tbuckley/cabot-search huggingface dataset:
Executive function in children with neurodevelopmental conditions: a systematic review and meta-analysis
Authors: Ayesha K. Sadozai, Carter Sun, Eleni A. Demetriou, Amit Lampit, Martha Munro, Nina Perry, Kelsie A. Boulton, Adam J. Guastella
Journal: Nature Human Behaviour (2024)

Abstract Executive function (EF) delays are well documented in paediatric neurodevelopmental conditions (NDCs). There is no consensus about whether EF delay represents a transdiagnostic feature of NDCs. This systematic review and meta-analysis synthesized 180 studies reporting two or more NDC comparisons on EF, examined differences between NDCs, and the moderating effects of gender, age, publication year, DSM editions and assessment types. Studies using established EF measures across seven domains (attention, fluency, set-shifting, set-switching, response inhibition, planning and working memory) in participants under 18 were included. Summary effects were compared: (1) for all reported NDCs relative to control, (2) for each individual NDC relative to control and (3) between NDC groups. Results confirmed that EF delay was a transdiagnostic feature of neurodevelopmental delay, with a moderate effect size of delay across all NDCs ( g = 0.56, 95% confidence interval (CI) 0.49–0.63) compared with control. This effect increased with comorbidities ( g = 0.72, 95% CI 0.59–0.86), DSM-5 criteria and informant measures. Comparisons between NDCs revealed few differences: children with tic disorders (TD) showed smaller EF delays, children with attention-deficit/hyperactivity disorder (ADHD) showed larger delays in attention, response inhibition, planning and working memory compared with TD and specific learning disorders, while children with autism spectrum disorders showed greater delays on set-switching compared with ADHD. Findings support transdiagnostic models of neurodevelopment to further a developmentally sensitive science that can reveal how EF delays contribute to brain circuitry, symptom profiles and functioning, and ultimately support early interventions and outcomes for all children with NDCs.
Base editing screens define the genetic landscape of cancer drug resistance mechanisms
Authors: Matthew A. Coelho, Magdalena E. Strauss, Alex Watterson, Sarah Cooper, Shriram Bhosle, Giuditta Illuzzi, Emre Karakoc, Cansu Dinçer, Sara F. Vieira, Mamta Sharma, Marie Moullet, Daniela Conticelli, Jonas Koeppel, Katrina McCarten, Chiara M. Cattaneo, Vivien Veninga, Gabriele Picco, Leopold Parts, Josep V. Forment, Emile E. Voest, John C. Marioni, Andrew Bassett, Mathew J. Garnett
Journal: Nature Genetics (2024)

Abstract Drug resistance is a principal limitation to the long-term efficacy of cancer therapies. Cancer genome sequencing can retrospectively delineate the genetic basis of drug resistance, but this requires large numbers of post-treatment samples to nominate causal variants. Here we prospectively identify genetic mechanisms of resistance to ten oncology drugs from CRISPR base editing mutagenesis screens in four cancer cell lines using a guide RNA library predicted to install 32,476 variants in 11 cancer genes. We identify four functional classes of protein variants modulating drug sensitivity and use single-cell transcriptomics to reveal how these variants operate through distinct mechanisms, including eliciting a drug-addicted cell state. We identify variants that can be targeted with alternative inhibitors to overcome resistance and functionally validate an epidermal growth factor receptor (EGFR) variant that sensitizes lung cancer cells to EGFR inhibitors. Our variant-to-function map has implications for patient stratification, therapy combinations and drug scheduling in cancer treatment.
Monkeypox Clade Ib virus introduction into Burundi: first findings, July to mid-August 2024
Authors: Néhémie Nzoyikorera, Cassien Nduwimana, Leonard Schuele, David F Nieuwenhuijse, Marion Koopmans, Saria Otani, Frank M Aarestrup, Théogène Ihorimbere, Denis Niyomwungere, Armstrong Ndihokubwayo, Idrissa Diawara, Alexis Niyomwungere, Dionis Nizigiyimana, Marie Noelle Uwineza, Bas B Oude Munnink, Joseph Nyandwi
Journal: Eurosurveillance (2024)

