tbuckley/cabot-search huggingface dataset:
Enhancement of Bone Tissue Regeneration with Multi‐Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses
Authors: Hyewoo Jeong, Hayeon Byun, Jinkyu Lee, Yujin Han, Seung Jae Huh, Heungsoo Shin
Journal: Advanced Healthcare Materials (2024)

Inorganic nanoparticles are promising materials for bone tissue engineering due to their chemical resemblance to the native bone structure. However, most studies are unable to capture the entirety of the defective environment, providing limited bone regenerative abilities. Hence, this study aims to develop a multifunctional nanoparticle to collectively control the defective bone niche, including immune, angiogenic, and osteogenic systems. The nanoparticles, self-assembled by biomimetic mineralization and tannic acid (TA)-mediated metal-polyphenol network (MPN), are released sustainably after the incorporation within a gelatin cryogel. The released nanoparticles display a reduction in M1 macrophages by means of reactive oxygen species (ROS) elimination. Consequently, osteoclast maturation is also reduced, which is observed by the minimal formation of multinucleated cells (0.4%). Furthermore, the proportion of M2 macrophages, osteogenic differentiation, and angiogenic potential are consistently increased by the effects of magnesium from the nanoparticles. This orchestrated control of multiple systems influences the in vivo vascularized bone regeneration in which 80% of the critical-sized bone defect is regenerated with new bones with mature lamellar structure and arteriole-scale micro-vessels. Altogether, this study emphasizes the importance of the coordinated modulation of immune, osteogenic, and angiogenic systems at the bone defect site for robust bone regeneration.
Low-intensity pulsed ultrasound protects from inflammatory dilated cardiomyopathy through inciting extracellular vesicles
Authors: Ping Sun, Yi Li, Yifei Li, Huan Ji, Ge Mang, Shuai Fu, Shuangquan Jiang, Stephen Choi, Xiaoqi Wang, Zhonghua Tong, Chao Wang, Fei Gao, Pingping Wan, Shuang Chen, You Li, Peng Zhao, Xiaoping Leng, Maomao Zhang, Jiawei Tian
Journal: Cardiovascular Research (2024)

CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms.
Targeting macrophages with multifunctional nanoparticles to detect and prevent atherosclerotic cardiovascular disease
Authors: Victoria Nankivell, Achini K Vidanapathirana, Ayla Hoogendoorn, Joanne T M Tan, Johan Verjans, Peter J Psaltis, Mark R Hutchinson, Brant C Gibson, Yiqing Lu, Ewa Goldys, Gang Zheng, Christina A Bursill
Journal: Cardiovascular Research (2024)

Abstract Despite the emergence of novel diagnostic, pharmacological, interventional, and prevention strategies, atherosclerotic cardiovascular disease remains a significant cause of morbidity and mortality. Nanoparticle (NP)-based platforms encompass diverse imaging, delivery, and pharmacological properties that provide novel opportunities for refining diagnostic and therapeutic interventions for atherosclerosis at the cellular and molecular levels. Macrophages play a critical role in atherosclerosis and therefore represent an important disease-related diagnostic and therapeutic target, especially given their inherent ability for passive and active NP uptake. In this review, we discuss an array of inorganic, carbon-based, and lipid-based NPs that provide magnetic, radiographic, and fluorescent imaging capabilities for a range of highly promising research and clinical applications in atherosclerosis. We discuss the design of NPs that target a range of macrophage-related functions such as lipoprotein oxidation, cholesterol efflux, vascular inflammation, and defective efferocytosis. We also provide examples of NP systems that were developed for other pathologies such as cancer and highlight their potential for repurposing in cardiovascular disease. Finally, we discuss the current state of play and the future of theranostic NPs. Whilst this is not without its challenges, the array of multifunctional capabilities that are possible in NP design ensures they will be part of the next frontier of exciting new therapies that simultaneously improve the accuracy of plaque diagnosis and more effectively reduce atherosclerosis with limited side effects.
Pulmonary vascular stenosis scoring in fibrosing mediastinitis
Authors: Yangyang Wang, Chao Bu, Mengdi Zhang, Juan Wang, Kaiyu Jiang, Mingwang Ding, Hongling Su, Xiaozhou Long, Mengfei Jia, Yu Li, Yunshan Cao
Journal:  (2024)

