bluuebunny/crossref_metadata_2025_split huggingface dataset:
Smart sealants for prevention and monitoring of gastrointestinal anastomotic leaks using portable smartphone-controlled ultrasound transducers
Authors: Anthis Alexandre H.C. , Abundo Maria Paulene , Neuer Anna L. , Tsolaki Elena , Rosendorf Jachym , Rduch Thomas , Starsich Fabian H.L. , Liska Vaclav , Schlegel Andrea A. , Shapiro Mikhail G. , Herrmann Inge K. 
Published: January 2022

ABSTRACTMillions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of the cases. Penetration of digestive fluids into the peritoneal cavity may lead to dreadful complications, including sepsis and premature death. Modern suture supports and tissue adhesives only insufficiently address the issue. Due to the scarcity of alternatives, surgeons rely on monitoring surrogate markers and clinical symptoms, which oftentimes lack sensitivity and specificity, hence only offering late-stage detection of already fully developed leaks.Here, a first-of-its-kind, modular, intelligent suture support patch capable of sealing and monitoring leaks under harsh gastrointestinal conditions is presented. The smart adhesive layered hydrogel patch provides, in addition to unprecedented tissue sealing under most demanding conditions, unique leak-detection capabilities based on pH and/or enzyme-responsive sensing elements, which can be read out by non-invasive point-of-need ultrasound imaging. Reliable detection of the breaching of sutures in as little as 3 hours in intestinal leak and 15 minutes in gastric leak conditions, and before an actual leak develops, is demonstrated. This technology paves the way for next-generation suture support materials that offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.SummaryElectronic-free smart surgical hydrogel sealants leveraging tissue-penetrating polymer networks and trigger-responsive echogenic entities to enable point-of-need monitoring and early anastomotic leak detection using a hand-held ultrasound transducer and a smartphone.
A cellular hierarchy framework for understanding heterogeneity and predicting drug response in AML
Authors: Zeng Andy G.X. , Bansal Suraj , Jin Liqing , Mitchell Amanda , Chen Weihsu Claire , Abbas Hussein A. , Chan-Seng-Yue Michelle , Voisin Veronique , van Galen Peter , Tierens Anne , Cheok Meyling , Preudhomme Claude , Dombret Hervé , Daver Naval , Futreal P Andrew , Minden Mark D. , Kennedy James A. , Wang Jean C.Y. , Dick John E. 
Published: January 2022

AbstractThe treatment landscape of AML is evolving with promising therapies entering clinical translation, yet patient responses remain heterogeneous and biomarkers for tailoring treatment are lacking. To understand how disease heterogeneity links with therapy response, we determined the leukemia cell hierarchy make-up from bulk transcriptomes of over 1000 patients through deconvolution using single-cell reference profiles of leukemia stem, progenitor, and mature cell types. Leukemia hierarchy composition was associated with functional, genomic, and clinical properties and converged into four overall classes, spanning Primitive, Mature, GMP, and Intermediate. Critically, variation in hierarchy composition along the Primitive vs GMP or Primitive vs Mature axes were associated with response to chemotherapy or drug sensitivity profiles of targeted therapies, respectively. A 7-gene biomarker derived from the Primitive vs Mature axis was predictive of patient response to 105 investigational drugs. Thus, hierarchy composition constitutes a novel framework for understanding disease biology and advancing precision medicine in AML.
Establishment and characterization of novel autologous pair primary cultures from two Indian non-habitual tongue carcinoma patients
Authors: Dwivedi Nehanjali , Charitha G , Pillai Vijay , Kuriakose Moni A , Suresh Amritha , Das Manjula 
Published: January 2022

