tbuckley/cabot-search huggingface dataset:
A systematic review and meta-analysis of heat exposure impacts on maternal, fetal and neonatal health
Authors: Darshnika P. Lakhoo, Nicholas Brink, Lebohang Radebe, Marlies H. Craig, Minh Duc Pham, Marjan M. Haghighi, Amy Wise, Ijeoma Solarin, Stanley Luchters, Gloria Maimela, Matthew F. Chersich, Admire Chikandiwa, Britt Nakstad, Caradee Y. Wright, Chloe Brimicombe, Karl-Günter Technau, Lois Harden, Melanie Boeckmann, Renate Strehlau, Robyn S. Hetem, Stanley Luchters, Gloria Maimela, Lebohang Radebe, Matthew Chersich, Darshnika Lakhoo, Ijeoma Solarin, Nicholas Brink
Journal: Nature Medicine (2024)
Cell type mapping reveals tissue niches and interactions in subcortical multiple sclerosis lesions
Authors: Celia Lerma-Martin, Pau Badia-i-Mompel, Ricardo O. Ramirez Flores, Patricia Sekol, Philipp S. L. Schäfer, Christian J. Riedl, Annika Hofmann, Thomas Thäwel, Florian Wünnemann, Miguel A. Ibarra-Arellano, Tim Trobisch, Philipp Eisele, Denis Schapiro, Maximilian Haeussler, Simon Hametner, Julio Saez-Rodriguez, Lucas Schirmer
Journal: Nature Neuroscience (2024)

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Inflammation is gradually compartmentalized and restricted to specific tissue niches such as the lesion rim. However, the precise cell type composition of such niches, their interactions and changes between chronic active and inactive stages are incompletely understood. We used single-nucleus and spatial transcriptomics from subcortical MS and corresponding control tissues to map cell types and associated pathways to lesion and nonlesion areas. We identified niches such as perivascular spaces, the inflamed lesion rim or the lesion core that are associated with the glial scar and a cilia-forming astrocyte subtype. Focusing on the inflamed rim of chronic active lesions, we uncovered cell–cell communication events between myeloid, endothelial and glial cell types. Our results provide insight into the cellular composition, multicellular programs and intercellular communication in tissue niches along the conversion from a homeostatic to a dysfunctional state underlying lesion progression in MS. Lerma-Martin et al. generated a paired single-nucleus RNA sequencing and spatial transcriptomics dataset from subcortical multiple sclerosis lesions, identifying spatial niches and key cell interactions driving inflammation and disease progression at the lesion rim.
3D‐Printed Polymeric Biomaterials for Health Applications
Authors: Yuxiang Zhu, Shenghan Guo, Dharneedar Ravichandran, Arunachalam Ramanathan, M. Taylor Sobczak, Alaina F. Sacco, Dhanush Patil, Sri Vaishnavi Thummalapalli, Tiffany V. Pulido, Jessica N. Lancaster, Johnny Yi, Jeffrey L. Cornella, David G. Lott, Xiangfan Chen, Xuan Mei, Yu Shrike Zhang, Linbing Wang, Xianqiao Wang, Yiping Zhao, Mohammad K. Hassan, Lindsay B. Chambers, Taylor G. Theobald, Sui Yang, Liang Liang, Kenan Song
Journal: Advanced Healthcare Materials (2024)

Abstract 3D printing, also known as additive manufacturing, holds immense potential for rapid prototyping and customized production of functional health‐related devices. With advancements in polymer chemistry and biomedical engineering, polymeric biomaterials have become integral to 3D‐printed biomedical applications. However, there still exists a bottleneck in the compatibility of polymeric biomaterials with different 3D printing methods, as well as intrinsic challenges such as limited printing resolution and rates. Therefore, this review aims to introduce the current state‐of‐the‐art in 3D‐printed functional polymeric health‐related devices. It begins with an overview of the landscape of 3D printing techniques, followed by an examination of commonly used polymeric biomaterials. Subsequently, examples of 3D‐printed biomedical devices are provided and classified into categories such as biosensors, bioactuators, soft robotics, energy storage systems, self‐powered devices, and data science in bioplotting. The emphasis is on exploring the current capabilities of 3D printing in manufacturing polymeric biomaterials into desired geometries that facilitate device functionality and studying the reasons for material choice. Finally, an outlook with challenges and possible improvements in the near future is presented, projecting the contribution of general 3D printing and polymeric biomaterials in the field of healthcare.
Revolutionizing medicine: Recent developments and future prospects in stem-cell therapy
Authors: Bashdar Mahmud Hussen, Mohammad Taheri, Raya Kh. Yashooa, Gaylany H. Abdullah, Snur Rasool Abdullah, Ramiar Kamal Kheder, Suhad A. Mustafa
Journal: International Journal of Surgery (2024)

