bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self-healing ionic gelatin/glycerol hydrogels for strain sensing applications
Authors: Hardman David , George Thuruthel Thomas , Iida Fumiya 
Published: February 2022

AbstractSoft sensing technologies have the potential to revolutionize wearable devices, haptic interfaces and robotic systems. However, there are numerous challenges in the deployment of these devices due to their poor resilience, high energy consumption, and omnidirectional strain responsivity. This work reports the development of a versatile ionic gelatin-glycerol hydrogel for soft sensing applications. The resulting sensing device is inexpensive and easy to manufacture, is self-healable at room temperature, can undergo strains of up to 454%, presents stability over long periods of time, and is biocompatible and biodegradable. This material is ideal for strain sensing applications, with a linear correlation coefficient R2 = 0.9971 and a pressure-insensitive conduction mechanism. The experimental results show the applicability of ionic hydrogels for wearable devices and soft robotic technologies for strain, humidity, and temperature sensing while being able to partially self-heal at room temperature.
Timing of emergence of modern rates of sea-level rise by 1863
Authors: Walker Jennifer S. , Kopp Robert E. , Little Christopher M. , Horton Benjamin P. 
Published: February 2022

AbstractSea-level rise is a significant indicator of broader climate changes, and the time of emergence concept can be used to identify when modern rates of sea-level rise emerged above background variability. Yet a range of estimates of the timing persists both globally and regionally. Here, we use a global database of proxy sea-level records of the Common Era (0–2000 CE) and show that globally, it is very likely that rates of sea-level rise emerged above pre-industrial rates by 1863 CE (P = 0.9; range of 1825 [P = 0.66] to 1873 CE [P = 0.95]), which is similar in timing to evidence for early ocean warming and glacier melt. The time of emergence in the North Atlantic reveals a distinct spatial pattern, appearing earliest in the mid-Atlantic region (1872–1894 CE) and later in Canada and Europe (1930–1964 CE). Regional and local sea-level changes occurring over different time periods drive the spatial pattern in emergence, suggesting regional processes underlie centennial-timescale sea-level variability over the Common Era.
Immunotherapy for early triple negative breast cancer: research agenda for the next decade
Authors: Tarantino Paolo , Corti Chiara , Schmid Peter , Cortes Javier , Mittendorf Elizabeth A. , Rugo Hope , Tolaney Sara M. , Bianchini Giampaolo , Andrè Fabrice , Curigliano Giuseppe 
Published: February 2022

AbstractFor decades, the systemic treatment of localized triple negative breast cancer (TNBC) has exclusively relied on chemotherapy. Recent advancements, however, are rapidly reshaping the treatment algorithms for this disease. The addition of pembrolizumab to neoadjuvant chemotherapy has indeed shown to significantly improve event-free survival for stage II–III TNBC, leading to its establishment as new standard of care in this setting. This landmark advancement has however raised several important scientific questions. Indeed, we desperately need strategies to identify upfront patients deriving benefit from the addition of immunotherapy. Moreover, the best integration of pembrolizumab with further recent advancements (capecitabine, olaparib) is yet to be defined. Lastly, extensive efforts are needed to minimize the impact on patients of immune-related adverse events and financial toxicity. The next decade of clinical research will be key to overcome these challenges, and ultimately learn how to optimally integrate immunotherapy in the treatment landscape of TNBC.
Clinical pharmacogenetic analysis in 5,001 individuals with diagnostic Exome Sequencing data
Authors: Lanillos Javier , Carcajona Marta , Maietta Paolo , Alvarez Sara , Rodriguez-Antona Cristina 
Published: February 2022

