tbuckley/cabot-search huggingface dataset:
TP8, A Novel Chondroinductive Peptide, Significantly Promoted Neo‐Cartilage Repair without Activating Bone Formation
Authors: Mingjing Zhu, Siqing Jiang, Xingyang Li, Wenchao Zhong, Wei Cao, Qianting Luo, Antong Wu, Gang Wu, Qingbin Zhang
Journal: Advanced Healthcare Materials (2024)

The repair of large cartilage defects remains highly challenging in the fields of orthopedics and oral and maxillofacial surgery. A chondroinductive agent is promising to activate endogenous mesenchymal stem cells (MSCs) so as to facilitate cartilage regeneration. In this study, we analyze the crystallographic data of the critical binding domain of transforming growth factor β3 (TGF-β3) with its type II receptor and successfully develop a novel chondroinductive peptide - TGF-β3-derived peptide No. 8 (TP8) that can induce an ectopic cartilage formation without obvious bone formation. TP8 shows a comparable capacity as TGF-β3 in enhancing glycosaminoglycans (GAGs) and proteoglycans (PGs) secretion in the micromass of bone marrow MSCs (BMSCs) and promoting the expression of chondrogenic markers in comparison with the Control group. TP8 induces a significantly higher expression of the SRY-box transcription factor 9 (Sox9) gene than TGF-β3. Moreover, TP8 significantly upregulates the phosphorylation of Smad1/5 but not MAPK/JNK or Smad 2/3. The knockdown of low-density lipoprotein receptor (LDLR) -related protein-1 (Lrp1), a transmembrane endocytosis receptor, nullifies the TP8-induced Sox9 expression. In the critical-size cartilage defects in rabbit medial femoral condyles, TP8 can induce neo-cartilage formation with a significantly thicker deep zone in comparison with the TGF-β3 and Control. These findings suggest a promising application potential of TP8 in cartilage tissue engineering.
Government must prioritise affordable healthy homes not just a target number, says Marmot
Authors: Jacqui Wise
Journal: BMJ (2024)

We have shown earlier that the evolution of rapid development is accompanied by a correlated decrease in larval feeding rate and competitive ability in laboratory populations of Drosophila melanogaster (Prasad et al. 2001; Shakarad et al. 2005). Here, we show that our faster developing populations have evolved higher hemocyte density and phenol oxidase activity in the larval hemolymph. The increased hemocyte density could be responsible for the evolution of decreased feeding rate as hemocytes and the cephalopharyngeal musculature share common embryonic precursor cells (Kraajiveld et al. 2001). We also show that the bacterial load in larval food vials of the faster developing populations is substantially higher than in controls. Our results suggest that the evolution of reduced competitive ability in the faster developing populations is probably due to larval feeding rate trading off with enhanced larval immune system function. Enhanced larval immune function, in turn, is most likely selected for due to the role of hemocytes (Lanot et al. 2001, Wood and Jacinto 2007) and phenol oxidase (Pentz et al. 1986) in development, and perhaps also due to inadvertent selection on immune performance resulting from the higher bacterial load faced by larvae in the faster developing populations.
Functionalized Bone Implant Inspired by Lattice Defense Strategy: Grid Management, Precise and Effective Multiple‐Prevention of Osteomyelitis Recurrence and Promote Bone Regeneration
Authors: Bo Zhang, Hao Zhang, Yani Sun, Lei Chen, Kaixin Sun, Yuming Zhang, Xiaofan Hu, Kang Zhao, Zixiang Wu, Yufei Tang
Journal: Advanced Healthcare Materials (2024)

Osteomyelitis with a high recurrence rate. Timely-prevention can avoid severe consequence and death. However, conventional drug response-release has the disadvantages of unnecessary release and waste, causing ineffective prevention. Inspired by "Lattice-defense technology", gridding lesion areas and constructing a "Triggered-precise response-release system" may be an effective multiple-prevention method. Here, a new strict pH-triggered response drug controlled-release mechanism was proposed innovatively to construct a "Triggered-precise response-release system" and achieve multiple-effective prevention. PO
Gut microbiota and microbial metabolites for osteoporosis
Authors: Xuan-Qi Zheng, Ding-Ben Wang, Yi-Rong Jiang, Chun-Li Song
Journal: Gut Microbes (2024)