We describe cases with monkeypox virus (MPXV) Clade Ib in Burundi from their first detection in July until 20 August 2024. Testing 442 people with vesicular lesions confirmed 170 cases (98 male; 72 female), 82 (48%) being &lt; 15 years old. Differential diagnosis of the first 30 individuals testing MPXV negative revealed chickenpox in 20. Cases occurred in 26 of 49 Burundi health districts, but mostly in Bujumbura Nord (88/170; 67%). Case-derived MPXV genetic sequences from Burundi and South-Kivu (Democratic Republic of the Congo), clustered together in phylogenetic analysis.
Highly pathogenic avian influenza management policy in domestic poultry: from reacting to preventing
Authors: Timothée Vergne, Mathilde C Paul, Claire Guinat, Mattias Delpont, Brandon H Hayes, Sébastien Lambert, Jean-Pierre Vaillancourt, Jean-Luc Guérin
Journal: Eurosurveillance (2024)

The emergence of clade 2.3.4.4b H5N1 highly pathogenic avian influenza (HPAI) viruses in 2021 has led to unprecedented epidemics in poultry, changing epidemiological patterns of year-round infections in resident wild avifauna and more frequent spill-over events to mammals. Given this situation, it is important that we recognise that traditional HPAI management strategies are no longer sufficient, and policy changes are required. Poultry vaccination has emerged as a crucial intervention in the current control of HPAI, as evidenced by France's nationwide campaign targeting domestic ducks. However, due to the logistical challenges and potential trade implications of vaccination, broader structural reforms appear also necessary. These include a shift from farm-level to territorial-level biosecurity approaches, putting into practice the concept of ‘regional biosecurity’. Given the role duck farm density has played in successive HPAI epidemics in France, there is a need to think about the spatial distribution of poultry farms as a structural component of regional biosecurity and to consider the reduction of farm concentration as a measure to prevent viral spread. The integration of regional biosecurity and poultry vaccination into prevention strategies should impact the way poultry are produced and traded in the future.
A SIRT7-dependent acetylation switch regulates early B cell differentiation and lineage commitment through Pax5
Authors: Andres Gamez-Garcia, Maria Espinosa-Alcantud, Alberto Bueno-Costa, Elisenda Alari-Pahissa, Anna Marazuela-Duque, Joshua K. Thackray, Chandni Ray, Clara Berenguer, Poonam Kumari, Joan Josep Bech, Thomas Braun, Alessandro Ianni, Jay A. Tischfield, Lourdes Serrano, Manel Esteller, Jose L. Sardina, Carolina De La Torre, Mikael Sigvardsson, Berta N. Vazquez, Alejandro Vaquero
Journal: Nature Immunology (2024)

