bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE UNCOUNTABILITY OF
Authors: NORMANN DAG , SANDERS SAM
Published: April 2022

Cantor’s first set theory paper (1874) establishes the uncountability of
${\mathbb R}$
. We study this most basic mathematical fact formulated in the language of higher-order arithmetic. In particular, we investigate the logical and computational properties of
${\mathsf {NIN}}$
(resp.
${\mathsf {NBI}}$
), i.e., the third-order statement there is no injection resp. bijection from 
$[0,1]$
to
${\mathbb N}$
. Working in Kohlenbach’s higher-order Reverse Mathematics, we show that
${\mathsf {NIN}}$
and
${\mathsf {NBI}}$
are hard to prove in terms of (conventional) comprehension axioms, while many basic theorems, like Arzelà’s convergence theorem for the Riemann integral (1885), are shown to imply
${\mathsf {NIN}}$
and/or
${\mathsf {NBI}}$
. Working in Kleene’s higher-order computability theory based on S1–S9, we show that the following fourth-order process based on
${\mathsf {NIN}}$
is similarly hard to compute: for a given
$[0,1]\rightarrow {\mathbb N}$
-function, find reals in the unit interval that map to the same natural number.
Using Neural Network Models for Wine Review Classification
Authors: Katumullage Duwani , Yang Chenyu , Barth Jackson , Cao Jing
Published: April 2022

Wines are usually evaluated by wine experts and enthusiasts who give numeric ratings as well as text reviews. While most wine classification studies have been based on conventional statistical models using numeric variables, there has been very limited work on implementing neural network models using wine reviews. In this paper, we apply neural network models (CNN, BiLSTM, and BERT) to extract useful information from wine reviews and classify wines according to different rating classes. Using a large collection of wine reviews from Wine Spectator, the study shows that BERT, a neural network framework recently developed by Google, has the best performance. In the two-class classification (90–100 and 80–89), BERT achieves an accuracy of 89.12%, followed by BiLSTM (88.69%) and CNN (88.02%). In the four-class classification (95–100, 90–94, 85–89, and 80–84), BERT yields an 81.57% accuracy, while the other two produce an 80% accuracy. The neural network models in the paper are independent of domain knowledge and thus can be easily extended to other kinds of text analysis. Expanding the limited work on wine text review classification studies, these models are up-to-date and provide valuable additions to wine data analysis. (JEL Classifications: C45, C88, D83)
Downsizing food: a systematic review and meta-analysis examining the effect of reducing served food portion sizes on daily energy intake and body weight
Authors: Robinson Eric , McFarland-Lesser India , Patel Zina , Jones Andrew
Published: April 2022

Portion sizes of many foods have increased over time. However, the size of effect that reducing food portion sizes has on daily energy intake and body weight is less clear. We used a systematic review methodology to identify eligible articles that used an experimental design to manipulate portion size served to human participants and measured energy intake for a minimum of 1 d. Searches were conducted in September 2020 and again in October 2021. Fourteen eligible studies contributing eighty-five effects were included in the primary meta-analysis. There was a moderate-to-large reduction in daily energy intake when comparing smaller v. larger portions (Standardised Mean Difference (SMD) = –0·709 (95 % CI: –0·956, –0·461), approximately 235 kcal (983·24 kJ)). Larger reductions to portion size resulted in larger decreases in daily energy intake. There was evidence of a curvilinear relationship between portion size and daily energy intake; reductions to daily energy intake were markedly smaller when reducing portion size from very large portions. In a subset of studies that measured body weight (four studies contributing five comparisons), being served smaller v. larger portions was associated with less weight gain (0·58 kg). Reducing food portion sizes may be an effective population-level strategy to prevent weight gain.
Ore genesis of the Huangshaping skarn W–Mo–Pb–Zn deposit, southern Hunan Province, China: insights from in situ LA-MC-ICP-MS sulphur isotopic compositions
Authors: Ding Teng , Tan Tingting , Wang Jia , Ma Dongsheng , Lu Jianjun , Zhang Rongqing , Wu Bin
Published: April 2022

The Huangshaping deposit is unique in southern Hunan Province, China, as it hosts economic reserves of both W–Mo and Pb–Zn mineralization, which are usually associated with granite and granodiorite porphyry in this area, respectively. This study reports results of in situ LA-MC-ICP-MS sulphur isotopic composition analyses conducted on sulphides from both W–Mo and Pb–Zn mineralization from the Huangshaping deposit with the aim of constraining ore genesis for this deposit. All samples from the proximal W–Mo mineralization have relatively uniform and high δ34S values (8.7 ‰ to 16.0 ‰), close to the range for carbonate sediments in this deposit (13.8 ‰ to 18.1 ‰). These patterns suggest that the granite porphyry in this deposit was the sulphur source for W–Mo mineralization, and that the assimilation of evaporite from the carbonate sediments led to the high δ34S values of the granite porphyry. Sulphides from the Pb–Zn mineralization have δ34S values (2.2 ‰ to 10.3 ‰) lower than those of the W–Mo mineralization, and generally increase in this paragenetic order, with the lowest δ34S values being similar to those of the basement (3.8 ‰ to 7.7 ‰). These patterns indicate that the original sulphur for the Pb–Zn mineralization was most likely derived from the basement, with input of sulphur from the carbonate sediments increasing during the evolution of ore-forming fluids. On the basis of the measured sulphur isotopic compositions, it is suggested that the ore-forming materials for the W–Mo mineralization were derived from the granite porphyry, whereas ore-forming materials extracted from the basement dominated the Pb–Zn mineralization.
Democracy's Violent Birth: The Czech Legionnaires and Statue Wars in the First Czechoslovak Republic
Authors: Wingfield Nancy M.
Published: April 2022

