bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Virtual Reality-Delivered Biofeedback and Yoga on Pediatric Headaches: A Pilot Study
Authors: Stassart Céline , Dupuis Gilles , Bouchard Stéphane 
Published: April 2024

Objectives: This study assessed the feasibility and acceptability of two types of innovative approaches, namely biofeedback-assisted relaxation in virtual reality ([VR]-delivered biofeedback) and yoga in the management of pediatric headaches. The secondary aim was to evaluate the preliminary efficacy of both interventions. Method: Children were randomized to three conditions: waiting list, yoga, and VR-delivered biofeedback. Feasibility was assessed by applicability to the pain problem, and acceptability by attendance (missed sessions, dropout rate) and the use of learned strategies in everyday life. Preliminary efficacy was evaluated with questionnaires: frequency of headaches, functional disabilities, pain anxiety, and pain catastrophizing. Mean scale scores postintervention and two months afterward were compared with the baseline with repeated-measures analyses of variance and contrast analyses. Results: A total of 46 children were enrolled; 39 completed the questionnaires at the baseline and participated in interventions. Regarding feasibility, the safety of the interventions seems demonstrated by the absence or infrequency of headaches during sessions. Regarding acceptability, compliance with the sessions was excellent for VR-delivered biofeedback condition and satisfactory for yoga. Most of the children reported using the strategies learned in daily life, even after the interventions. Regarding efficacy, participants reported significantly fewer headaches and functional disabilities postintervention and 2 months later. Minimal or no effects were observed on pain anxiety and pain catastrophizing. Conclusion: This pilot study indicates that VR-delivered biofeedback and yoga exercises may be feasible and acceptable interventions for the treatment of pediatric headaches. Implications for Impact Statement This study evaluates the feasibility and preliminary efficacy of two innovative interventions for pediatric headaches: virtual reality-delivered biofeedback and yoga exercises. The findings indicate that these interventions are feasible and applicable (good attendance, limited or no discomfort, and positive evaluation) and show preliminary efficacy (improvements in frequency of headaches and functional disabilities).
Exploring inheritance, and clinical penetrance of distal Xq28 duplication syndrome: insights from 47 new unpublished cases
Authors: Levy Michal , Elron Eyal , Shohat Mordechai , Lifshitz Shira , Kahana Sarit , Shani Hagit , Grossman Anat , Amar Shirly , Narkis Ginat , Sagi-Dain Lena , Basel-Salmon Lina , Maya Idit 
Published: April 2024

Abstract
Background
Distal Xq28 duplication, or int22h1/int22h2-mediated Xq28 duplication syndrome, leads to cognitive impairment, neurobehavioral issues, and facial dysmorphisms. Existing literature has limited information on clinical traits and penetrance.

Methods
We identified cases of distal Xq28 duplication (chrX: 154,126,575–154,709,680, GRCh37/hg19) through a review of clinical records and microarray reports from five centers, encompassing both postnatal and prenatal cases, with no prior family knowledge of the duplication.

Results
Our search found 47 cases across 26 families, with duplications ranging from 208 to 935 Kb. In total, 8 out of 26 index cases featured a 200–300 kb partial duplication, mainly from Armenian/Caucasian Jewish backgrounds. Most prenatal cases showed no major fetal ultrasound malformations. Of cases with known inheritance mode (15 out of 26), maternal inheritance was more common (80%). The study identified seven male carriers of the duplication from six unrelated families, indicating partial penetrance in males.

Conclusion
Our study provides key insights into distal Xq28 duplication. Most prenatal tests showed no major fetal ultrasound issues. Maternal inheritance was common, with unaffected mothers. In the postnatal group, a balanced gender distribution was observed. Among male family members, two fathers had ADHD, one was healthy, and one brother had mild symptoms, indicating partial penetrance in males.
Improving the power of drug toxicity measurements by quantitative nuclei imaging
Authors: Mikheeva Alesya M. , Bogomolov Mikhail A. , Gasca Valentina A. , Sementsov Mikhail V. , Spirin Pavel V. , Prassolov Vladimir S. , Lebedev Timofey D. 
Published: April 2024