AbstractOral tongue squamous cell carcinoma (OTSCC) is one of the major causes of fatality in India owing to very high percentages of patients with smoking and chewing habits. Being highly heterogeneous in nature, every patient poses a different challenge clinically. To better understand disease progression, knowledge of cross talk between tumor stroma and the tumor cells becomes indispensable. Patient-derived in vitro cell line models are helpful to understand the complexity of diseases. However, they have very low efficiency of establishment from the tumor samples, especially the cancer associated fibroblasts (CAFs). In the present study, two novel autologous pairs have been immortalized spontaneously from non-habitual, HPV-positive patients, presented with tongue squamous cell carcinoma. The epithelial and fibroblast primary lines had typical polygonal and spindle shaped morphology, respectively. Positive staining with Pan-cytokeratin (PanCK) and Fibroblast Specific Protein (FSP-1) further confirmed their epithelial and fibroblast origin. Unique Short Tandem Repeat (STR) profile of the cultures confirmed their novelty, while the similarity of the STR profiles between the epithelial and fibroblast cells from the same patient, confirmed their autologous nature. DNA analysis revealed aneuploidy of the established cultures. Increase in the tumorigenic potential of the established epithelial cultures upon treatment with CAF-conditioned medium proved the “CAF-ness” of the established fibroblast cells. The established cultures are the first of their kind which would serve as an useful platform in understanding the cross talk between tumor-stroma and tumor, along with studying tongue cancer progression.
Needler: An Algorithm to Develop a Comprehensive Targeted MS Method Capable of Monitoring the Human Proteome
Authors: Ready Damien B. , Potts Gregory K. 
Published: January 2022

AbstractTargeted proteomics for addressing biological hypotheses through quantitative mass spectrometry (MS) is increasingly popular because of its ability to deliver sensitive and reproducible results to inform protein concentration and dynamics. While the technique is powerful, the associated tooling to develop unique targeted data acquisition methods per experiment is limited, often focused on producing a minimally viable analytical approach for a limited set of analytes, rather than one which can maximally quantitate all targets of interest. We developed the Needler algorithm to produce comprehensive targeted MS methods capable of quantitating the maximum number of proteins given available instrument constraints. Using this algorithm, we demonstrate that the minimum instrument parameters required to produced targeted MS quantitation of all tryptic peptides from the human proteome are well in excess of current capabilities. Given these constraints, we provide a visualized scope of the boundaries for practical MS monitoring to maximize proteome and subproteome coverage dependent upon instrument duty cycle capabilities.
A computational method for predicting the most likely evolutionary trajectories in the step-wise accumulation of resistance mutations
Authors: Eccleston R. Charlotte , Manko Emilia , Campino Susana , Clark Taane G. , Furnham Nicholas 
Published: January 2022

AbstractPathogen evolution of drug resistance often occurs in a stepwise manner via the accumulation of multiple mutations that in combination have a non-additive impact on fitness, a phenomenon known as epistasis. The evolution of resistance via the accumulation of point mutations in the DHFR genes ofPlasmodium falciparum(Pf) andPlasmodium vivax(Pv) has been studied extensively and multiple studies have shown epistatic interactions between these mutations determine the accessible evolutionary trajectories to highly resistant multiple mutations. Here, we simulated these evolutionary trajectories using a model of molecular evolution, parameterized using Rosetta Flex ddG predictions, where selection acts to reduce the target-drug binding affinity. We observe strong agreement with pathways determined using experimentally measured IC50 values of pyrimethamine binding, which suggests binding affinity is strongly predictive of resistance and epistasis in binding affinity strongly influences the order of fixation of resistance mutations. We also infer pathways directly from the frequency of mutations found in isolate data, and observe remarkable agreement with the most likely pathways predicted by our mechanistic model, as well as those determined experimentally. This suggests mutation frequency data can be used to intuitively infer evolutionary pathways, provided sufficient sampling of the population.
PIMT suppresses endothelial activation and vascular inflammation through methylation of TRAF6
Authors: Zhang Chen , Guo Zhi-Fu , Yi Bing , Kazama Kyosuke , Liu Wennan , Sun Xiaobo , Wang Lu , Yang Xiao-Feng , Summer Ross , Sun Jianxin 
Published: January 2022