“Oh, home of tears, but let her bear this blazoned to the end of time: No nation rose so white and fair, none fell so pure of crime.” So reads the stanza from a poem popular in the South during the Civil War engraved on a Confederate soldier statue unveiled in 1911 on the lawn of the Cooke County courthouse in Gainesville, Texas (Figure 1). It is one of two Confederate statues long on display in the city of some 16,000 some ninety miles north of Dallas. This larger-than-life soldier, standing high upon a column, towers over an important public space. It is among many Confederate monuments that long occupied public spaces across the United States, often with little local debate, despite their often white-supremacist inscriptions.
Ditransitive structures in child language acquisition: An investigation of production and comprehension in children aged five to seven
Authors: SCHERGER Anna-Lena , KIZILIRMAK Jasmin M. , FOLTA-SCHOOFS Kristian
Published: April 2022

The aim of the present study was to investigate the acquisition of ditransitive structures beyond production. We conducted an elicitation task (production) and a picture-sentence matching task measuring accuracy and response times (comprehension). We examined German five-to seven-year-old typically developing children and an adult control group. Our data showed quasi-perfect performance in comprehension in adults and in those children who had already mastered ditransitives productively. However, children who had not yet mastered the production of ditransitives showed comprehension abilities preceding production abilities. Unlike adults, in the comprehension task children did not react explicitly before the end of the auditory stimulus.
Johannes de Muris's Musica speculativa cited by Jacobus de Ispania
Authors: WITKOWSKA-ZAREMBA ELŻBIETA
Published: April 2022

It is known that the seventh book of Jacobus's Speculum musicae contains, alongside other quotations from Ars Nova treatises, the earliest extant transmission of the salient passage of Johannes de Muris's Musica speculativa, Conclusio XVIII, where Muris questions the nature of the fourth as a perfect consonance. However, the relevant passages of Musica speculativa cited and discussed by Jacobus have not yet been analysed in the context of the rich manuscript tradition of the Musica speculativa, which served the needs of musical education throughout Latin Europe for at least two hundred years. In order to position Jacobus's citations of Muris within the framework of the Musica speculativa tradition, I examine several significant variant readings contained in Speculum musicae, comparing them to two French, most probably Parisian, manuscripts transmitting versions A (A-SPL Cod. 264/4) and B (BnF lat. 7378A) of Musica speculativa. Both A and B versions are provided with colophons dated 1323 and 1325, respectively. Establishing which version of Musica speculativa was the source of Jacobus's citations provides a new basis for the dating of two other treatises by Muris to which Jacobus refers, namely Notitia artis musicae and Compendium musicae practicae, and, more generally, for the date of the seventh book of Speculum musicae.
TABULARITY AND POST-COMPLETENESS IN TENSE LOGIC
Authors: CHEN QIAN , MA MINGHUI
Published: April 2022

A new characterization of tabularity in tense logic is established, namely, a tense logic L is tabular if and only if
$\mathsf {tab}_n^T\in L$
for some
$n\geq 1$
. Two characterization theorems for the Post-completeness in tabular tense logics are given. Furthermore, a characterization of the Post-completeness in the lattice of all tense logics is established. Post numbers of some tense logics are shown.
Non-nutritive bioactive components in maternal milk and offspring development: a scoping review
Authors: Eisha Shafinaz , Joarder Ishraq , Wijenayake Sanoji , McGowan Patrick O.
Published: April 2022

Lactation is a critical time in mammalian development, where maternal factors shape offspring outcomes. In this scoping review, we discuss current literature concerning maternal factors that influence lactation biology and highlight important associations between changes in milk composition and offspring outcomes. Specifically, we explore maternal nutritional, psychosocial, and environmental exposures that influence non-nutritive bioactive components in milk and their links to offspring growth, development, metabolic, and behavioral outcomes. A comprehensive literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. Predetermined eligibility criteria were used to analyze 3,275 papers, and the final review included 40 primary research articles. Outcomes of this review identify maternal obesity to be a leading maternal factor influencing the non-nutritive bioactive composition of milk with notable links to offspring outcomes. Offspring growth and development are the most common modes of programming associated with changes in non-nutritive milk composition due to maternal factors in early life. In addition to discussing studies investigating these key associations, we also identify knowledge gaps in the current literature and suggest opportunities and considerations for future studies.
Electrical Resistivity of Fe and Fe‐3 wt%P at 5 GPa With Implications for the Moon's Core Conductivity and Dynamo
Authors: Yin Yuan , Wang Lin , Zhai Shuangmeng , Fei Yingwei
Published: April 2022

