bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clearance of defective muscle stem cells by senolytics restores myogenesis in myotonic dystrophy type 1
Authors: Conte Talita C. , Duran-Bishop Gilberto , Orfi Zakaria , Mokhtari Inès , Deprez Alyson , Côté Isabelle , Molina Thomas , Kim Tae-Yeon , Tellier Lydia , Roussel Marie-Pier , Maggiorani Damien , Benabdallah Basma , Leclerc Severine , Feulner Lara , Pellerito Ornella , Mathieu Jean , Andelfinger Gregor , Gagnon Cynthia , Beauséjour Christian , McGraw Serge , Duchesne Elise , Dumont Nicolas A. 
Published: July 2023

AbstractMuscle stem cells, the engine of muscle repair, are affected in myotonic dystrophy type 1 (DM1); however, the underlying molecular mechanism and the impact on the disease severity are still elusive. Here, we show using patients’ samples that muscle stem cells/myoblasts exhibit signs of cellular senescence in vitro and in situ. Single cell RNAseq uncovers a subset of senescent myoblasts expressing high levels of genes related to the senescence-associated secretory phenotype (SASP). We show that the levels of interleukin-6, a prominent SASP cytokine, in the serum of DM1 patients correlate with muscle weakness and functional capacity limitations. Drug screening revealed that the senolytic BCL-XL inhibitor (A1155463) can specifically remove senescent DM1 myoblasts by inducing their apoptosis. Clearance of senescent cells reduced the expression of SASP, which rescued the proliferation and differentiation capacity of DM1 myoblasts in vitro and enhanced their engraftment following transplantation in vivo. Altogether, this study identifies the pathogenic mechanism associated with muscle stem cell defects in DM1 and opens a therapeutic avenue that targets these defective cells to restore myogenesis.
Circulating trans fatty acids are associated with prostate cancer in Ghanaian and American men
Authors: Minas Tsion Zewdu , Lord Brittany D. , Zhang Amy L. , Candia Julián , Dorsey Tiffany H. , Baker Francine S. , Tang Wei , Bailey-Whyte Maeve , Smith Cheryl J. , Obadi Obadi M. , Ajao Anuoluwapo , Jordan Symone V. , Tettey Yao , Biritwum Richard B. , Adjei Andrew A. , Mensah James E. , Hoover Robert N. , Hsing Ann W. , Liu Jia , Loffredo Christopher A. , Yates Clayton , Cook Michael B. , Ambs Stefan 
Published: July 2023

AbstractThe association between fatty acids and prostate cancer remains poorly explored in African-descent populations. Here, we analyze 24 circulating fatty acids in 2934 men, including 1431 prostate cancer cases and 1503 population controls from Ghana and the United States, using CLIA-certified mass spectrometry-based assays. We investigate their associations with population groups (Ghanaian, African American, European American men), lifestyle factors, the fatty acid desaturase (FADS) genetic locus, and prostate cancer. Blood levels of circulating fatty acids vary significantly between the three population groups, particularly trans, omega-3 and omega-6 fatty acids. FADS1/2 germline genetic variants and lifestyle factors explain some of the variation in fatty acid levels, with the FADS1/2 locus showing population-specific associations, suggesting differences in their control by germline genetic factors. All trans fatty acids, namely elaidic, palmitelaidic, and linoelaidic acids, associated with an increase in the odds of developing prostate cancer, independent of ancestry, geographic location, or potential confounders.
SIX1 and EWS/FLI1 co-regulate an anti-metastatic gene network in Ewing Sarcoma
Authors: Hughes Connor J. , Fields Kaiah M. , Danis Etienne P. , Hsu Jessica Y. , Neelakantan Deepika , Vincent Melanie Y. , Gustafson Annika L. , Oliphant Michael J. , Sreekanth Varsha , Zaberezhnyy Vadym , Costello James C. , Jedlicka Paul , Ford Heide L. 
Published: July 2023