AbstractAs a repair enzyme, protein L-isoaspartyl O-methyltransferase (PIMT) methylates and converts isoaspartyl residues (isoAsp) back to conventional forms to avoid protein damage during aging and stress responses. This study aims to investigate the pathological significance of PIMT in vascular inflammation. Herein, we show that PIMT is highly expressed in lung endothelial cells (ECs), and its reduction significantly exacerbates pulmonary inflammation in a murine model of acute lung injury (ALI). Mechanistically, we identify tumor necrosis factor receptor-associated factor 6 (TRAF6) as a substrate of PIMT. PIMT-mediated methylation of TRAF6 inhibits TRAF6 oligomerization, autoubiquitination, and LPS-induced NF-κB transactivation in ECs. Importantly, in addition to transcriptionally attenuating expression of adhesion molecules, PIMT post-translationally impedes site specific N-glycosylation of intercellular adhesion molecule-1 (ICAM-1), which leads to an increased protein degradation of ICAM-1 and a subsequent inhibition of EC interaction with immune cells during inflammatory process. Our results for the first time identify PIMT-mediated protein O-methylation as a key post-translational mechanism in controlling vascular inflammation, and suggest that PIMT may represent a novel therapeutic target in inflammatory vascular diseases.
Despite the odds: formation of the SARS-CoV-2 methylation complex
Authors: Matsuda Alex , Plewka Jacek , Chykunova Yuliya , Jones Alisha N. , Pachota Magdalena , Rawski Michał , Mourão André , Karim Abdulkarim , Kresik Leanid , Lis Kinga , Minia Igor , Hartman Kinga , Sonani Ravi , Dubin Grzegorz , Sattler Michael , Suder Piotr , Mak Paweł , Popowicz Grzegorz M. , Pyrć Krzysztof , Czarna Anna 
Published: January 2022

AbstractCoronaviruses protect their single-stranded RNA genome with a methylated cap during replication. The capping process is initiated by several nonstructural proteins (nsp) encoded in the viral genome. The methylation is performed by two methyltransferases, nsp14 and nsp16 where nsp10 acts as a co-factor to both. Aditionally, nsp14 carries an exonuclease domain, which operates in the proofreading system during RNA replication of the viral genome. Both nsp14 and nsp16 were reported to independently bind nsp10, but the available structural information suggests that the concomitant interaction between these three proteins should be impossible due to steric clashes. Here, we show that nsp14, nsp10, and nsp16 can form a heterotrimer complex. This interaction is expected to encourage formation of mature capped viral mRNA, modulating the nsp14’s exonuclease activity, and protecting the viral RNA. Our findings show that nsp14 is amenable to allosteric regulation and may serve as a novel target for therapeutic approaches.
Binocular visual experience and sleep promote visual cortex plasticity and restore binocular vision in a mouse model of amblyopia
Authors: Martinez Jessy D. , Donnelly Marcus J. , Popke Donald S. , Torres Daniel , Wilson Lydia G. , Brancaleone William P. , Clawson Brittany C. , Jiang Sha , Aton Sara J. 
Published: January 2022

AbstractAmblyopia arises from an altered balance of input from the two eyes to the binocular zone of primary visual cortex (bV1) during childhood, causing long-lasting visual impairment. Amblyopia is commonly treated by patching the dominant eye, however, the relative impacts of monocular vs. binocular visual experiences on restoration of bV1 function remains unclear. Moreover, while sleep has been implicated in V1 plasticity in response to vision loss, its role in recovery from amblyopia is unknown. We used monocular deprivation (MD) in juvenile mice to model amblyopia in bV1. We compared recovery of visual responses for the two eyes among bV1 regular spiking (RS, putative principal) neurons and fast-spiking (FS, putative parvalbumin-expressing [PV+]) interneurons after identical-duration, identical-quality binocular recovery (BR) or monocular, reverse occlusion (RO) experiences. We find that BR is quantitatively superior to RO with respect to renormalizing both bV1 populations’ visual responses. However, this recovery was seen only in freely-sleeping mice; post-BR sleep deprivation prevented functional recovery. Thus, both binocular visual experience and subsequent sleep are required to optimally renormalize bV1 responses in a mouse model of amblyopia.
The SARS-CoV-2 protein NSP2 impairs the microRNA-induced silencing capacity of human cells
Authors: Zou Limei , Moch Clara , Graille Marc , Chapat Clément 
Published: January 2022