Abstract B lymphopoiesis is orchestrated by lineage-specific transcription factors. In B cell progenitors, lineage commitment is mediated by Pax5, which is commonly mutated in B cell acute lymphoblastic leukemia. Despite its essential role in immunity, the mechanisms regulating Pax5 function remain largely unknown. Here, we found that the NAD + -dependent enzyme SIRT7 coordinates B cell development through deacetylation of Pax5 at K198, which promotes Pax5 protein stability and transcriptional activity. Neither Pax5 K198 deacetylated nor acetylated mimics rescued B cell differentiation in Pax5 −/− pro-B cells, suggesting that B cell development requires Pax5 dynamic deacetylation. The Pax5 K198 deacetylation mimic restored lineage commitment in Pax5 −/− pro-B cells and B cell differentiation in Sirt7 −/− pro-B cells, suggesting the uncoupling of differentiation from lineage commitment. The SIRT7–Pax5 interplay was conserved in B cell acute lymphoblastic leukemia, where SIRT7 expression correlated with good prognosis. Our findings reveal a crucial mechanism for B lymphopoiesis and highlight the relevance of sirtuins in immune function.
An ethics assessment tool for artificial intelligence implementation in healthcare: CARE-AI
Authors: Yilin Ning, Xiaoxuan Liu, Gary S. Collins, Karel G. M. Moons, Melissa McCradden, Daniel Shu Wei Ting, Jasmine Chiat Ling Ong, Benjamin Alan Goldstein, Siegfried K. Wagner, Pearse A. Keane, Eric J. Topol, Nan Liu
Journal: Nature Medicine (2024)
A hematology-based clock derived from the Study of Longitudinal Aging in Mice to estimate biological age
Authors: Jorge Martinez-Romero, Maria Emilia Fernandez, Michel Bernier, Nathan L. Price, William Mueller, Julián Candia, Simonetta Camandola, Osorio Meirelles, Yi-Han Hu, Zhiguang Li, Nigus Asefa, Andrew Deighan, Camila Vieira Ligo Teixeira, Dushani L. Palliyaguru, Carlos Serrano, Nicolas Escobar-Velasquez, Stephanie Dickinson, Eric J. Shiroma, Luigi Ferrucci, Gary A. Churchill, David B. Allison, Lenore J. Launer, Rafael de Cabo
Journal: Nature Aging (2024)
Patients with crush syndrome and kidney disease: lessons learned from the earthquake in Kahramanmaraş, Türkiye
Authors: Savas Ozturk, Serhan Tuglular, Refik Olmaz, Ismail Kocyigit, Muge Uzerk Kibar, Kenan Turgutalp, Dilek Torun, Tuncay Sahutoglu, Ozlem Usalan, Ozkan Gungor, Ramazan Danis, Gursel Yildiz, Ali Gurel, Mehmet Horoz, Mehmet Kucuksu, Suleyman Karakose, Tolga Yildirim, Mehmet Riza Altiparmak, Mehmet Deniz Ayli, Murat Tugcu, Zehra Eren, Eray Eroglu, Yasemin Coskun Yavuz, Esra Akcali, Dede Sit, Mehmet Polat, Saliha Yildirim, Selma Alagoz, Sibel Gokcay Bek, Irem Pembegul, Tahsin Karaaslan, Mustafa Keles, Funda Sari, Ayca Inci, Numan Gorgulu, Gulizar Sahin, Zeki Aydin, Serap Yadigar, Ozkan Ulutas, Nedim Yilmaz Selcuk, Yavuz Ayar, Zeynep Bal, Murat Altunok, Ayse Jini Günes Keskin, Murat Hayri Sipahioglu, Meliha Ozkutlu, Belda Dursun, Aysegul Oruc, Nuri Baris Hasbal, Mustafa Sevinc, Semih Gul, Seda Safak Ozturk, Alaattin Yildiz, Mehmet Sukru Sever
Journal: Kidney International (2024)
Corrigendum to “Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats.” Kidney International 2013;85:112–123
Authors: Hailin Zhao, Xianghong Luo, Zhaowei Zhou, Juying Liu, Catherine Tralau-Stewart, Andrew J T George, Daqing Ma
Journal: Kidney International (2024)
Urinary casts containing crystals in light chain proximal tubulopathy
Authors: Yusuke Ushio, Takashi Yokoyama, Shun Manabe, Momoko Seki, Yuki Kawaguchi, Shizuka Kobayashi, Shiho Makabe, Hiroshi Seino, Naoko Ito, Hideki Nakayama, Shigeru Horita, Hiroshi Kataoka, Sekiko Taneda, Kazuho Honda, Junichi Hoshino
Journal: Kidney International (2024)
Novel imported clades accelerated the RSV surge in Beijing, China, 2023-2024
Authors: Xiaofeng Wei, Liang Wang, Maozhong Li, Jianxun Qi, Lu Kang, Geng Hu, Cheng Gong, Chengcheng Wang, Yiting Wang, Prof Fang Huang, Prof George F Gao
Journal: Journal of Infection (2024)
ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease
Authors: Tomoki Yanagi, Hiroaki Kikuchi, Koh Takeuchi, Koichiro Susa, Takayasu Mori, Motoko Chiga, Kouhei Yamamoto, Asuka Furukawa, Takumi Kanazawa, Yuki Kato, Naohiro Takahashi, Takefumi Suzuki, Yutaro Mori, Benjamin C Carter, Makiko Mori, Yuta Nakano, Tamami Fujiki, Yu Hara, Soichiro Suzuki, Fumiaki Ando, Shintaro Mandai, Shinya Honda, Satoru Torii, Shigeomi Shimizu, Hajime Tanaka, Yasuhisa Fujii, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Journal: Kidney International (2024)
Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP
Authors: Minjun Kang, Choon-Soo Lee, HyunJu Son, Jeongha Lee, Jaewon Lee, Hyun Ju Seo, Moo-Kang Kim, Murim Choi, Hyun-Jai Cho, Hyo-Soo Kim
Journal: Circulation Research (2024)

