tbuckley/cabot-search huggingface dataset:
Vitamin D and Its Analogues in Immune System Regulation
Authors: Patricio Artusa, John H White
Journal: Pharmacological Reviews (2024)

Vitamin D was discovered as the cure for nutritional rickets, a disease of bone growth arising from inadequate intestinal calcium absorption, and for much of the 20th century, it was studied for its critical role in calcium homeostasis. However, we now recognize that the vitamin D receptor and vitamin D metabolic enzymes are expressed in numerous tissues unrelated to calcium homeostasis. Notably, vitamin D signaling can induce cellular differentiation and cell cycle arrest. Moreover, the vitamin D receptor and the enzyme CYP27B1, which produces the hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), are expressed throughout the immune system. In addition, CYP27B1 expression in immune cells is regulated by physiological inputs independent of those controlling its expression in calcium homeostatic tissues. These observations have driven the development of 1,25D-like secosteroidal analogs and nonsecosteroidal analogs to separate the effects of vitamin D on cell differentiation and function from its calcemic activities. Notably, some of these analogs have had considerable success in the clinic in the treatment of inflammatory and immune-related disorders. In this review, we described in detail the mechanisms of vitamin D signaling and the physiological signals controlling 1,25D synthesis and catabolism, with a focus on the immune system. We also surveyed the effects of 1,25D and its analogs on the regulation of immune system function and their implications for human immune-related disorders. Finally, we described the potential of vitamin D analogs as anticancer therapeutics, in particular, their use as adjuncts to cancer immunotherapy. SIGNIFICANCE STATEMENT: Vitamin D signaling is active in both the innate and adaptive arms of the immune system. Numerous vitamin D analogs, developed primarily to minimize the dose-limiting hypercalcemia of the active form of vitamin D, have been used widely in preclinical and clinical studies of immune system regulation. This review presents a description of the mechanisms of action of vitamin D signaling, an overview of analog development, and an in-depth discussion of the immunoregulatory roles of vitamin D analogs.
Interferon-ε loss is elusive 9p21 link to immune-cold tumors, resistant to immune-checkpoint therapy and endogenous CXCL9/10 induction
Authors: Xin Zhao, Bin Liu, William N William, Kaloyan M Tsanov, Yu-Jui Ho, Francisco M Barriga, Raymond J Lim, Maria Trifas, Yushen Du, Scott W Lowe, Steven M Dubinett, Teresa Davoli, Scott M Lippman
Journal: Journal of Thoracic Oncology (2024)
Decoding community-acquired pneumonia: a systematic review and analysis of diagnostic criteria and definitions used in clinical trials
Authors: Markus Fally, Jan Hansel, Rebecca C Robey, Faiuna Haseeb, Ahmed Kouta, Thomas Williams, Timothy Felton, Alexander G Mathioudakis
Journal: Clinical Microbiology and Infection (2024)

Community-acquired pneumonia (CAP) is a frequent and potentially life-threatening condition. Even though the disease is common, evidence on CAP management is often of variable quality. This may be reinforced by the lack of a systematic and homogeneous way of defining the disease in randomised controlled trials (RCTs).
Natural antibodies to polysaccharide capsules enable Kupffer cells to capture invading bacteria in the liver sinusoids
Authors: Xianbin Tian, Yanni Liu, Kun Zhu, Haoran An, Jie Feng, Linqi Zhang, Jing-Ren Zhang
Journal: The Journal of Experimental Medicine (2024)

The interception of blood-borne bacteria in the liver defines the outcomes of invasive bacterial infections, but the mechanisms of this antibacterial immunity are not fully understood. This study shows that natural antibodies (nAbs) to capsules enable liver macrophage Kupffer cells (KCs) to rapidly capture and kill blood-borne encapsulated bacteria in mice. Affinity pulldown with serotype-10A capsular polysaccharides (CPS10A) of Streptococcus pneumoniae (Spn10A) led to the identification of CPS10A-binding nAbs in serum. The CPS10A–antibody interaction enabled KCs to capture Spn10A bacteria from the bloodstream, in part through complement receptors on KCs. The nAbs were found to recognize the β1-6-linked galactose branch of CPS10A and similar moieties of serotype-39 S. pneumoniae and serotype-K50 Klebsiella pneumoniae capsules. More importantly, the nAbs empowered KCs to capture serotype-39 S. pneumoniae and serotype-K50 K. pneumoniae in the liver. Collectively, our data have revealed a highly effective immune function of nAb against encapsulated bacteria and emphasize the concept of treating septic encapsulated bacterial diseases with monoclonal antibodies.
Next step towards functional precision medicine in neuro-oncology
Authors: Tobias Weiss, Sohyon Lee, Berend Snijder, Michael Weller
Journal: Neuro-Oncology (2024)