A high‐magnetic field once existed in the early history of the Moon, suggesting the core once possessed a thermally driven dynamo. The thermal conductivity of core materials is a significant parameter of the dynamo. The lunar core composition is thought to be iron or iron‐alloyed with some light elements (e.g., S, P, Si, and C), but its transport properties remain uncertain. We measured the electrical resistivity of iron and Fe‐3 wt%P alloys at 5 GPa and high temperatures. Apart from the quasi four‐point technique, the four‐probe van der Pauw technique was also employed to measure the resistivity of pure iron. Adding ∼3 wt% phosphorus to iron slightly increases the resistivity at 5 GPa and 1000–1500 K due to the impurity effect. The resistivity of Fe‐3 wt%P alloys increases at the onset of melting. Via the Wiedemann‐Franz law, the thermal conductivity at the lunar core‐mantle boundary (CMB) is estimated to be 28.6–34.2 Wm−1K−1 for a light‐element free core and 31.5 ± 1.9 Wm−1K−1 for a phosphorus‐bearing (∼3 wt% P) core. Therefore, small amounts of phosphorus in the lunar core slightly impact its thermal conductivity. The estimated conductive heat flow across the lunar CMB varies from 4.5 to 5.7 GW, and the adiabatic heat flux varies from 3.3 to 4.2 mW/m2, depending on the core's composition (Fe or Fe‐3 wt%P). Integrating our results with previous lunar core evolution models, we suggest that a thermally driven dynamo persisted until 3.63–3.88 Ga ago.
Graphene-driving strain engineering to enable strain-free epitaxy of AlN film for deep ultraviolet light-emitting diode
Authors: Chang Hongliang , Liu Zhetong , Yang Shenyuan , Gao Yaqi , Shan Jingyuan , Liu Bingyao , Sun Jingyu , Chen Zhaolong , Yan Jianchang , Liu Zhiqiang , Wang Junxi , Gao Peng , Li Jinmin , Liu Zhongfan , Wei Tongbo
Published: April 2022

The energy-efficient deep ultraviolet (DUV) optoelectronic devices suffer from critical issues associated with the poor quality and large strain of nitride material system caused by the inherent mismatch of heteroepitaxy. In this work, we have prepared the strain-free AlN film with low dislocation density (DD) by graphene (Gr)-driving strain-pre-store engineering and a unique mechanism of strain-relaxation in quasi-van der Waals (QvdW) epitaxy is presented. The DD in AlN epilayer with Gr exhibits an anomalous sawtooth-like evolution during the whole epitaxy process. Gr can help to enable the annihilation of the dislocations originated from the interface between AlN and Gr/sapphire by impelling a lateral two-dimensional growth mode. Remarkably, it can induce AlN epilayer to pre-store sufficient tensile strain during the early growth stage and thus compensate the compressive strain caused by hetero-mismatch. Therefore, the low-strain state of the DUV light-emitting diode (DUV-LED) epitaxial structure is realized on the strain-free AlN template with Gr. Furthermore, the DUV-LED with Gr demonstrate 2.1 times enhancement of light output power and a better stability of luminous wavelength compared to that on bare sapphire. An in-depth understanding of this work reveals diverse beneficial impacts of Gr on nitride growth and provides a novel strategy of relaxing the vital requirements of hetero-mismatch in conventional heteroepitaxy.
Engaging children and young people on the potential role of artificial intelligence in medicine
Authors: Visram Sheena , Leyden Deirdre , Annesley Oceiah , Bappa Dauda , Sebire Neil J.
Published: April 2022

Introduction

There is increasing interest in Artificial Intelligence (AI) and its application to medicine. Perceptions of AI are less well-known, notably amongst children and young people (CYP). This workshop investigates attitudes towards AI and its future applications in medicine and healthcare at a specialised paediatric hospital using practical design scenarios.

Method

Twenty-one members of a Young Persons Advisory Group for research contributed to an engagement workshop to ascertain potential opportunities, apprehensions, and priorities.

Results

When presented as a selection of practical design scenarios, we found that CYP were more open to some applications of AI in healthcare than others. Human-centeredness, governance and trust emerged as early themes, with empathy and safety considered as important when introducing AI to healthcare. Educational workshops with practical examples using AI to help, but not replace humans were suggested to address issues, build trust, and effectively communicate about AI.

Conclusion

Whilst policy guidelines acknowledge the need to include children and young people to develop AI, this requires an enabling environment for human-centred AI involving children and young people with lived experiences of healthcare. Future research should focus on building consensus on enablers for an intelligent healthcare system designed for the next generation, which fundamentally, allows co-creation.

Impact

Children and young people (CYP) want to be included to share their insights about the development of research on the potential role of Artificial Intelligence (AI) in medicine and healthcare and are more open to some applications of AI than others.

Whilst it is acknowledged that a research gap on involving and engaging CYP in developing AI policies exists, there is little in the way of pragmatic and practical guidance for healthcare staff on this topic.

