tbuckley/cabot-search huggingface dataset:
Best Vitelliform Macular Dystrophy Natural History Study Report 1
Authors: Yannik Laich, Michalis Georgiou, Kaoru Fujinami, Malena Daich Varela, Yu Fujinami-Yokokawa, Shaima Awadh Hashem, Thales Antonio Cabral de Guimaraes, Omar A. Mahroo, Andrew R. Webster, Michel Michaelides
Journal: Ophthalmology (2024)

PurposeTo analyze the genetic findings, clinical spectrum and natural history of Best vitelliform macular dystrophy (BVMD) in a cohort of 222 children and adults.DesignSingle-center retrospective, consecutive, observational study.ParticipantsPatients with a clinical diagnosis of BVMD, from pedigrees with a likely disease-causing monoallelic sequence variant in the BEST1 gene.MethodsData were extracted from electronic and physical case notes. Electrophysiologic assessment and molecular genetic testing were analyzed.Main outcome measurementsMolecular genetic testing, clinical findings including best-corrected visual acuity (BCVA), choroidal neovascularization (CNV) rates, and electrophysiology parameters.Results222 patients (127 males and 95 females) from 141 families were identified, harboring 69 BEST1 variants, including 22 novel variants. Mean age at presentation was 26.8 years (range 1.3-84.8 years) and most patients (61.5%) presented with a deterioration of central vision. Major funduscopic findings at presentation included: 128 eyes (30.6%) with yellow vitelliform lesions, 78 eyes (18.7%) with atrophic changes, 49 eyes (11.7%) with fibrotic changes, 48 eyes (11.5%) with mild pigmentary changes and 43 eyes (10.3%) showing a vitelliruptive appearance. Mean BCVA was 0.37 LogMAR (20/47) for the right eye and 0.33 LogMAR (20/43) for the left eye at presentation, with a mean annual loss rate of 0.013 LogMAR and 0.009 LogMAR respectively over a mean follow-up of 9.6 years. 37 patients (17.3%) were diagnosed with CNV over a mean follow-up period of 8.0 years (range 0-55 years). Eyes with CNV that received treatment with anti-VEGF had a better mean VA compared to eyes that were not treated with anti-VEGF (0.28 LogMAR (20/38) versus 0.62 LogMAR (20/83). The majority of eyes exhibited a hyperopic refractive error (185/235, 78.7%) and 13 patients (6.1%) were diagnosed with amblyopia. Among the three most common variants, p.A243V was associated with a later age of onset, a better age-adjusted VA and less advanced Gass stages compared to p.R218C and p.R218H.ConclusionsBVMD shows a wide spectrum of phenotypic variability. The disease is very slowly progressive, and the observed phenotype-genotype correlations allow for more accurate prognostication and counselling.
Nanoadjuvant-triggered STING activation evokes systemic immunotherapy for repetitive implant-related infections
Authors: Dongdong Xu, Jun Hu, Jiawei Mei, Jun Zhou, Zhengxi Wang, Xudong Zhang, Quan Liu, Zheng Su, Wanbo Zhu, Hongjian Liu, Chen Zhu
Journal: Bioactive Materials (2024)

Repetitive implant-related infections (IRIs) are devastating complications in orthopedic surgery, threatening implant survival and even the life of the host. Biofilms conceal bacterial-associated antigens (BAAs) and result in a "cold tumor"-like immune silent microenvironment, allowing the persistence of IRIs. To address this challenge, an iron-based covalent organic framed nanoadjuvant doped with curcumin and platinum (CFCP) was designed in the present study to achieve efficient treatment of IRIs by inducing a systemic immune response. Specifically, enhanced sonodynamic therapy (SDT) from CFCP combined with iron ion metabolic interference increased the release of bacterial-associated double-stranded DNA (dsDNA). Immunogenic dsDNA promoted dendritic cell (DC) maturation through activation of the stimulator of interferon gene (STING) and amplified the immune stimulation of neutrophils via interferon-β (IFN-β). At the same time, enhanced BAA presentation aroused humoral immunity in B and T cells, creating long-term resistance to repetitive infections. Encouragingly, CFCP served as neoadjuvant immunotherapy for sustained antibacterial protection on implants and was expected to guide clinical IRI treatment and relapse prevention.
A theragenerative bio-nanocomposite consisting of black phosphorus quantum dots for bone cancer therapy and regeneration
Authors: Ashkan Bigham, Ines Fasolino, Silvia Borsacchi, Carmen Valente, Lucia Calucci, Gabriele Turacchio, Marianna Pannico, Manuel Serrano-Ruiz, Luigi Ambrosio, Maria Grazia Raucci
Journal: Bioactive Materials (2024)

