tbuckley/cabot-search huggingface dataset:
A precision functional atlas of personalized network topography and probabilities
Authors: Robert J. M. Hermosillo, Lucille A. Moore, Eric Feczko, Óscar Miranda-Domínguez, Adam Pines, Ally Dworetsky, Gregory Conan, Michael A. Mooney, Anita Randolph, Alice Graham, Babatunde Adeyemo, Eric Earl, Anders Perrone, Cristian Morales Carrasco, Johnny Uriarte-Lopez, Kathy Snider, Olivia Doyle, Michaela Cordova, Sanju Koirala, Gracie J. Grimsrud, Nora Byington, Steven M. Nelson, Caterina Gratton, Steven Petersen, Sarah W. Feldstein Ewing, Bonnie J. Nagel, Nico U. F. Dosenbach, Theodore D. Satterthwaite, Damien A. Fair
Journal: Nature Neuroscience (2024)

Abstract Although the general location of functional neural networks is similar across individuals, there is vast person-to-person topographic variability. To capture this, we implemented precision brain mapping functional magnetic resonance imaging methods to establish an open-source, method-flexible set of precision functional network atlases—the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. This atlas is an evolving resource comprising 53,273 individual-specific network maps, from more than 9,900 individuals, across ages and cohorts, including the Adolescent Brain Cognitive Development study, the Developmental Human Connectome Project and others. We also generated probabilistic network maps across multiple ages and integration zones (using a new overlapping mapping technique, Overlapping MultiNetwork Imaging). Using regions of high network invariance improved the reproducibility of executive function statistical maps in brain-wide associations compared to group average-based parcellations. Finally, we provide a potential use case for probabilistic maps for targeted neuromodulation. The atlas is expandable to alternative datasets with an online interface encouraging the scientific community to explore and contribute to understanding the human brain function more precisely.
Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort
Authors: Masatake Kobayashi, João Pedro Ferreira, Kevin Duarte, Emmanuel Bresso, Olivier Huttin, Erwan Bozec, Hans‐Peter Brunner La Rocca, Christian Delles, Andrew L. Clark, Frank Edelmann, Arantxa González, Stephane Heymans, Pierpaolo Pellicori, Johannes Petutschnigg, Job A.J. Verdonschot, Patrick Rossignol, John G.F. Cleland, Faiez Zannad, Nicolas Girerd
Journal: European Journal of Heart Failure (2024)

Aims High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables. Methods and results In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m 2 ). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population‐based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m 2 ). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase‐2 (MMP‐2), insulin‐like growth factor binding protein‐2 (IGFBP‐2) and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) (false discovery rates [FDR] &lt;0.05). These associations were externally replicated in STANISLAS (all FDR &lt;0.05). Among these biomarkers, spironolactone decreased concentrations of MMP‐2 and NT‐proBNP, regardless of baseline LAVi ( p interaction &gt; 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e', blood pressure and serum procollagen type I C‐terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi ( p interaction &gt; 0.10). Conclusion In individuals without heart failure, LAVi was associated with MMP‐2, IGFBP‐2 and NT‐proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.
Medical management of tobacco dependency for hospital clinicians
Authors: Wendy Preston
Journal: Thorax (2024)

Tobacco dependency continues to be the largest avoidable cause of death, and it is the biggest comorbidity however is often not recognised.1 All clinicians should become familiar with the new British Thoracic Society (BTS) clinical statement on the medical management of tobacco dependency for hospital clinicians.2 Whether a nurse, doctor, pharmacist or allied health professional, it is an important element of patient assessment and treatment. We are in a privileged position to make every contact count, with a responsibility to make a difference and optimise every opportunity.3 Influencing people to quit tobacco should be seen as lifesaving and recognised as such. Sadly, many opportunities are missed. Hospital-based clinicians will see many patients already harmed by smoking and will see a cohort of people with higher prevalence of tobacco dependence.4 The BTS clinical statement with three supplements is essential reading for every clinician as well as those who commission tobacco dependency treatment services. It has been developed with representation from respiratory medicine, nursing, pharmacists and tobacco dependency specialists. The clinical statement is set out in six building blocks that will develop the optimal treatment plan for inpatients with tobacco dependence (Box 1). Box 1 ### Building blocks for optimal treatment plan
Medical management of inpatients with tobacco dependency
Authors: Sanjay Agrawal, Matthew Evison, Sachin Ananth, Duncan Fullerton, Helen McDill, Melanie Perry, Jacqueline Pollington, Louise Restrick, Elspeth Spencer, Ameet Vaghela
Journal: Thorax (2024)

