bluuebunny/crossref_metadata_2025 huggingface dataset:
A social turn for Construction Grammar: double modals on British Twitter
Authors: MORIN CAMERON , DESAGULIER GUILLAUME , GRIEVE JACK
Published: February 2024

Construction Grammar is an emerging theory of language, but the analysis of sociolinguistic variation is still relatively underdeveloped in the framework. In this article, we consider the representation of social meaning in Construction Grammar through a corpus-based analysis of double modals in British English on social media. We describe the use of double modals in a large corpus of geolocated Twitter posts, including presenting an inventory of observed double modals and maps showing the regional distribution of each of these forms. We find that double modals show a general northern pattern and are concentrated in the Scottish Borders. We also find various rare double modals that occur more widely across the UK. To account for these results, we propose a Construction Grammar account of double modals. We argue that defining double modals as grammatical constructions requires that aspects of their social meaning be delimited, especially register and region. Furthermore, we argue that double modals may be enregistered as dialect constructions, distinguished from standard constructions of British English. We conclude by considering the importance of incorporating social meaning into Construction Grammar, underlining the value of a Cognitive Sociolinguistic approach to grammatical theory.
Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO programme
Authors: Oken Emily , Musci Rashelle J , Westlake Matthew , Gachigi Kennedy , Aschner Judy L , Barnes Kathrine L , Bastain Theresa M , Buss Claudia , Camargo Carlos A , Cordero Jose F , Dabelea Dana , Dunlop Anne L , Ghassabian Akhgar , Hipwell Alison E , Hockett Christine W , Karagas Margaret R , Lugo-Candelas Claudia , Margolis Amy E , O’Connor Thomas G , Shuster Coral L , Straughen Jennifer K , Lyall Kristen
Published: February 2024

Objective:

n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake.

Design:

Pooled pregnancy cohort studies.

Setting:

Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020.

Participants:

A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use.

Results:

Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1–2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35–40 v. <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v. healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v. never).

Conclusions:

One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n-3 supplement use was uncommon, even among those who did not consume fish.
Teaching Greek: from school to university via fifteenth century Florence
Authors: Letchford Clive
Published: February 2024

The scene is Florence, Italy in 1493. The scholar and teacher Guarino of Favera is holding a series of classes for beginners in the Greek language. Few people know Greek since materials for learning it are few. We have an account of his method by Girolamo Amaseo, one of his pupils. Amaseo is one of 16 students whose ages range from youths to a 50-year old poet, and Guarino is teaching them some Iliad, Odyssey and Aristophanes each day.

Primo sententiam lectionis paucis et dilucide eleganterque colligit; post interpretationem primam, verborum et nominum inflexionem, si duriuscula est, reperit; etimologiam non tacet et figuras reliquas. Secundo eam ipsam lectionem percurrit et, ne quae prius dixerat obliviscamur confirmat, examinatque nos omnes et, post ipsam statim lectionem, aliquis e numero nostro eam exponit. Cogimur declinare, nec displicet: omnia enim studia suam habet infanciam.

First, he elegantly and lucidly expresses the meaning of the text in a few words. After the first translation, if the case of the verbs and nouns is a little difficult, he clarifies it. He does not neglect etymology or the other figures of speech. Second, he goes on through the same text and, so that we do not forget what he has just said, he reinforces it, examines us all and immediately after the reading of the text, one of us expounds it. We are required to decline the nouns, and this is not a chore: every study has its infancy. (Botley, 2010)
Is it Time to Include Wearable Sleep Trackers in the Applied Psychologists’ Toolbox?
Authors: Menghini Luca , Balducci Cristian , de Zambotti Massimiliano
Published: February 2024

Wearable sleep trackers are increasingly used in applied psychology. Particularly, the recent boom in the fitness tracking industry has resulted in a number of relatively inexpensive consumer-oriented devices that further enlarge the potential applications of ambulatory sleep monitoring. While being largely positioned as wellness tools, wearable sleep trackers could be considered useful health devices supported by a growing number of independent peer-reviewed studies evaluating their accuracy. The inclusion of sensors that monitor cardiorespiratory physiology, diurnal activity data, and other environmental signals allows for a comprehensive and multidimensional approach to sleep health and its impact on psychological well-being. Moreover, the increasingly common combination of wearable trackers and experience sampling methods has the potential to uncover within-individual processes linking sleep to daily experiences, behaviors, and other psychosocial factors. Here, we provide a concise overview of the state-of-the-art, challenges, and opportunities of using wearable sleep-tracking technology in applied psychology. Specifically, we review key device profiles, capabilities, and limitations. By providing representative examples, we highlight how scholars and practitioners can fully exploit the potential of wearable sleep trackers while being aware of the most critical pitfalls characterizing these devices. Overall, consumer wearable sleep trackers are increasingly recognized as a valuable method to investigate, assess, and improve sleep health. Incorporating such devices in research and professional practice might significantly improve the quantity and quality of the collected information while opening the possibility of involving large samples over representative time periods. However, a rigorous and informed approach to their use is necessary.
Geochemical Characteristics of Thermal Springs and Insights Into the Intersection Between the Xiaojiang Fault and the Red River Fault, Southeastern Tibet Plateau
Authors: Shao Weiye , Liu Zhaofei , Li Ying , Chen Zhi , Lu Chang , Zhao Ciping , Wang Yun , Li Qilin , Gao Zihan , Luo Yili , Ran Hua , Fan Shaohui
Published: February 2024

