapy.
Future perspective for the application of predictive biomarker testing in advanced stage non-small cell lung cancer
Authors: Vincent D. de Jager, Wim Timens, Arnaud Bayle, Johan Botling, Luka Brcic, Reinhard Büttner, Maria Gabriela O. Fernandes, Libor Havel, Maximilian Hochmair, Paul Hofman, Annelies Janssens, Léon van Kempen, Izidor Kern, José Carlos Machado, Katja Mohorčič, Sanjay Popat, Aleš Ryška, Jürgen Wolf, Ed Schuuring, Anthonie J. van der Wekken
Journal: The Lancet Regional Health - Europe (2024)

For patients with advanced stage non-small cell lung cancer (NSCLC), treatment strategies have changed significantly due to the introduction of targeted therapies and immunotherapy. In the last few years, we have seen an explosive growth of newly introduced targeted therapies in oncology and this development is expected to continue in the future. Besides primary targetable aberrations, emerging diagnostic biomarkers also include relevant co-occurring mutations and resistance mechanisms involved in disease progression, that have impact on optimal treatment management. To accommodate testing of pending biomarkers, it is necessary to establish routine large-panel next-generation sequencing (NGS) for all patients with advanced stage NSCLC. For cost-effectiveness and accessibility, it is recommended to implement predictive molecular testing using large-panel NGS in a dedicated, centralized expert laboratory within a regional oncology network. The central molecular testing center should host a regional Molecular Tumor Board and function as a hub for interpretation of rare and complex testing results and clinical decision-making.
Current and Future Approaches to Pediatric Anxiety Disorder Treatment
Authors: Andre Zugman, Anderson M. Winkler, Purnima Qamar, Daniel S. Pine
Journal: American Journal of Psychiatry (2024)

This overview critically appraises the literature on the treatment of pediatric anxiety disorders. The two established treatments for these conditions comprise cognitive-behavioral therapy (CBT) and antidepressant medications. Many youths receiving these treatments fail to achieve remission, which creates a need for new treatments. After summarizing the literature on CBT and currently available medications, the authors describe research that lays a foundation for improvements in the treatment of pediatric anxiety disorders. This foundation leverages neuroscientific investigations, also described in the overview, which provide insights on mechanisms of successful treatment.