### Building block 1: screen for tobacco dependence ### Building block 2: advise on the role of nicotine ### Building block 3: initiate combination nicotine replacement therapy (NRT) as soon as possible ### Building block 4: complete a referral to an on-site tobacco dependency advisor (TDA) ### Building block 5: provide accurate and consistent information on Vaping
Commentary: Liquid Biopsy for Average-Risk Colorectal Cancer Screening
Authors: David A. Lieberman, Aasma Shaukat, Folasade P. May, John M. Carethers, Iris Lansdorp-Vogelaar, Uri Ladabaum, Timothy R. Church, Anjelica Davis, Chyke A. Doubeni, John M. Inadomi, Richard C. Wender, Pedro Nascimento de Lima, Rosita van den Puttelaar
Journal: Clinical Gastroenterology and Hepatology (2024)
An Injectable Magnesium‐Based Cement Stimulated with NIR for Drug‐Controlled Release and Osteogenic Potential
Authors: Yanbin Zhao, Yangyang Li, Bin Wang, Junyan Yao, Yue Fan, Peng He, Jing Bai, Cheng Wang, Feng Xue, Chenglin Chu
Journal: Advanced Healthcare Materials (2024)

Abstract Magnesium phosphate bone cement (MPC) has gained widespread usage in orthopedic implantation due to its fast‐setting and high initial strength benefits. However, the simultaneous attainment of drug‐controlled release and osteogenic potential in MPC remains a significant challenge. Herein, a strategy to create a smart injectable cement system using nanocontainers and chondroitin sulfate is proposed. It employs nanocontainers containing alendronate‐loaded mesoporous silica nanoparticles, which are surface‐modified with polypyrrole to control drug release in response to near‐infrared (NIR) stimulation. The alendronate‐incorporated cement (ACMPC) exhibits improved compressive strength (70.6 ± 5.9 MPa), prolonged setting time (913 s), and exceptional injectability (96.5% of injection rate and 242 s of injection time). It also shows the capability to prevent degradation, thus preserving mechanical properties. Under NIR irradiation, the cement shows good antibacterial properties due to the combined impact of hyperthermia, reactive oxygen species, and alendronate. Furthermore, the ACMPC (NIR) group displays good biocompatibility and osteogenesis capabilities, which also lead to an increase in alkaline phosphatase activity, extracellular matrix mineralization, and the upregulation of osteogenic genes. This research has significant implications for developing multifunctional biomaterials and clinical applications.
Are there new relevant therapeutic endpoints in the modern era of the BCR::ABL1 tyrosine kinase inhibitors in chronic myeloid leukemia?
Authors: Hagop Kantarjian, Susan Branford, Massimo Breccia, Jorge Cortes, Fadi G. Haddad, Andreas Hochhaus, Timothy Hughes, Ghayas C. Issa, Elias Jabbour, Franck E. Nicolini, Koji Sasaki, Francois Xavier-Mahon
Journal: Leukemia (2024)
Divergent composition and transposon-silencing activity of small RNAs in mammalian oocytes
Authors: Li Hou, Wei Liu, Hongdao Zhang, Ronghong Li, Miao Liu, Huijuan Shi, Ligang Wu
Journal: Genome biology (2024)

Abstract Background Small RNAs are essential for germ cell development and fertilization. However, fundamental questions remain, such as the level of conservation in small RNA composition between species and whether small RNAs control transposable elements in mammalian oocytes. Results Here, we use high-throughput sequencing to profile small RNAs and poly(A)-bearing long RNAs in oocytes of 12 representative vertebrate species (including 11 mammals). The results show that miRNAs are generally expressed in the oocytes of each representative species (although at low levels), whereas endo-siRNAs are specific to mice. Notably, piRNAs are predominant in oocytes of all species (except mice) and vary widely in length. We find PIWIL3-associated piRNAs are widespread in mammals and generally lack 3′-2′-O-methylation. Additionally, sequence identity is low between homologous piRNAs in different species, even among those present in syntenic piRNA clusters. Despite the species-specific divergence, piRNAs retain the capacity to silence younger TE subfamilies in oocytes. Conclusions Collectively, our findings illustrate a high level of diversity in the small RNA populations of mammalian oocytes. Furthermore, we identify sequence features related to conserved roles of small RNAs in silencing TEs, providing a large-scale reference for future in-depth study of small RNA functions in oocytes.
Discovery of TK-642 as a highly potent, selective, orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor
Authors: Kai Tang, Shu Wang, Siqi Feng, Xinyu Yang, Yueyang Guo, Xiangli Ren, Linyue Bai, Bin Yu, Hong-Min Liu, Yihui Song
Journal: Acta Pharmaceutica Sinica B (2024)