Journal Article Corrected proof Next step towards functional precision medicine in neuro-oncology Get access Tobias Weiss, Tobias Weiss Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland Corresponding Author: Tobias Weiss, MD, PhD, Department of Neurology, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland ([email protected]). https://orcid.org/0000-0002-5533-9429 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sohyon Lee, Sohyon Lee Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Berend Snijder, Berend Snijder Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Weller Michael Weller Department of Neurology, Clinical Neuroscience Center, University Hospital and University of Zurich, Zurich, Switzerland https://orcid.org/0000-0002-1748-174X Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noae233, https://doi.org/10.1093/neuonc/noae233 Published: 24 December 2024 Article history Corrected and typeset: 24 December 2024 Published: 24 December 2024
The Combination of Aligned PDA‐Fe@PLCL Conduit with Aligned GelMA Hydrogel Promotes Peripheral Nerve Regeneration
Authors: Penghui Wang, Jiongming You, Guang Liu, Qiming Wang, Linjie Zhang, Xinwu Lu, Jinbao Qin, Zhihui Dong, Bingcheng Yi, Qun Huang
Journal: Advanced Healthcare Materials (2024)

Abstract Biomaterial‐assisted therapeutic strategies enable precise modulation to direct endogenous cellular responses and harness regenerative capabilities for nerve repair. However, achieving effective cellular engagement during nerve remodeling remains challenging. Herein, a novel composite nerve guidance conduit (NGC), the GelMA/PLys@PDA‐Fe@PLCL conduit is developed by combining aligned poly( l ‐lactide‐co‐caprolactone) (PLCL) nanofibers modified with polydopamine (PDA), ferrous iron (Fe 3 ⁺), and polylysine (PLys) with aligned methacrylate‐anhydride gelatin (GelMA) hydrogel nanofibers. PDA films exhibit strong adhesion and metal coordination properties, allowing Fe 3 ⁺ irons to chelate with phenolic hydroxyl groups of dopamine derivatives, forming a metal‐phenolic network on PLCL. PLys molecules are then grafted onto PDA‐Fe 3 ⁺ coating via Schiff base and Michael addition reactions. This multifunctional coating enhances surface roughness and zeta potential of PLCL nanofibers, imparts superhydrophilicity with anisotropic wetting behavior, and maintains wet tensile properties of substrates. In vitro studies show that the PLys@PDA‐Fe coating significantly promotes aligned distribution of Schwann cells, improves cell adhesion and differentiation, and demonstrates notable antioxidant and anti‐inflammatory properties. When implanted into nerve defects in rats, the multifunctional coating conduit combined with aligned GelMA hydrogel effectively accelerates axonal regeneration, remyelination, and angiogenesis, leading to enhanced motor function recovery. Overall, the GelMA/PLys@PDA‐Fe@PLCL conduit presents a promising strategy for advancing peripheral nerve repair.
In Vivo‐Like Scaffold‐Free 3D In Vitro Models of Muscular Dystrophies: The Case for Anchored Cell Sheet Engineering in Personalized Medicine
Authors: Alireza Shahin‐Shamsabadi, John Cappuccitti
Journal: Advanced Healthcare Materials (2024)

Abstract Progress in understanding the underlying mechanisms of muscular dystrophies is hindered by the lack of pathophysiologically relevant in vitro models. Here, an entirely scaffold‐free anchored cell sheet engineering platform is used to create patient‐specific three‐dimensional (3D) skeletal muscle in vitro models. This approach effectively replicates mature muscle phenotypes and tissue‐ and disease‐specific extracellular matric (ECM). Models were developed using primary cells from healthy individuals and patients with Duchenne Muscular Dystrophy and Myotonic Dystrophy Type 1. Through a combination of quantified histological staining (Hematoxylin &amp; Eosin, Movat's Pentachrome, Masson's Trichrome) and immunostaining (desmin, myosin heavy chain, laminin, and dystrophin), it was demonstrated that the models formed mature constructs closely resembling their respective in vivo conditions. Proteomics analysis revealed that the models exhibited appropriate upregulation and downregulation of disease‐relevant pathways. Models of diseased tissues accurately reflected key phenotypic features of the diseases, including alterations in muscle fiber integrity and ECM composition. Upon treatment with therapeutically beneficial drugs, significant changes in their proteomic profiles were documented, highlighting the models’ potential for drug screening. This novel in vitro modeling approach, unlike other 3D techniques that rely on exogenous biomaterials that interfere with natural cellular behaviors, provides a promising platform for studying muscular dystrophies.
Transcriptomic Profiles of the Nasal Mucosa Following Birch Pollen Provocation Differ Between Birch Pollen‐Allergic and Non‐Allergic Individuals
Authors: Srinidhi Sudharson, Julia Eckl‐Dorna, Anastasia Meshcheryakova, José Basílio, Sophia Derdak, Tanja Kalic, Nina Lengger, Nina Schweitzer, Diana Mechtcheriakova, Heimo Breiteneder, Christine Hafner
Journal: Allergy (2024)

