tbuckley/cabot-search huggingface dataset:
Development and preclinical validation of 2-deoxy 2-[ <sup>18</sup> F]fluorocellobiose as an <i>Aspergillus</i> -specific PET tracer
Authors: Swati Shah, Jianhao Lai, Falguni Basuli, Neysha Martinez-Orengo, Reema Patel, Mitchell L. Turner, Benjamin Wang, Zhen-Dan Shi, Suman Sourabh, Morteza Peiravi, Anna Lyndaker, Sichen Liu, Seyedmojtaba Seyedmousavi, Peter R. Williamson, Rolf E. Swenson, Dima A. Hammoud
Journal: Science Translational Medicine (2024)

The global incidence of invasive fungal infections (IFIs) has increased over the past few decades, mainly in immunocompromised patients, and is associated with high mortality and morbidity. Aspergillus fumigatus is one of the most common and deadliest IFI pathogens. Major hurdles to treating fungal infections remain the lack of rapid and definitive diagnosis, including the frequent need for invasive procedures to provide microbiological confirmation, and the lack of specificity of structural imaging methods. To develop an Aspergillus -specific positron emission tomography (PET) imaging agent, we focused on fungal-specific sugar metabolism. We radiolabeled cellobiose, a disaccharide known to be metabolized by Aspergillus species, and synthesized 2-deoxy-2-[ 18 F]fluorocellobiose ([ 18 F]FCB) by enzymatic conversion of 2-deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG) with a radiochemical yield of 60 to 70%, a radiochemical purity of &gt;98%, and 1.5 hours of synthesis time. Two hours after [ 18 F]FCB injection in A. fumigatus pneumonia as well as A. fumigatus , bacterial, and sterile inflammation myositis mouse models, retained radioactivity was only seen in foci with live A. fumigatus infection. In vitro testing confirmed production of β-glucosidase enzyme by A. fumigatus and not by bacteria, resulting in hydrolysis of [ 18 F]FCB into glucose and [ 18 F]FDG, the latter being retained by the live fungus. The parent molecule was otherwise promptly excreted through the kidneys, resulting in low background radioactivity and high target-to-nontarget ratios at A. fumigatus infectious sites. We conclude that [ 18 F]FCB is a promising and clinically translatable Aspergillus -specific PET tracer.
Reversal of immune exhaustion for functional cure of chronic hepatitis B: Is the time right?
Authors: Arshi Khanam, Shyam Kottilil
Journal: Hepatology (2024)

Division of Clinical Care and Research, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA Correspondence Shyam Kottilil, Division of Clinical Care and Research, Institute of Human Virology, University of Maryland, School of Medicine, Baltimore, MD, USA. Email: [email protected] Correspondence Arshi Khanam. Email: [email protected]
Natural killer cells promote neutrophil extracellular traps and restrain macular degeneration in mice
Authors: Xue Dong, Yinting Song, Yuming Liu, Xuejing Kou, Tianjing Yang, Samuel X. Shi, Kai He, Yiming Li, Ziqi Li, Xueming Yao, Ju Guo, Bohao Cui, Ziru Wu, Yi Lei, Mei Du, Mei Chen, Heping Xu, Qiang Liu, Fu-Dong Shi, Xiaohong Wang, Hua Yan
Journal: Science Translational Medicine (2024)

Neovascular age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Although it is known that nvAMD is associated with focal inflammation, understanding of the precise immune components governing this process remains limited. Here, we identified natural killer (NK) cells as a prominent lymphocyte population infiltrating the perivascular space of choroidal neovascularization (CNV) lesions in patients with nvAMD and in mouse models. Olink proteomic analysis and single-cell RNA sequencing combined with knockout studies demonstrated the involvement of C-C chemokine receptor 5 (CCR5) in NK cell recruitment and extravasation at the CNV sites of mice. Depletion of NK cells or inhibition of activating receptor NK group 2, member D (NKG2D) inhibited the formation of neutrophil extracellular traps, increased vascular leakage, and exacerbated pathological angiogenesis, indicating that NK cells restrain pathogenesis in this mouse model. Age is the strongest risk factor for AMD, and we show that NK cells from aged human donors exhibited a less cytotoxic phenotype. NK cells from old mice exhibited compromised protective effects in the CNV mouse model. In addition, interleukin-2 complex–mediated expansion of NK cells improved CNV formation in mice. Collectively, our study highlights NK cells as a potential therapeutic target for patients with nvAMD.
Elevated Suicide Risk in Idiopathic Pulmonary Fibrosis Patients
Authors: Jui-Ting Yu, Chen‐Pi Li, Hui-Chin Chang, Shuo-Yan Gau
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