During the ongoing uplift and expansion of the southeastern margin of the Tibetan Plateau, the front edge of the Sichuan‐Yunnan rhombic block (SYB) has experienced intense tectonic activity and frequent seismicity. In this study, the fluid geochemistry in the primary active faults at the front edge of the SYB was investigated, with the aim of understanding the tectonic activity and intersection relationship between the Xiaojiang fault (XJF) and the Red River fault (RRF). Thermal spring water and gases exhibit a coupled spatial distribution relationship; relatively high ion concentrations and 3He/4He ratios (Rc/Ra ratios of 0.21 to 0.62Ra) are observed along the RRF, Qujiang fault (QJF), and Shiping‐Jianshui fault (SJF). Multidisciplinary research results have indicated that mantle‐derived intrusion has been detected in the crust beneath the QJF and SJF. The current tectonic activity in the front edge of the SYB remains intense, with compressive stresses shifting toward the western side of the XJF and accumulating on the QJF and SJF. This has led to the development of fractures, enhancing the water–rock interaction and deep‐derived gas degassing along the faults. The unmixing characteristics of fluids at the intersection area of these two faults suggest the absence of conduits for fluid migration between the faults. Owing to the lower gas 3He/4He ratios, lower shear strain rates, stable reservoir temperature field, and extremely low historical seismicity in the Indo‐Chinese block, it is speculated that the current movement of the XJF may not cut through the RRF and continue southward.
Dynamical Downscaling of Climate Simulations in the Tropics
Authors: Liu Shuchang , Zeman Christian , Schär Christoph
Published: February 2024

The long‐existing double‐Intertropical Convergence Zone (ITCZ) problem in global climate models (GCMs) hampers accurate climate simulations in the tropics. Using a regional climate model (RCM) over the tropical and sub‐tropical Atlantic with a horizontal resolution of 12 km and explicit convection, we develop a bias‐corrected downscaling methodology to produce limited‐area simulations with a realistic ITCZ, despite the double ITCZ in the driving GCM. The methodology effectively removes GCM biases in the RCM boundary conditions, such as to produce more realistic large‐scale driving conditions. We show that the double‐ITCZ problem persists with conventional dynamical downscaling, but with bias‐corrected downscaling the RCM simulations yield credible ITCZ with a realistic seasonal cycle. Detailed analysis attributes the main cause of the double‐ITCZ problem of the selected GCM to the sea surface temperature bias. Compared to the GCM's AMIP simulations, RCMs with higher resolution allow explicit deep convection and enable a better simulation of tropical convection and clouds.
On the Unloading‐Induced Fault Reactivation: The Effect of Stress Path on Failure Criterion and Rupture Dynamics
Authors: Dong Peng , Xu Ying , Xu Ran , Xia Kaiwen , Peng Jianbing
Published: February 2024

Fault reactivations induced by deep excavation can pose significant challenges to underground construction or resource extraction. Laboratory experiments on rock faults demonstrate that unloading‐induced fault reactivations obey the Coulomb failure criterion derived from loading‐induced events. However, the effect of stress path during unloading on the failure criterion and rupture dynamics of fault reactivations remains poorly understood. Here, we present findings from a series of laboratory experiments aimed at elucidating the effect of the unloading path on the failure criterion and rupture dynamics of fault reactivations. We conducted experiments under various stress conditions, examining two cases of unloading paths. In Case I, we unloaded the minimum principal stress, while in Case II, the maximum principal stress was unloaded. Strain gauges and high‐speed photography were employed to capture the transient dynamic rupture process. Our investigations have yielded new insights into the effect of unloading path on the rupture dynamics when the fault is reactivated. In Case I, we observed fault reactivations resembling those loading‐induced events characterized by forward sliding. Conversely, in Case II, fault reactivations associated with stress reversal produce mild reversed sliding with lower stress drop and rupture velocity. Furthermore, we find that there is a remarkable reduction in static friction for reversed sliding, indicating that the failure criterion for fault reactivation is influenced by the stress path. We demonstrate that enhanced stress heterogeneity, caused by stress reversal, serves as a mechanism for reduced static friction. These findings contribute to our understanding of the mechanisms underlying fault reactivations, particularly those involving reversed sliding.
Impacts of Marine Heatwaves on Subsurface Temperatures and Dissolved Oxygen in the Chesapeake Bay
Authors: Shunk Nathan P. , Mazzini Piero L. F. , Walter Ryan K.
Published: February 2024