Osteoporosis is an age-related bone metabolic disease. As an essential endocrine organ, the skeletal system is intricately connected with extraosseous organs. The crosstalk between bones and other organs supports this view. In recent years, the link between the gut microecology and bone metabolism has become an important research topic, both in preclinical studies and in clinical trials. Many studies have shown that skeletal changes are accompanied by changes in the composition and structure of the gut microbiota (GM). At the same time, natural or artificial interventions targeting the GM can subsequently affect bone metabolism. Moreover, microbiome-related metabolites may have important effects on bone metabolism. We aim to review the relationships among the GM, microbial metabolites, and bone metabolism and to summarize the potential mechanisms involved and the theory of the gut‒bone axis. We also describe existing bottlenecks in laboratory studies, as well as existing challenges in clinical settings, and propose possible future research directions.
Assessing alternative strategies for measuring metabolic risk
Authors: Elizabeth J. Enichen, Kimia Heydari, Joseph C. Kvedar
Journal: npj Digital Medicine (2024)

Qiao et al. recently investigated the ability of dual-energy X-ray absorptiometry (DXA) scans and a smartphone app to provide detailed body composition and shape data. In a healthcare system that continues to rely on crude and stigmatizing measurements like body-mass index (BMI), their findings point to the potential of newer technologies to capture markers (i.e., visceral adiposity and fat distribution patterns) that provide clearer insights into metabolic health.
The dangers of industrialisation: why we need to rebuild a convivial society
Authors: Richard Smith
Journal: BMJ (2024)

Writer Ivan Illich foresaw out current global polycrisis 50 years ago, which he blamed on us succumbing to industrial tools, not least in "health" care, writes <b>Richard Smith</b>. We need to maximise "convivial tools" that enrich us and minimise "industrial tools" that can enslave and kill us
Effect of heated mittens on physical hand function in people with hand osteoarthritis: randomised controlled trial
Authors: Cecilie Bartholdy, Anna Døssing, Zara R Stisen, Sabrina M Nielsen, Robin Christensen, Bente Danneskiold-Samsøe, Henning Bliddal, Marius Henriksen, Karen Ellegaard
Journal: BMJ (2024)

Abstract Objective To assess the effect of electrically heated mittens on physical hand function in people with osteoarthritis of the hands compared with control mittens. Design Randomised controlled trial. Setting Osteoarthritis outpatient clinic, Copenhagen, Denmark. Participants 200 people with hand osteoarthritis aged 42-90 years. 100 participants were assigned to the intervention group and 100 to the control group. Interventions Electrically heated mittens or control mittens (heating elements disconnected) worn for at least 15 minutes daily for six weeks. Main outcome measures The primary outcome was change in hand function measured on the function subscale of the Australian/Canadian hand osteoarthritis index (AUSCAN; score 0-100 points) at six weeks. Key secondary outcomes included changes in the AUSCAN hand pain subscale (score 0-100 points), global rating of hand osteoarthritis related problems (0-100 visual analogue scale), and grip strength (newtons) at six weeks. Analysis of secondary outcomes was performed using a hierarchical gatekeeping approach. Results 91 participants in the intervention group and 95 in the control group completed the trial. The mean age of participants was 71 years, 87% (n=173) were women, and mean body mass index was 24.9 (SD 4.4). Median disease duration was 10 years (interquartile range 5-15 years). The between group difference for change in AUSCAN function at week 6 was 3.0 points (95% confidence interval (CI) −0.4 to 6.3; P=0.09) in favour of heated mittens. For the key secondary outcome, change in AUSCAN hand pain score from baseline, a group difference was observed of 5.9 points (95% CI 2.2 to 9.5) in favour of heated mittens. Changes in global rating of hand osteoarthritis related problems and grip strength did not differ between the groups with an observed difference between groups of 2.8 points (95% CI −3.7 to 9.2) and 2.3 newtons (95% CI −16.3 to 21.0) in favour of heated mittens, respectively. Conclusion Use of electrically heated mittens for six weeks was not related to a positive change in physical hand function compared with control mittens. Heated mittens provided no additional benefits on global rating of hand osteoarthritis related problems and grip strength. A small benefit was detected for hand pain, but this could have been overestimated. Trial registration ClinicalTrials.gov NCT04576403
Degrowth: a new logic for the global economy
Authors: Omer Tayyab, Meghna Goyal, Morena Hanbury Lemos, Jason Hickel
Journal: BMJ (2024)