"Elevated Suicide Risk in Idiopathic Pulmonary Fibrosis Patients." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Targeting the transferrin receptor to transport antisense oligonucleotides across the mammalian blood-brain barrier
Authors: Scarlett J. Barker, Mai B. Thayer, Chaeyoung Kim, David Tatarakis, Matthew J. Simon, Rebekah Dial, Lizanne Nilewski, Robert C. Wells, Yinhan Zhou, Megan Afetian, Padma Akkapeddi, Alfred Chappell, Kylie S. Chew, Johann Chow, Allisa Clemens, Claire B. Discenza, Jason C. Dugas, Chrissa Dwyer, Timothy Earr, Connie Ha, Yvonne S. Ho, David Huynh, Edwin I. Lozano, Srini Jayaraman, Wanda Kwan, Cathal Mahon, Michelle Pizzo, Yaneth Robles-Colmenares, Elysia Roche, Laura Sanders, Alexander Stergioulis, Raymond Tong, Hai Tran, Y. Zuchero, Anthony A. Estrada, Kapil Gadkar, Christopher M. M. Koth, Pascal E. Sanchez, Robert G. Thorne, Ryan J. Watts, Thomas Sandmann, Lesley A. Kane, Frank Rigo, Mark S. Dennis, Joseph W. Lewcock, Sarah L. DeVos
Journal: Science Translational Medicine (2024)

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfR mu/hu KI) mice and nonhuman primates. Intravenous injection and systemic delivery of OTV to TfR mu/hu KI mice resulted in sustained knockdown of the ASO target RNA, Malat1 , across multiple mouse CNS regions and cell types, including endothelial cells, neurons, astrocytes, microglia, and oligodendrocytes. In addition, systemic delivery of OTV enabled Malat1 RNA knockdown in mouse quadriceps and cardiac muscles, which are difficult to target with oligonucleotides alone. Systemically delivered OTV enabled a more uniform ASO biodistribution profile in the CNS of TfR mu/hu KI mice and greater knockdown of Malat1 RNA compared with a bivalent, high-affinity TfR antibody. In cynomolgus macaques, an OTV directed against MALAT1 displayed robust ASO delivery to the primate CNS and enabled more uniform biodistribution and RNA target knockdown compared with intrathecal dosing of the same unconjugated ASO. Our data support systemically delivered OTV as a potential platform for delivering therapeutic ASOs across the BBB.
Efficacy and safety of emodepside compared with albendazole in adolescents and adults with hookworm infection in Pemba Island, Tanzania: a double-blind, superiority, phase 2b, randomised controlled trial
Authors: Lyndsay Taylor, Ahmada Ali Ahmada, Msanif Said Ali, Said Mohammed Ali, Jan Hattendorf, Ibrahim Said Mohammed, Jennifer Keiser
Journal: The Lancet (2024)

Human hookworm is a cause of enormous global morbidity. Current treatments have insufficient efficacy and their extensive and indiscriminate distribution could also result in drug resistance. Therefore, we tested the efficacy and safety of emodepside, a strong anthelmintic candidate that is currently undergoing clinical development for onchocerciasis and soil-transmitted helminth infections.
Effect of high versus standard protein provision on functional recovery in people with critical illness (PRECISe): an investigator-initiated, double-blinded, multicentre, parallel-group, randomised controlled trial in Belgium and the Netherlands
Authors: Julia L M Bels, Steven Thiessen, Rob J J van Gassel, Albertus Beishuizen, Ashley De Bie Dekker, Vincent Fraipont, Stoffel Lamote, Didier Ledoux, Clarissa Scheeren, Elisabeth De Waele, Arthur R H van Zanten, Laura Bormans-Russell, Bas C T van Bussel, Marlies M J Dictus, Tom Fivez, Ingeborg Harks, Iwan C C van der Horst, Joop Jonckheer, Hugues Marechal, Paul B Massion, Ingrid Meex, Michelle C Paulus, Martin Rinket, Susanne van Santen, Katrien Tartaglia, Adam M Deane, Frieda Demuydt, Zudin Puthucheary, Lilian C M Vloet, Peter J M Weijs, Sander M J van Kuijk, Marcel C G van de Poll, Dieter Mesotten
Journal: The Lancet (2024)
Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial
Authors: Filip Rega, Guillaume Lebreton, Marylou Para, Sebastian Michel, René Schramm, Emmanuelle Begot, Katrien Vandendriessche, Christine Kamla, Gino Gerosa, Marius Berman, Udo Boeken, Steven Clark, Aaron Ranasinghe, Fabio Ius, Alberta Forteza, Aldina Pivodic, Felix Hennig, Sabina Guenther, Andreas Zuckermann, Christoph Knosalla, Göran Dellgren, Andreas Wallinder
Journal: The Lancet (2024)
Recent insights into the pathophysiology of narcolepsy type 1
Authors: Marieke Vringer, Jingru Zhou, Jari K Gool, Denise Bijlenga, Gert Jan Lammers, Rolf Fronczek, Mink S Schinkelshoek
Journal: Sleep Medicine Reviews (2024)