Recently, the term theragenerative has been proposed for biomaterials capable of inducing therapeutic approaches followed by repairing/regenerating the tissue/organ. This study is focused on the design of a new theragenerative nanocomposite composed of an amphiphilic non-ionic surfactant (Pluronic F127), bioactive glass (BG), and black phosphorus (BP). The nanocomposite was prepared through a two-step synthetic strategy, including a microwave treatment that turned BP nanosheets (BPNS) into quantum dots (BPQDs) with 5 ± 2 nm dimensions in situ. The effects of surfactant and microwave treatment were assessed in vitro: the surfactant distributes the ions homogenously throughout the composite and the microwave treatment chemically stabilizes the composite. The presence of BP enhanced bioactivity and promoted calcium phosphate formation in simulated body fluid. The inherent anticancer activity of BP-containing nanocomposites was tested against osteosarcoma cells in vitro, finding that 150 μg mL−1 was the lowest concentration which prevented the proliferation of SAOS-2 cells, while the counterpart without BP did not affect the cell growth rate. Moreover, the apoptosis pathways were evaluated and a mechanism of action was proposed. NIR irradiation was applied to induce further proliferation suppression on SAOS-2 cells through hyperthermia. The inhibitory effects of bare BP nanomaterials and nanocomposites on the migration and invasion of bone cancer, breast cancer, and prostate cancer cells were assessed in vitro to determine the anticancer potential of nanomaterials against primary and secondary bone cancers. The regenerative behavior of the nanocomposites was tested with healthy osteoblasts and human mesenchymal stem cells; the BPQDs-incorporated nanocomposite significantly promoted the proliferation of osteoblast cells and induced the osteogenic differentiation of stem cells. This study introduces a new multifunctional theragenerative platform with promising potential for simultaneous bone cancer therapy and regeneration.
Using routine health-care data to search for unknown transfusion-transmitted disease: a nationwide, agnostic retrospective cohort study
Authors: Torsten Dahlén, Jingcheng Zhao, Michael P Busch, Gustaf Edgren
Journal: The Lancet Digital Health (2024)

Identification and prevention of transfusion-transmitted disease is essential for blood transfusion safety. However, current surveillance systems are largely driven by reports of sentinel events, which is an approach that might be inadequate for identifying transmission of pathogens not known to be transmissible or pathogens with long incubation periods. Using a combination of health-data registers and blood-bank databases, we aimed to perform an agnostic search for potential transfusion-transmitted diseases and to identify unknown threats to the blood supply.
Brain abscess caused by Listeria monocytogenes and Toxoplasma gondii
Authors: Pierre Goudy, Coline Vavasseur, Xavier Boumaza, Sabrina Bryant, Judith Fillaux, Xavier Iriart, Marion Grare, Mohamed Yassine Beltaïfa, Franck-Emmanuel Roux, Fabrice Bonneville, Guillaume Martin-Blondel, Thomas Geeraerts
Journal: The Lancet Infectious Diseases (2024)
A scalable federated learning solution for secondary care using low-cost microcomputing: privacy-preserving development and evaluation of a COVID-19 screening test in UK hospitals
Authors: Andrew A S Soltan, Anshul Thakur, Jenny Yang, Anoop Chauhan, Leon G D’Cruz, Phillip Dickson, Marina A Soltan, David R Thickett, David W Eyre, Tingting Zhu, David A Clifton
Journal: The Lancet Digital Health (2024)

Multicentre training could reduce biases in medical artificial intelligence (AI); however, ethical, legal, and technical considerations can constrain the ability of hospitals to share data. Federated learning enables institutions to participate in algorithm development while retaining custody of their data but uptake in hospitals has been limited, possibly as deployment requires specialist software and technical expertise at each site. We previously developed an artificial intelligence-driven screening test for COVID-19 in emergency departments, known as CURIAL-Lab, which uses vital signs and blood tests that are routinely available within 1 h of a patient's arrival. Here we aimed to federate our COVID-19 screening test by developing an easy-to-use embedded system-which we introduce as full-stack federated learning-to train and evaluate machine learning models across four UK hospital groups without centralising patient data.
An intentional approach to managing bias in general purpose embedding models
Authors: Wei-Hung Weng, Andrew Sellergen, Atilla P Kiraly, Alexander D’Amour, Jungyeon Park, Rory Pilgrim, Stephen Pfohl, Charles Lau, Vivek Natarajan, Shekoofeh Azizi, Alan Karthikesalingam, Heather Cole-Lewis, Yossi Matias, Greg S Corrado, Dale R Webster, Shravya Shetty, Shruthi Prabhakara, Krish Eswaran, Leo A G Celi, Yun Liu
Journal: The Lancet Digital Health (2024)