Objective To evaluate the association between intakes of refined grains, whole grains, and white rice with cardiovascular disease, total mortality, blood lipids, and blood pressure in the Prospective Urban and Rural Epidemiology (PURE) study.
Alzheimer’s disease mortality among taxi and ambulance drivers: population based cross sectional study
Authors: Vishal R Patel, Michael Liu, Christopher M Worsham, Anupam B Jena
Journal: BMJ (2024)

Abstract Objective To analyze mortality attributed to Alzheimer’s disease among taxi drivers and ambulance drivers, occupations that demand frequent spatial and navigational processing, compared with other occupations. Design Population based cross-sectional study. Setting Use of death certificates from the National Vital Statistics System in the United States, which were linked to occupation, 1 January 2020-31 December 2022. Participants Deceased adults aged 18 years and older. Main outcomes measures Among 443 occupations studied, percentage of deaths attributed to Alzheimer’s disease for taxi drivers and ambulance drivers and each of the remaining 441 occupations, adjusting for age at death and other sociodemographic factors. Results Of 8 972 221 people who had died with occupational information, 3.88% (348 328) had Alzheimer’s disease listed as a cause of death. Among taxi drivers, 1.03% (171/16 658) died from Alzheimer’s disease, while among ambulance drivers, the rate was 0.74% (10/1348). After adjustment, ambulance drivers (0.91% (95% confidence interval 0.35% to 1.48%)) and taxi drivers (1.03% (0.87% to 1.18%)) had the lowest proportion of deaths due to Alzheimer’s disease of all occupations examined. This trend was not observed in other transportation related jobs that are less reliant on real time spatial and navigational processing or for other types of dementia. Results were consistent whether Alzheimer’s disease was recorded as an underlying or contributing cause of death. Conclusions Taxi drivers and ambulance drivers, occupations involving frequent navigational and spatial processing, had the lowest proportions of deaths attributed to Alzheimer’s disease of all occupations.
Gang of four: when BMJ editors met
Authors: Kamran Abbasi
Journal: BMJ (2024)

Rabiah Fardoos1,2,*, Sarah K. Nyquist3,4,14,*, Osaretin E. Asowata1, Samuel W. Kazer3, Alveera Singh1, Abigail Ngoepe1, Janifer Giandhari5, Ntombifuthi Mthabela1, Dirhona Ramjit1, Samita Singh1, Farina Karim1, Søren Buus2, Frank Anderson6, James Z. Porterfield1,7, Andile L. Sibiya8, Rishan Bipath9, Kumeshan Moodley10, Warren Kuhn8,10, Bonnie Berger11, Son Nguyen3, Tulio de Oliveira5, Thumbi Ndung'u1,12,14, Philip Goulder1,13,14, Alex K. Shalek3,15,16, Alasdair Leslie1,12 and Henrik N. Kløverpris1,2,12,#Africa Health Research Institute (AHRI), Durban 4001, South AfricaDepartment of Immunology and Microbiology, University of Copenhagen, Copenhagen 2200N, DenmarkInstitute for Medical Engineering Science, Department of Chemistry, and Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139,-4307, USAProgram in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, MA 02139. USAKwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South AfricaDiscipline of General Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South AfricaUniversity of Kentucky, Department of Otolaryngology-Head Neck Surgery, Department of Microbiology, Immunology and Molecular Genetics, Department of Internal Medicine - Division of Infectious Diseases, USDepartment of Otorhinolaryngology Head Neck Surgery, Inkosi Albert Luthuli Central Hospital, University of KwaZulu-Natal, Durban, South AfricaDepartment of Otorhinolaryngology, King Edward VIII hospital, University of KwaZulu-Natal, Durban, South AfricaDepartment of ENT, General Justice Gizenga Mpanza Regional Hospital (Stanger Hospital), University of KwaZulu-Natal, Durban 4001, South AfricaComputer Science Artificial Intelligence Lab and Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA 02139, USAUniversity College London, Division of Infection and Immunity, London WC1E 6AE, UKDepartment of Paediatrics, University of Oxford, Oxford, UKHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South AfricaBroad Institute of MIT and Harvard, Cambridge, MA 02142Ragon Institute of MGH, Harvard, Cambridge, MA 02139↵Corresponding author Address correspondence to: Henrik N. Kløverpris, Africa Health Research Institute, K-RITH Tower Building, 719 Umbilo Road, Durban 4001, South Africa and University of Copenhagen, MAERSK tower building 07-13, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. Phone: 27.74.546.6625;45.29720910, Email: henrik.kloverpris{at}ahri.org hkloverpris{at}sund.ku.dk↵* These authors contributed equally to this work
US abortion: Texas sues New York doctor accused of prescribing abortion drugs
Authors: Janice Hopkins Tanne
Journal: BMJ (2024)