Narcolepsy type 1 (NT1) is a sleep-wake disorder in which people typically experience excessive daytime sleepiness, cataplexy and other sleep-wake disturbances impairing daily life activities. NT1 symptoms are due to hypocretin deficiency. The cause for the observed hypocretin deficiency remains unclear, even though the most likely hypothesis is that this is due to an auto-immune process. The search for autoantibodies and autoreactive T-cells has not yet produced conclusive evidence for or against the auto-immune hypothesis. Other mechanisms, such as reduced corticotrophin-releasing hormone production in the paraventricular nucleus have recently been suggested. There is no reversive treatment, and the therapeutic approach is symptomatic. Early diagnosis and appropriate NT1 treatment is essential, especially in children to prevent impaired cognitive, emotional and social development. Hypocretin receptor agonists have been designed to replace the attenuated hypocretin signalling. Pre-clinical and clinical trials have shown encouraging initial results. A better understanding of NT1 pathophysiology may contribute to faster diagnosis or treatments, which may cure or prevent it.
Prognostic relevance of molecular measurable residual disease detection in AML with mutated <i>CEBPA</i>
Authors: Christian M. Vonk, Emma L. Boertjes, Francois G. Kavelaars, Melissa Rijken, Jolinda M. L. Konijnenburg, Roxanne E. Cromwell, Bob Löwenberg, Tim Grob, Peter J. M. Valk
Journal: HemaSphere (2024)
Mpox outbreaks in Africa—we must avert another failure of global solidarity
Authors: Ifedayo MO Adetifa, Madhukar Pai
Journal: BMJ (2024)

mpox outbreaks, write Ifedayo MO Adetifa and Madhukar Pai Ifedayo MO Adetifa, 1 Madhukar Pai 2On 13 August 2024, the Africa Centres for Disease Control and Prevention (Africa CDC) declared the ongoing mpox outbreak a public health emergency of continental security. 1This outbreak is driven by the emergence of a new clade 1b variant that is better adapted to human-to-human transmission.On 14 August, the World Health Organization (WHO) declared the current outbreak a public health emergency of international concern (PHEIC) under the International Health Regulations (2005). 2 Amid another widespread epidemic is another unfolding story of vaccine inequity, and yet another looming failure of global solidarity.We have seen this before, and it does not end well for anyone.
Evaluation of person-centered interventions to eliminate perinatal HIV transmission in Kisumu County, Kenya: A repeated cross-sectional study using aggregated registry data
Authors: Francesca Odhiambo, Raphael Onyango, Edwin Mulwa, Maurice Aluda, Linda Otieno, Elizabeth A. Bukusi, Craig R. Cohen, Pamela M. Murnane
Journal: PLoS Medicine (2024)

Following a decline in perinatal HIV transmission from 20% to 10% between 2010 and 2017 in Kenya, rates have since plateaued with an estimated 8% transmission rate in 2021. Between October 2016 and September 2021, Family AIDS Care & Education Services (FACES) supported HIV care and treatment services across 61 facilities in Kisumu County, Kenya with an emphasis on service strengthening for pregnant and postpartum women living with HIV to reduce perinatal HIV transmission. This included rigorous implementation of national HIV guidelines and implementation of 3 locally adapted evidence-based interventions targeted to the unique needs of women and their infants. We examined whether these person-centered program enhancements were associated with changes in perinatal HIV transmission at FACES-supported sites over time.
Modulation of NOX2 causes obesity-mediated atrial fibrillation
Authors: Arvind Sridhar, Jaime DeSantiago, Hanna Chen, Mahmud Arif Pavel, Olivia Ly, Asia Owais, Miles Barney, Jordan Jousma, Sarath Babu Nukala, Khaled Abdelhady, Malek Massad, Lona Ernst Rizkallah, Sang-Ging Ong, Jalees Rehman, Dawood Darbar
Journal: Journal of Clinical Investigation (2024)

