tbuckley/cabot-search huggingface dataset:
Highly pathogenic avian influenza A(H5N1) virus infections on fur farms connected to mass mortalities of black-headed gulls, Finland, July to October 2023
Authors: Lauri Kareinen, Niina Tammiranta, Ari Kauppinen, Bianca Zecchin, Ambra Pastori, Isabella Monne, Calogero Terregino, Edoardo Giussani, Riikka Kaarto, Veera Karkamo, Tanja Lähteinen, Hanna Lounela, Tuija Kantala, Ilona Laamanen, Tiina Nokireki, Laura London, Otto Helve, Sohvi Kääriäinen, Niina Ikonen, Jari Jalava, Laura Kalin-Mänttäri, Anna Katz, Carita Savolainen-Kopra, Erika Lindh, Tarja Sironen, Essi M Korhonen, Kirsi Aaltonen, Monica Galiano, Alice Fusaro, Tuija Gadd
Journal: Eurosurveillance (2024)

Highly pathogenic avian influenza (HPAI) has caused widespread mortality in both wild and domestic birds in Europe 2020-2023. In July 2023, HPAI A(H5N1) was detected on 27 fur farms in Finland. In total, infections in silver and blue foxes, American minks and raccoon dogs were confirmed by RT-PCR. The pathological findings in the animals include widespread inflammatory lesions in the lungs, brain and liver, indicating efficient systemic dissemination of the virus. Phylogenetic analysis of Finnish A(H5N1) strains from fur animals and wild birds has identified three clusters (Finland I-III), and molecular analyses revealed emergence of mutations known to facilitate viral adaptation to mammals in the PB2 and NA proteins. Findings of avian influenza in fur animals were spatially and temporally connected with mass mortalities in wild birds. The mechanisms of virus transmission within and between farms have not been conclusively identified, but several different routes relating to limited biosecurity on the farms are implicated. The outbreak was managed in close collaboration between animal and human health authorities to mitigate and monitor the impact for both animal and human health.
Effect of diet on the evolution of gut commensal bacteria
Authors: Tanja Dapa, Karina B. Xavier
Journal: Gut Microbes (2024)

The gut microbiota, comprising trillions of diverse microorganisms inhabiting the intestines of animals, forms a complex and indispensable ecosystem with profound implications for the host's well-being. Its functions include contributing to developing the host's immune response, aiding in nutrient digestion, synthesizing essential compounds, acting as a barrier against pathogen invasion, and influencing the development or regression of various pathologies. The dietary habits of the host directly impact this intricate community of gut microbes. Diet influences the composition and function of the gut microbiota through alterations in gene expression, enzymatic activity, and metabolome. While the impact of diet on gut ecology is well-established, the investigation into the relationship between dietary consumption and microbial genotypic diversity has been limited. This review provides an overview of the relationship between diet and gut microbiota, emphasizing the impact of host nutrition on both short- and long-term evolution in the mammalian gut. It is evident that the evolution of the gut microbiota occurs even on short timescales through the acquisition of novel mutations, within the gut bacteria of individual hosts. Consequently, we discuss the importance of considering alterations in bacterial genomic diversity when analyzing microbiota-dependent effects on host physiology. Future investigations into the various microbiota-related traits shall greatly benefit from a deeper understanding of commensal bacterial evolutionary adaptation.
Modulation of Alzheimer’s disease brain pathology in mice by gut bacterial depletion: the role of IL-17a
Authors: Wenlin Hao, Qinghua Luo, Inge Tomic, Wenqiang Quan, Tobias Hartmann, Michael D. Menger, Klaus Fassbender, Yang Liu
Journal: Gut Microbes (2024)