AbstractEwing sarcoma (ES), which is characterized by the presence of oncogenic fusion proteins such as EWS/FLI1, is an aggressive pediatric malignancy with a high rate of early dissemination and poor outcome after distant spread. Here we demonstrate that the SIX1 homeoprotein, whichenhancesmetastasis in most tumor types, suppresses ES metastasis by co-regulating EWS/FLI1 target genes. Like EWS/FLI1, SIX1 promotes cell growth/transformation, yet dramatically inhibits migration and invasion, as well as metastasis in vivo. We show that EWS/FLI1 promotes SIX1 protein expression, and that the two proteins share genome-wide binding profiles and transcriptional regulatory targets, including many metastasis-associated genes such as integrins, which they co-regulate. We further show that SIX1 downregulation of integrins is critical to its ability to inhibit invasion, a key characteristic of metastatic cells. These data demonstrate an unexpected anti-metastatic function for SIX1, through coordinate gene regulation with the key oncoprotein in ES, EWS/FLI1.
Spatially controlled construction of assembloids using bioprinting
Authors: Roth Julien G. , Brunel Lucia G. , Huang Michelle S. , Liu Yueming , Cai Betty , Sinha Sauradeep , Yang Fan , Pașca Sergiu P. , Shin Sungchul , Heilshorn Sarah C. 
Published: July 2023

AbstractThe biofabrication of three-dimensional (3D) tissues that recapitulate organ-specific architecture and function would benefit from temporal and spatial control of cell-cell interactions. Bioprinting, while potentially capable of achieving such control, is poorly suited to organoids with conserved cytoarchitectures that are susceptible to plastic deformation. Here, we develop a platform, termed Spatially Patterned Organoid Transfer (SPOT), consisting of an iron-oxide nanoparticle laden hydrogel and magnetized 3D printer to enable the controlled lifting, transport, and deposition of organoids. We identify cellulose nanofibers as both an ideal biomaterial for encasing organoids with magnetic nanoparticles and a shear-thinning, self-healing support hydrogel for maintaining the spatial positioning of organoids to facilitate the generation of assembloids. We leverage SPOT to create precisely arranged assembloids composed of human pluripotent stem cell-derived neural organoids and patient-derived glioma organoids. In doing so, we demonstrate the potential for the SPOT platform to construct assembloids which recapitulate key developmental processes and disease etiologies.
Covalent organic frameworks for direct photosynthesis of hydrogen peroxide from water, air and sunlight
Authors: Liu Fuyang , Zhou Peng , Hou Yanghui , Tan Hao , Liang Yin , Liang Jialiang , Zhang Qing , Guo Shaojun , Tong Meiping , Ni Jinren 
Published: July 2023

AbstractSolar-driven photosynthesis is a sustainable process for the production of hydrogen peroxide, the efficiency of which is plagued by side reactions. Metal-free covalent organic frameworks (COFs) that can form suitable intermediates and inhibit side reactions show great promise to photo-synthesize H2O2. However, the insufficient formation and separation/transfer of photogenerated charges in such materials restricts the efficiency of H2O2production. Herein, we provide a strategy for the design of donor-acceptor COFs to greatly boost H2O2photosynthesis. We demonstrate that the optimal intramolecular polarity of COFs, achieved by using suitable amounts of phenyl groups as electron donors, can maximize the free charge generation, which leads to high H2O2yield rates (605 μmol g−1h−1) from water, oxygen and visible light without sacrificial agents. Combining in-situ characterization with computational calculations, we describe how the triazine N-sites with optimal N2pstates play a crucial role in H2O activation and selective oxidation into H2O2. We further experimentally demonstrate that H2O2can be efficiently produced in tap, river or sea water with natural sunlight and air for water decontamination.
A signal peptide peptidase is required for ER-symbiosome proximal association and protein secretion
Authors: Yang Jian , Zhai Niu , Chen Yuhui , Wang Luying , Chen Rujin , Pan Huairong 
Published: July 2023