This requires research on enabling environments for ongoing digital cooperation to identify and prioritise unmet needs in the application and development of AI.
Variegation of autism related traits across seven neurogenetic disorders
Authors: Lee Nancy Raitano , Niu Xin , Zhang Fengqing , Clasen Liv S. , Kozel Beth A. , Smith Ann C. M. , Wallace Gregory L. , Raznahan Armin
Published: April 2022

Gene dosage disorders (GDDs) constitute a major class of genetic risks for psychopathology, but there is considerable debate regarding the extent to which different GDDs induce different psychopathology profiles. The current research speaks to this debate by compiling and analyzing dimensional measures of several autism-related traits (ARTs) across seven diverse GDDs. The sample included 350 individuals with one of 7 GDDs, as well as reference idiopathic autism spectrum disorder (ASD;n = 74) and typically developing control (TD;n = 171) groups. The GDDs were: Down, Williams–Beuren, and Smith–Magenis (DS, WS, SMS) syndromes, and varying sex chromosome aneuploidies (“plusX”, “plusXX”, “plusY”, “plusXY”). The Social Responsiveness Scale (SRS-2) was used to measure ARTs at different levels of granularity—item, subscale, and total. General linear models were used to examine ART profiles in GDDs, and machine learning was used to predict genotype from SRS-2 subscales and items. These analyses were completed with and without covariation for cognitive impairment. Twelve of all possible 21 pairwise GDD group contrasts showed significantly different ART profiles (7/21 when co-varying for IQ, all Bonferroni-corrected). Prominent GDD–ART associations in post hoc analyses included relatively preserved social motivation in WS and relatively low levels of repetitive behaviors in plusX. Machine learning revealed that GDD group could be predicted with plausible accuracy (~60–80%) even after controlling for IQ. GDD effects on ARTs are influenced by GDD subtype and ART dimension. This observation has consequences for mechanistic, clinical, and translational aspects of psychiatric neurogenetics.
Inhibition of the CEBPβ-NFκB interaction by nanocarrier-packaged Carnosic acid ameliorates glia-mediated neuroinflammation and improves cognitive function in an Alzheimer’s disease model
Authors: Yi-Bin Wang , Xiang Li , Bing Yang , Qi Zhang , Fei-Tong Jiao , Minghong Wang , Xiangxiang Zhang , Le Kang , Yan Li , Ping Sui , Yufei Gao , Ye Xu , Chun-Yan Wang
Published: April 2022

Neuroinflammation occurs early in Alzheimer’s disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aβ clearance and disruption of synaptic connection. CEBPβ, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPβ-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPβ facilitated the interaction of CEBPβ with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1β, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced β-amyloid (Aβ) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPβ with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aβ secretion by inhibiting the CEBPβ-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEβCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEβCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.
Virally programmed extracellular vesicles sensitize cancer cells to oncolytic virus and small molecule therapy
Authors: Wedge Marie-Eve , Jennings Victoria A. , Crupi Mathieu J. F. , Poutou Joanna , Jamieson Taylor , Pelin Adrian , Pugliese Giuseppe , de Souza Christiano Tanese , Petryk Julia , Laight Brian J. , Boileau Meaghan , Taha Zaid , Alluqmani Nouf , McKay Hayley E. , Pikor Larissa , Khan Sarwat Tahsin , Azad Taha , Rezaei Reza , Austin Bradley , He Xiaohong , Mansfield David , Rose Elaine , Brown Emily E. F. , Crawford Natalie , Alkayyal Almohanad , Surendran Abera , Singaravelu Ragunath , Roy Dominic G. , Migneco Gemma , McSweeney Benjamin , Cottee Mary Lynn , Jacobus Egon J. , Keller Brian A. , Yamaguchi Takafumi N. , Boutros Paul C. , Geoffrion Michele , Rayner Katey J. , Chatterjee Avijit , Auer Rebecca C. , Diallo Jean-Simon , Gibbings Derrick , tenOever Benjamin R. , Melcher Alan , Bell John C. , Ilkow Carolina S.
Published: April 2022

Recent advances in cancer therapeutics clearly demonstrate the need for innovative multiplex therapies that attack the tumour on multiple fronts. Oncolytic or “cancer-killing” viruses (OVs) represent up-and-coming multi-mechanistic immunotherapeutic drugs for the treatment of cancer. In this study, we perform an in-vitro screen based on virus-encoded artificial microRNAs (amiRNAs) and find that a unique amiRNA, herein termed amiR-4, confers a replicative advantage to the VSVΔ51 OV platform. Target validation of amiR-4 reveals ARID1A, a protein involved in chromatin remodelling, as an important player in resistance to OV replication. Virus-directed targeting of ARID1A coupled with small-molecule inhibition of the methyltransferase EZH2 leads to the synthetic lethal killing of both infected and uninfected tumour cells. The bystander killing of uninfected cells is mediated by intercellular transfer of extracellular vesicles carrying amiR-4 cargo. Altogether, our findings establish that OVs can serve as replicating vehicles for amiRNA therapeutics with the potential for combination with small molecule and immune checkpoint inhibitor therapy.
Glyco-Decipher enables glycan database-independent peptide matching and in-depth characterization of site-specific N-glycosylation
Authors: Fang Zheng , Qin Hongqiang , Mao Jiawei , Wang Zhongyu , Zhang Na , Wang Yan , Liu Luyao , Nie Yongzhan , Dong Mingming , Ye Mingliang
Published: April 2022