Obesity is linked to an increased risk of atrial fibrillation (AF) via increased oxidative stress. While NADPH oxidase 2 (NOX2), a major source of oxidative stress and reactive oxygen species (ROS) in the heart, predisposes to AF, the underlying mechanisms remain unclear. Here, we studied NOX2-mediated ROS production in obesity-mediated AF using Nox2-knockout mice and mature human induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs). Diet-induced obesity (DIO) mice and hiPSC-aCMs treated with palmitic acid (PA) were infused with a NOX blocker (apocynin) and a NOX2-specific inhibitor, respectively. We showed that NOX2 inhibition normalized atrial action potential duration and abrogated obesity-mediated ion channel remodeling with reduced AF burden. Unbiased transcriptomics analysis revealed that NOX2 mediates atrial remodeling in obesity-mediated AF in DIO mice, PA-treated hiPSC-aCMs, and human atrial tissue from obese individuals by upregulation of paired-like homeodomain transcription factor 2 (PITX2). Furthermore, hiPSC-aCMs treated with hydrogen peroxide, a NOX2 surrogate, displayed increased PITX2 expression, establishing a mechanistic link between increased NOX2-mediated ROS production and modulation of PITX2. Our findings offer insights into possible mechanisms through which obesity triggers AF and support NOX2 inhibition as a potential novel prophylactic or adjunctive therapy for patients with obesity-mediated AF.
Consolidating multiple evolutionary theories of ageing suggests a need for new approaches to study genetic contributions to ageing decline
Authors: Luke Slade, Timothy Etheridge, Nathaniel J Szewczyk
Journal: Ageing Research Reviews (2024)

Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with progressive declines in biochemical and molecular processes resulting from damage accumulation, yet the role of continued developmental gene activation is less appreciated. Natural selection pressures are at their highest in youthful periods to modify gene expression towards maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene functions that were once beneficial for developmental growth but become pathogenic later in life. Due to this selective 'shadowing' in ageing, mechanisms to counter such hyper/hypofunctional genes are unlikely to evolve. Interventions aimed at targeting gene hyper/hypofunction during ageing might, therefore, represent an attractive therapeutic strategy. The nematode Caenorhabditis elegans offers a strong model for post-reproductive mechanistic and therapeutic investigations, yet studies examining the mechanisms of, and countermeasures against, ageing decline largely intervene from larval stages onwards. Importantly, however, lifespan extending conditions frequently impair early-life fitness and fail to correspondingly increase healthspan. Here, we consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutations alter these dynamics. The relevance of such mutant models for exploring mechanisms of ageing are discussed, highlighting that post-reproductive gene optimisation represents a more translatable approach for C. elegans research that is not constrained by evolutionary trade-offs. Where some genetic mutations in C. elegans that promote late-life health map accordingly with healthy ageing in humans, other widely used genetic mutations that extend worm lifespan are associated with life-limiting pathologies in people. Lifespan has also become the gold standard for quantifying 'ageing', but we argue that gerospan compression (i.e., 'healthier' ageing) is an appropriate goal for anti-ageing research, the mechanisms of which appear distinct from those regulating lifespan alone. There is, therefore, an evident need to re-evaluate experimental approaches to study the role of hyper/hypofunctional genes in ageing in C. elegans.
Early detection of cervical and breast cancer in transgender and allogender individuals assigned female at birth: a scoping review
Authors: Romel Jonathan Velasco Yanez, Denise Montenegro da Silva, Judith Sixsmith, Francisca Elisângela Teixeira Lima, Samila Gomes Ribeiro, Cristiana Brasil de Almeida Rebouças, Ana Fátima Carvalho Fernandes, Victor Fernandes Apolonio dos Santos
Journal: International Journal of Transgender Health (2024)

