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JOURNAL ARTICLE
Mengyang Chang, Feng Gao, Giri Gnawali, Hang Xu, Yue Dong, Xiang Meng, Wenpan Li, Zhiren Wang, Byrdie Lopez, Jennifer S Carew, Steffan T Nawrocki, Jianqin Lu, Qing-Yu Zhang, Wei Wang
Although the selective and effective clearance of senescent cancer cells can improve cancer treatment, their development is confronted by many challenges. As part of efforts designed to overcome these problems, prodrugs, whose design is based on senescence-associated β-galactosidase (SA-β-gal), have been developed to selectively eliminate senescent cells. However, chemotherapies relying on targeted molecular inhibitors as senolytic drugs can induce drug resistance. In the current investigation, we devised a new strategy for selective degradation of target proteins in senescent cancer cells that utilizes a prodrug composed of the SA-β-gal substrate galactose (galacto) and the proteolysis-targeting chimeras (PROTACs) as senolytic agents...
April 18, 2024: Journal of Medicinal Chemistry
#2
JOURNAL ARTICLE
Heidi Auerswald, Julia Guillebaud, Benoit Durand, Mathilde Le Vu, Sopheak Sorn, Saraden In, Vutha Pov, Holl Davun, Veasna Duong, Sowath Ly, Philippe Dussart, Véronique Chevalier
Rabies control remains challenging in low and middle-income countries, mostly due to lack of financial resources, rapid turnover of dog populations and poor accessibility to dogs. Rabies is endemic in Cambodia, where no national rabies vaccination program is implemented. The objective of this study was to assess the short and long-term vaccination-induced immunity in Cambodian dogs under field conditions, and to propose optimized vaccination strategies. A cohort of 351 dogs was followed at regular time points following primary vaccination only (PV) or PV plus single booster (BV)...
April 18, 2024: PLoS Neglected Tropical Diseases
#3
JOURNAL ARTICLE
Bichen Wang, Deyang Shi, Shuang Yang, Yu Lian, Haoyuan Li, Mutian Cao, Yifei He, Lele Zhang, Chen Qiu, Tong Liu, Wei Wen, Yuanwu Ma, Lei Shi, Tao Cheng, Lihong Shi, Weiping Yuan, Yajing Chu, Jun Shi
Pseudouridine is the most prevalent RNA modification, and its aberrant function is implicated in various human diseases. However, the specific impact of pseudouridylation on hematopoiesis remains poorly understood. In this study, we investigated the role of tRNA pseudouridylation in erythropoiesis and its association with mitochondrial myopathy, lactic acidosis, and sideroblastic anemia syndrome (MLASA) pathogenesis. By utilizing patient-specific induced pluripotent stem cells (iPSCs) carrying a genetic PUS1 mutation and a corresponding mutant mouse model, we demonstrated impaired erythropoiesis in MLASA iPSCs and anemia in the MLASA mouse model...
April 18, 2024: Blood
#4
JOURNAL ARTICLE
Sangjun Eom, Seijung Kim, Joshua Jackson, David Sykes, Shervin Rahimpour, Maria Gorlatova
External ventricular drain (EVD) is a common, yet challenging neurosurgical procedure of placing a catheter into the brain ventricular system that requires prolonged training for surgeons to improve the catheter placement accuracy. In this paper, we introduce NeuroLens, an Augmented Reality (AR) system that provides neurosurgeons with guidance that aides them in completing an EVD catheter placement. NeuroLens builds on prior work in AR-assisted EVD to present a registered hologram of a patient's ventricles to the surgeons, and uniquely incorporates guidance on the EVD catheter's trajectory, angle of insertion, and distance to the target...
April 18, 2024: IEEE Transactions on Visualization and Computer Graphics
#5
JOURNAL ARTICLE
Fatemeh Koochaki, Laleh Najafizadeh
Timely diagnosis of mild traumatic brain injury (mTBI) remains challenging due to the rapid recovery of acute symptoms and the absence of evidence of injury in static neuroimaging scans. Furthermore, while longitudinal tracking of mTBI is essential in understanding how the diseases progresses/regresses over time for enhancing personalized patient care, a standardized approach for this purpose is not yet available. Recent functional neuroimaging studies have provided evidence of brain function alterations following mTBI, suggesting mTBI-detection models can be built based on these changes...
April 18, 2024: IEEE Transactions on Neural Systems and Rehabilitation Engineering
#6
JOURNAL ARTICLE
Andrés J Consoli, Beatriz Gómez, María Del Pilar Grazioso, Sergi Corbella
This article memorializes Héctor Fernández-Álvarez (1944-2023). Héctor was an exceptional mentor, therapist, supervisor, professor, researcher, author, and leader, as well as a beloved brother, partner, father, and grandfather. The consummate renaissance person who embraced all manners of cultural expressions through an intentional wanderlust, he sought to understand all forms of human suffering and to alleviate senseless ones. Héctor's career spanned well over 5 decades. He received a licenciatura degree in 1967 from the University of Buenos Aires and a PhD in 1995 from the National University of San Luis, Argentina...