Ghulam Hassan Dar1, Cláudia C. Mendes2, Wei-Li Kuan3, Mariana Conceição1, Samir El-Andaloussi4, Imre Mager1, Thomas C. Roberts1,5, Roger A. Barker3, Deborah C. I. Goberdhan2, Clive Wilson2,✉ and Matthew J.A. Wood1,5,✉Department of Paediatrics, University of Oxford, OX1 3QX, Oxford, UKDepartment of Physiology, Anatomy and Genetics, University of Oxford, OX1 3QX, Oxford, UKCentre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, CB2 0PY, Cambridge, UKDepartment of Laboratory Medicine, Karolinska Institute, 14186, SwedenMDUK Oxford Neuromuscular Centre, University of Oxford, OX2 9DU, Oxford, UK↵Correspondence: matthew.wood{at}paediatrics.ox.ac.uk, clive.wilson{at}dpag.ox.ac.uk
3D Bioprinting and Artificial Intelligence‐Assisted Biofabrication of Personalized Oral Soft Tissue Constructs
Authors: Yichen Dai, Peter Wang, Apurva Mishra, Kui You, Yuheng Zong, Wen Feng Lu, Edward Kai‐Hua Chow, Philip M Preshaw, Dejian Huang, Jacob Ren Jie Chew, Dean Ho, Gopu Sriram
Journal: Advanced Healthcare Materials (2024)

Abstract Regeneration of oral soft tissue defects, including mucogingival defects associated with the recession or loss of gingival and/or mucosal tissues around teeth and implants, is crucial for restoring oral tissue form, function, and health. This study presents a novel approach using three‐dimensional (3D) bioprinting to fabricate individualized grafts with precise size, shape, and layer‐by‐layer cellular organization. A multicomponent polysaccharide/fibrinogen‐based bioink is developed, and bioprinting parameters are optimized to create shape‐controlled oral soft tissue (gingival) constructs. Rheological, printability, and shape‐fidelity assays, demonstrated the influence of thickener concentration and print parameters on print resolution and shape fidelity. Artificial intelligence (AI)‐derived tool enabled streamline the iterative bioprinting parameter optimization and analysis of the interaction between the bioprinting parameters. The cell‐laden polysaccharide/fibrinogen‐based bioinks exhibited excellent cellular viability and shape fidelity of shape‐controlled, full‐thickness gingival tissue constructs over the 18‐day culture period. While variations in thickener concentrations within the bioink minimally impact the cellular organization and morphogenesis (gingival epithelial, connective tissue, and basement membrane markers), they influence the shape fidelity of the bioprinted constructs. This study represents a significant step toward the biofabrication of personalized soft tissue grafts, offering potential applications in the repair and regeneration of mucogingival defects associated with periodontal disease and dental implants.
PSMA‐Targeting Imprinted Nanogels for Prostate Tumor Localization and Imaging
Authors: Tong Zhang, Melanie Berghaus, Yuan Li, Qingmei Song, Maria M. Stollenwerk, Jenny Persson, Kenneth J. Shea, Börje Sellergren, Yongqin Lv
Journal: Advanced Healthcare Materials (2024)

Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer cells and tumor vasculature, making it an important biomarker. However, conventional PSMA-targeting agents like antibodies and small molecules have limitations. Antibodies exhibit instability and complex production, while small molecules show lower specificity and higher toxicity. Herein, this work develops a novel PSMA-targeting synthetic antibody to address prior limitations. This work synthesizes fluorescently labelled, N-isopropylacrylamide-based epitope imprinted nanogels (MIP-M) using a dispersion of magnetic nanoparticles as template carriers with a linear epitope from PSMA's extracellular apical domain as the template. MIP-M demonstrates high binding affinities for both the epitope template (apparent K
Synergistic Enhancement of Antibacterial and Osteo‐Immunomodulatory Activities of Titanium Implants via Dual‐Responsive Multifunctional Surfaces
Authors: Qing Wang, Ya Gao, Yanzheng Chen, Xuan Wang, Qingguo Pei, Taiyu Zhang, Changping Wang, Jinsong Pan
Journal: Advanced Healthcare Materials (2024)