Stem-cell therapy is a revolutionary frontier in modern medicine, offering enormous capacity to transform the treatment landscape of numerous debilitating illnesses and injuries. This review examines the revolutionary frontier of treatments utilizing stem cells, highlighting the distinctive abilities of stem cells to undergo regeneration and specialized cell differentiation into a wide variety of phenotypes. This paper aims to guide researchers, physicians, and stakeholders through the intricate terrain of stem-cell therapy, examining the processes, applications, and challenges inherent in utilizing stem cells across diverse medical disciplines. The historical journey from foundational contributions in the late 19th and early 20th centuries to recent breakthroughs, including ESC isolation and iPSC discovery, has set the stage for monumental leaps in medical science. Stem cells’ regenerative potential spans embryonic, adult, induced pluripotent, and perinatal stages, offering unprecedented therapeutic opportunities in cancer, neurodegenerative disorders, cardiovascular ailments, spinal cord injuries, diabetes, and tissue damage. However, difficulties, such as immunological rejection, tumorigenesis, and precise manipulation of stem-cell behavior, necessitate comprehensive exploration and innovative solutions. This manuscript summarizes recent biotechnological advancements, critical trial evaluations, and emerging technologies, providing a nuanced understanding of the triumphs, difficulties, and future trajectories in stem cell-based regenerative medicine. Future directions, including precision medicine integration, immune modulation strategies, advancements in gene-editing technologies, and bioengineering synergy, offer a roadmap in stem cell treatment. The focus on stem-cell therapy’s potential highlights its significant influence on contemporary medicine and points to a future in which individualized regenerative therapies will alleviate various medical disorders.
Shock wave-pretreated ADMSCs of cell-sheet scaffold (CSS) patched on left ventricular wall (LVW) inhibited LVW remodeling in mini-pig MI ---role CSS on counteracting Laplace’s Law of LVW stress: Experimental study
Authors: Jiunn-Jye Sheu, Jui-Ning Yeh, Yin-Chia Chen, John Y. Chiang, Pei-Hsun Sung, Chi-Ruei Huang, Yi-Chen Li, Hon-Kan Yip
Journal: International Journal of Surgery (2024)

Background: We investigated whether shock wave (SW)-pretreated autologous adipocyte-derived mesenchymal stem cells (ADMSCs) seeded in the cell-sheet scaffold (CSS) could inhibit left ventricular (LV) remodeling and improve LV ejection fraction (LVEF) in old myocardial infarction (MI). Methods: Mini-pigs (n=20) were divided into group 1 (sham-operated control), group 2 (old MI), group 3 (old MI + autologous ADMSCs/1.0×10 7 in CSS on LV myocardium), and group 4 [old MI + SW (0.12 mJ/mm 2 for total 140 shots)-pretreated ADMSCs in CSS on LV myocardium]. Treatments started on day 28 after MI induction. In vivo and in vitro studies were conducted. Results: Cell viability/relative mitochondria DNA expression/mitochondrial cytochrome C/adenosine triphosphate concentration in ADMCSs and protein expressions of angiogenesis factors (vascular endothelial growth factor [VEGF]/stromal cell-derived factor-1 [SDF-1])/mitochondrial respiratory chain complexes I–IV/oxygen consumption rate were higher in group 4 than in group 3 ( P &lt;0.001). By day 180, LVEF and small vessel numbers in the peri-infarct or infarct area were highest in group 1, lowest in group 2, and significantly lower in group 3 than in group 4. In contrast, the LV dimension was opposite to the pattern of change in LVEF in all groups ( P &lt;0.0001). The basal/middle/apical infarct and fibrotic areas were inversely related to LVEF in all groups (all P &lt;0.0001). Protein levels of angiogenetic markers (SDF-1α/C-X-C chemokine receptor type 4/VEGF/angiopoietin-1) were significantly and persistently increased from groups 1 to 4. In contrast, protein levels of endothelial-cell markers (von Willebrand factor or endothelial nitric oxide synthase) showed an identical pattern to LVEF in all groups (all P &lt;0.0001). Conclusion: SW pretreatment of ADMSCs seeded in CSS offered significant benefits in preserving LV performance and ameliorating LV remodeling in mini-pigs with old MI.
Long‐term clinical outcomes and healthcare resource utilization in male and female patients following hospitalization for heart failure
Authors: Tauben Averbuch, Shun Fu Lee, Brandon Zagorski, Ambarish Pandey, Mark C. Petrie, Tor Biering‐Sorensen, Feng Xie, Harriette G.C. Van Spall
Journal: European Journal of Heart Failure (2024)