April 18, 2024: American Psychologist
#7
JOURNAL ARTICLE
Sarah Mares, Anna Ziersch
OBJECTIVE: This paper identifies the multiple adversities and trauma experienced by children who are detained after seeking asylum. A conceptual framework identifies the specific impact of immigration detention on the psychosocial development and mental health of refugee children that can inform policy and prevent additional migration-related trauma. METHOD: The paper draws on international evidence about the impact of childhood adversity, challenges faced by all displaced children, and the additional negative consequences of immigration detention...
April 18, 2024: Psychological Trauma: Theory, Research, Practice and Policy
#8
JOURNAL ARTICLE
Indigo Weller, Maura Spiegel, Marco Antonio de Carvalho Filho, Andrés Martin
Despite the ubiquity of healthcare simulation and the humanities in medical education, the two domains of learning remain unintegrated. The stories suffused within healthcare simulation have thus remained unshaped by the developments of narrative medicine and the health humanities. Healthcare simulation, in turn, has yet to utilize concepts like co-construction and narrative competence to enrich learners' understanding of patient experience alongside their clinical competencies. To create a conceptual bridge between these two fields (including narrative-based inquiry more broadly), we redescribe narrative competence via Ronald Heifetz's distinction of "technical" and "adaptive" challenges outlined in his adaptive leadership model...
April 18, 2024: Journal of Medical Humanities
#9
JOURNAL ARTICLE
Wei-Hsiang Ma, Che-Chia Chang, Te-Sheng Lin, Yu-Chie Chen
Pathogenic bacteria, including drug-resistant variants such as methicillin-resistant Staphylococcus aureus (MRSA), can cause severe infections in the human body. Early detection of MRSA is essential for clinical diagnosis and proper treatment, considering the distinct therapeutic strategies for methicillin-sensitive S. aureus (MSSA) and MRSA infections. However, the similarities between MRSA and MSSA properties present a challenge in promptly and accurately distinguishing between them. This work introduces an approach to differentiate MRSA from MSSA utilizing matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) in conjunction with a neural network-based classification model...
April 18, 2024: Mikrochimica Acta
#10
JOURNAL ARTICLE
Hemodynamic Mechanisms Initiating Salt-Sensitive Hypertension in Rat Model of Primary Aldosteronism.
M Pravenec, P Mlejnek, M Šimáková, J Šilhavý
Few studies have investigated the hemodynamic mechanism whereby primary hyperaldosteronism causes hypertension. The traditional view holds that hyperaldosteronism initiates hypertension by amplifying salt-dependent increases in cardiac output (CO) by promoting increases in sodium retention and blood volume. Systemic vascular resistance (SVR) is said to increase only as a secondary consequence of the increased CO and blood pressure. Recently, we investigated the primary hemodynamic mechanism whereby hyperaldosteronism promotes salt sensitivity and initiation of salt-dependent hypertension...
April 18, 2024: Physiological Research
#11
JOURNAL ARTICLE
Jing Xu, Qiong Wu, Yanfei Rao, Zhenjiang Li, Wenfeng He, Wanlei Sun, Jifu Zheng, Qingming Wang, Aiping Tang
A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry...
April 4, 2024: Histology and Histopathology
#12
REVIEW
Michelle L Oblak, Hui Yu Lu, Ann S Ram, Charly McKenna
There is a significant overlap in the genetic, metabolic and epigenetic alterations between human and companion animal cancers, including those of the oral cavity, breast, bladder, skin, lungs and pancreas. In many cancer types, the identification and removal of affected lymph nodes are essential for accurate cancer management, including treatment and prognosis. Historically, lymphadenectomy and subsequent radical resection based on regional anatomy, palpation and lymph node aspirates were considered sufficient; however, modern approaches with sentinel lymph node mapping (SLN) mapping have increased the accuracy of surgical decision-making...
2024: Frontiers in Medicine
#13
REVIEW
Xiaojian Zhang, Ted M Ross
INTRODUCTION: Anti-neuraminidase (NA) immunity correlates with the protection against influenza virus infection in both human and animal models. The aim of this review is to better understand the mechanism of anti-NA immunity, and also to evaluate the approaches on developing NA-based influenza vaccines or enhancing immune responses against NA for current influenza vaccines. AREAS COVERED: In this review, the structure of influenza neuraminidase, the contribution of anti-NA immunity to protection, as well as the efforts and challenges of targeting the immune responses to NA were discussed...
April 17, 2024: Expert Review of Vaccines
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JOURNAL ARTICLE
Lei Zhang, Min-Ye Li, Chen Zhi, Min Zhu, Hui Ma
The global incidence of infectious diseases has increased in recent years, posing a significant threat to human health. Hospitals typically serve as frontline institutions for detecting infectious diseases. However, accurately identifying warning signals of infectious diseases in a timely manner, especially emerging infectious diseases, can be challenging. Consequently, there is a pressing need to integrate treatment and disease prevention data to conduct comprehensive analyses aimed at preventing and controlling infectious diseases within hospitals...