BACKGROUND: Latrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear. METHODS: The embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2 flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre [Cyclization recombinase] recombinase) under the α-myosin heavy chain promoter. RESULTS: Tamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK (p38 mitogen-activated protein kinases), which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins. CONCLUSIONS: Lphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.
EPHB4-RASA1 Inhibition of PIEZO1 Ras Activation Drives Lymphatic Valvulogenesis
Authors: Di Chen, Yipei Tang, Philip E. Lapinski, David Wiggins, Eva M. Sevick, Michael J. Davis, Philip D. King
Journal: Circulation Research (2024)

EPHB4 (ephrin receptor B4) and the RASA1 (p120 Ras GTPase-activating protein) are necessary for the development of lymphatic vessel (LV) valves. However, precisely how EPHB4 and RASA1 regulate LV valve development is unknown. In this study, we examine the mechanisms by which EPHB4 and RASA1 regulate the development of LV valves.
Ferroptosis Mediated Inflammation Promotes Pulmonary Hypertension
Authors: Felipe Kazmirczak, Neal T. Vogel, Sasha Z. Prisco, Michael T. Patterson, Jeffrey Annis, Ryan T. Moon, Lynn M. Hartweck, Jenna B. Mendelson, Minwoo Kim, Natalia Calixto Mancipe, Todd Markowski, LeeAnn Higgins, Candace Guerrero, Ben Kremer, Madelyn L. Blake, Christopher J. Rhodes, Jesse W. Williams, Evan L. Brittain, Kurt W. Prins
Journal: Circulation Research (2024)

Mitochondrial dysfunction, characterized by impaired lipid metabolism and heightened reactive oxygen species generation, results in lipid peroxidation and ferroptosis. Ferroptosis is an inflammatory mode of cell death that promotes complement activation and macrophage recruitment. In pulmonary arterial hypertension (PAH), pulmonary arterial endothelial cells exhibit cellular phenotypes that promote ferroptosis. Moreover, there is ectopic complement deposition and inflammatory macrophage accumulation in the pulmonary vasculature. However, the effects of ferroptosis inhibition on these pathogenic mechanisms and the cellular landscape of the pulmonary vasculature are incompletely defined.
Gut microbial metabolic signatures in diabetes mellitus and potential preventive and therapeutic applications
Authors: Enriqueta Garcia-Gutierrez, A. Kate O’Mahony, Reinaldo Sousa Dos Santos, Laura Marroquí, Paul D. Cotter
Journal: Gut Microbes (2024)