AbstractDuring legume-rhizobia symbiosis, differentiation of the symbiosome (engulfed intracellular rhizobia) is necessary for successful nitrogen fixation. To control symbiosome differentiation, host cell subcellular components, e.g., ER (endoplasmic reticulum), must adapt robustly to ensure large-scale host protein secretion to the new organelle. However, the key components controlling the adaption of ER in nodule cells remain elusive. We report that Medicago BID1, a nodule-specific signal peptide peptidase (SPP), is central to ER structural dynamics and host protein secretion. In bid1, symbiosome differentiation is blocked. BID1 localizes specifically to the ER membrane and expresses exclusively in nodule cells with symbiosomes. In the wild type ER forms proximal association structures with symbiosomes, but not in bid1. Consequently, in bid1 excessive ER stress responses are induced and ER-to-symbiosome protein secretion is impaired. In summary, a nodule-specific SPP is necessary for ER-symbiosome proximal association, host protein secretion, and symbiosome differentiation.
Nucleus reuniens transiently synchronizes memory networks at beta frequencies
Authors: Jayachandran Maanasa , Viena Tatiana D. , Garcia Andy , Veliz Abdiel Vasallo , Leyva Sofia , Roldan Valentina , Vertes Robert P. , Allen Timothy A. 
Published: July 2023

AbstractEpisodic memory-based decision-making requires top-down medial prefrontal cortex and hippocampal interactions. This integrated prefrontal-hippocampal memory state is thought to be organized by synchronized network oscillations and mediated by connectivity with the thalamic nucleus reuniens (RE). Whether and how the RE synchronizes prefrontal-hippocampal networks in memory, however, remains unknown. Here, we recorded local field potentials from the prefrontal-RE-hippocampal network while rats engaged in a nonspatial sequence memory task, thereby isolating memory-related activity from running-related oscillations. We found that synchronous prefrontal-hippocampal beta bursts (15–30 Hz) dominated during memory trials, whereas synchronous theta activity (6–12 Hz) dominated during non-memory–related running. Moreover, RE beta activity appeared first, followed by prefrontal and hippocampal synchronized beta, suggesting that prefrontal-hippocampal beta could be driven by the RE. To test whether the RE is capable of driving prefrontal-hippocampal beta synchrony, we used an optogenetic approach (retroAAV-ChR2). RE activation induced prefrontal-hippocampal beta coherence and reduced theta coherence, matching the observed memory-driven network state in the sequence task. These findings are the first to demonstrate that the RE contributes to memory by driving transient synchronized beta in the prefrontal-hippocampal system, thereby facilitating interactions that underlie memory-based decision-making.
Molecular and phenotypic characteristics of RSV infections in infants during two nirsevimab randomized clinical trials
Authors: Ahani Bahar , Tuffy Kevin M. , Aksyuk Anastasia A. , Wilkins Deidre , Abram Michael E. , Dagan Ron , Domachowske Joseph B. , Guest Johnathan D. , Ji Hong , Kushnir Anna , Leach Amanda , Madhi Shabir A. , Mankad Vaishali S. , Simões Eric A. F. , Sparklin Benjamin , Speer Scott D. , Stanley Ann Marie , Tabor David E. , Hamrén Ulrika Wählby , Kelly Elizabeth J. , Villafana Tonya 
Published: July 2023

AbstractNirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.
Opposing gene regulatory programs governing myofiber development and maturation revealed at single nucleus resolution
Authors: Dos Santos Matthieu , Shah Akansha M. , Zhang Yichi , Bezprozvannaya Svetlana , Chen Kenian , Xu Lin , Lin Weichun , McAnally John R. , Bassel-Duby Rhonda , Liu Ning , Olson Eric N. 
Published: July 2023

AbstractSkeletal muscle fibers express distinct gene programs during development and maturation, but the underlying gene regulatory networks that confer stage-specific myofiber properties remain unknown. To decipher these distinctive gene programs and how they respond to neural activity, we generated a combined multi-omic single-nucleus RNA-seq and ATAC-seq atlas of mouse skeletal muscle development at multiple stages of embryonic, fetal, and postnatal life. We found that Myogenin, Klf5, and Tead4 form a transcriptional complex that synergistically activates the expression of muscle genes in developing myofibers. During myofiber maturation, the transcription factor Maf acts as a transcriptional switch to activate the mature fast muscle gene program. In skeletal muscles of mutant mice lacking voltage-gated L-type Ca2+ channels (Cav1.1), Maf expression and myofiber maturation are impaired. These findings provide a transcriptional atlas of muscle development and reveal genetic links between myofiber formation, maturation, and contraction.
Biodegradable polyphosphoester micelles act as both background-free 31P magnetic resonance imaging agents and drug nanocarriers
Authors: Koshkina Olga , Rheinberger Timo , Flocke Vera , Windfelder Anton , Bouvain Pascal , Hamelmann Naomi M. , Paulusse Jos M. J. , Gojzewski Hubert , Flögel Ulrich , Wurm Frederik R. 
Published: July 2023