Birch pollen (BP) interacts with airway epithelial cells to cause allergic sensitization and allergy in predisposed individuals. However, the basic mechanisms underlying the clinical effects are poorly understood. Changes in gene expression and cytokine secretion in nasal mucosal cells upon BP exposure were determined in BP-allergic and non-allergic individuals.
A comparison between 64-projection and 32-projection myocardial perfusion scintigraphy
Authors: Seyed Mohammad Abedi, Erfan Ghadirzadeh, Hanie Karimi, Pedram Nezhadnaderi, Seyede Sepide Daryabari, Amir Moradi, Alireza Khorrami Moghaddam, Seyed Jalal Hosseinimehr, Morteza Taghavi, Samad Golshani, Ali Asghar Farsavian, Alireza Mardanshahi, Ali Mostafavinia
Journal:  (2024)

Abstract Aims While most clinical guidelines recommend using a 64-projection view technique, some protocols do not specify a preference between 32-projection and 64-projection methods for conducting myocardial perfusion scintigraphy (MPS), which shows the lack of consensus in this matter. Nevertheless, these guidelines and protocols have not provided us with compelling evidence to support why the 64-projection technique is usually chosen. Thus, we aimed to determine if there is a significant difference between them in the assessment of cardiac perfusion and functional indices. Methods and results Sixty-nine patients were included in this pilot prospective, cross-sectional, cross-over, same patient control protocol study and underwent 32- and 64-projection MPS at both stress and rest phases after injecting 740–925 MBq of 99mTc-MIBI for every patient. Then, cardiac indices, including summed stress, rest, and difference scores, extent-stress and rest, left ventricular volumes and ejection-fraction, peak filling rate (PFR), and time to peak filling rate (TTPF) were recorded. Lin’s concordance correlation coefficient was used to assess the agreement between protocols, and a paired sample t-test was used to compare the means of variables where appropriate. Findings revealed no significant difference as well as excellent/good agreement between the two methods in either the stress or rest state, except for the TTPF and PFR. Conclusion The findings suggest that lower-projection techniques could be adequate for routine clinical assessments without sacrificing diagnostic accuracy. However, the poor agreement for PFR and TTPF indicates that the 32-projection method may not reliably assess diastolic function, implying that the 64-projection protocol is preferable when precise evaluations are necessary.
The potential of Generative Pre-trained Transformer 4 (GPT-4) to analyse medical notes in three different languages: a retrospective model-evaluation study
Authors: Maria Clara Saad Menezes, Alexander F Hoffmann, Amelia L M Tan, Mariné Nalbandyan, Gilbert S Omenn, Diego R Mazzotti, Alejandro Hernández-Arango, Shyam Visweswaran, Shruthi Venkatesh, Kenneth D Mandl, Florence T Bourgeois, James W K Lee, Andrew Makmur, David A Hanauer, Michael G Semanik, Lauren T Kerivan, Terra Hill, Julian Forero, Carlos Restrepo, Matteo Vigna, Piero Ceriana, Noor Abu-El-Rub, Paul Avillach, Riccardo Bellazzi, Thomas Callaci, Alba Gutiérrez-Sacristán, Alberto Malovini, Jomol P Mathew, Michele Morris, Venkatesh L Murthy, Tommaso M Buonocore, Enea Parimbelli, Lav P Patel, Carlos Sáez, Malarkodi Jebathilagam Samayamuthu, Jeffrey A Thompson, Valentina Tibollo, Zongqi Xia, Isaac S Kohane
Journal: The Lancet Digital Health (2024)
Leveraging artificial intelligence for predicting spontaneous closure of perimembranous ventricular septal defect in children: a multicentre, retrospective study in China
Authors: Jing Sun, Tienan Feng, Bo Wang, Fen Li, Bo Han, Maoping Chu, Fangqi Gong, Qijian Yi, Xin Zhou, Sun Chen, Xin Sun, Kun Sun
Journal: The Lancet Digital Health (2024)
A prospectively deployed deep learning-enabled automated quality assurance tool for oncological palliative spine radiation therapy
Authors: Christopher E Kehayias, Dennis Bontempi, Sarah Quirk, Scott Friesen, Jeremy Bredfeldt, Tara Kosak, Meghan Kearney, Roy Tishler, Itai Pashtan, Mai Anh Huynh, Hugo J W L Aerts, Raymond H Mak, Christian V Guthier
Journal: The Lancet Digital Health (2024)
Tachykinin signaling in the right parabrachial nucleus mediates early-phase neuropathic pain development
Authors: Yinxia Li, Ngoc T Ha, Juan Li, Yaxin Yan, Qian Chen, Liping Cai, Weike Li, Shoupei Liu, Bo Li, Tianlin Cheng, Yangang Sun, Yingwei Wang, Juan Deng
Journal: Neuron (2024)