Glycopeptides with unusual glycans or poor peptide backbone fragmentation in tandem mass spectrometry are unaccounted for in typical site-specific glycoproteomics analysis and thus remain unidentified. Here, we develop a glycoproteomics tool, Glyco-Decipher, to address these issues. Glyco-Decipher conducts glycan database-independent peptide matching and exploits the fragmentation pattern of shared peptide backbones in glycopeptides to improve the spectrum interpretation. We benchmark Glyco-Decipher on several large-scale datasets, demonstrating that it identifies more peptide-spectrum matches than Byonic, MSFragger-Glyco, StrucGP and pGlyco 3.0, with a 33.5%-178.5% increase in the number of identified glycopeptide spectra. The database-independent and unbiased profiling of attached glycans enables the discovery of 164 modified glycans in mouse tissues, including glycans with chemical or biological modifications. By enabling in-depth characterization of site-specific protein glycosylation, Glyco-Decipher is a promising tool for advancing glycoproteomics analysis in biological research.
Enhancing biofuels production by engineering the actin cytoskeleton in Saccharomyces cerevisiae
Authors: Liu Hui , Zhou Pei , Qi Mengya , Guo Liang , Gao Cong , Hu Guipeng , Song Wei , Wu Jing , Chen Xiulai , Chen Jian , Chen Wei , Liu Liming
Published: April 2022

Saccharomyces cerevisiae is widely employed as a cell factory for the production of biofuels. However, product toxicity has hindered improvements in biofuel production. Here, we engineer the actin cytoskeleton in S. cerevisiae to increase both the cell growth and production of n-butanol and medium-chain fatty acids. Actin cable tortuosity is regulated using an n-butanol responsive promoter-based autonomous bidirectional signal conditioner in S. cerevisiae. The budding index is increased by 14.0%, resulting in the highest n-butanol titer of 1674.3 mg L−1. Moreover, actin patch density is fine-tuned using a medium-chain fatty acid responsive promoter-based autonomous bidirectional signal conditioner. The intracellular pH is stabilized at 6.4, yielding the highest medium-chain fatty acids titer of 692.3 mg L−1 in yeast extract peptone dextrose medium. Engineering the actin cytoskeleton in S. cerevisiae can efficiently alleviate biofuels toxicity and enhance biofuels production.
Phase 1b study of berzosertib and cisplatin in patients with advanced triple-negative breast cancer
Authors: Telli Melinda L. , Tolaney Sara M. , Shapiro Geoffrey I. , Middleton Mark , Lord Simon R. , Arkenau Hendrik Tobias , Tutt Andrew , Abramson Vandana , Dean Emma , Haddad Tufia C. , Wesolowski Robert , Ferrer-Playan Jordi , Goddemeier Thomas , Grombacher Thomas , Dong Jennifer , Fleuranceau-Morel Patricia , Diaz-Padilla Ivan , Plummer Ruth
Published: April 2022

Platinum derivatives are commonly used for the treatment of patients with metastatic triple-negative breast cancer (TNBC). However, resistance often develops, leading to treatment failure. This expansion cohort (part C2) of the previously reported phase 1b trial (NCT02157792) is based on the recommended phase 2 dose of the combination of the ataxia-telangiectasia and Rad3-related (ATR) inhibitor berzosertib and cisplatin observed in patients with advanced solid tumors, including TNBC. Forty-seven patients aged ≥18 years with advanced TNBC received cisplatin (75 mg/m2; day 1) and berzosertib (140 mg/m2; days 2 and 9), in 21-day cycles. Berzosertib was well tolerated, with a similar toxicity profile to that reported previously for this combination. The overall response rate (90% confidence interval) was 23.4% (13.7, 35.8). No relevant associations were observed between response and gene alterations. Further studies combining ATR inhibitors with platinum compounds may be warranted in highly selected patient populations.
Deciphering Bitcoin Blockchain Data by Cohort Analysis
Authors: Liu Yulin , Zhang Luyao , Zhao Yinhong
Published: April 2022

Bitcoin is a peer-to-peer electronic payment system that has rapidly grown in popularity in recent years. Usually, the complete history of Bitcoin blockchain data must be queried to acquire variables with economic meaning. This task has recently become increasingly difficult, as there are over 1.6 billion historical transactions on the Bitcoin blockchain. It is thus important to query Bitcoin transaction data in a way that is more efficient and provides economic insights. We apply cohort analysis that interprets Bitcoin blockchain data using methods developed for population data in the social sciences. Specifically, we query and process the Bitcoin transaction input and output data within each daily cohort. This enables us to create datasets and visualizations for some key Bitcoin transaction indicators, including the daily lifespan distributions of spent transaction output (STXO) and the daily age distributions of the cumulative unspent transaction output (UTXO). We provide a computationally feasible approach for characterizing Bitcoin transactions that paves the way for future economic studies of Bitcoin.
Fusarium species isolated from post-hatchling loggerhead sea turtles (Caretta caretta) in South Africa
Authors: Greeff-Laubscher Mariska R. , Jacobs Karin
Published: April 2022

Species in the Fusarium solani species complex are fast growing, environmental saprophytic fungi. Members of this genus are filamentous fungi with a wide geographical distribution. Fusarium keratoplasticum and F. falciforme have previously been isolated from sea turtle nests and have been associated with high egg mortality rates. Skin lesions were observed in a number of stranded, post-hatchling loggerhead sea turtles (Caretta caretta) in a rehabilitation facility in South Africa. Fungal hyphae were observed in epidermal scrapes of affected turtles and were isolated. The aim of this study was to characterise the Fusarium species that were isolated from these post-hatchling loggerhead sea turtles (Caretta caretta) that washed up on beaches along the South African coastline. Three gene regions were amplified and sequenced, namely the internal transcribed spacer region (ITS), a part of the nuclear large subunit (LSU), and part of the translation elongation factor 1 α (tef1) gene region. Molecular characteristics of strains isolated during this study showed high similarity with Fusarium isolates, which have previously been associated with high egg mortality rates in loggerhead sea turtles. This is the first record of F. keratoplasticum, F. falciforme and F. crassum isolated from stranded post-hatchling loggerhead sea turtles in South Africa.
Comparing protein–protein interaction networks of SARS-CoV-2 and (H1N1) influenza using topological features
Authors: Khojasteh Hakimeh , Khanteymoori Alireza , Olyaee Mohammad Hossein
Published: April 2022