AbstractImaging-based anticancer drug screens are becoming more prevalent due to development of automated fluorescent microscopes and imaging stations, as well as rapid advancements in image processing software. Automated cell imaging provides many benefits such as their ability to provide high-content data, modularity, dynamics recording and the fact that imaging is the most direct way to access cell viability and cell proliferation. However, currently most publicly available large-scale anticancer drugs screens, such as GDSC, CTRP and NCI-60, provide cell viability data measured by assays based on colorimetric or luminometric measurements of NADH or ATP levels. Although such datasets provide valuable data, it is unclear how well drug toxicity measurements can be integrated with imaging data. Here we explored the relations between drug toxicity data obtained by XTT assay, two quantitative nuclei imaging methods and trypan blue dye exclusion assay using a set of four cancer cell lines with different morphologies and 30 drugs with different mechanisms of action. We show that imaging-based approaches provide high accuracy and the differences between results obtained by different methods highly depend on drug mechanism of action. Selecting AUC metrics over IC50 or comparing data where significantly drugs reduced cell numbers noticeably improves consistency between methods. Using automated cell segmentation protocols we analyzed mitochondria activity in more than 11 thousand drug-treated cells and showed that XTT assay produces unreliable data for CDK4/6, Aurora A, VEGFR and PARP inhibitors due induced cell size growth and increase in individual mitochondria activity. We also explored several benefits of image-based analysis such as ability to monitor cell number dynamics, dissect changes in total and individual mitochondria activity from cell proliferation, and ability to identify chromatin remodeling drugs. Finally, we provide a web tool that allows comparing results obtained by different methods.
Inequality in economic shock exposures across the global firm-level supply network
Authors: Chakraborty Abhijit , Reisch Tobias , Diem Christian , Astudillo-Estévez Pablo , Thurner Stefan 
Published: April 2024

AbstractFor centuries, national economies have been engaging in international trade and production. The resulting international supply networks not only increase wealth for countries, but also allow for economic shocks to propagate across borders. Using global, firm-level supply network data, we estimate a country’s exposure to direct and indirect economic losses caused by the failure of a company in another country. We show the network of international systemic risk-flows. We find that rich countries expose poor countries stronger to systemic risk than vice-versa. The risk is highly concentrated, however, higher risk levels are not compensated with a risk premium in GDP levels, nor higher GDP growth. Our findings put the often praised benefits for developing countries from globalized production in a new light, by relating them to risks involved in the production processes. Exposure risks present a new dimension of global inequality that most affects the poor in supply shock crises.
Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering
Authors: Isaac Alisa H. , Recalde Phillips Sarea Y. , Ruben Elizabeth , Estes Matthew , Rajavel Varsha , Baig Talia , Paleti Carol , Landsgaard Kirsten , Lee Ryang Hwa , Guda Teja , Criscitiello Michael F. , Gregory Carl , Alge Daniel L. 
Published: April 2024

AbstractWhile poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.
Rapid evolutionary change in trait correlations of single proteins
Authors: Dasmeh Pouria , Zheng Jia , Erdoğan Ayşe Nisan , Tokuriki Nobuhiko , Wagner Andreas 
Published: April 2024

AbstractMany organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability – the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study two evolvable systems, a yellow fluorescent protein and the antibiotic resistance protein VIM-2 metallo beta-lactamase. We consider two traits in the fluorescent protein, namely the ability to emit yellow and green light, and three traits in our enzyme, namely the resistance against ampicillin, cefotaxime, and meropenem. We show that correlations between these traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein’s ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.
Late-stage meta-C–H alkylation of pharmaceuticals to modulate biological properties and expedite molecular optimisation in a single step
Authors: Guillemard Lucas , Ackermann Lutz , Johansson Magnus J. 
Published: April 2024

AbstractCatalysed C–H activation has emerged as a transformative platform for molecular synthesis and provides new opportunities in drug discovery by late-stage functionalisation (LSF) of complex molecules. Notably, small aliphatic motifs have gained significant interest in medicinal chemistry for their beneficial properties and applications as sp3-rich functional group bioisosteres. In this context, we disclose a versatile strategy with broad applicability for the ruthenium-catalysed late-stage meta-C(sp2)–H alkylation of pharmaceuticals. This general protocol leverages numerous directing groups inherently part of bioactive scaffolds to selectivity install a variety of medicinally relevant bifunctional alkyl units within drug compounds. Our strategy enables the direct modification of unprotected lead structures to quickly generate an array of pharmaceutically useful analogues without resorting to de novo syntheses. Moreover, productive late-stage modulation of key biological characteristics of drug candidates upon remote C–H alkylation proves viable, highlighting the major benefits of our approach to offer in drug development programmes.
Extrinsic hydrophobicity-controlled silver nanoparticles as efficient and stable catalysts for CO2 electrolysis
Authors: Ko Young-Jin , Lim Chulwan , Jin Junyoung , Kim Min Gyu , Lee Ji Yeong , Seong Tae-Yeon , Lee Kwan-Young , Min Byoung Koun , Choi Jae-Young , Noh Taegeun , Hwang Gyu Weon , Lee Woong Hee , Oh Hyung-Suk 
Published: April 2024