Src homology-2-containing protein tyrosine phosphatase 2 (SHP2) is a promising therapeutic target for cancer therapy. In this work, we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors, leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent, selective, orally bioavailable allosteric SHP2 inhibitor (SHP2
Evaluation of metagenomic and pathogen-targeted next-generation sequencing for diagnosis of meningitis and encephalitis in adults: A multicenter prospective observational cohort study in China
Authors: Weibi Chen, Gang Liu, Lili Cui, Fei Tian, Jiatang Zhang, Jiahua Zhao, Ying Lv, Jianxin Du, Xinyu Huan, Yingfeng Wu, Yan Zhang
Journal: Journal of Infection (2024)

Next-generation sequencing (NGS) might aid in the identification of causal pathogens. However, the optimal approaches applied to cerebrospinal fluid (CSF) for detection are unclear, and studies evaluating the application of different NGS workflows for the diagnosis of intracranial infections are limited.
Restoring T and B cell generation in X-linked severe combined immunodeficiency mice through hematopoietic stem cells adenine base editing
Authors: Lu Zhang, Kai Li, Zhiwei Liu, Lisha An, Haikun Wei, Shanshan Pang, Zongfu Cao, Xingxu Huang, Xiaohua Jin, Xu Ma
Journal: Molecular Therapy (2024)
Phase 1 trial of the safety, pharmacokinetics, and antiviral activity of EDP-514 in untreated viremic chronic hepatitis B patients
Authors: Man-Fung Yuen, Wan-Long Chuang, Cheng-Yuan Peng, Wen-Juei Jeng, Wei-Wen Su, Ting-Tsung Chang, Chi-Yi Chen, Yao-Chun Hsu, Guy De La Rosa, Alaa Ahmad, Ed Luo, Annie L. Conery
Journal: Clinical and Molecular Hepatology (2024)

Oral EDP-514 is a potent core protein inhibitor of hepatitis B virus (HBV) replication, which produced a >4-log viral load reduction in HBV-infected chimeric mice with human liver cells. This study evaluated the safety, pharmacokinetics, and antiviral activity of three doses of EDP-514 in treatment-naive viremic patients with HBeAgpositive or -negative chronic HBV infection. Patients with HBsAg detectable at screening and at least 6 months previously were eligible. HBeAg-positive and -negative patients had a serum/plasma HBV DNA level ≥20,000 and ≥2,000 IU/mL, respectively. Twenty-five patients were randomized to EDP-514 200 (n=6), 400 (n=6) or 800 mg (n=7) or placebo (n=6) once daily for 28 days. A dose-related increase in EDP-514 exposure (AUClast and Cmax) was observed across doses. At Day 28, mean reductions in HBV DNA were -2.9, -3.3, -3.5 and -0.2 log10 IU/mL with EDP-514 200 mg, 400 mg, 800 mg, and placebo groups, respectively. The corresponding mean change from baseline for HBV RNA levels was -2.9, -2.4, -2.0, and -0.02 log10 U/mL. No virologic failures were observed. No clinically meaningful changes from baseline were observed for HBsAg, HBeAg or HBcrAg. Nine patients reported treatment emergent adverse events of mild or moderate severity with no discontinuations, serious AEs or deaths. In treatment-naïve viremic patients, oral EDP-514 was generally safe and well-tolerated, displayed PK profile supportive of once-daily dosing, and markedly reduced HBV DNA and HBV RNA.
A remote digital memory composite to detect cognitive impairment in memory clinic samples in unsupervised settings using mobile devices
Authors: David Berron, Wenzel Glanz, Lindsay Clark, Kristin Basche, Xenia Grande, Jeremie Güsten, Ornella V. Billette, Ina Hempen, Muhammad Hashim Naveed, Nadine Diersch, Michaela Butryn, Annika Spottke, Katharina Buerger, Robert Perneczky, Anja Schneider, Stefan Teipel, Jens Wiltfang, Sterling Johnson, Michael Wagner, Frank Jessen, Emrah Düzel
Journal: npj Digital Medicine (2024)