The lateral parabrachial nucleus (PBN) is critically involved in neuropathic pain modulation. However, the cellular and molecular mechanisms underlying this process remain largely unknown. Here, we report that in mice, the right-sided, but not the left-sided, PBN plays an essential role in the development of hyperalgesia following nerve injury, irrespective of the injury side. Spino-parabrachial pathways targeting the right-sided PBN display short-term facilitation, and right-sided PBN neurons exhibit an increase in the excitability and activity after nerve injury. Inhibiting Tacr1-positive neurons, blocking Tacr1-encoding tachykinin 1 receptor (NK1R), or knocking down the Tacr1 gene in the right-sided, rather than left-sided, PBN alleviates neuropathic pain-induced sensory hypersensitivity. Additionally, the right-sided PBN plays a critical role in the development of hyperalgesia during the early phase of neuropathic pain. These results highlight the essential role of NK1R in the lateralized modulation of neuropathic pain by the PBN, providing new insights into the mechanisms underlying neuropathic pain.
An intermediate open structure reveals the gating transition of the mechanically activated PIEZO1 channel
Authors: Sijia Liu, Xuzhong Yang, Xudong Chen, Xiaochun Zhang, Jinghui Jiang, Jingyi Yuan, Wenhao Liu, Li Wang, Heng Zhou, Kun Wu, Boxue Tian, Xueming Li, Bailong Xiao
Journal: Neuron (2024)
Durable lymphocyte subset elimination upon a single dose of AAV-delivered depletion antibody dissects immune control of chronic viral infection
Authors: Anna Lena Kastner, Anna-Friederike Marx, Mirela Dimitrova, Tiago Abreu-Mota, Yusuf I Ertuna, Weldy V Bonilla, Karsten Stauffer, Marco Künzli, Ingrid Wagner, Mario Kreutzfeldt, Doron Merkler, Daniel D Pinschewer
Journal: Immunity (2024)

To interrogate the role of specific immune cells in infection, cancer, and autoimmunity, immunologists commonly use monoclonal depletion antibodies (depletion-mAbs) or genetically engineered mouse models (GEMMs). To generate a tool that combines specific advantages and avoids select drawbacks of the two methods, we engineered adeno-associated viral vectors expressing depletion mAbs (depletion-AAVs). Single-dose depletion-AAV administration durably eliminated lymphocyte subsets in mice and avoided accessory deficiencies of GEMMs, such as marginal zone defects in B cell-deficient animals. Depletion-AAVs can be used in animals of different genetic backgrounds, and multiple depletion-AAVs can readily be combined. Exploiting depletion-AAV technology, we showed that B cells were required for unimpaired CD4
CRISPR-Cas spacer acquisition is a rare event in human gut microbiome
Authors: An-Ni Zhang, Jeffry M Gaston, Pablo Cárdenas, Shijie Zhao, Xiaoqiong Gu, Eric J Alm
Journal: Cell Genomics (2024)

Host-parasite relationships drive the evolution of both parties. In microbe-phage dynamics, CRISPR functions as an adaptive defense mechanism, updating immunity via spacer acquisition. Here, we investigated these interactions within the human gut microbiome, uncovering low frequencies of spacer acquisition at an average rate of one spacer every ∼2.9 point mutations using isolates' whole genomes and ∼2.7 years using metagenome time series. We identified a highly prevalent CRISPR array in Bifidobacterium longum spreading via horizontal gene transfer (HGT), with six spacers found in various genomic regions in 15 persons from the United States and Europe. These spacers, targeting two prominent Bifidobacterium phages, comprised 76% of spacer occurrence of all spacers targeting these phages in all B. longum populations. This result suggests that HGT of an entire CRISPR-Cas system introduced three times more spacers than local CRISPR-Cas acquisition in B. longum. Overall, our findings identified key ecological and evolutionary factors in prokaryote adaptive immunity.
A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion
Authors: Anna Flury, Leen Aljayousi, Hye-Jin Park, Mohammadparsa Khakpour, Jack Mechler, Siaresh Aziz, Jackson D McGrath, Pragney Deme, Colby Sandberg, Fernando González Ibáñez, Olivia Braniff, Thi Ngo, Simira Smith, Matthew Velez, Denice Moran Ramirez, Dvir Avnon-Klein, John W Murray, Jia Liu, Martin Parent, Susana Mingote, Norman J Haughey, Sebastian Werneburg, Marie-Ève Tremblay, Pinar Ayata
Journal: Neuron (2024)
A brain-wide map of descending inputs onto spinal V1 interneurons
Authors: Phillip D Chapman, Anand S Kulkarni, Alexandra J Trevisan, Katie Han, Jennifer M Hinton, Paulina Deltuvaite, Lief E Fenno, Charu Ramakrishnan, Mary H Patton, Lindsay A Schwarz, Stanislav S Zakharenko, Karl Deisseroth, Jay B Bikoff
Journal: Neuron (2024)