Advances in machine learning for health care have brought concerns about bias from the research community; specifically, the introduction, perpetuation, or exacerbation of care disparities. Reinforcing these concerns is the finding that medical images often reveal signals about sensitive attributes in ways that are hard to pinpoint by both algorithms and people. This finding raises a question about how to best design general purpose pretrained embeddings (GPPEs, defined as embeddings meant to support a broad array of use cases) for building downstream models that are free from particular types of bias. The downstream model should be carefully evaluated for bias, and audited and improved as appropriate. However, in our view, well intentioned attempts to prevent the upstream components—GPPEs—from learning sensitive attributes can have unintended consequences on the downstream models. Despite producing a veneer of technical neutrality, the resultant end-to-end system might still be biased or poorly performing. We present reasons, by building on previously published data, to support the reasoning that GPPEs should ideally contain as much information as the original data contain, and highlight the perils of trying to remove sensitive attributes from a GPPE. We also emphasise that downstream prediction models trained for specific tasks and settings, whether developed using GPPEs or not, should be carefully designed and evaluated to avoid bias that makes models vulnerable to issues such as distributional shift. These evaluations should be done by a diverse team, including social scientists, on a diverse cohort representing the full breadth of the patient population for which the final model is intended.
T cell lymphoma and secondary primary malignancy risk after commercial CAR T cell therapy
Authors: Guido Ghilardi, Joseph A. Fraietta, James N. Gerson, Vivianna M. Van Deerlin, Jennifer J. D. Morrissette, Gabriel C. Caponetti, Luca Paruzzo, Jaryse C. Harris, Elise A. Chong, Sandra P. Susanibar Adaniya, Jakub Svoboda, Sunita D. Nasta, Ositadimma H. Ugwuanyi, Daniel J. Landsburg, Eugenio Fardella, Adam J. Waxman, Emeline R. Chong, Vrutti Patel, Raymone Pajarillo, Irina Kulikovskaya, David B. Lieberman, Adam D. Cohen, Bruce L. Levine, Edward A. Stadtmauer, Noelle V. Frey, Dan T. Vogl, Elizabeth O. Hexner, Stefan K. Barta, David L. Porter, Alfred L. Garfall, Stephen J. Schuster, Carl H. June, Marco Ruella
Journal: Nature Medicine (2024)
Changes in smoking use and subsequent lung cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study
Authors: Daniela S Gutiérrez-Torres, Sungduk Kim, Demetrius Albanes, Stephanie J Weinstein, Maki Inoue-Choi, Paul S Albert, Neal D Freedman
Journal: JNCI Journal of the National Cancer Institute (2024)

Reducing cigarettes per day may lower the risk of lung cancer compared with continuing to smoke at the same intensity. Other changes in smoking behaviors, such as increasing cigarette consumption or quitting for a period and relapsing, may also affect lung cancer risk.
Long-term simulated microgravity fosters carotid aging-like changes via Piezo1
Authors: Jiaxin Zhang, Xinpei Wang, Zihao Fu, Changyang Xing, Zhen Wang, Hongyan Yang, Jiahui Li, Meijie Liu, Ling Dong, Xing Zhang, Yongzhi Li, Jiaping Wang, Jiangang Long, Jiankang Liu, Shengpeng Wang, Jia Li, Feng Gao
Journal: Cardiovascular Research (2024)

Elucidating the impacts of long-term spaceflight on cardiovascular health is urgently needed in face of the rapid development of human space exploration. Recent reports including the NASA Twins Study on vascular deconditioning and aging of astronauts in spaceflight are controversial. The aims of this study were to elucidate whether long-term microgravity promotes vascular aging and the underlying mechanisms.
Encyclopaedia of family A DNA polymerases localized in organelles: Evolutionary contribution of bacteria including the proto-mitochondrion
Authors: Ryo Harada, Yoshihisa Hirakawa, Akinori Yabuki, Eunsoo Kim, Euki Yazaki, Ryoma Kamikawa, Kentaro Nakano, Marek Eliáš, Yuji Inagaki
Journal: Molecular Biology and Evolution (2024)