AbstractIn vivo monitoring of polymers is crucial for drug delivery and tissue regeneration. Magnetic resonance imaging (MRI) is a whole-body imaging technique, and heteronuclear MRI allows quantitative imaging. However, MRI agents can result in environmental pollution and organ accumulation. To address this, we introduce biocompatible and biodegradable polyphosphoesters, as MRI-traceable polymers using the 31P centers in the polymer backbone. We overcome challenges in 31P MRI, including background interference and low sensitivity, by modifying the molecular environment of 31P, assembling polymers into colloids, and tailoring the polymers’ microstructure to adjust MRI-relaxation times. Specifically, gradient-type polyphosphonate-copolymers demonstrate improved MRI-relaxation times compared to homo- and block copolymers, making them suitable for imaging. We validate background-free imaging and biodegradation in vivo using Manduca sexta. Furthermore, encapsulating the potent drug PROTAC allows using these amphiphilic copolymers to simultaneously deliver drugs, enabling theranostics. This first report paves the way for polyphosphoesters as background-free MRI-traceable polymers for theranostic applications.
A detailed land use/land cover map for the European Alps macro region
Authors: Marsoner Thomas , Simion Heidi , Giombini Valentina , Egarter Vigl Lukas , Candiago Sebastian 
Published: July 2023

AbstractSpatially and thematically detailed land use maps are of special importance to study and manage populated mountain regions. Due to the complex terrain, high elevational gradients as well as differences in land demand, these regions are characterized by a high density of different land uses that form heterogeneous landscapes. Here, we present a new highly detailed land use/landcover map for the areas included in the European Strategy for the Alpine Region. The map has a spatial resolution of up to 5 m and a temporal extent from 2015 to 2020. It was created by aggregating 15 high-resolution layers resulting in 65 land use/cover classes. The overall map accuracy was assessed at 88.8%. The large number of land use classes and the high spatial resolution allow an easy customization of the map for research and management purposes, making it useable by a broad audience for various applications. Our map shows that by combining theme specific “high-resolution” land use products to build a comprehensive land use/land cover map, a high thematic and spatial detail can be achieved.
Comparison of goat and cow milk-derived extracellular vesicle miRNomes
Authors: Krupova Zuzana , Leroux Christine , Péchoux Christine , Bevilacqua Claudia , Martin Patrice 
Published: July 2023

AbstractmiRNAs present in milk are mainly found in extracellular vesicles (EVs), which are nanosized membrane vesicles released by most of the cell types to ensure intercellular communication. The majority of the studies performed so far on these vesicles have been conducted on human and cow’s milk and focused on their miRNA content. The objectives of this study were to profile the miRNA content of purified EVs from five healthy goats and to compare their miRNome to those obtained from five healthy cows, at an early stage of lactation. EV populations were morphologically characterized using Transmission Electron Microscopy and Nanoparticle Tracking Analysis. The presence of EV protein markers checked by Western blotting and the absence of contamination of preparations by milk proteins. The size distribution and concentration of bovine and goat milk-derived EVs were similar. RNA-sequencing were performed, and all sequences were mapped to the cow genome identifying a total of 295 miRNAs. This study reports for the first-time a goat miRNome from milk EVs and its validation using cow miRNomes.
Validity of two weight prediction models for community-living patients participating in a weight loss program
Authors: Dent Robert , Harris Neil , van Walraven Carl 
Published: July 2023