AbstractThe coronavirus SARS-CoV-2 is the cause of the ongoing pandemic of COVID-19. Given the absence of effective treatments against SARS-CoV-2, there is an urgent need for a molecular understanding of how the virus influences the machineries of the host cell. The SARS-CoV-2 generates 16 Non-Structural Proteins (NSPs) through proteolytic cleavage of a large precursor protein. In the present study, we focused our attention on the SARS-CoV-2 protein NSP2, whose role in the viral pathogenicity is poorly understood. Recent proteomic studies shed light on the capacity of NSP2 to bind the 4EHP-GIGYF2 complex, a key factor involved in microRNA-mediated silencing of gene expression in human cells. In order to gain a better understanding of the function of NSP2, we attempted to identify the molecular basis of its interaction with 4EHP-GIGYF2. Our data demonstrate that NSP2 physically associates with the endogenous 4EHP-GIGYF2 complex in the cytoplasm. Using co-immunoprecipitation and in vitro interaction assays, we identified both 4EHP and a central segment in GIGYF2 as binding sites for NSP2. We also provide functional evidence that NSP2 impairs the function of GIGYF2 in mediating mRNA silencing using reporter-based assays, thus leading to a reduced activity of microRNAs. Altogether, these data reveal the profound impact of NSP2 on the post-transcriptional silencing of gene expression in human cells, pointing out 4EHP-GIGYF2 targeting as a possible strategy of SARS-CoV-2 to take over the silencing machinery and to suppress host defenses.
Wearable technology for health monitoring during pregnancy: an observational cross-sectional survey study
Authors: Wakefield Colin , Yao Lena , Self Steve , Frasch Martin G. 
Published: January 2022

AbstractObjectiveTelemedicine has advanced to the forefront of healthcare delivery, including maternal-fetal medicine. Smart wearable electrocardiogram (ECG) devices can enable pregnant women to monitor their health and that of their fetuses. Such technology would be a logical extension of the telemedicine ecosystem. However, it is not known how pregnant women perceive the ability to use such technologies.DesignObservational cross-sectional study.SettingOnline survey in the United States in 2019.PopulationA representative sample of 507 women aged 18-45 were polled from 45 states.MethodsStudy participants were recruited using the SurveyMonkey Audience Polling system and responded virtually.Main Outcome MeasuresWomen were asked to identify willingness to use a wearable ECG device the size of a patch-sized large band-aid on their abdomen. Ten binary or multiple-choice questions were used to gauge population interest and related demographics towards the usage of a wearable ECG device.Results91% of women expecting to become pregnant in the next five years accept wearable ECG technology as a mechanism for increased frequency of monitoring of maternal and fetal health throughout the pregnancy outside the hospital. 78% of women demonstrated a willingness to wear devices day and night or at least during sleep and 42% of women would spend up to $200 on such a device.ConclusionsEven though conducted prior to the COVID-19 pandemic, this study clearly indicates a high degree of readiness of prospective pregnant women for telemedicine with continuous health monitoring of the mother-fetus dyad during the entire antepartum period.Fundingn/a
The small GTPase Arf1 regulates ATP synthesis and mitochondria homeostasis by modulating fatty acid metabolism
Authors: Enkler Ludovic , Pennauer Mirjam , Szentgyörgyi Viktoria , Prescianotto-Baschong Cristina , Riezman Isabelle , Wiesyk Aneta , Kucharczyk Roza , Spiess Martin , Riezman Howard , Spang Anne 
Published: January 2022

AbstractLipid mobilization through fatty acid β-oxidation is a central process essential for energy production during nutrient shortage. In yeast, this catabolic process starts in the peroxisome from where β-oxidation products enter mitochondria and fuel the TCA cycle. Little is known about the physical and metabolic cooperation between these organelles. We found that expression of fatty acid transporters and of the rate-limiting enzyme involved in β-oxidation are decreased in cells expressing a hyperactive mutant of the small GTPase Arf1, leading to an accumulation of fatty acids in lipid droplets. As a consequence, mitochondria became fragmented and ATP synthesis decreased. Genetic and pharmacological depletion of fatty acids phenocopied the arf1 mutant mitochondrial phenotype. Although β-oxidation occurs mainly in mitochondria in mammals, Arf1’s role in fatty acid metabolism is conserved. Together, our results indicate that Arf1 integrates metabolism into energy production by regulating fatty acid storage and utilization, and presumably organelle contact-sites.
Humans recognize affective cues in primate vocalizations: Acoustic and phylogenetic perspectives
Authors: Debracque C. , Clay Z. , Grandjean D. , Gruber T. 
Published: January 2022