Bone implant-associated infections and inflammations, primarily caused by bacteria colonization, frequently result in unsuccessful procedures and pose significant health risks to patients. To mitigate these challenges, the development of engineered implants with spatiotemporal regulation capabilities, designed to inhibit bacterial survival and modulate immune responses in the early stage, while promoting bone defect healing in the late stage is proposed. The implants are functionalized with ε-poly-l-lysine-phenylboronic acid (PP) via dynamic boronic ester bonds, which facilitate its release through a reactive oxygen species (ROS) and pH-responsive strategy, thereby establishing an antibacterial microenvironment on and around the implants. Additionally, the dynamic metal coordination interaction facilitates the loading and sustained release of Sr2+ under an acidic environment, providing immunomodulatory and osteogenic effects. The ROS/pH-responsive feature, coupled with the implant-bone tissue integration process, affords precise spatiotemporal regulation of the Ti-TA-Sr-PP implants. This strategy represents a promising approach for the preparation of advanced bone implants.
Synovial innate immune exhaustion is associated with worse pain in knee osteoarthritis
Authors: Holly T. Philpott, Trevor B. Birmingham, Garth Blackler, J. Daniel Klapak, Alexander J. Knights, Easton C. Farrell, Benoit Fiset, Logan A. Walsh, J. Robert Giffin, Edward M. Vasarhelyi, Steven J. MacDonald, Brent A. Lanting, Tristan Maerz, C. Thomas Appleton
Journal: Arthritis & Rheumatology (2024)

Objective Uncontrolled pain remains a major clinical challenge in the management of knee osteoarthritis (OA), the most common disabling joint disease. Worse pain is associated with synovial innate immune cell infiltration (synovitis), but the role of innate immune regulatory cells in pain is unknown. Our objective was to identify synovial innate immune cell subsets and pathophysiologic mechanisms associated with worse pain in patients with knee OA. Methods Synovial tissue biopsies from 122 patients with mild to severe knee OA pain (Knee injury and OA Outcome Score; KOOS) were analyzed to identify associations between synovial histopathology and worse pain. We then used spatial transcriptomics and proteomics of synovial tissue microenvironments (n=32), followed by single cell RNA sequencing (n=8), to identify synovial cell composition and cell‐cell communication networks in patients with more severe OA pain. Results Histopathological signs of synovial microvascular dysfunction, perivascular edema, were associated with worse KOOS pain (‐10.76 [95%CI ‐18.90, ‐2.61]). Patients with worse pain had fewer immune‐regulatory macrophages, expanded fibroblast subsets, and enrichment in neurovascular remodeling pathways. Synovial macrophages from patients with worse pain expressed markers of immune exhaustion, decreased phagocytic function (‐19.42% [95%CI ‐35.96, ‐2.89]) and their conditioned media increased neuronal cell stress in dorsal root ganglia. Conclusions Although synovitis increases during OA, our findings suggest that exhaustion, dysfunction, and loss of immune‐regulatory macrophages is associated with worse pain and may be an important therapeutic target.
Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
Authors: Yogesh Godiyal, Drishti Maheshwari, Hiroaki Taniguchi, Shweta S. Zinzuwadia, Yanelys Morera-Díaz, Devesh Tewari, Anupam Bishayee
Journal: Military Medical Research (2024)

Abstract Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1). The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system. Furthermore, it controls the phenotype and functionality of innate and adaptive immune components. A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints. This could contribute to the existing arsenal of anticancer drugs. Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis, promoting tumor cell apoptosis, influencing cell proliferation, and eventually leading to tumor cell death and inhibiting cancer progression. However, there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer. Hence, this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
Genomic island-encoded LmiA regulates acid resistance and biofilm formation in enterohemorrhagic <i>Escherichia coli</i> O157:H7
Authors: Hongmin Sun, Lingyan Jiang, Jingnan Chen, Chenbo Kang, Jun Yan, Shuai Ma, Mengjie Zhao, Houliang Guo, Bin Yang
Journal: Gut Microbes (2024)

Enterohemorrhagic