SARS-CoV-2 pandemic first emerged in late 2019 in China. It has since infected more than 298 million individuals and caused over 5 million deaths globally. The identification of essential proteins in a protein–protein interaction network (PPIN) is not only crucial in understanding the process of cellular life but also useful in drug discovery. There are many centrality measures to detect influential nodes in complex networks. Since SARS-CoV-2 and (H1N1) influenza PPINs pose 553 common human proteins. Analyzing influential proteins and comparing these networks together can be an effective step in helping biologists for drug-target prediction. We used 21 centrality measures on SARS-CoV-2 and (H1N1) influenza PPINs to identify essential proteins. We applied principal component analysis and unsupervised machine learning methods to reveal the most informative measures. Appealingly, some measures had a high level of contribution in comparison to others in both PPINs, namely Decay, Residual closeness, Markov, Degree, closeness (Latora), Barycenter, Closeness (Freeman), and Lin centralities. We also investigated some graph theory-based properties like the power law, exponential distribution, and robustness. Both PPINs tended to properties of scale-free networks that expose their nature of heterogeneity. Dimensionality reduction and unsupervised learning methods were so effective to uncover appropriate centrality measures.
An agent-based model reveals lost person behavior based on data from wilderness search and rescue
Authors: Hashimoto Amanda , Heintzman Larkin , Koester Robert , Abaid Nicole
Published: April 2022

Thousands of people are reported lost in the wilderness in the United States every year and locating these missing individuals as rapidly as possible depends on coordinated search and rescue (SAR) operations. As time passes, the search area grows, survival rate decreases, and searchers are faced with an increasingly daunting task of searching large areas in a short amount of time. To optimize the search process, mathematical models of lost person behavior with respect to landscape can be used in conjunction with current SAR practices. In this paper, we introduce an agent-based model of lost person behavior which allows agents to move on known landscapes with behavior defined as independent realizations of a random variable. The behavior random variable selects from a distribution of six known lost person reorientation strategies to simulate the agent’s trajectory. We systematically simulate a range of possible behavior distributions and find a best-fit behavioral profile for a hiker with the International Search and Rescue Incident Database. We validate these results with a leave-one-out analysis. This work represents the first time-discrete model of lost person dynamics validated with data from real SAR incidents and has the potential to improve current methods for wilderness SAR.
A prenatal acoustic signal of heat affects thermoregulation capacities at adulthood in an arid-adapted bird
Authors: Pessato Anaïs , McKechnie Andrew E. , Mariette Mylene M.
Published: April 2022

Understanding animal physiological adaptations for tolerating heat, and the causes of inter-individual variation, is key for predicting climate change impacts on biodiversity. Recently, a novel mechanism for transgenerational heat adaptation was identified in a desert-adapted bird, where parents acoustically signal hot conditions to embryos. Prenatal exposure to “heat-calls” adaptively alters zebra finch development and their thermal preferences in adulthood, suggesting a long-term shift towards a heat-adapted phenotype. However, whether such acoustic experience improves long-term thermoregulatory capacities is unknown. We measured metabolic rate (MR), evaporative water loss (EWL) and body temperature in adults exposed to a stepped profile of progressively higher air temperatures (Ta) between 27 and 44 °C. Remarkably, prenatal acoustic experience affected heat tolerance at adulthood, with heat-call exposed individuals more likely to reach the highest Ta in morning trials. This was despite MR and EWL reaching higher levels at the highest Ta in heat-call individuals, partly driven by a stronger metabolic effect of moderate activity. At lower Ta, however, heat-call exposed individuals had greater relative water economy, as expected. They also better recovered mass lost during morning trials. We therefore provide the first evidence that prenatal acoustic signals have long-term consequences for heat tolerance and physiological adaptation to heat.
Age-related deficits in dip-listening evident for isolated sentences but not for spoken stories
Authors: Irsik Vanessa C. , Johnsrude Ingrid S. , Herrmann Björn
Published: April 2022

Fluctuating background sounds facilitate speech intelligibility by providing speech ‘glimpses’ (masking release). Older adults benefit less from glimpses, but masking release is typically investigated using isolated sentences. Recent work indicates that using engaging, continuous speech materials (e.g., spoken stories) may qualitatively alter speech-in-noise listening. Moreover, neural sensitivity to different amplitude envelope profiles (ramped, damped) changes with age, but whether this affects speech listening is unknown. In three online experiments, we investigate how masking release in younger and older adults differs for masked sentences and stories, and how speech intelligibility varies with masker amplitude profile. Intelligibility was generally greater for damped than ramped maskers. Masking release was reduced in older relative to younger adults for disconnected sentences, and stories with a randomized sentence order. Critically, when listening to stories with an engaging and coherent narrative, older adults demonstrated equal or greater masking release compared to younger adults. Older adults thus appear to benefit from ‘glimpses’ as much as, or more than, younger adults when the speech they are listening to follows a coherent topical thread. Our results highlight the importance of cognitive and motivational factors for speech understanding, and suggest that previous work may have underestimated speech-listening abilities in older adults.
Genetic diversity for agromorphological traits, phytochemical profile, and antioxidant activity in Moroccan sorghum ecotypes
Authors: Bouargalne Youssef , Ben Mrid Reda , Bouchmaa Najat , Zouaoui Zakia , Benmrid Bouchra , Kchikich Anass , El Omari Redouane , Kabach Imad , Mohamed Nhiri
Published: April 2022