AbstractHumans are adept in extracting affective information from the vocalisations of not only humans but also other animals. Current research has mainly focused on phylogenetic proximity to explain such cross-species emotion recognition abilities. However, because research protocols are inconsistent across studies, it remains unclear whether human recognition of vocal affective cues of other species is due to cross-taxa similarities between acoustic parameters, the phylogenetic distances between species, or a combination of both. To address this, we first analysed acoustic variation in 96 affective vocalizations, including agonistic and affiliative contexts, of humans and three other primate species – rhesus macaques, chimpanzees and bonobos – the latter two being equally phylogenetically distant from humans. Using Mahalanobis distances, we found that chimpanzee vocalizations were acoustically closer to those of humans than to those of bonobos, confirming a potential derived vocal evolution in the bonobo lineage. Second, we investigated whether 68 human participants recognized the affective basis of vocalisations through tasks by asking them to categorize (‘A vs B’) or discriminate (‘A vs non-A’) vocalisations based on their affective content. Results showed that participants could reliably categorize and discriminate most of the affective vocal cues expressed by other primates, except threat calls by bonobos and macaques. Overall, participants showed greatest accuracy in detecting chimpanzee vocalizations; but not bonobo vocalizations, which provides support for both the phylogenetic proximity and acoustic similarity hypotheses. Our results highlight for the first time the importance of both phylogenetic and acoustic parameter level explanations in cross-species affective perception, drawing a more complex picture to explain our natural understanding of animal signals.
In situ tomographic study of a 3D-woven SiC/SiC composite part subjected to severe thermo-mechanical loads
Authors: Turpin Léonard , Roux Stéphane , Caty Olivier , King Andrew , Denneulin Sébastien , Martin Éric 
Published: January 2022

A high-temperature multi-axial test is carried out to characterize the thermo-mechanical behaviour of a 3D-woven SiC/SiC composite aeronautical part under loads representative of operating conditions. The sample is L-shaped and cut out from the part. It is subjected to severe thermal gradients and a superimposed mechanical load that progressively increases up to the first damage. The sample shape and its associated microstructure, the heterogeneity of the stress field and the limited accessibility to regions susceptible to damage require non-contact imaging modalities. An in situ experiment, conducted with a dedicated testing machine at the SOLEIL synchrotron facility, provides the sample microstructure from computed micro-tomographic imaging and thermal loads from infrared thermography. Experimental constraints lead to non-ideal acquisition conditions for both measurement modalities. This article details the procedure of correcting artefacts to use the volumes for quantitative exploitation (i.e. full-field measurement, model validation and identification). After proper processing, despite its complexity, the in situ experiment provides high-quality data about a part under realistic operating conditions. The influence of the mesostructure on fracture phenomena can be inferred from the tomography in the damaged state. Experiments show that the localization of damage initiation is driven by the geometry, while the woven structure moderates the crack propagation. This study widens the scope of in situ thermo-mechanical experiments to more complex loading states, closer to in-service conditions.
The influence of the onboard servicescape on cruisers’ experiential state, delight and memorability
Authors: Sorrentino Annarita , Ferretti Marco , Risitano Marcello , Del Chiappa Giacomo , Okumus Fevzi 
Published: January 2022

Purpose
This study aims to examine the effects of the servicescape on experiential state, delight and memorability in the context of the cruise experience. This study also analyzes the moderating effects of sociodemographic characteristics (income and place of residency) and prior travel experience.

Design/methodology/approach
Drawing on the Stimulus-Organism-Response theory, structural equation modeling via partial least squares path modeling was applied to a sample of 415 cruisers. A multi-group analysis was used to test the moderating effects.

Findings
Study results confirm the predictive role of the servicescape in creating experience, delight and memorability, with a place of residence, past travel experience and income exerting moderating effects on the aforementioned relationships.

Practical implications
The results offer useful insights for managers who operate not only in the cruise industry but also in other service contexts. Moreover, the moderating effects offer novel insights into smarter marketing on the part of service companies oriented toward value co-creation.

Originality/value
Only a few recent studies have focused on the servicescape in the context of the cruise industry. This study contributes to the literature by providing a theoretical framework and empirical evidence for analyzing the role of the onboard servicescape in cruisers’ experience, delight and memorability while also considering the moderating effects that of sociodemographic and travel-related characteristics exert on the different paths.