Abstract Remote monitoring of cognition holds the promise to facilitate case-finding in clinical care and the individual detection of cognitive impairment in clinical and research settings. In the context of Alzheimer’s disease, this is particularly relevant for patients who seek medical advice due to memory problems. Here, we develop a remote digital memory composite (RDMC) score from an unsupervised remote cognitive assessment battery focused on episodic memory and long-term recall and assess its construct validity, retest reliability, and diagnostic accuracy when predicting MCI-grade impairment in a memory clinic sample and healthy controls. A total of 199 participants were recruited from three cohorts and included as healthy controls ( n = 97), individuals with subjective cognitive decline ( n = 59), or patients with mild cognitive impairment ( n = 43). Participants performed cognitive assessments in a fully remote and unsupervised setting via a smartphone app. The derived RDMC score is significantly correlated with the PACC5 score across participants and demonstrates good retest reliability. Diagnostic accuracy for discriminating memory impairment from no impairment is high (cross-validated AUC = 0.83, 95% CI [0.66, 0.99]) with a sensitivity of 0.82 and a specificity of 0.72. Thus, unsupervised remote cognitive assessments implemented in the neotiv digital platform show good discrimination between cognitively impaired and unimpaired individuals, further demonstrating that it is feasible to complement the neuropsychological assessment of episodic memory with unsupervised and remote assessments on mobile devices. This contributes to recent efforts to implement remote assessment of episodic memory for case-finding and monitoring in large research studies and clinical care.
Overlaps and divergences between tauopathies and synucleinopathies: a duet of neurodegeneration
Authors: Wen Li, Jia-Yi Li
Journal: Translational Neurodegeneration (2024)

Proteinopathy, defined as the abnormal accumulation of proteins that eventually leads to cell death, is one of the most significant pathological features of neurodegenerative diseases. Tauopathies, represented by Alzheimer's disease (AD), and synucleinopathies, represented by Parkinson's disease (PD), show similarities in multiple aspects. AD manifests extrapyramidal symptoms while dementia is also a major sign of advanced PD. We and other researchers have sequentially shown the cross-seeding phenomenon of α-synuclein (α-syn) and tau, reinforcing pathologies between synucleinopathies and tauopathies. The highly overlapping clinical and pathological features imply shared pathogenic mechanisms between the two groups of disease. The diagnostic and therapeutic strategies seemingly appropriate for one distinct neurodegenerative disease may also apply to a broader spectrum. Therefore, a clear understanding of the overlaps and divergences between tauopathy and synucleinopathy is critical for unraveling the nature of the complicated associations among neurodegenerative diseases. In this review, we discuss the shared and diverse characteristics of tauopathies and synucleinopathies from aspects of genetic causes, clinical manifestations, pathological progression and potential common therapeutic approaches targeting the pathology, in the aim to provide a timely update for setting the scheme of disease classification and provide novel insights into the therapeutic development for neurodegenerative diseases.
Elimination of the hepatitis B virus: A goal, a challenge
Authors: Robério Amorim de Almeida Pondé, Guilherme de Sousa Pondé Amorim
Journal: Medicinal Research Reviews (2024)

Abstract The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines—blocking transmission and antiviral therapy—inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother‐to‐child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.
Indole-3-acetic acid alleviates DSS-induced colitis by promoting the production of R-equol from <i>Bifidobacterium pseudolongum</i>
Authors: Miaomiao Li, Xue Han, Lijun Sun, Xinjuan Liu, Weizhen Zhang, Jianyu Hao
Journal: Gut Microbes (2024)

Background Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis.
Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway
Authors: Shicheng Fan, Yue Gao, Pengfei Zhao, Guomin Xie, Yanying Zhou, Xiao Yang, Xuan Li, Shuaishuai Zhang, Frank J. Gonzalez, Aijuan Qu, Min Huang, Huichang Bi
Journal: Acta Pharmaceutica Sinica B (2024)

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.
A Phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis
Authors: Wolfgang C. Winkelmayer, Anthonie W.A. Lensing, Ravi I. Thadhani, Kenneth W. Mahaffey, Michael Walsh, Ákos F. Pap, Stefan Willmann, Kirstin Thelen, Sophie Hodge, Alexander Solms, Sheila J.M. Ingham, John Eikelboom
Journal: Kidney International (2024)
MOFs‐Based Magnetic Nanozyme to Boost Cascade ROS Accumulation for Augmented Tumor Ferroptosis
Authors: Ying Yuan, Bo Chen, Xingxing An, Zhanhang Guo, Xin Liu, Hao Lu, Fangxin Hu, Zhigang Chen, Chunxian Guo, Chang Ming Li
Journal: Advanced Healthcare Materials (2024)

The emerging cell death modality of ferroptosis has garnered increasing attention for antitumor treatment but still suffers from low therapeutic efficacy. A metal-organic frameworks (MOFs)-based magnetic nanozyme (PZFH) comprising porphyrin-based Zr-MOF (PCN) on zinc ferrite (ZF) nanoparticles modified with hyaluronic acid, delivering excellent magnetophotonic response for efficient ferroptosis, is reported here. PZFH shows multienzyme-like cascade activity encompassing a photon-triggered oxidase-like catalysis to generate O