Gut bacteria regulate brain pathology of Alzheimer's disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study, 3-month-old APP-transgenic female mice with and without knock-out of Il-17a gene were treated with antibiotics-supplemented or normal drinking water for 2 months. The antibiotic treatment eradicated almost all intestinal bacteria, which led to a reduction in Il-17a-expressing CD4-positive T lymphocytes in the spleen and gut, and to a decrease in bacterial DNA in brain tissue. Depletion of gut bacteria inhibited inflammatory activation in both brain tissue and microglia, lowered cerebral Aβ levels, and promoted transcription of Arc gene in the brain of APP-transgenic mice, all of which effects were abolished by deficiency of Il-17a. As possible mechanisms regulating Aβ pathology, depletion of gut bacteria inhibited β-secretase activity and increased the expression of Abcb1 and Lrp1 in the brain or at the blood-brain barrier, which were also reversed by the absence of Il-17a. Interestingly, a crossbreeding experiment between APP-transgenic mice and Il-17a knockout mice further showed that deficiency of Il-17a had already increased Abcb1 and Lrp1 expression at the blood-brain barrier. Thus, depletion of gut bacteria attenuates inflammatory activation and amyloid pathology in APP-transgenic mice via Il-17a-involved signaling pathways. Our study contributes to a better understanding of the gut-brain axis in AD pathophysiology and highlights the therapeutic potential of Il-17a inhibition or specific depletion of gut bacteria that stimulate the development of Il-17a-expressing T cells.
Targeting CD300ld to normalize the tumor microenvironment: an emerging insight in cancer immunotherapy
Authors: Lin‐Zhu Zhang, Xu He, Hai‐Dong Zhu
Journal: MedComm (2024)

Abstract In a recent Nature elegant study, Wang et al. identified CD300ld, a novel functionally highly conserved tumor immunosuppressive receptor, highly expressed specifically on polymorphonuclear myeloid‐derived suppressor cells (PMN‐MDSCs), as well as a key receptor in the regulation of recruitment and immunosuppressive function of PMN‐MDSCs. Targeting CD300ld could remodel the tumor immune microenvironment, resulting in a broad‐spectrum anti‐tumor effect.
Magnetic resonance imaging‐based radiomics analysis for prediction of treatment response to neoadjuvant chemoradiotherapy and clinical outcome in patients with locally advanced rectal cancer: A large multicentric and validated study
Authors: TingDan Hu, Jing Gong, YiQun Sun, MengLei Li, ChongPeng Cai, XinXiang Li, YanFen Cui, XiaoYan Zhang, Tong Tong
Journal: MedComm (2024)

Our study investigated whether magnetic resonance imaging (MRI)-based radiomics features could predict good response (GR) to neoadjuvant chemoradiotherapy (nCRT) and clinical outcome in patients with locally advanced rectal cancer (LARC). Radiomics features were extracted from the T2 weighted (T2W) and Apparent diffusion coefficient (ADC) images of 1070 LARC patients retrospectively and prospectively recruited from three hospitals. To create radiomic models for GR prediction, three classifications were utilized. The radiomic model with the best performance was integrated with important clinical MRI features to create the combined model. Finally, two clinical MRI features and ten radiomic features were chosen for GR prediction. The combined model, constructed with the tumor size, MR-detected extramural venous invasion, and radiomic signature generated by Support Vector Machine (SVM), showed promising discrimination of GR, with area under the curves of 0.799 (95% CI, 0.760-0.838), 0.797 (95% CI, 0.733-0.860), 0.754 (95% CI, 0.678-0.829), and 0.727 (95% CI, 0.641-0.813) in the training and three validation datasets, respectively. Decision curve analysis verified the clinical usefulness. Furthermore, according to Kaplan-Meier curves, patients with a high likelihood of GR as determined by the combined model had better disease-free survival than those with a low probability. This radiomics model was developed based on large-sample size, multicenter datasets, and prospective validation with high radiomics quality score, and also had clinical utility.
Brigatinib in <i>NF2</i> -Related Schwannomatosis with Progressive Tumors
Authors: Scott R. Plotkin, Kaleb H. Yohay, Phioanh L. Nghiemphu, Christine T. Dinh, Dusica Babovic-Vuksanovic, Vanessa L. Merker, Annette Bakker, Geoffrey Fell, Lorenzo Trippa, Jaishri O. Blakeley
Journal: New England Journal of Medicine (2024)