Abstract DNA polymerases (DNAPs) synthesize DNA from deoxyribonucleotides in a semi-conservative manner and serve as the core of DNA replication and repair machineries. In eukaryotic cells, there are two genome-containing organelles, mitochondria and plastids, that were derived from an alphaproteobacterium and a cyanobacterium, respectively. Except for rare cases of genome-lacking mitochondria and plastids, both organelles must be served by nucleus-encoded DNAPs that localize and work in them to maintain their genomes. The evolution of organellar DNAPs has yet to be fully understood because of two unsettled issues. First, the diversity of organellar DNAPs has not been elucidated in the full spectrum of eukaryotes. Second, it is unclear when the DNAPs that were used originally in the endosymbiotic bacteria giving rise to mitochondria and plastids were discarded, as the organellar DNAPs known to date show no phylogenetic affinity to those of the extant alphaproteobacteria or cyanobacteria. In this study, we identified from diverse eukaryotes 134 family A DNAP sequences, which were classified into 10 novel types, and explored their evolutionary origins. The subcellular localizations of selected DNAPs were further examined experimentally. The results presented here suggest that the diversity of organellar DNAPs has been shaped by multiple transfers of the PolI gene from phylogenetically broad bacteria, and their occurrence in eukaryotes was additionally impacted by secondary plastid endosymbioses. Finally, we propose that the last eukaryotic common ancestor may have possessed two mitochondrial DNAPs, POP and a candidate of the direct descendant of the proto-mitochondrial DNAP, rdxPolA, identified in this study.
Why is early-onset atrial fibrillation uncommon in patients with Duchenne muscular dystrophy? Insights from the <i>mdx</i> mouse
Authors: My-Nhan Nguyen, Charlotte Hooper, Matilde Stefanini, Besarte Vrellaku, Ricardo Carnicer, Matthew J Wood, Jillian N Simon, Barbara Casadei
Journal: Cardiovascular Research (2024)

A reduction in both dystrophin and neuronal nitric oxide synthase (NOS1) secondary to microRNA-31 (miR-31) up-regulation contributes to the atrial electrical remodelling that underpins human and experimental atrial fibrillation (AF). In contrast, patients with Duchenne muscular dystrophy (DMD), who lack dystrophin and NOS1 and, at least in the skeletal muscle, have raised miR-31 expression, do not have increase susceptibility to AF in the absence of left ventricular (LV) dysfunction. Here, we investigated whether dystrophin deficiency is also associated with atrial up-regulation of miR-31, loss of NOS1 protein, and increased AF susceptibility in young mdx mice.
Molecular magnetic resonance imaging of myeloperoxidase activity identifies culprit lesions and predicts future atherothrombosis
Authors: James Nadel, Xiaoying Wang, Prakash Saha, André Bongers, Sergey Tumanov, Nicola Giannotti, Weiyu Chen, Niv Vigder, Mohammed M Chowdhury, Gastao Lima da Cruz, Carlos Velasco, Claudia Prieto, Andrew Jabbour, René M Botnar, Roland Stocker, Alkystis Phinikaridou
Journal:  (2024)

Abstract Aims Unstable atherosclerotic plaques have increased activity of myeloperoxidase (MPO). We examined whether molecular magnetic resonance imaging (MRI) of intraplaque MPO activity predicts future atherothrombosis in rabbits and correlates with ruptured human atheroma. Methods and results Plaque MPO activity was assessed in vivo in rabbits (n = 12) using the MPO-gadolinium (Gd) probe at 8 and 12 weeks after induction of atherosclerosis and before pharmacological triggering of atherothrombosis. Excised plaques were used to confirm MPO activity by liquid chromatography–tandem mass spectrometry (LC–MSMS) and to determine MPO distribution by histology. MPO activity was higher in plaques that caused post-trigger atherothrombosis than plaques that did not. Among the in vivo MRI metrics, the plaques’ R1 relaxation rate after administration of MPO-Gd was the best predictor of atherothrombosis. MPO activity measured in human carotid endarterectomy specimens (n = 30) by MPO-Gd–enhanced MRI was correlated with in vivo patient MRI and histological plaque phenotyping, as well as LC–MSMS. MPO-Gd retention measured as the change in R1 relaxation from baseline was significantly greater in histologic and MRI-graded American Heart Association (AHA) type VI than type III–V plaques. This association was confirmed by comparing AHA grade to MPO activity determined by LC–MSMS. Conclusion We show that elevated intraplaque MPO activity detected by molecular MRI employing MPO-Gd predicts future atherothrombosis in a rabbit model and detects ruptured human atheroma, strengthening the translational potential of this approach to prospectively detect high-risk atherosclerosis.
Invasive growth of brain metastases is linked to CHI3L1 release from pSTAT3-positive astrocytes
Authors: Matthew Dankner, Sarah M Maritan, Neibla Priego, Georgia Kruck, Andriniaina Nkili-Meyong, Javad Nadaf, Rebecca Zhuang, Matthew G Annis, Dongmei Zuo, Alexander Nowakowski, Marco Biondini, Alexander Kiepas, Caitlyn Mourcos, Phuong Le, François Charron, Yanis Inglebert, Paul Savage, Louis Théret, Marie-Christine Guiot, R Anne McKinney, William J Muller, Morag Park, Manuel Valiente, Kevin Petrecca, Peter M Siegel
Journal: Neuro-Oncology (2024)