Aims Heart failure ( HF ) is a leading cause of hospitalization, and sex differences in care have been described. We assessed sex‐specific clinical outcomes and healthcare resource utilization following hospitalization for HF. Methods and results This was an exploratory analysis of patients hospitalized for HF across 10 Canadian hospitals in the Patient‐Centered Care Transitions in HF (PACT‐HF) cluster‐randomized trial. The primary outcome was all‐cause mortality. Secondary outcomes included all‐cause readmissions, HF readmissions, emergency department (ED) visits, and healthcare resource utilization. Outcomes were obtained via linkages with administrative datasets. Among 4441 patients discharged alive, 50.7% were female. By 5 years, 63.6% and 65.5% of male and female patients, respectively, had died ( p = 0.19); 85.4% and 84.4%, respectively, were readmitted ( p = 0.35); and 72.2% and 70.9%, respectively, received ED care without hospitalization ( p = 0.34). There were no sex differences in mean [SD] number of all‐cause readmissions (males, 2.8 [7.8] and females, 3.0 [8.4], p = 0.54), HF readmissions (males, 0.9 [3.6] and females, 0.9 [4.5], p = 0.80), or ED visits (males, 1.8 [11.3] and females, 1.5 [6.0], p = 0.24) per person. There were no sex differences in mean [SD] annual direct healthcare cost per patient (males, $80 334 [116 762] versus females, $81 010 [112 625], p = 0.90), but males received more specialist, multidisciplinary HF clinic, haemodialysis, and day surgical care, and females received more home visits, continuing/convalescent care, and long‐term care. Annualized clinical events were highest in first year following index discharge in both males and females. Conclusions Among people discharged alive after hospitalization for HF, there were no sex differences in total and annual deaths, readmissions, and ED visits, or in total direct healthcare costs. Despite similar risk profiles, males received relatively more specialist care and day surgical procedures, and females received more supportive care. Clinical Trial Registration: ClinicalTrials.gov NCT02112227.
Tumor-intrinsic PRMT5 upregulates FGL1 via methylating TCF12 to inhibit CD8+ T-cell-mediated antitumor immunity in liver cancer
Authors: Jiao Sun, Hongfeng Yuan, Linlin Sun, Lina Zhao, Yufei Wang, Chunyu Hou, Huihui Zhang, Pan Lv, Guang Yang, Ningning Zhang, Wei Lu, Xiaodong Zhang
Journal: Acta Pharmaceutica Sinica B (2024)

Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8+ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8+ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.
Dietary antioxidant capacity, genetic susceptibility and polymorphism, and inflammatory bowel disease risk in a prospective cohort
Authors: Jie Chen, Lintao Dan, Shuai Yuan, Tian Fu, Jiangwei Sun, Alicja Wolk, Jonas F Ludvigsson, Xue Li, Xiaoyan Wang, Susanna C Larsson
Journal: Clinical Gastroenterology and Hepatology (2024)

Oxidative stress is an essential factor in the pathogenesis of inflammatory bowel disease (IBD). A previous study found protective potential of some antioxidative nutrients against IBD. However, the association between total antioxidant capacity (TAC) of the diet and incident IBD is unclear. We conducted a prospective cohort study including 186,195 IBD-free participants at baseline from the UK Biobank. We calculated dietary TAC using the oxygen radical absorbance capacity method based on repeated online 24-hour dietary recalls. Crohn's disease (CD) and ulcerative colitis (UC) were identified via inpatient register and primary care data. Genetic susceptibility for IBD was assessed by a polygenic risk score. Cox proportional hazard models were applied to estimate multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 11.4 years, we identified 396 CD and 809 UC incident cases. Individuals with the highest quintile of dietary TAC had a lower risk of CD (27.0 vs 17.0 cases/100,000 person-years; aHR, 0.66; 95% CI, 0.49-0.90) but not UC (46.7 vs 35.5 cases/100,000 person-years; aHR, 0.85; 95% CI, 0.69-1.06) compared with the lowest group. We observed interactions between TAC and genetic susceptibility at both multiplicative (P-interaction = .008/0.063 for CD/UC) and additive (both P values > 1) scales. Additionally, a polymorphism of the endogenous antioxidant enzyme gene SOD2 (rs4880) modified the dietary TAC-UC association (P-interaction = .039). This study suggests that a diet with high TAC may help prevent the development of IBD, particularly in individuals at high genetic risk of IBD and in mutation carriers of rs4880 in SOD2.
Integrating contact tracing data to enhance outbreak phylodynamic inference: a deep learning approach
Authors: Ruopeng Xie, Dillon C Adam, Shu Hu, Benjamin J Cowling, Olivier Gascuel, Anna Zhukova, Vijaykrishna Dhanasekaran
Journal: Molecular Biology and Evolution (2024)