-related schwannomatosis (
Leptomeningeal metastases from solid tumors: A Society for Neuro-Oncology and American Society of Clinical Oncology consensus review on clinical management and future directions
Authors: Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O’Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire
Journal: Neuro-Oncology (2024)

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, best clinical practices with multimodality treatment options, clinical trial design and standardization of response assessments, and avenues worthy of further research. An international group of multi-disciplinary experts in the research and management of LM, supported by the Society for Neuro-Oncology and American Society of Clinical Oncology, were assembled to reach a consensus opinion on these pressing topics and provide a roadmap for future directions. Our hope is that these recommendations will accelerate collaboration and progress in the field of LM and serve as a platform for further discussion and patient advocacy.
Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells
Authors: Nicolas Chatain, Julian Baumeister, Marcelo A. Szymanski de Toledo, Dickson W. L. Wong, Siddharth Gupta, Kristina Pannen, Bärbel Junge, Tim H. Brümmendorf, Peter Boor, Steffen Koschmieder
Journal: Leukemia (2024)

Philadelphia chromosome-positive (Ph+) lymphoid blast crisis (BC), emanating from chronic myeloid leukemia (CML), is a fatal disease with limited treatment options. Asciminib (ABL001) is a novel selective allosteric inhibitor of the ABL kinase with high efficacy against TKI-resistant BCR::ABL1. In this study, we demonstrate significant suppression of an aggressive B-lymphoblastic disease and restoration of normal hematopoiesis in an inducible transgenic mouse model of p210-BCR::ABL1-positive CML-BC. Molecularly, asciminib treatment significantly reduced BCR::ABL1 transcripts to background levels, demonstrating its ability to suppress BCR::ABL1-induced disease. Furthermore, asciminib treatment normalized the long-term repopulating hematopoietic stem cell (LT-HSC) population in the BM, suggesting the selective targeting of malignant LT-HSCs. This was supported by secondary transplantation experiments, resulting in absence of BC in a proportion of mice. Importantly, none of the secondary transplanted mice that received further asciminib treatment developed leukemia. Sanger sequencing of the BCR::ABL1 myristoyl pocket region of both treatment-naïve and treated mice demonstrated a high mutational load. However, there was no indication of asciminib-specific mutations. These promising findings highlight the potential of asciminib as a drug that targets BC stem cells and as an alternative stand-alone or combinatorial therapy for first-line treatment of CML BC or Ph+ acute lymphoblastic leukemia.
Bone marrow transplantation reduces FGF-23 levels and restores bone formation in myelodysplastic neoplasms
Authors: Heike Weidner, Ulrike Baschant, Maria G. Ledesma-Colunga, Karolina Basiak, Elena Tsourdi, Katja Sockel, Katharina S. Götze, Jennifer Rivière, Uwe Platzbecker, Lorenz C. Hofbauer, Martina Rauner
Journal: Leukemia (2024)

Myelodysplastic neoplasms (MDS) are hematopoietic stem cell disorders characterized by ineffective hematopoiesis and dysplastic cells in the bone marrow (BM) [1].In addition, patients with MDS display an increased susceptibility to osteoporosis [2].Evidence points towards dysregulation in the BM niche that concurrently impairs bone turnover and hematopoiesis.We identified fibroblast growth factor (FGF)-23 as a critical regulator of bone mineralization and erythropoiesis.FGF-23 serum levels were higher in both patients and mice with MDS, and its neutralization resulted in improved erythropoiesis and bone mineralization in NUP98/HOXD13 (NHD13) mice [3].FGF-23 is mainly produced by osteoblasts/osteocytes [4] and exerts phosphaturic effects leading to poor bone mineralization [5].However, in NHD13 mice, intact FGF-23 (iFGF-23) and C-terminal FGF-23 (cFGF-23; produced by the cleavage of the intact form) protein levels were unchanged in the bone tissue, but erythroid progenitors secreted more FGF-23 compared to littermate wildtype (WT) controls (Fig. S1A,B).Here, we tested the hypothesis that erythroid precursors contribute to increased FGF-23 production/cleavage in MDS as a cause for impaired erythropoiesis and bone mineralization.To that end, we used BM transplantation as a first approach to substitute myelodysplastic erythroblasts with healthy ones in NHD13 mice.Four months after the BM transplantation, all mice that received the NHD13 BM showed MDS-like symptoms.In WT recipients, a reduction in hemoglobin levels [-32%; p < 0.001], platelets [-20%; p < 0.05], and lymphocytes [-71%; p < 0.001], but not in neutrophils or monocytes was observed compared to WT controls (transplanted with WT BM), showing a similar MDS status as NHD13 controls.In turn, NHD13 mice transplanted with WT BM did not develop MDS during the observation period.Compared to NHD13 controls, blood count reached normal levels [hemoglobin: +22%; p < 0.001; platelets: +26%; p < 0.05;
Validation and application of computer vision algorithms for video-based tremor analysis
Authors: Maximilian U. Friedrich, Anna-Julia Roenn, Chiara Palmisano, Jane Alty, Steffen Paschen, Guenther Deuschl, Chi Wang Ip, Jens Volkmann, Muthuraman Muthuraman, Robert Peach, Martin M. Reich
Journal: npj Digital Medicine (2024)