AbstractExome sequencing is utilized in routine clinical genetic diagnosis. The technical robustness of repurposing large-scale next-generation sequencing data for pharmacogenetics has been demonstrated, supporting the implementation of preemptive pharmacogenetic strategies based on adding clinical pharmacogenetic interpretation to exomes. However, a comprehensive study analyzing all actionable pharmacogenetic alleles contained in international guidelines and applied to diagnostic exome data has not been performed. Here, we carried out a systematic analysis based on 5001 Spanish or Latin American individuals with diagnostic exome data, either Whole Exome Sequencing (80%), or the so-called Clinical Exome Sequencing (20%) (60 Mb and 17 Mb, respectively), to provide with global and gene-specific clinical pharmacogenetic utility data. 788 pharmacogenetic alleles, distributed through 19 genes included in Clinical Pharmacogenetics Implementation Consortium guidelines were analyzed. We established that Whole Exome and Clinical Exome Sequencing performed similarly, and 280 alleles in 11 genes (CACNA1S, CYP2B6, CYP2C9, CYP4F2, DPYD, G6PD, NUDT15, RYR1, SLCO1B1, TPMT, and UGT1A1) could be used to inform of pharmacogenetic phenotypes that change drug prescription. Each individual carried in average 2.2 alleles and overall 95% (n = 4646) of the cohort could be informed of at least one actionable pharmacogenetic phenotype. Differences in variant allele frequency were observed among the populations studied and the corresponding gnomAD population for 7.9% of the variants. In addition, in the 11 selected genes we uncovered 197 novel variants, among which 27 were loss-of-function. In conclusion, we provide with the landscape of actionable pharmacogenetic information contained in diagnostic exomes, that can be used preemptively in the clinics.
Unsupervised clustering for identifying spatial inhomogeneity on local electronic structures
Authors: Iwasawa Hideaki , Ueno Tetsuro , Masui Takahiko , Tajima Setsuko 
Published: February 2022

AbstractSpatial inhomogeneity on the electronic structure is one of the vital keys to provide a better understanding of the emergent quantum phenomenon. Given the recent developments on spatially resolved ARPES (ARPES: angle-resolved photoemission spectroscopy), the information on the spatial inhomogeneity on the local electronic structure is now accessible. However, the next challenge becomes apparent as the conventional analysis encounters difficulty handling a large volume of a spatial mapping dataset, typically generated in the spatially resolved ARPES experiments. Here, we propose a machine-learning-based approach using unsupervised clustering algorithms (K-means and fuzzy-c-means) to examine the spatial mapping dataset. Our analysis methods enable automated categorization of the spatial mapping dataset with a much-reduced human intervention and workload, thereby allowing quick identification and visualization of the spatial inhomogeneity on the local electronic structures.
Olfactory receptors contribute to progression of kidney fibrosis
Authors: Motahharynia Ali , Moein Shiva , Kiyanpour Farnoush , Moradzadeh Kobra , Yaqubi Moein , Gheisari Yousof 
Published: February 2022

AbstractOlfactory receptors (ORs) which are mainly known as odor-sensors in the olfactory epithelium are shown to be expressed in several non-sensory tissues. Despite the specified role of some of these receptors in normal physiology of the kidney, little is known about their potential effect in renal disorders. In this study, using the holistic view of systems biology, it was determined that ORs are significantly changed during the progression of kidney fibrosis. For further validation, common differentially expressed ORs resulted from reanalysis of two time-course microarray datasets were selected for experimental evaluation in a validated murine model of unilateral ureteral obstruction (UUO). Transcriptional analysis by real-time quantitative polymerase chain reaction demonstrated considerable changes in the expression pattern of Olfr433, Olfr129, Olfr1393, Olfr161, and Olfr622 during the progression of kidney fibrosis. For localization of these ORs, single-cell RNA-sequencing datasets of normal and UUO mice were reanalyzed. Results showed that Olfr433 is highly expressed in macrophages in day-2 and 7 post-injury in UUO mice and not in normal subgroups. Besides, like previous findings, Olfr1393 was shown to be expressed prominently in the proximal tubular cells of the kidney. In conclusion, our combinatorial temporal approach to the underlying mechanisms of chronic kidney disease highlighted the potential role of ORs in progression of fibrosis. The expression of Olfr433 in the macrophages provides some clue about its relation to molecular mechanisms promoted in the fibrotic kidney. The proposed ORs in this study could be the subject of further functional assessments in the future.
Calibrated comparison of SARS-CoV-2 neutralizing antibody levels in response to protein-, mRNA-, and vector-based COVID-19 vaccines
Authors: Karbiener Michael , Farcet Maria R. , Zollner Andreas , Masuda Taisei , Mori Mitsuhiro , Moschen Alexander R. , Kreil Thomas R. 
Published: February 2022