Diabetes mellitus can be subdivided into several categories based on origin and clinical characteristics. The most common forms of diabetes are type 1 (T1D), type 2 diabetes (T2D) and gestational diabetes mellitus (GDM). T1D and T2D are chronic diseases affecting around 537 million adults worldwide and it is projected that these numbers will increase by 12% over the next two decades, while GDM affects up to 30% of women during pregnancy, depending on diagnosis methods. These forms of diabetes have varied origins: T1D is an autoimmune disease, while T2D is commonly associated with, but not limited to, certain lifestyle patterns and GDM can result of a combination of genetic predisposition and pregnancy factors. Despite some pathogenic differences among these forms of diabetes, there are some common markers associated with their development. For instance, gut barrier impairment and inflammation associated with an unbalanced gut microbiota and their metabolites may be common factors in diabetes development and progression. Here, we summarize the microbial signatures that have been linked to diabetes, how they are connected to diet and, ultimately, the impact on metabolite profiles resulting from host-gut microbiota-diet interactions. Additionally, we summarize recent advances relating to promising preventive and therapeutic interventions focusing on the targeted modulation of the gut microbiota to alleviate T1D, T2D and GDM.
Durable Muscle Extracellular Matrix Engineered with Adhesive Phenolic Moieties for Effective Skeletal Muscle Regeneration in Muscle Atrophy
Authors: Soojeong Choi, Mi Jeong Lee, Moohyun Kim, Yunsu Bae, Jang‐Ung Park, Seung‐Woo Cho
Journal: Advanced Healthcare Materials (2024)

Abstract Muscle atrophy detrimentally impacts health and exacerbates physical disability, leading to increased mortality. In particular, sarcopenia, aging‐related degenerative muscle loss, necessitates urgent remedies. Current approaches for treating muscle atrophy include exercise and nutrition, while drug exploration remains in its early stages. Cell therapy, focusing on satellite cells, faces significant challenge due to poor engraftment, safety issue, and high cost. Cell‐free approach using extracellular matrix (ECM) shows a regenerative potential, but a lack of mechanical and adhesive properties hinders prolonged efficacy of ECM therapy. Here, durable muscle ECM (MEM) hydrogels for muscle atrophy by fortifying MEM with adhesive phenolic moieties including catechol and pyrogallol are demonstrated. The resultant phenolic MEM hydrogels exhibit enhanced mechanical and adhesive properties and provide sustained muscle‐like microenvironments to address muscle atrophy. No local and systemic toxicities are observed after phenolic MEM injection into tibialis anterior muscle. Notably, these engineered MEM hydrogels, devoid of cells or drugs, induce tissue rejuvenation by promoting muscle protein synthesis and facilitating functional muscle recovery in mouse models of disuse‐ and age‐induced atrophy. This study introduces cell‐free, ECM‐based therapeutics with translational potential for muscle atrophy by reversing muscle loss and restoring function.
Genetic analysis of asymptomatic antinuclear antibody production
Authors: Mehmet Hocaoǧlu, Desiré Casares‐Marfil, Amr H. Sawalha
Journal: Arthritis & Rheumatology (2024)

Antinuclear antibodies (ANA) are detected in up to 14% of the population, and many individuals with ANA are asymptomatic. The literature on the genetic contribution to asymptomatic ANA positivity is limited. In this study, we aimed to perform a genome-wide association study of asymptomatic ANA positivity in multiple populations.
Feasibility of snapshot testing using wearable sensors to detect cardiorespiratory illness (COVID infection in India)
Authors: Olivia K. Botonis, Jonathan Mendley, Shreya Aalla, Nicole C. Veit, Michael Fanton, JongYoon Lee, Vikrant Tripathi, Venkatesh Pandi, Akash Khobragade, Sunil Chaudhary, Amitav Chaudhuri, Vaidyanathan Narayanan, Shuai Xu, Hyoyoung Jeong, John A. Rogers, Arun Jayaraman
Journal: npj Digital Medicine (2024)