Abstract Aims This study aims to develop a scoring system for evaluating the degree of pulmonary vascular stenosis in fibrosing mediastinitis (FM). Methods and results A retrospective single-centre study was conducted on 56 patients with FM in China between April 2014 and August 2021. The involvement of pulmonary vessels in patients with FM was assessed using dual-phase computed tomography pulmonary angiography, and we found that 85.7% of the patients had both pulmonary artery (PA) and vein (PV) involvement. PA involvement was mainly located proximal to both the upper PA and the bilateral basal trunk levels in the lower lungs. The involvement of the superior PV was more common than that of the inferior PV, and the right inferior PV was the least involved. Most of these lesions exhibited moderate or severe stenosis. Additionally, a scoring system for evaluating the degree of pulmonary vascular stenosis was developed. A correlation analysis revealed a negative correlation between the final pulmonary vascular score and the pulmonary arterial pressure, pulmonary vascular resistance, and maximum tricuspid regurgitation velocity. The calculated score of 17.1 was the best cut-off value for the diagnosis of mild and severe pulmonary hypertension (PH). Conclusion We successfully developed a scoring system for pulmonary vascular stenosis that can be used to evaluate the severity of pulmonary vessel involvement and PH. This scoring system may be relevant in the future development of target-based strategies for percutaneous interventions.
Genetic algorithm based deep learning model adaptation for improvising the motor imagery classification
Authors: Vishnupriya R, Neethu Robinson, Ramasubba Reddy M
Journal: Brain-Computer Interfaces (2024)

Deep learning methods have proved a promising performance for electroencephalography-based brain-computer interfaces (EEG-BCI). It is particularly encouraging that a subject-independent model can be trained using a large amount of other subjects' data. Transfer learning methods such as adaptation or fine-tuning can be used on the pre-trained model to improve the performance. This study examined the influence of fine-tuning on the subject-independent model for EEG-based motor imagery (MI) classification using a genetic algorithm (GA). The proposed method is evaluated on the binary class MI dataset from the Korea University EEG dataset. Results show that the proposed GA-based fine-tuning approach statistically improved the average classification accuracy of the baseline model from 84.46% to 87.29%. More interestingly, our approach shows significant improvement in cases where the performance of the baseline model is poor after fine-tuning using other approaches. Further, layer-wise relevance propagation (LRP) is used to analyze the adapted models to gain a deeper understanding of the neurophysiological explanations underlying the model's decision.
Physical activity across midlife and health-related quality of life in Australian women: A target trial emulation using a longitudinal cohort
Authors: Binh Nguyen, Philip Clare, Gregore I. Mielke, Wendy J. Brown, Ding Ding
Journal: PLoS Medicine (2024)

Background There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women. Methods and findings We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women’s Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year “exposure period” (2001 to 2016; when women aged 50–55 to 65–70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women. Conclusions Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life.
TLR8 agonist selgantolimod regulates Kupffer cell differentiation status and impairs HBV entry into hepatocytes via an IL-6-dependent mechanism
Authors: Armando Andres Roca Suarez, Marie-Laure Plissonnier, Xavier Grand, Maud Michelet, Guillaume Giraud, Maria Saez-Palma, Anaëlle Dubois, Sarah Heintz, Audrey Diederichs, Nicolaas Van Renne, Thomas Vanwolleghem, Stephane Daffis, Li Li, Nikita Kolhatkar, Yao-Chun Hsu, Jeffrey J Wallin, Audrey H Lau, Simon P Fletcher, Michel Rivoire, Massimo Levrero, Barbara Testoni, Fabien Zoulim
Journal: Gut (2024)