AbstractSARS-CoV-2 neutralizing antibodies have been suggested to reflect the efficacy of COVID-19 vaccines. This study reports the direct comparison of the SARS-CoV-2 neutralizing antibody response elicited by a protein- (NVX-CoV2373), an mRNA- (Comirnaty), and a vector-based (Vaxzevria) COVID-19 vaccine, calibrated against the WHO international SARS-CoV-2 antibody standard, and further supports the use of neutralizing antibody levels as a correlate of protection.
Sleep improvements on days with later school starts persist after 1 year in a flexible start system
Authors: Biller Anna M. , Molenda Carmen , Zerbini Giulia , Roenneberg Till , Winnebeck Eva C. 
Published: February 2022

AbstractEarly school times fundamentally clash with the late sleep of teenagers. This mismatch results in chronic sleep deprivation posing acute and long-term health risks and impairing students' learning. Despite immediate short-term benefits for sleep, the long-term effects of later starts remain unresolved. In a pre-post design over 1 year, we studied a unique flexible school start system, in which 10–12th grade students chose daily between an 8:00 or 8:50AM-start. Missed study time (8:00–8:50) was compensated for during gap periods or after classes. Based on 2 waves (6–9 weeks of sleep diary each), we found that students maintained their ~ 1-h-sleep gain on later days, longitudinally (n = 28) and cross-sectionally (n = 79). This gain was independent of chronotype and frequency of later starts but attenuated for boys after 1 year. Students showed persistently better sleep quality and reduced alarm-driven waking and reported psychological benefits (n = 93) like improved motivation, concentration, and study quality on later days. Nonetheless, students chose later starts only infrequently (median 2 days/week), precluding detectable sleep extensions in the flexible system overall. Reasons for not choosing late starts were the need to make up lost study time, preference for extra study time and transport issues. Whether flexible systems constitute an appealing alternative to fixed delays given possible circadian and psychological advantages warrants further investigation.
Evaluation of the collagen-binding properties and virulence of killed Streptococcus mutans in a silkworm model
Authors: Suehiro Yuto , Nomura Ryota , Matayoshi Saaya , Otsugu Masatoshi , Iwashita Naoki , Nakano Kazuhiko 
Published: February 2022

AbstractStreptococcus mutans, a major pathogen of dental caries, is also known as a causative agent of cardiovascular disease. A 120 kDa collagen-binding protein (Cnm) of S. mutans is an important contributor to the pathogenicity of cardiovascular disease. Although dead bacteria have been detected in cardiovascular specimens by molecular biological methods, the pathogenicity of the bacteria remains unknown. Here, we analyzed the pathogenicity of killed S. mutans by focusing on collagen-binding ability and the effects on silkworms. In live S. mutans, Cnm-positive S. mutans had high collagen-binding activity, while Cnm-negative S. mutans had no such activity. After treatment with killed Cnm-positive S. mutans, amoxicillin-treated bacteria still had collagen-binding ability, while lysozyme-treated bacteria lost this ability. When live and amoxicillin-treated S. mutans strains were administered to silkworms, the survival rates of the silkworms were reduced; this reduction was more pronounced in Cnm-positive S. mutans infection than in Cnm-negative S. mutans infection. However, the administration of any of the lysozyme-treated bacteria did not reduce the survival rate of the silkworms. These results suggest that amoxicillin-killed Cnm-positive S. mutans strains maintain collagen-binding properties and pathogenicity in the silkworm model, and are possibly associated with pathogenicity in cardiovascular diseases.
An overview of Brazilian working age adults vulnerability to COVID-19
Authors: de Souza Fernanda Sumika Hojo , Hojo-Souza Natália Satchiko , de Oliveira Daniela Carine Ramires , Silva Cristiano Maciel da , Guidoni Daniel Ludovico 
Published: February 2022