AbstractModels predicting individual body weights over time clarify patient expectations in weight loss programs. The accuracy of two commonly used weight prediction models in community living people is unclear. All eligible people entering a weight management program between 1992 and 2015 were included. Patients’ diet was 1200 kcal/day for week 0 followed by 900 kcal/day for weeks 1–7 and were excluded from the analysis if they were nonadherent. We generated expected weights using the National Institutes of Health Body Weight Planner (NIH-BWP) and the Pennington Biomedical Research Center Weight Loss Predictor (PBRC-WLP). 3703 adherent people were included (mean age 46 years, 72.6% women, mean [SD] weight 262.3 pounds [54.2], mean [SD] BMI 42.4 [7.6]). Mean (SD) relative body weight differences (100*[observed−expected]/expected) for NIH-BWP and PBRC-WLP models was − 1.5% (3.8) and − 2.9% (3.2), respectively. At week 7, mean squared error with NIH-BWP (98.8, 83%CI 89.7–108.8) was significantly lower than that with PBRC-WLP (117.7, 83%CI 112.4–123.4). Notable variation in relative weight difference were seen (for NIH-BWP, 5th–95th percentile was − 6.2%, + 3.7%; Δ 9.9%). During the first 7 weeks of a weight loss program, both weight prediction models returned expected weights that were very close to observed values with the NIH-BWP being more accurate. However, notable variability between expected and observed weights in individual patients were seen. Clinicians can monitor patients in weight loss programs by comparing their progress with these data.
Shifting into Action: from Data Segmentation to Equitable Interoperability for Adolescents (and Everyone Else)
Authors: Sarabu Chethan , Sharko Marianne , Petersen Carolyn , Galvin Hannah 
Published: July 2023

Abstract
Background Technological improvements and, subsequently, the federal 21st Century Cures Act have resulted in increased access to and interoperability of electronic protected health information (ePHI). These not only have many benefits, but also have created unique challenges for privacy and confidentiality for adolescent patients. The inability to granularly protect sensitive data and a lack of standards have resulted in limited confidentiality protection and inequitable access to health information.
Objectives This study aimed to understand the challenges to safe, equitable access, and interoperability of ePHI for adolescents and to identify strategies that have been developed, ongoing needs, and work in progress.
Methods Shift, a national task force formalized in 2020, is a group of more than 200 expert stakeholder members working to improve functionality to standardize efforts to granularly identify and protect sensitive ePHI to promote equitable interoperability.
Results Shift has created high-priority clinical use cases and organized challenges into the areas of Standards and Terminology; Usability and Implementation; and Ethics, Legal, and Policy.
Conclusion Current technical standards and value sets of terminology for sensitive data have been immature and inconsistent. Shift, a national diverse working group of stakeholders, is addressing challenges inherent in the protection of privacy and confidentiality for adolescent patients. The diversity of expertise and perspectives has been essential to identify and address these challenges.
Medical Research Productivity and Barriers from the Perspective of Faculty Members at the University of Tripoli
Authors: Atia Ahmed , Mohammed Safa , Mohammed Marwa , Alhemmali Ghofran , Fayad Samah 
Published: July 2023

Background University-based research is critical for primary care, particularly in low- and middle-income countries like Libya. The current study was aimed at exploring the research productivity and potential barriers among academic medical staff at the University of Tripoli, Libya.Methods A cross-sectional questionnaire-based study was done at the University of Tripoli for the period from November 2022 to March 2023 to determine health research barriers among staff members in different medical faculties. Data collected included participant's demographics, years of experience as a faculty member, workplace, academic status, highest educational qualification, education type, and number of research studies published. Data also contained questions around personal, access, administrative, and resource barriers to and facilitators of research activity.Results A total of 132 questionnaires were distributed by the authors, of which only 102 were successfully answered, giving a response rate of 76%. The majority of participants 49 (48.04%) conducted a cross-sectional study, followed by 34 (33.3%) who carried out a review study. The most important reason of doing research was to improve knowledge of the field (62.75%), while 77.47% stated that they made use of and were comfortable using advanced technology in their research activities. The top barriers to research were a lack of financial support (76 [74.51%]), followed by the complex publication process (43 [42.16%]). Lack of writing skills (4 [3.92%]) was the bottom perceived barrier.Conclusion Faculty members at the University of Tripoli face various barriers that can impede their productivity in medical research, such as a lack of resources, and limited research opportunities. These factors, combined with a lack of support from administrators, can lead to low morale and a lack of motivation among faculty members, which can further inhibit their research productivity.