Tremor is one of the most common neurological symptoms. Its clinical and neurobiological complexity necessitates novel approaches for granular phenotyping. Instrumented neurophysiological analyses have proven useful, but are highly resource-intensive and lack broad accessibility. In contrast, bedside scores are simple to administer, but lack the granularity to capture subtle but relevant tremor features. We utilise the open-source computer vision pose tracking algorithm Mediapipe to track hands in clinical video recordings and use the resulting time series to compute canonical tremor features. This approach is compared to marker-based 3D motion capture, wrist-worn accelerometry, clinical scoring and a second, specifically trained tremor-specific algorithm in two independent clinical cohorts. These cohorts consisted of 66 patients diagnosed with essential tremor, assessed in different task conditions and states of deep brain stimulation therapy. We find that Mediapipe-derived tremor metrics exhibit high convergent clinical validity to scores (Spearman's ρ = 0.55-0.86, p≤ .01) as well as an accuracy of up to 2.60 mm (95% CI [-3.13, 8.23]) and ≤0.21 Hz (95% CI [-0.05, 0.46]) for tremor amplitude and frequency measurements, matching gold-standard equipment. Mediapipe, but not the disease-specific algorithm, was capable of analysing videos involving complex configurational changes of the hands. Moreover, it enabled the extraction of tremor features with diagnostic and prognostic relevance, a dimension which conventional tremor scores were unable to provide. Collectively, this demonstrates that current computer vision algorithms can be transformed into an accurate and highly accessible tool for video-based tremor analysis, yielding comparable results to gold standard tremor recordings.
Political dimensions of misinformation, trust, and vaccine confidence in a digital age
Authors: Luisa Enria, Harriet Dwyer, Mark Marchant, Nadine Beckmann, Megan Schmidt-Sane, Abu Conteh, Anthony Mansaray, Alhaji N’Jai
Journal: BMJ (2024)

Global health leaders often dismiss politics as antithetical to the aims of public health, but <b>Luisa Enria and colleagues</b> argue that political analysis can offer new ways to build trust in vaccination in the context of growing online misinformation
Communication inequalities and incomplete data hinder understanding of how social media affect vaccine uptake
Authors: Kasisomayajula Viswanath, Edmund J Lee, Eliza Dryer
Journal: BMJ (2024)