AbstractBrazil is a country of continental dimensions, where many smaller countries would fit. In addition to demographic, socioeconomic, and cultural differences, hospital infrastructure and healthcare varies across all 27 federative units. Therefore, the evolution of COVID-19 pandemic did not manifest itself in a homogeneous and predictable trend across the nation. In late 2020 and early 2021, new waves of the COVID-19 outbreak have caused an unprecedented sanitary collapse in Brazil. Unlike the first COVID-19 wave, in subsequent waves, preliminary evidence has pointed to an increase in the daily reported cases among younger people being hospitalized, overloading the healthcare system. In this comprehensive retrospective cohort study, confirmed cases of hospitalization, ICU admission, IMV requirement and in-hospital death from Brazilian COVID-19 patients throughout 2020 until the beginning of 2021 were analyzed through a spatio-temporal study for patients aged 20–59 years. All Brazilian federative units had their data disaggregated in six periods of ten epidemiological weeks each. We found that there is a wide variation in the waves dynamic due to SARS-CoV-2 infection, both in the first and in subsequent outbreaks in different federative units over the analyzed periods. As a result, atypical waves can be seen in the Brazil data as a whole. The analysis showed that Brazil is experiencing a numerical explosion of hospitalizations and deaths for patients aged 20–59 years, especially in the state of São Paulo, with a similar proportion of hospitalizations for this age group but higher proportion of deaths compared to the first wave.
Curation, inference, and assessment of a globally reconstructed gene regulatory network for Streptomyces coelicolor
Authors: Zorro-Aranda Andrea , Escorcia-Rodríguez Juan Miguel , González-Kise José Kenyi , Freyre-González Julio Augusto 
Published: February 2022

AbstractStreptomyces coelicolorA3(2) is a model microorganism for the study of Streptomycetes, antibiotic production, and secondary metabolism in general. Even thoughS. coelicolorhas an outstanding variety of regulators among bacteria, little effort to globally study its transcription has been made. We manually curated 29 years of literature and databases to assemble a meta-curated experimentally-validated gene regulatory network (GRN) with 5386 genes and 9707 regulatory interactions (~ 41% of the total expected interactions). This provides the most extensive and up-to-date reconstruction available for the regulatory circuitry of this organism. Only ~ 6% (534/9707) are supported by experiments confirming the binding of the transcription factor to the upstream region of the target gene, the so-called “strong” evidence. While for the remaining interactions there is no confirmation of direct binding. To tackle network incompleteness, we performed network inference using several methods (including two proposed here) for motif identification in DNA sequences and GRN inference from transcriptomics. Further, we contrasted the structural properties and functional architecture of the networks to assess the reliability of the predictions, finding the inference from DNA sequence data to be the most trustworthy approach. Finally, we show two applications of the inferred and the curated networks. The inference allowed us to propose novel transcription factors for the keyStreptomycesantibiotic regulatory proteins (SARPs). The curated network allowed us to study the conservation of the system-level components betweenS. coelicolorandCorynebacterium glutamicum.There we identified the basal machinery as the common signature between the two organisms. The curated networks were deposited in Abasy Atlas (https://abasy.ccg.unam.mx/) while the inferences are available as Supplementary Material.
Probing the antioxidant activity of functional proteins and bioactive peptides in Hermetia illucens larvae fed with food wastes
Authors: Lu Jiaxin , Guo Yuwen , Muhmood Atif , Zeng Bei , Qiu Yizhan , Wang Pan , Ren Lianhai 
Published: February 2022