April 18, 2024: Current Medical Science
#15
JOURNAL ARTICLE
Jin-Ming Wang, Zheng-Dong Li, Chang-Sheng Cai, Ying Fan, Xin-Biao Liao, Fu Zhang, Jian-Hua Zhang, Dong-Hua Zou
PURPOSE: The toughest challenge in pedestrian traffic accident identification lies in ascertaining injury manners. This study aimed to systematically simulate and parameterize 3 types of craniocerebral injury including impact injury, fall injury, and run-over injury, to compare the injury response outcomes of different injury manners. METHODS: Based on the Total Human Model for Safety (THUMS) and its enhanced human model THUMS-hollow structures, a total of 84 simulations with 3 injury manners, different loading directions, and loading velocities was conducted...
March 30, 2024: Chinese Journal of Traumatology
#16
JOURNAL ARTICLE
Nicola J Wyatt, Hannah Watson, Carl A Anderson, Nicholas A Kennedy, Tim Raine, Tariq Ahmad, Dean Allerton, Michelle Bardgett, Emma Clark, Dawn Clewes, Cristina Cotobal Martin, Mary Doona, Jennifer A Doyle, Katherine Frith, Helen C Hancock, Ailsa L Hart, Victoria Hildreth, Peter M Irving, Sameena Iqbal, Ciara Kennedy, Andrew King, Sarah Lawrence, Charlie W Lees, Robert Lees, Laura Letchford, Trevor Liddle, James O Lindsay, Rebecca H Maier, John C Mansfield, Julian R Marchesi, Naomi McGregor, Rebecca E McIntyre, Jasmin Ostermayer, Tolulope Osunnuyi, Nick Powell, Natalie J Prescott, Jack Satsangi, Shriya Sharma, Tara Shrestha, Ally Speight, Michelle Strickland, James Ms Wason, Kevin Whelan, Ruth Wood, Gregory R Young, Xinyue Zhang, Miles Parkes, Christopher J Stewart, Luke Jostins-Dean, Christopher A Lamb
INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients...
April 17, 2024: BMJ Open
#17
JOURNAL ARTICLE
Teng Zhang, Shang Gao, Shao-Wu Zhang, Xiao-Dong Cui
As the most abundant mRNA modification, m6 A controls and influences many aspects of mRNA metabolism including the mRNA stability and degradation. However, the role of specific m6 A sites in regulating gene expression still remains unclear. In additional, the multicollinearity problem caused by the correlation of methylation level of multiple m6 A sites in each gene could influence the prediction performance. To address the above challenges, we propose an elastic-net regularized negative binomial regression model (called m6 Aexpress-enet) to predict which m6 A site could potentially regulate its gene expression...
April 15, 2024: Methods: a Companion to Methods in Enzymology
#18
JOURNAL ARTICLE
Ovokeroye Akpojevwe Abafe, Stuart Harrad, Mohamed Abou-Elwafa Abdallah
To overcome ethical and technical challenges impeding the study of human dermal uptake of chemical additives present in microplastics (MPs), we employed 3D human skin equivalent (3D-HSE) models to provide first insights into the dermal bioavailability of polybrominated diphenyl ether (PBDEs) present in MPs; and evaluated different factors influencing human percutaneous absorption of PBDEs under real-life exposure scenario. PBDEs were bioavailable to varying degrees (up to 8 % of the exposure dose) and percutaneous permeation was evident, albeit at low levels (≤0...
April 5, 2024: Environment International
#19
JOURNAL ARTICLE
Feng Gao, Jun Guo, Shihao Liu, Feng Zhang, Yi Zhang, Liping Wang
The current state of drug delivery systems allows for the resolution of specific issues like inadequate solubility, limited targeting capabilities, and complex preparation processes, requiring tailored designs for different drugs. Yet, the major challenge in clinical application lies in surmounting these obstacles with a universal carrier that is effective for a variety of anticancer drugs. Herein, with the help of computer simulation, we rationally design ultrashort peptides GY and CCYRGD, which can co-assemble with hydrophobic anticancer drugs into nanoparticles with enhanced solubility, targeting ability and anticancer efficacy...
April 3, 2024: Journal of Colloid and Interface Science
#20
JOURNAL ARTICLE
Iris Ertl, Shahrokh F Shariat, Walter Berger, Bernard Englinger
PURPOSE OF REVIEW: Bladder cancer (BC) is a highly heterogenous disease comprising tumours of various molecular subtypes and histologic variants. This heterogeneity represents a major challenge for the development of novel therapeutics. Preclinical models that closely mimic in vivo tumours and reflect their diverse biology are indispensable for the identification of therapies with specific activity in various BC subtypes. In this review, we summarize efforts and progress made in this context during the last 24 months...
April 17, 2024: Current Opinion in Urology
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