AbstractTo realize economically feasible electrochemical CO2 conversion, achieving a high partial current density for value-added products is particularly vital. However, acceleration of the hydrogen evolution reaction due to cathode flooding in a high-current-density region makes this challenging. Herein, we find that partially ligand-derived Ag nanoparticles (Ag-NPs) could prevent electrolyte flooding while maintaining catalytic activity for CO2 electroreduction. This results in a high Faradaic efficiency for CO (>90%) and high partial current density (298.39 mA cm‒2), even under harsh stability test conditions (3.4 V). The suppressed splitting/detachment of Ag particles, due to the lipid ligand, enhance the uniform hydrophobicity retention of the Ag-NP electrode at high cathodic overpotentials and prevent flooding and current fluctuations. The mass transfer of gaseous CO2 is maintained in the catalytic region of several hundred nanometers, with the smooth formation of a triple phase boundary, which facilitate the occurrence of CO2RR instead of HER. We analyze catalyst degradation and cathode flooding during CO2 electrolysis through identical-location transmission electron microscopy and operando synchrotron-based X-ray computed tomography. This study develops an efficient strategy for designing active and durable electrocatalysts for CO2 electrolysis.
Sustained increase in suspended sediments near global river deltas over the past two decades
Authors: Hou Xuejiao , Xie Danghan , Feng Lian , Shen Fang , Nienhuis Jaap H. 
Published: April 2024

AbstractRiver sediments play a critical role in sustaining deltaic wetlands. Therefore, concerns are raised about wetlands’ fate due to the decline of river sediment supply to many deltas. However, the dynamics and drivers of suspended sediment near deltaic coasts are not comprehensively assessed, and its response to river sediment supply changes remains unclear. Here we examine patterns of coastal suspended sediment concentration (SSC) and river sediment plume area (RPA) for 349 deltas worldwide using satellite images from 2000 to 2020. We find a global increase in SSC and RPA, averaging +0.46% and +0.48% yr−1, respectively, with over 59.0% of deltas exhibiting an increase in both SSC and RPA. SSC and RPA increases are prevalent across all continents, except for Asia. The relationship between river sediment supply and coastal SSCs varies between deltas, with as much as 45.2% of the deltas showing opposing trends between river sediments and coastal SSCs. This is likely because of the impacts of tides, waves, salinity, and delta morphology. Our observed increase in SSCs near river delta paints a rare promising picture for wetland resilience against sea-level rise, yet whether this increase will persist remains uncertain.
Modulation of peroxisomal import by the PEX13 SH3 domain and a proximal FxxxF binding motif
Authors: Gaussmann Stefan , Peschel Rebecca , Ott Julia , Zak Krzysztof M. , Sastre Judit , Delhommel Florent , Popowicz Grzegorz M. , Boekhoven Job , Schliebs Wolfgang , Erdmann Ralf , Sattler Michael 
Published: April 2024

AbstractImport of proteins into peroxisomes depends on PEX5, PEX13 and PEX14. By combining biochemical methods and structural biology, we show that the C-terminal SH3 domain of PEX13 mediates intramolecular interactions with a proximal FxxxF motif. The SH3 domain also binds WxxxF peptide motifs in the import receptor PEX5, demonstrating evolutionary conservation of such interactions from yeast to human. Strikingly, intramolecular interaction of the PEX13 FxxxF motif regulates binding of PEX5 WxxxF/Y motifs to the PEX13 SH3 domain. Crystal structures reveal how FxxxF and WxxxF/Y motifs are recognized by a non-canonical surface on the SH3 domain. The PEX13 FxxxF motif also mediates binding to PEX14. Surprisingly, the potential PxxP binding surface of the SH3 domain does not recognize PEX14 PxxP motifs, distinct from its yeast ortholog. Our data show that the dynamic network of PEX13 interactions with PEX5 and PEX14, mediated by diaromatic peptide motifs, modulates peroxisomal matrix import.
An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission
Authors: Ding Jiarui , Garber John J. , Uchida Amiko , Lefkovith Ariel , Carter Grace T. , Vimalathas Praveen , Canha Lauren , Dougan Michael , Staller Kyle , Yarze Joseph , Delorey Toni M. , Rozenblatt-Rosen Orit , Ashenberg Orr , Graham Daniel B. , Deguine Jacques , Regev Aviv , Xavier Ramnik J. 
Published: April 2024

AbstractCoordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand–receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.
Detecting m6A at single-molecular resolution via direct RNA sequencing and realistic training data
Authors: Chan Adrian , Naarmann-de Vries Isabel S. , Scheitl Carolin P. M. , Höbartner Claudia , Dieterich Christoph 
Published: April 2024