Sorghum, the fifth most important cereal crop, is a well-adapted cereal to arid/semi-arid regions. Sorghum is known for multiple end-uses as food, feed, fuel, forage, and as source of bioactive compounds that could be used for medical applications. Although the great improvement in the process of sorghum breeding, the average yield of this crop is still very low. Therefore, exploring the genetic diversity in sorghum accessions is a critical step for improving this crop. The main objective of the current work was to study the genetic variation existing in a Moroccan sorghum collection. Indeed, 10 sorghum ecotypes were characterized based on agromorphological descriptors. Both quantitative (25) and qualitative (7) traits revealed variability (p < 0.05) among the studied ecotypes. At the seedling stage, most of the ecotypes showed good to high vigor (70%). However, as the sorghum plants grow, the difference between genotypes become more apparent, especially at the generative phase. For instance, three different panicle shapes have been observed, erect (50%), semi-bent (30%), and bent (20%) with different degree of compactness (20% for loose, semi-compact, and compact panicles, and 30% for semi-loose panicles). In another part of this study, the phytochemical composition and antioxidant activities of the sorghum ecotypes have been determined. The results showed variable total phenolic contents, and total flavonoid contents ranging from 125.86 ± 1.36 to 314.91 ± 3.60 mg GAE/g dw and 114.0 ± 13.2 to 138.5 ± 10.8 (mg catechin equivalent/100 g, dw) respectively, with a differential antioxidant activities as well. These results indicate that for any crop breeding program, it is preferable to take into consideration both morphological and biochemical traits for a better selection of high yielding varieties with high added value compounds. Therefore, the implication of these results in the context of sorghum breeding activities could be a resourceful option for farmers.
Integrated bioinformatic analysis of gene expression profiling data to identify combinatorial biomarkers in inflammatory skin disease
Authors: Bang Heejin , Kim Ja Eun , Lee Hyun Su , Park Sang Man , Park Dong-Joon , Lee Eun Jung
Published: April 2022

Selection of appropriate biomarker to identify inflammatory skin diseases is complicated by the involvement of thousands of differentially expressed genes (DEGs) across multiple cell types and organs. This study aimed to identify combinatorial biomarkers in inflammatory skin diseases. From one gene expression microarray profiling dataset, we performed bioinformatic analyses on dataset from lesional skin biopsies of patients with inflammatory skin diseases (atopic dermatitis [AD], contact eczema [KE], lichen planus [Li], psoriasis vulgaris [Pso]) and healthy controls to identify the involved pathways, predict upstream regulators, and potential measurable extracellular biomarkers. Overall, 434, 629, 581, and 738 DEGs were mapped in AD, KE, Li, and Pso, respectively; 238 identified DEGs were shared among four different inflammatory skin diseases. Bioinformatic analysis on four inflammatory skin diseases showed significant activation of pathways with known pathogenic relevance. Common upstream regulators, with upregulated predicted activity, identified were CNR1 and BMP4. We found the following common serum biomarkers: ACR, APOE, ASIP, CRISP1, DKK1, IL12B, IL9, MANF, MDK, NRTN, PCSK5, and VEGFC. Considerable differences of gene expression changes, involved pathways, upstream regulators, and biomarkers were found in different inflammatory skin diseases. Integrated bioinformatic analysis identified 12 potential common biomarkers of inflammatory skin diseases requiring further evaluation.
Implementation of quantum compression on IBM quantum computers
Authors: Pivoluska Matej , Plesch Martin
Published: April 2022

Advances in development of quantum computing processors brought ample opportunities to test the performance of various quantum algorithms with practical implementations. In this paper we report on implementations of quantum compression algorithm that can efficiently compress unknown quantum information. We restricted ourselves to compression of three pure qubits into two qubits, as the complexity of even such a simple implementation is barely within the reach of today’s quantum processors. We implemented the algorithm on IBM quantum processors with two different topological layouts—a fully connected triangle processor and a partially connected line processor. It turns out that the incomplete connectivity of the line processor affects the performance only minimally. On the other hand, it turns out that the transpilation, i.e. compilation of the circuit into gates physically available to the quantum processor, crucially influences the result. We also have seen that the compression followed by immediate decompression is, even for such a simple case, on the edge or even beyond the capabilities of currently available quantum processors.
Gadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway
Authors: Ariyani Winda , Miyazaki Wataru , Tsushima Yoshito , Koibuchi Noriyuki
Published: April 2022