<b>Kasisomayajula Viswanath and colleagues</b> argue that to gain a more accurate and complete understanding of how social media influence vaccine sentiments and vaccination, gaining a better understanding of communication inequalities and data absenteeism is critical
The epidemiology of dermatofibrosarcoma protuberans incidence, metastasis, and death among various population groups: A Surveillance, Epidemiology, and End Results database analysis
Authors: Jalal Maghfour, Xavier Genelin, Justin Olson, Anqi Wang, Lonni Schultz, Travis W. Blalock
Journal: Journal of the American Academy of Dermatology (2024)
Corrigendum to “Triclosan-based supramolecular hydrogels as nanoantibiotics for enhanced antibacterial activity” [Journal of Controlled Release 324 (2020) 354–365]
Authors: Lijun Yang, Congrou Zhang, Fan Huang, Jinjian Liu, Yumin Zhang, Cuihong Yang, Chunhua Ren, Liping Chu, Bin Liu, Jianfeng Liu
Journal: Journal of Controlled Release (2024)
Role of signaling pathways in age-related orthopedic diseases: focus on the fibroblast growth factor family
Authors: Heng-Zhen Li, Jing-lve Zhang, Dong-Liang Yuan, Wen-Qing Xie, Christoph H. Ladel, Ali Mobasheri, Yu-Sheng Li
Journal: Military Medical Research (2024)

Abstract Fibroblast growth factor (FGF) signaling encompasses a multitude of functions, including regulation of cell proliferation, differentiation, morphogenesis, and patterning. FGFs and their receptors (FGFR) are crucial for adult tissue repair processes. Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage, bone loss, muscle reduction, and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis (OA), intervertebral disc degeneration (IVDD), osteoporosis (OP), and sarcopenia. In OA and IVDD pathologies specifically, FGF1, FGF2, FGF8, FGF9, FGF18, FGF21, and FGF23 regulate the synthesis, catabolism, and ossification of cartilage tissue. Additionally, the dysregulation of FGFR expression (FGFR1 and FGFR3) promotes the pathological process of cartilage degradation. In OP and sarcopenia, endocrine-derived FGFs (FGF19, FGF21, and FGF23) modulate bone mineral synthesis and decomposition as well as muscle tissues. FGF2 and other FGFs also exert regulatory roles. A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration. Moreover, an increasing number of potential targets within the FGF signaling have been identified, such as FGF9, FGF18, and FGF23. However, it should be noted that most of these discoveries are still in the experimental stage, and further studies are needed before clinical application can be considered. Presently, this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases. Besides, current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.
Neurology under the midnight sun: EAN Congress 2024 comes to Helsinki
Authors: Heather Wood
Journal: Nature Reviews Neurology (2024)

The 10th Congress of the European Academy of Neurology is being held in Helsinki, Finland from 29 June to 2 July 2024, and Nature Reviews Neurology is publishing a series of Comments on the overarching theme, neuromodulation. We asked Programme Committee Chairs Ulf Kallweit and Reetta Kälviäinen about their roles and their expectations for the congress.
Embryonic alcohol exposure in zebrafish predisposes adults to cardiomyopathy and diastolic dysfunction
Authors: Olivia Weeks, Xinlei Gao, Sandeep Basu, Jennifer Galdieri, Kaifu Chen, C Geoffrey Burns, Caroline E Burns
Journal: Cardiovascular Research (2024)

Fetal alcohol spectrum disorders (FASDs) impact up to 0.8% of the global population. However, cardiovascular health outcomes in adult patients, along with predictive biomarkers for cardiac risk stratification, remain unknown. Our aim was to utilize a longitudinal cohort study in an animal model to evaluate the impact of embryonic alcohol exposure (EAE) on cardiac structure, function, and transcriptional profile across the lifespan.
Using a Virtual Scribe May Shorten EHR Time
Authors: Anna Bock
Journal: JAMA (2024)

Lisa Rotenstein, MD, MBA, MSc; Edward R. Melnick, MD, MHS; Christine Iannaccone, MPH; Jianyi Zhang, PhD; Aqsa Mugal, BA; Stuart R. Lipsitz, PhD; Michael J. Healey, MD; Christopher Holland, MBA; Richard Snyder, MBA; Christine A. Sinsky, MD; David Ting, MD; David W. Bates, MD, MSc
Pulmonary sarcoidosis: differences in lung function change over time
Authors: Michelle Sharp, Kevin J Psoter, Ali M Mustafa, Edward S Chen, Nancy W Lin, Stephen C Mathai, Nisha A Gilotra, Michelle N Eakin, Robert A Wise, David R Moller, Meredith C McCormack
Journal: Thorax (2024)

Given the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes and whether there were differential longitudinal changes by race and sex.