AbstractDirect RNA sequencing offers the possibility to simultaneously identify canonical bases and epi-transcriptomic modifications in each single RNA molecule. Thus far, the development of computational methods has been hampered by the lack of biologically realistic training data that carries modification labels at molecular resolution. Here, we report on the synthesis of such samples and the development of a bespoke algorithm, mAFiA (m6A Finding Algorithm), that accurately detects single m6A nucleotides in both synthetic RNAs and natural mRNA on single read level. Our approach uncovers distinct modification patterns in single molecules that would appear identical at the ensemble level. Compared to existing methods, mAFiA also demonstrates improved accuracy in measuring site-level m6A stoichiometry in biological samples.
The genetic landscape of a metabolic interaction
Authors: Nguyen Thuy N. , Ingle Christine , Thompson Samuel , Reynolds Kimberly A. 
Published: April 2024

AbstractWhile much prior work has explored the constraints on protein sequence and evolution induced by physical protein-protein interactions, the sequence-level constraints emerging from non-binding functional interactions in metabolism remain unclear. To quantify how variation in the activity of one enzyme constrains the biochemical parameters and sequence of another, we focus on dihydrofolate reductase (DHFR) and thymidylate synthase (TYMS), a pair of enzymes catalyzing consecutive reactions in folate metabolism. We use deep mutational scanning to quantify the growth rate effect of 2696 DHFR single mutations in 3 TYMS backgrounds under conditions selected to emphasize biochemical epistasis. Our data are well-described by a relatively simple enzyme velocity to growth rate model that quantifies how metabolic context tunes enzyme mutational tolerance. Together our results reveal the structural distribution of epistasis in a metabolic enzyme and establish a foundation for the design of multi-enzyme systems.
Consistent survival in consecutive cases of life-supporting porcine kidney xenotransplantation using 10GE source pigs
Authors: Eisenson Daniel , Hisadome Yu , Santillan Michelle , Iwase Hayato , Chen WeiLi , Shimizu Akira , Schulick Alex , Gu Du , Akbar Armaan , Zhou Alice , Koenig Kristy , Kuravi Kasinath , Rahman Farzana , Sorrells Lori , Burdorf Lars , DeSmet Kristina , Warren Daniel , Peterson Leigh , Lorber Marc , Ayares David , Cameron Andrew , Yamada Kazuhiko 
Published: April 2024

AbstractXenotransplantation represents a possible solution to the organ shortage crisis and is an imminent clinical reality with long-term xenograft survival in pig-to-nonhuman primate (NHP) heart and kidney large animal models, and short-term success in recent human decedent and clinical studies. However, concerns remain about safe clinical translation of these results, given the inconsistency in published survival as well as key differences between preclinical procurement and immunosuppression and clinical standards-of-care. Notably, no studies of solid organ pig-to-NHP transplantation have achieved xenograft survival longer than one month without CD40/CD154 costimulatory blockade, which is not currently an FDA-approved immunosuppression strategy. We now present consistent survival in consecutive cases of pig-to-NHP kidney xenotransplantation, including long-term survival after >3 hours of xenograft cold preservation time as well as long-term survival using FDA-approved immunosuppression. These data provide critical supporting evidence for the safety and feasibility of clinical kidney xenotransplantation. Moreover, long-term survival without CD40/CD154 costimulatory blockade may provide important insights for immunosuppression regimens to be considered for first-in-human clinical trials.
Towards establishing a fungal economics spectrum in soil saprobic fungi
Authors: Camenzind Tessa , Aguilar-Trigueros Carlos A. , Hempel Stefan , Lehmann Anika , Bielcik Milos , Andrade-Linares Diana R. , Bergmann Joana , dela Cruz Jeane , Gawronski Jessie , Golubeva Polina , Haslwimmer Heike , Lartey Linda , Leifheit Eva , Maaß Stefanie , Marhan Sven , Pinek Liliana , Powell Jeff R. , Roy Julien , Veresoglou Stavros D. , Wang Dongwei , Wulf Anja , Zheng Weishuang , Rillig Matthias C. 
Published: April 2024

AbstractTrait-based frameworks are promising tools to understand the functional consequences of community shifts in response to environmental change. The applicability of these tools to soil microbes is limited by a lack of functional trait data and a focus on categorical traits. To address this gap for an important group of soil microorganisms, we identify trade-offs underlying a fungal economics spectrum based on a large trait collection in 28 saprobic fungal isolates, derived from a common grassland soil and grown in culture plates. In this dataset, ecologically relevant trait variation is best captured by a three-dimensional fungal economics space. The primary explanatory axis represents a dense-fast continuum, resembling dominant life-history trade-offs in other taxa. A second significant axis reflects mycelial flexibility, and a third one carbon acquisition traits. All three axes correlate with traits involved in soil carbon cycling. Since stress tolerance and fundamental niche gradients are primarily related to the dense-fast continuum, traits of the 2nd (carbon-use efficiency) and especially the 3rd (decomposition) orthogonal axes are independent of tested environmental stressors. These findings suggest a fungal economics space which can now be tested at broader scales.