Objective Achieving HBV cure will require novel combination therapies of direct-acting antivirals and immunomodulatory agents. In this context, the toll-like receptor 8 (TLR8) agonist selgantolimod (SLGN) has been investigated in preclinical models and clinical trials for chronic hepatitis B (CHB). However, little is known regarding its action on immune effectors within the liver. Our aim was to characterise the transcriptomic changes and intercellular communication events induced by SLGN in the hepatic microenvironment. Design We identified TLR8 -expressing cell types in the human liver using publicly available single-cell RNA-seq data and established a method to isolate Kupffer cells (KCs). We characterised transcriptomic and cytokine KC profiles in response to SLGN. SLGN’s indirect effect was evaluated by RNA-seq in hepatocytes treated with SLGN-conditioned media (CM) and quantification of HBV parameters following infection. Pathways mediating SLGN’s effect were validated using transcriptomic data from HBV-infected patients. Results Hepatic TLR8 expression takes place in the myeloid compartment. SLGN treatment of KCs upregulated monocyte markers (eg, S100A12 ) and downregulated genes associated with the KC identity (eg, SPIC ). Treatment of hepatocytes with SLGN-CM downregulated NTCP and impaired HBV entry. Cotreatment with an interleukin 6-neutralising antibody reverted the HBV entry inhibition. Conclusion Our transcriptomic characterisation of SLGN sheds light into the programmes regulating KC activation. Furthermore, in addition to its previously described effect on established HBV infection and adaptive immunity, we show that SLGN impairs HBV entry. Altogether, SLGN may contribute through KCs to remodelling the intrahepatic immune microenvironment and may thus represent an important component of future combinations to cure HBV infection.
Diagnostic yield from symptomatic gastroscopy in the UK: British Society of Gastroenterology analysis using data from the National Endoscopy Database
Authors: David Robert Beaton, Linda Sharp, Liya Lu, Nigel J Trudgill, Mo Thoufeeq, Brian D Nicholson, Peter Rogers, James Docherty, Anna Jenkins, Allan John Morris, Thomas Rösch, Matthew D Rutter
Journal: Gut (2024)

Objective This national analysis aimed to calculate the diagnostic yield from gastroscopy for common symptoms, guiding improved resource utilisation. Design A cross-sectional study was conducted of diagnostic gastroscopies between 1 March 2019 and 29 February 2020 using the UK National Endoscopy Database. Mixed-effect logistic regression models were used, incorporating random (endoscopist) and fixed (symptoms, age and sex) effects on two dependent variables (endoscopic cancer; Barrett’s oesophagus (BO) diagnosis). Adjusted positive predictive values (aPPVs) were calculated. Results 382 370 diagnostic gastroscopies were analysed; 30.4% were performed in patients aged &lt;50 and 57.7% on female patients. The overall unadjusted PPV for cancer was 1.0% (males 1.7%; females 0.6%, p&lt;0.01). Other major pathology was found in 9.1% of procedures, whereas 89.9% reported only normal findings or minor pathology (92.5% in females; 94.6% in patients &lt;50). Highest cancer aPPVs were reached in the over 50s (1.3%), in those with dysphagia (3.0%) or weight loss plus another symptom (1.4%). Cancer aPPVs for all other symptoms were below 1%, and for those under 50, remained below 1% regardless of symptom. Overall, 73.7% of gastroscopies were carried out in patient groups where aPPV cancer was &lt;1%. The overall unadjusted PPV for BO was 4.1% (males 6.1%; females 2.7%, p&lt;0.01). The aPPV for BO for reflux was 5.8% and ranged from 3.2% to 4.0% for other symptoms. Conclusions Cancer yield was highest in elderly male patients, and those over 50 with dysphagia. Three-quarters of all gastroscopies were performed on patients whose cancer risk was &lt;1%, suggesting inefficient resource utilisation.
Democratic Republic of the Congo: a strengthened response to mpox could help revitalise the country’s healthcare system
Authors: Faraan Rahim, Cameron Sabet, Serge Holenn, Julian Hertz
Journal: BMJ (2024)

Over the past year, the Democratic Republic of the Congo has grappled with the largest outbreak of mpox in the past half century. Despite obstacles, an enhanced response to the crisis can provide a blueprint for fortifying the healthcare system
Wright’s Hierarchical <i>F</i>-Statistics
Authors: Marcy K Uyenoyama
Journal: Molecular Biology and Evolution (2024)