Abstract Phylodynamics is central to understanding infectious disease dynamics through the integration of genomic and epidemiological data. Despite advancements, including the application of deep learning to overcome computational limitations, significant challenges persist due to data inadequacies and statistical unidentifiability of key parameters. These issues are particularly pronounced in poorly resolved phylogenies, commonly observed in outbreaks such as SARS-CoV-2. In this study, we conducted a thorough evaluation of PhyloDeep, a deep learning inference tool for phylodynamics, assessing its performance on poorly resolved phylogenies. Our findings reveal the limited predictive accuracy of PhyloDeep (and other state-of-the-art approaches) in these scenarios. However, models trained on poorly resolved, realistically simulated trees demonstrate improved predictive power, despite not being infallible, especially in scenarios with superspreading dynamics, whose parameters are challenging to capture accurately. Notably, we observe markedly improved performance through the integration of minimal contact tracing data, which refines poorly resolved trees. Applying this approach to a sample of SARS-CoV-2 sequences partially matched to contact tracing from Hong Kong yields informative estimates of superspreading potential, extending beyond the scope of contact tracing data alone. Our findings demonstrate the potential for enhancing phylodynamic analysis through complementary data integration, ultimately increasing the precision of epidemiological predictions crucial for public health decision-making and outbreak control.
Reply to the letter regarding the article ‘Heart failure with improved versus persistently reduced left ventricular ejection fraction: A comparison of the <scp>BIOSTAT</scp>‐<scp>CHF</scp> (European) study with the <scp>ASIAN</scp>‐<scp>HF</scp> registry’
Authors: Thong Huy Cao, Adriaan A. Voors, Leong L. Ng
Journal: European Journal of Heart Failure (2024)
Cancer-associated fibroblasts shape early myeloid cell response to chemotherapy-induced immunogenic signals in next generation tumor organoid cultures
Authors: Julijan Kabiljo, Anna Theophil, Jakob Homola, Annalena F Renner, Nathalie Stürzenbecher, Daphni Ammon, Rebecca Zirnbauer, Simone Stang, Loan Tran, Johannes Laengle, Askin Kulu, Anna Chen, Markus Fabits, Velina S Atanasova, Oliver Pusch, Wolfgang Weninger, Henning Walczak, Dietmar Herndler Brandstetter, Gerda Egger, Helmut Dolznig, Anna Kusienicka, Matthias Farlik, Michael Bergmann
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Patient-derived colorectal cancer (CRC) organoids (PDOs) solely consisting of malignant cells led to major advances in the understanding of cancer treatments. Yet, a major limitation is the absence of cells from the tumor microenvironment, thereby prohibiting potential investigation of treatment responses on immune and structural cells. Currently there are sparse reports describing the interaction of PDOs, cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) in complex primary co-culture assay systems. Methods Primary PDOs and patient matched CAF cultures were generated from surgical resections. Co-culture systems of PDOs, CAFs and monocytic myeloid cells were set up to recapitulate features seen in patient tumors. Single-cell transcriptomics and flow cytometry was used to show effects of culture systems on TAM populations in the co-culture assays under chemotherapeutic and oncolytic viral treatment. Results In contrast to co-cultures of tumor cells and monocytes, CAF/monocyte co-cultures and CAF/monocyte/tumor cell triple cultures resulted in a partial differentiation into macrophages and a phenotypic switch, characterized by the expression of major immunosuppressive markers comparable to TAMs in CRC. Oxaliplatin and 5-fluorouracil, the standard-of-care chemotherapy for CRC, induced polarization of macrophages to a pro-inflammatory phenotype comparable to the immunogenic effects of treatment with an oncolytic virus. Monitoring phagocytosis as a functional proxy to macrophage activation and subsequent onset of an immune response, revealed that chemotherapy-induced cell death, but not virus-mediated cell death, is necessary to induce phagocytosis of CRC cells. Moreover, CAFs enhanced the phagocytic activity in chemotherapy treated CRC triple cultures. Conclusions Primary CAF-containing triple cultures successfully model TAM-like phenotypes ex vivo and allow the assessment of their functional and phenotypic changes in response to treatments following a precision medicine approach.
Effect of Valve Type and Anesthesia Strategy for TAVR
Authors: Hans-Josef Feistritzer, Thomas Kurz, Reinhard Vonthein, Leonie Schröder, Georg Stachel, Ingo Eitel, Christoph Marquetand, Roza Saraei, Eva Kirchhof, Matthias Heringlake, Mohamed Abdel-Wahab, Steffen Desch, Holger Thiele
Journal: Journal of the American College of Cardiology (2024)
Hypertensive Disorders of Pregnancy Increase the Risk for Myocardial Infarction
Authors: Lisa E Vaughan, Yoshihisa Kanaji, Sonja Suvakov, Santosh Parashuram, Yvonne S Butler Tobah, Alanna M Chamberlain, Suzette J Bielinski, Natasa Milic, Rajiv Gulati, Karl A Nath, Amir Lerman, Vesna D Garovic
Journal: Journal of the American College of Cardiology (2024)
a fall
Authors: James M. Wilkins
Journal: JAMA (2024)

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