Background: Transgender and Allogender Individuals Assigned Female At Birth (transgender and allogender individuals AFAB) face obstacles and inequalities in healthcare access compared to cisgender individuals. These challenges derive from social stigma, knowledge gaps, and scarcity of professionals trained to address the specific needs of these populations. Since transgender and allogender individuals AFAB may retain breast tissue and a cervix, they require integral sexual health care, including early detection of cervical and breast cancer. However, specific barriers and guidelines for early detection in these populations remain undefined.Aim: To review literature on early cervical and breast cancer screening in transgender and allogender individuals AFAB and identify research gaps.Methods: This scoping review followed the Joanna Briggs Institute methodology, and the report adhered to the PRISMA-ScR checklist. Searches were conducted across seven databases, including peer-reviewed and grey literature. Study selection was conducted independently by two reviewers using RAYYAN software. Data from selected studies were analyzed qualitatively by thematic analysis.Results: Out of 709 identified studies, 61 articles and 5 grey literature documents were included in the review dataset. The majority of these were published in 2020 (24.2%), originating from the USA (72.7%), and employing a cross-sectional design (39.4%). From the thematic analysis, six main themes were identified for cervical cancer and five for breast cancer. Among these, five themes were common to both types of cancer: screening rates, barriers, strategies, guidelines, and the role of healthcare professionals. The theme of knowledge, beliefs, and attitudes was found solely in the context of cervical cancer. Conclusions: The evidence indicates that healthcare attention for cervical and breast cancer remains predominantly linked to sex assigned at birth, neglecting gender implications for transgender and allogender AFAB populations. The existing disparities in detection rates and access present a significant challenge in gynecological care for these groups.
MicroRNA-455-3P as a peripheral biomarker and Therapeutic Target for Mild Cognitive Impairment and Alzheimer’s disease
Authors: Md Ariful Islam, Omme Fatema Sultana, Madhuri Bandari, Sudhir Kshirsagar, Pulak R. Manna, P. Hemachandra Reddy
Journal: Ageing Research Reviews (2024)
Does personality affect the cognitive decline in aging? A systematic review
Authors: Giovanna Troisi, Andrea Marotta, Juan Lupiañez, Maria Casagrande
Journal: Ageing Research Reviews (2024)

Cognitive decline is a natural consequence of aging, but several genetic, environmental, and psychological factors can influence its trajectories. Among the most enduring factors, the Big Five personality traits - defined as relatively stable tendencies to think, behave, and react to the environment - can influence both directly (e.g., by physiological correlates) and indirectly (e.g., healthy or risky behaviors) the risk of developing dementia and mild cognitive impairment (MCI) - a preclinical form of cognitive decline. Despite the great amount of studies focusing on the relationship between personality and cognitive decline, an updated systematic synthesis of the results including a broader range of study designs is still lacking. This systematic review aims to summarize the findings of studies investigating: (i) differences in personality traits between groups of healthy individuals and those with MCI, (ii) the impact of personality traits on the risk for both MCI and dementia, and (iii) changes in personality traits among individuals progressing from normal cognition to MCI. Neuroticism emerged as a significant risk factor for MCI and dementia; Conscientiousness and Openness appear to offer protection against dementia and moderate cognitive decline. Overall, these findings suggest a pivotal role of personality structure in shaping cognitive outcomes on the long run.
PRMT5 mediated FUBP1 methylation accelerates prostate cancer progression
Authors: Weiwei Yan, Xun Liu, Xuefeng Qiu, Xuebin Zhang, Jiahui Chen, Kai Xiao, Ping Wu, Chao Peng, Xiaolin Hu, Zengming Wang, Jun Qin, Liming Sun, Luonan Chen, Denglong Wu, Shengsong Huang, Lichen Yin, Zhenfei Li
Journal: Journal of Clinical Investigation (2024)

Strategies beyond hormone-related therapy need to be developed to improve prostate cancer mortality. Here, we show that FUBP1 and its methylation were essential for prostate cancer progression, and a competitive peptide interfering with FUBP1 methylation suppressed the development of prostate cancer. FUBP1 accelerated prostate cancer development in various preclinical models. PRMT5-mediated FUBP1 methylation, regulated by BRD4, was crucial for its oncogenic effect and correlated with earlier biochemical recurrence in our patient cohort. Suppressed prostate cancer progression was observed in various genetic mouse models expressing the FUBP1 mutant deficient in PRMT5-mediated methylation. A competitive peptide, which was delivered through nanocomplexes, disrupted the interaction of FUBP1 with PRMT5, blocked FUBP1 methylation, and inhibited prostate cancer development in various preclinical models. Overall, our findings suggest that targeting FUBP1 methylation provides a potential therapeutic strategy for prostate cancer management.
Precision Pore Structure Optimization of Additive Manufacturing Porous Tantalum Scaffolds for Bone Regeneration : A proof-of-concept study
Authors: Jiale Jin, Dongyu Wang, Hu Qian, Chengxin Ruan, Yiqi Yang, Dongdong Li, Guohua Wang, Xiaobo Zhu, Yihe Hu, Pengfei Lei
Journal: Biomaterials (2024)