Abstract This perspective article offers a meditation on FST and other quantities developed by Sewall Wright to describe the population structure, defined as any departure from reproduction through random union of gametes. Concepts related to the F-statistics draw from studies of the partitioning of variation, identity coefficients, and diversity measures. Relationships between the first two approaches have recently been clarified and unified. This essay addresses the third pillar of the discussion: Nei’s GST and related measures. A hierarchy of probabilities of identity-by-state provides a description of the relationships among levels of a structured population with respect to genetic diversity. Explicit expressions for the identity-by-state probabilities are determined for models of structured populations undergoing regular inbreeding and recurrent mutation. Levels of genetic diversity within and between subpopulations reflect mutation as well as migration. Accordingly, indices of the population structure are inherently locus-specific, contrary to the intentions of Wright. Some implications of this locus-specificity are explored.
Longer Interval Between First Colonoscopy With Negative Findings for Colorectal Cancer and Repeat Colonoscopy
Authors: Qunfeng Liang, Trasias Mukama, Kristina Sundquist, Jan Sundquist, Hermann Brenner, Elham Kharazmi, Mahdi Fallah
Journal: JAMA Oncology (2024)

For individuals without a family history of colorectal cancer (CRC), colonoscopy screening every 10 years is recommended to reduce CRC incidence and mortality. However, debate exists about whether and for how long this 10-year interval could be safely expanded.
Endovascular Therapy and Outcomes Among Patients With Very Large Ischemic Core Stroke
Authors: Dongjing Xie, Jiacheng Huang, Shitao Fan, Changwei Guo, Wenzhe Sun, Zhouzhou Peng, Lingyu Zhang, Chengsong Yue, Zhongming Qiu, Hongfei Sang, Dingwen Liang, Jinrong Hu, Jie Yang, Jiandi Huang, Linyu Li, Juan Liu, Dahong Yang, Xiang Liu, Weilin Kong, Shuai Liu, Qingwu Yang, Wenjie Zi, Fengli Li
Journal: JAMA Network Open (2024)

Importance The association of endovascular therapy (EVT) with outcomes is unclear for patients with very low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) within 24 hours of stroke onset. Objective To explore the association of EVT with functional and safety outcomes among patients with ASPECTS of 0 to 2 scored with noncontrast computed tomography. Design, Setting, and Participants This cohort study used data from an ongoing, prospective, observational, nationwide registry including all patients treated at 38 stroke centers in China with an occlusion in the internal carotid artery or M1 or M2 segment of the middle cerebral artery within 24 hours of witnessed symptom onset. Patients with ASPECTS of 0 to 2 between November 1, 2021, and February 8, 2023, were included in analysis. Data were analyzed October to November 2023. Exposures EVT vs standard medical treatment (SMT). Main Outcomes and Measures The primary outcome was favorable functional outcome, defined as modified Rankin Scale score (mRS) of 0 to 3, at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) within 48 hours and mortality at 90 days. Results A total of 245 patients (median [IQR] age, 71 [63-78] years; 118 [48%] women) with ASPECTS of 0 to 2 were included, of whom 111 patients (45.1%) received SMT and 135 patients (54.9%) received EVT. The EVT group had significantly greater odds of favorable functional outcome at 90 days than the SMT group (30 patients [22.2%] vs 11 patients [9.9%]; P = .01; adjusted odds ratio [aOR], 3.07 [95% CI, 1.29-7.31]; P = .01). Patients in the EVT group, compared with the SMT group, had significantly greater odds of any ICH (56 patients [41.5%] vs 16 patients [11.4%]; P &amp;amp;lt; .001; aOR, 4.27 [95% CI, 2.19-8.35]; P &amp;amp;lt; .001) and sICH (24 patients [17.8%] vs 1 patient [0.9%]; P &amp;amp;lt; .001; aOR, 23.07 [95% CI, 2.99-177.79]; P = .003) within 48 hours. There were no differences between groups for 90-day mortality (80 patients [59.3%] vs 59 patients [53.2%]; P = .34; aOR, 1.38 [95% CI, 0.77-2.47]; P = .28). The results remained robust in the propensity score–matched analysis. Conclusions and Relevance In this cohort study of patients with very low ASPECTS based on NCCT within 24 hours of stroke onset, those treated with EVT had higher odds of a favorable functional outcome compared with those who received SMT. Randomized clinical trials are needed to assess these findings.
Measurable Residual <i>FLT3</i> Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia
Authors: Laura W. Dillon, Gege Gui, Niveditha Ravindra, Georgia Andrew, Devdeep Mukherjee, Zoë C. Wong, Ying Huang, Jason Gerhold, Matt Holman, Julian D’Angelo, Jeffrey Miller, Jake Higgins, Jesse J. Salk, Jeffery J. Auletta, Firas El Chaer, Steven M. Devine, Antonio Martin Jimenez-Jimenez, Marcos J. G. De Lima, Mark R. Litzow, Partow Kebriaei, Wael Saber, Stephen R. Spellman, Scott L. Zeger, Kristin M. Page, Christopher S. Hourigan
Journal: JAMA Oncology (2024)

Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown.
Routine Vaccination During Pregnancy Among People Living With HIV in the United States
Authors: Saba Berhie, Deborah Kacanek, Jessica Lee, Jennifer Jao, Kathleen Powis, Liz Salomon, Danish Siddiqui, Lynn M. Yee, Jessica D'Angelo, Margarent Ann Sanders, Malle Kathleen, Mary Paul, Ruth Eser-Jose, Chivon McMullen-Jackson, Lynnette Harris, Murli Purswani, Mahoobullah Mirza Baig, Alma Villegas, Marvin Alvarado, Lisa-Gaye Robinson, Jawara Dia Cooley, James Blood, Patricia Garvie, William Borkowsky, Nagamah Deygoo, Jennifer Lewis, Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Suroweic, Katherine Knapp, Jamie Russell-Bell, Megan Wilkins, Stephanie Love, Nicolas Rosario, Lourdes Angeli-Nieves, Vivian Olivera, Stephan Kohlhoff, Ava Dennie, Jean Kaye, Jenny Wallier, Karen Craig, Russell Van Dyke, Patricia Sirois, Cecelia Hutto, Paige Hickman, Julie Huldtquist, Dan Marullo, Stephen A. Spector, Veronica Figueroa, Megan Loughran, Sharon Nichols, Elizabeth McFarland, Christine Kwon, Carrie Glenny, Jennifer Englund, Mobeen Rathore, Saniyyah Mahmoudi, Sarah El-Hassan, Jamilah Tejan, Karen Hayani, Lourdes Richardson, Renee Smith, Alina Miller, Gwendolyn Scott, Gustavo Gil Garcia, Gabriel Fernandez, Anai Cuadra, Toni Frederick, Mariam Davtyan, Guadalupe Morales-Avendano, Zoe M. Rodriguez, Lizmarie Torres, Nydia Scalley
Journal: JAMA Network Open (2024)

Pregnancy represents a window of opportunity for vaccination due to established maternal and fetal benefits of vaccination. Little is known about receipt of routinely recommended vaccines in pregnancy, specifically tetanus, diphtheria, plus acellular pertussis (Tdap) and influenza, among pregnant people living with HIV (PLHIV).
Genetic Testing in Men With Metastatic Castration-Resistant Prostate Cancer
Authors: Pedro C. Barata, Jonathan Assayag, Benjamin Li, Gordon Siu, Alexander Niyazov
Journal: JAMA Oncology (2024)

This cross-sectional study assesses homologous recombination repair mutation genetic testing and associated characteristics among men with metastatic castration-resistant prostate cancer (mCRPC).
Medically Assisted Reproduction and Risk of Cancer Among Offspring
Authors: Paula Rios, Philippe Herlemont, Patricia Fauque, Brigitte Lacour, Pierre Jouannet, Alain Weill, Mahmoud Zureik, Jacqueline Clavel, Rosemary Dray-Spira
Journal: JAMA Network Open (2024)

Cancer is a leading cause of death among children worldwide. Treatments used for medically assisted reproduction (MAR) are suspected risk factors because of their potential for epigenetic disturbance and associated congenital malformations.
Comparative Outcomes of Empagliflozin to Dapagliflozin in Patients With Heart Failure
Authors: Katherine L. Modzelewski, Alexandra Pipilas, Nicholas A. Bosch
Journal: JAMA Network Open (2024)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been shown to have benefits when used in patients with heart failure. The comparative outcomes of SGLT2 inhibitors relative to each other has not been well defined and may impact medication selection.