Gadolinium (Gd)-based contrast agents (GBCAs) are chemicals injected intravenously during magnetic resonance imaging to enhance the diagnostic yield. Repeated use of GBCAs causes their deposition in the brain. Such deposition may affect various neuronal cells, including astrocytes. In this study, we examined the effect of GBCAs (Omniscan, Magnescope, Magnevist, and Gadovist) on astrocyte migration, which is critical for formation of neurons during development and maintaining brain homeostasis. All GBCAs increased cell migration and adhesion with increased actin remodelling. Knockdown of integrin αvβ3 by RNAi or exposure to integrin αvβ3 inhibitor reduced astrocyte migration. GBCAs increased phosphorylation of downstream factors of αvβ3, such as FAK, ERK1/2, and Akt. The phosphorylation of all these factors were reduced by RNAi or integrin αvβ3 inhibitor. GBCAs also increased the phosphorylation of their downstream factor, Rac1/cdc42, belonging to the RhoGTPases family. Coexposure to the selective RhoGTPases inhibitors, decreased the effects of GBCAs on cell migration. These findings indicate that GBCAs exert their action via integrin αvβ3 to activate the signaling pathway, resulting in increased astrocyte migration. Thus, the findings of the study suggest that it is important to avoid the repeated use of GBCAs to prevent adverse side effects in the brain, particularly during development.
Seroprevalence of SARS-CoV-2 spike IgG antibodies after the second BNT162b2 mRNA vaccine in Japanese kidney transplant recipients
Authors: Hamaya Tomoko , Hatakeyama Shingo , Yoneyama Tohru , Tobisawa Yuki , Kodama Hirotake , Fujita Takeshi , Murakami Reiichi , Fujita Naoki , Okamoto Teppei , Yamamoto Hayato , Yoneyama Takahiro , Hashimoto Yasuhiro , Saitoh Hisao , Narumi Shunji , Tomita Hirofumi , Ohyama Chikara
Published: April 2022

We aimed to evaluate the seroprevalence and investigated factors associated with seropositivity after the second SARS-CoV-2 mRNA vaccination in kidney transplant (KT) recipients. This retrospective study conducted between June and November 2021 included 106 KT recipients and 127 healthy controls who received the second dose of the BNT162b2 mRNA vaccine at least 7 days before the measurement of antibody titers. The antibody titer against the receptor-binding domain of SARS-CoV-2 spike (S) protein was determined. We compared seroprevalence rates (immunoglobulin G [IgG] level of ≥ 0.8 or ≥ 15 U/mL) between the healthy controls and KT recipients and identified factors associated with impaired humoral response. The seroprevalence rate of the healthy controls and KT recipients was 98% and 22%, respectively. Univariate logistic regression analysis revealed that age > 53 years, rituximab use, mycophenolate mofetil use, and KT vintage < 7 years were negatively associated with the rate of anti-SARS-CoV-2 S IgG ≥ 15 U/mL in KT recipients. ABO blood type incompatible KT was not significantly associated with seroprevalence. Humoral response after the second BNT162b2 mRNA vaccine was greatly hindered by immunosuppression therapy in KT recipients. Older age, rituximab use, mycophenolate mofetil use, and KT vintage may play key roles in seroconversion.
Stone toolmaking difficulty and the evolution of hominin technological skills
Authors: Muller Antoine , Shipton Ceri , Clarkson Chris
Published: April 2022

Stone tools are a manifestation of the complex cognitive and dexterous skills of our hominin ancestors. As such, much research has been devoted to understanding the skill requirements of individual lithic technologies. Yet, comparing skill across different technologies, and thus across the vast timespan of the Palaeolithic, is an elusive goal. We seek to quantify a series of commensurable metrics of knapping skill across four different lithic technologies (discoids, handaxes, Levallois, and prismatic blades). To compare the requisite dexterity, coordination, and care involved in each technology, we analysed video footage and lithic material from a series of replicative knapping experiments to quantify deliberation (strike time), precision (platform area), intricacy (flake size relative to core size), and success (relative blank length). According to these four metrics, discoidal knapping appears to be easiest among the sample. Levallois knapping involved an intricate reduction sequence, but did not require as much motor control as handaxes and especially prismatic blades. Compared with the other Palaeolithic technologies, we conclude that prismatic blade knapping is set apart by being a skill intensive means of producing numerous standardised elongate end-products.
Herding then farming in the Nile Delta
Authors: Zhao Xiaoshuang , Liu Yan , Thomas Ian , Salem Alaa , Wang Yanna , Alassal Said E. , Jiang Feng , Sun Qianli , Chen Jing , Finlayson Brian , Wilson Penelope , Chen Zhongyuan
Published: April 2022

The Nile Delta in Egypt represents a valuable location to study the history of human societal development and agricultural advancement. However, the livelihood patterns of the earliest settlers – whether they were farmers or herders – remains poorly understood. Here we use non-pollen palynomorphs and pollen grains from a sediment core taken at Sais, one of the earliest archaeological sites in the west-central Nile Delta, to investigate the livelihood patterns and transition of early settlers there. We find that animal microfossils (dung and hair) occur in substantial quantities from around 7,000 years ago in our high-resolution-dated non-pollen palynomorphs spectrum, while domesticated cereals emerge in the spectrum around 300 years later. We also identify evidence of fire-enhanced land exploitation after this time. We interpret our microfossil evidence to indicate that the earliest settlers in the Nile Delta were herders and that this then developed into a combination of herding and farming.