Abstract Background Compared to minimally invasive brain metastases (MI BrM), highly invasive (HI) lesions form abundant contacts with cells in the peritumoral brain parenchyma and are associated with poor prognosis. Reactive astrocytes (RAs) labeled by phosphorylated STAT3 (pSTAT3) have recently emerged as a promising therapeutic target for BrM. Here, we explore whether the BrM invasion pattern is influenced by pSTAT3+ RAs and may serve as a predictive biomarker for STAT3 inhibition. Methods We used immunohistochemistry to identify pSTAT3+ RAs in HI and MI human and patient-derived xenograft (PDX) BrM. Using PDX, syngeneic, and transgenic mouse models of HI and MI BrM, we assessed how pharmacological STAT3 inhibition or RA-specific STAT3 genetic ablation affected BrM growth in vivo. Cancer cell invasion was modeled in vitro using a brain slice-tumor co-culture assay. We performed single-cell RNA sequencing of human BrM and adjacent brain tissue. Results RAs expressing pSTAT3 are situated at the brain–tumor interface and drive BrM invasive growth. HI BrM invasion pattern was associated with delayed growth in the context of STAT3 inhibition or genetic ablation. We demonstrate that pSTAT3+ RAs secrete Chitinase 3-like-1 (CHI3L1), which is a known STAT3 transcriptional target. Furthermore, single-cell RNA sequencing identified CHI3L1-expressing RAs in human HI BrM. STAT3 activation, or recombinant CHI3L1 alone, induced cancer cell invasion into the brain parenchyma using a brain slice-tumor plug co-culture assay. Conclusions Together, these data reveal that pSTAT3+ RA-derived CHI3L1 is associated with BrM invasion, implicating STAT3 and CHI3L1 as clinically relevant therapeutic targets for the treatment of HI BrM.
Reply to: Leveraging Microbiome Composition Variability for Precision Medicine in Idiopathic Pulmonary Fibrosis
Authors: David O'Dwyer, Imre Noth, Justin M. Oldham
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Reply to: Leveraging Microbiome Composition Variability for Precision Medicine in Idiopathic Pulmonary Fibrosis." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
One-Day Peer-Delivered Cognitive Behavioral Therapy-Based Workshops for Postpartum Depression: A Randomized Controlled Trial
Authors: Zoryana Babiy, Haley Layton, Calan D Savoy, Feng Xie, June S L Brown, Peter J Bieling, David L Streiner, Mark A Ferro, Ryan J Van Lieshout
Journal: Psychotherapy and Psychosomatics (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Myriad treatment barriers prevent birthing parents with postpartum depression (PPD) from receiving timely treatment. We aimed to determine whether a peer-delivered online 1-day cognitive behavioral therapy (CBT)-based workshop added to treatment as usual (TAU) improves PPD and its comorbidities and is more cost-effective than TAU alone. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This parallel-group, randomized controlled trial took place in Ontario, Canada (June 7, 2021, to February 18, 2022). Participants were ≥18 years old, had an infant ≤12 months old, and an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Participants were allocated to receive the workshop plus TAU (&lt;i&gt;n&lt;/i&gt; = 202) or TAU and waitlisted to complete the workshop 12 weeks later (&lt;i&gt;n&lt;/i&gt; = 203). The primary outcome was change in PPD (EPDS score) from enrollment to 12 weeks later. The secondary outcome was cost-effectiveness and tertiary outcomes included anxiety, social support, partner relationship quality, the mother-infant relationship, parenting stress, and infant temperament. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Participants had a mean age of 32.3 years (SD = 4.30) and 65% were White. The workshop led to a significant reduction in EPDS scores (15.95–11.37; &lt;i&gt;d&lt;/i&gt; = 0.92, &lt;i&gt;p&lt;/i&gt; &amp;lt; 0. 01) and was associated with higher odds of exhibiting a clinically significant decrease in EPDS scores (OR = 2.03; 95% CI: 1.26–3.29). The workshop plus TAU was more cost-effective than TAU alone. It also led to improvements in postpartum anxiety, infant-focused anxiety, parenting stress, and infant temperament. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Peer-delivered 1-day CBT-based workshops can improve PPD and are a potentially scalable low-intensity treatment that could help increase treatment access.