The COVID-19 pandemic has challenged the current paradigm of clinical and community-based disease detection. We present a multimodal wearable sensor system paired with a two-minute, movement-based activity sequence that successfully captures a snapshot of physiological data (including cardiac, respiratory, temperature, and percent oxygen saturation). We conducted a large, multi-site trial of this technology across India from June 2021 to April 2022 amidst the COVID-19 pandemic (Clinical trial registry name: International Validation of Wearable Sensor to Monitor COVID-19 Like Signs and Symptoms; NCT05334680; initial release: 04/15/2022). An Extreme Gradient Boosting algorithm was trained to discriminate between COVID-19 infected individuals (n = 295) and COVID-19 negative healthy controls (n = 172) and achieved an F1-Score of 0.80 (95% CI = [0.79, 0.81]). SHAP values were mapped to visualize feature importance and directionality, yielding engineered features from core temperature, cough, and lung sounds as highly important. The results demonstrated potential for data-driven wearable sensor technology for remote preliminary screening, highlighting a fundamental pivot from continuous to snapshot monitoring of cardiorespiratory illnesses.
Inulin-based nanoparticles for targeted siRNA delivery in acute kidney injury
Authors: Chinmay M Jogdeo, Sudipta Panja, Neha Kumari, Weimin Tang, Ekta Kapoor, Kasturi Siddhanta, Ashish Das, Erika I Boesen, Kirk W Foster, David Oupický
Journal: Journal of Controlled Release (2024)
Low-boiling-point perfluorocarbon nanodroplets for adaptable ultrasound-induced blood-brain barrier opening
Authors: Ambre Dauba, Claire Spitzlei, Kathlyne Jayne B Bautista, Laurène Jourdain, Erwan Selingue, Kelly E VanTreeck, Jacob A Mattern, Caroline Denis, Malika Ouldali, Ana-Andreea Arteni, Charles Truillet, Benoit Larrat, James Tsuruta, Phillip G Durham, Virginie Papadopoulou, Paul A Dayton, Nicolas Tsapis, Anthony Novell
Journal: Journal of Controlled Release (2024)

Low-boiling point perfluorocarbon nanodroplets (NDs) are valued as effective sonosensitive agents, encapsulating a liquid perfluorocarbon that would instantaneously vaporize at body temperature without the NDs shell. Those NDs have been explored for both therapeutic and diagnostic purposes. Here, phospholipid-shelled nanodroplets containing octafluoropropane (C3F8) or decafluorobutane (C4F10) formed by condensation of microbubbles were thoroughly characterized before blood-brain (BBB) permeabilization. Transmission electron microscopy (TEM) and cryo-TEM were employed to confirm droplet formation while providing high-resolution insights into the droplet surface and lipid arrangement assessed from electron density observation after condensation. The vaporization threshold of NDs was determined with a high-speed camera, and the frequency signal emitted by the freshly vaporized bubbles was analyzed using cavitation detection. C3F8 NDs exhibited vaporization at 0.3 MPa (f0 = 1.5 MHz, 50 cycles), and emitted signals at 2 f0 and 1.5 f0 from 0.45 MPa onwards (f0 = 1.5 MHz, 50 cycles), while broadband noise was measured starting from 0.55 MPa. NDs with the higher boiling point C4F10 vaporized at 1.15 MPa and emitted signals at 2 f0 from 0.65 MPa and 1.5 f0 from 0.9 MPa, while broadband noise was detected starting from 0.95 MPa. Both ND formulations were used to permeabilize the BBB in healthy mice using tailored ultrasound sequences, allowing for the identification of optimal applications for each NDs type. C3F8 NDs proved suitable and safe for permeabilizing a large area, potentially the entire brain, at low acoustic pressure. Meanwhile, C4F10 droplets facilitated very localized (400 μm isotropic) permeabilization at higher pressure. This study prompts a closer examination of the structural rearrangements occurring during the condensation of microbubbles into NDs and highlights the potential to tailor solutions for different brain pathologies by choosing the composition of the NDs and adjusting the ultrasound sequence.