Motor output results from the coordinated activity of neural circuits distributed across multiple brain regions that convey information to the spinal cord via descending motor pathways. Yet the organizational logic through which supraspinal systems target discrete components of spinal motor circuits remains unclear. Here, using viral transsynaptic tracing along with serial two-photon tomography, we have generated a whole-brain map of monosynaptic inputs to spinal V1 interneurons, a major inhibitory population involved in motor control. We identified 26 distinct brain structures that directly innervate V1 interneurons, spanning medullary and pontine regions in the hindbrain as well as cortical, midbrain, cerebellar, and neuromodulatory systems. Moreover, we identified broad but biased input from supraspinal systems onto V1
Isolation of circulating tumor cells: recent progress and future perspectives
Authors: Ziheng Guo, Weiliang Xia
Journal: Med-X (2024)

Abstract Circulating tumor cells (CTCs) are cancer cells that shed from the primary tumor and enter into body fluids of the patient, where they travel to distant sites and ultimately form metastasis. Understanding the biology of CTCs, in particular at the critical stages of their itinerary, holds promises for better cancer cure. Since the beginning of this century, liquid biopsy has steadily grown to be a keen area of research due to its non-invasive features. As one of the most promising tumor biomarkers, CTCs have shown great potential in cancer diagnosis, prognosis, treatment response monitoring, and the exploration of biological mechanisms. Although various types of isolation and detection technologies emerge constantly, the rarity and heterogeneity of CTCs still pose huge challenges for these methods and make them inefficient. In addition, the clinical practice of different technologies still lacks reasonable and uniform standards. In this review, we provide a detailed overview of the isolation and enrichment strategies of CTCs, as well as their advantages and limitations. By summarizing the current status and suggesting future areas of CTCs research, we hope to continue the concerted effort for pushing forward the clinical application of CTCs, which may represent a paradigm shift for cancer theranostics in the future. Graphical Abstract
Targeted Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE Alters Joints Inflammation
Authors: Sharjeel Usmani, Rashid Rasheed, Najeeb Ahmed, Yehia Omar, Shah P. Numani
Journal: Clinical Nuclear Medicine (2024)

High and frequent expression of somatostatin receptors in differentiated neuroendocrine neoplasms has paved the way for receptor-based, targeted peptide receptor radionuclide therapy especially for nonoperable or metastatic disease. Besides tumors, radiation, in one form or another, has been tested to treat inflammatory disease as well, and this goes back to the early 1990s when the first case of pneumonia treated with radiation showed complete resolution. Currently, radiotracers help in not only in vivo inflammation detection, characterization, and staging but also, and more importantly, for selection of treatment in individual patients. The same concept could be applied to treatment of infection, by coupling the radioisotopes to ligands that target sterile or nonsterile inflammation. In our case, targeted peptide receptor radionuclide therapy showed remarkable resolution of inflammatory joint disease.
Transduction enhancing EF-C peptide nanofibrils are endocytosed by macropinocytosis and subsequently degraded
Authors: Lena Rauch-Wirth, Desiree Schütz, Rüdiger Groß, Sascha Rode, Bernhard Glocker, Janis A Müller, Paul Walther, Clarissa Read, Jan Münch
Journal: Biomaterials (2024)
Functionalized aluminum hydroxide-based self-adjuvanted nanovaccine orchestrates antitumor immune responses via Dectin-1 signaling
Authors: Xiaoli Ling, Zhipeng Tian, Dong Chen, Yujia Zhang, Ziyan Dong, Dan He, Jiayu Li, Zhidi He, Jiaxin Li, Fang Chen, Qin He, Man Li
Journal: Journal of Controlled Release (2024)