AbstractFood waste is becoming more prevalent, and managing it is one of the most important issues in terms of food safety. In this study, functional proteins and bioactive peptides produced from the enzymatic digestion of black soldier fly (Hermetia illucens L., BSF) fed with food wastes were characterized and quantified using proteomics-based analysis. The results revealed approximately 78 peptides and 57 proteins, including 40S ribosomal protein S4, 60S ribosomal protein L8, ATP synthase subunit alpha, ribosomal protein S3, Histone H2A, NADP-glutamate dehydrogenase, Fumarate hydratase, RNA helicase, Chitin binding Peritrophin-A, Lectin C-type protein, etc. were found in BSF. Furthermore, functional analysis of the proteins revealed that the 60S ribosomal protein L5 (RpL5) in BSF interacted with a variety of ribosomal proteins and played a key role in the glycolytic process (AT14039p). Higher antioxidant activity was found in peptide sequences such as GYGFGGGAGCLSMDTGAHLNR, VVPSANRAMVGIVAGGGRIDKPILK, AGLQFPVGR, GFKDQIQDVFK, and GFKDQIQDVFK. It was concluded that the bioconversion of food wastes by BSF brought about the generation of a variety of functional proteins and bioactive peptides with strong antioxidant activity. However, more studies are required to exploit BSF's potential in the value addition of food wastes.
Comparative analysis of genome code complexity and manufacturability with engineering benchmarks
Authors: Riolo Joseph , Steckl Andrew J. 
Published: February 2022

AbstractWhen knowledge has advanced to a state that includes a predictive understanding of the relationship between genome sequence and organism phenotype it will be possible for future engineers to design and produce synthetic organisms. However, the possibility of synthetic biology does not necessarily guarantee its feasibility, in much the same way that the possibility of a brute force attack fails to ensure the timely breaking of robust encryption. The size and range of natural genomes, from a few million base pairs for bacteria to over 100 billion base pairs for some plants, suggests it is necessary to evaluate the practical limits of designing genomes of similar complexity. This analysis characterizes the complexity of natural genomes, compares them to existing engineering benchmarks, and shows that existing large software programs are on similar scale with the genome of complex natural organisms.
Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module
Authors: Lee Hye Kyung , Knabl Ludwig , Knabl Ludwig , Wieser Manuel , Mur Anna , Zabernigg August , Schumacher Jana , Kapferer Sebastian , Kaiser Norbert , Furth Priscilla A. , Hennighausen Lothar 
Published: February 2022

AbstractFast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.
Long horns protect Hestina japonica butterfly larvae from their natural enemies
Authors: Kandori Ikuo , Hiramatsu Mamoru , Soda Minako , Nakashima Shinya , Funami Shun , Yokoi Tomoyuki , Tsuchihara Kazuko , Papaj Daniel R. 
Published: February 2022

AbstractAnimals sometimes have prominent projections on or near their heads serving diverse functions such as male combat, mate attraction, digging, capturing prey, sensing or defence against predators. Some butterfly larvae possess a pair of long frontal projections; however, the function of those projections is not well known. Hestina japonica butterfly larvae have a pair of long hard projections on their heads (i.e., horns). Here we hypothesized that they use these horns to protect themselves from natural enemies (i.e., predators and parasitoids). Field surveys revealed that the primary natural enemies of H. japonica larvae were Polistes wasps. Cage experiments revealed that larvae with horns intact and larvae with horns removed and fitted with horns of other individuals succeeded in defending themselves against attacks of Polistes wasps significantly more often than larvae with horns removed. We discuss that the horns counter the paper wasps’ hunting strategy of first biting the larvae’s ‘necks’ and note that horns evolved repeatedly only within the Nymphalidae in a phylogeny of the Lepidoptera. This is the first demonstration that arthropods use head projections for physical defence against predators.