Subsurface impacts associated with Marine Heatwaves (MHWs) in estuaries are not well understood, largely due to data scarcity. Using over three decades (1986–2021) of observations from several monitoring programs, this study investigates subsurface temperature and dissolved oxygen (DO) anomalies associated with surface MHWs in the Chesapeake Bay (CB). Seasonal variability in temperature anomalies followed a simple 1‐D response to surface heating with downward heat transport and diffusion controlled by seasonally variable stratification and mixing. Two distinct temperature regimes were found: a thermally stratified spring‐summer regime, when positive temperature anomalies were confined to the surface mixed layer (SML); and a homogeneous fall‐winter regime. Additionally, surface (subsurface) temperatures were elevated for months (days to weeks) before and after MHWs, indicating individual events were shorter than the timescales of elevated temperatures. A simple 1‐D SML heat budget identified air‐estuary heat flux changes as the leading driver of MHW onsets and declines, with latent heat flux being the dominant term. DO anomaly patterns were more complex, with considerable along‐channel gradients. Notable DO decreases (1–4 mg L−1) primarily occurred in the winter/spring below the SML, and the hypoxic zone expanded from spring through fall. Only a small fraction of these DO anomalies could be attributed to MHW temperature‐induced solubility changes, demonstrating that other physical and/or biogeochemical processes dominate changes in DO during these events. In CB, concurrent low DO and persistent high temperatures could compound the impacts of MHWs on this valuable ecosystem, with MHW event impacts likely to be exacerbated by climate change.
Antarctic Ice Cores Capture Heavy Metal Pollution—And History
Authors: Kornei Katherine
Published: February 2024

An ice core record stretching back more than 2 millennia hints at the mining and metallurgy that waxed and waned with events such as wars and epidemics.
LncRNA MACC1-AS1 induces gemcitabine resistance in pancreatic cancer cells through suppressing ferroptosis
Authors: Zhu Jiyun , Yu Zehao , Wang Xuguang , Zhang Jinghui , Chen Yi , Chen Kaibo , Zhang Bin , Sun Jianhong , Jiang Jianshuai , Zheng Siming
Published: February 2024

Pancreatic ductal adenocarcinoma (PDA) mortality is primarily attributed to metastasis and chemotherapy resistance. In this research, the long non-coding RNA MACC1-AS1 was studied, playing a significant role in regulating lipid oxidation processes. This regulation could further lead to the inhibition of ferroptosis induced by chemotherapeutic drugs, making it a contributing factor to gemcitabine resistance in PDA. In both gemcitabine-resistant PDA patients and mouse models, the elevated expression level of MACC1-AS1 in the tumors was noted. Additionally, overexpression of MACC1-AS1 in pancreatic cancer cells was found to enhance tolerance to gemcitabine and suppress ferroptosis. Proteomic analysis of drug-resistant pancreatic cells revealed that overexpressed MACC1-AS1 inhibited the ubiquitination degradation of residues in the protein kinase STK33 by MDM4. Furthermore, its accumulation in the cytoplasm activated STK33, further activating the ferroptosis-suppressing proteins GPX4, thereby counteracting gemcitabine-induced cellular oxidative damage. These findings suggested that the long non-coding RNA MACC1-AS1 could play a significant role in the ability of pancreatic cancer cells to evade iron-mediated ferroptosis induced by gemcitabine. This discovery holds promise for developing clinical therapeutic strategies to combat chemotherapy resistance in pancreatic cancer.
The E3 ubiquitin ligase MARCH2 protects against myocardial ischemia-reperfusion injury through inhibiting pyroptosis via negative regulation of PGAM5/MAVS/NLRP3 axis
Authors: Liu Shuolin , Bi Yaguang , Han Tianting , Li Yiran E. , Wang Qihang , Wu Ne Natalie , Xu Chenguo , Ge Junbo , Hu Ronggui , Zhang Yingmei
Published: February 2024

Inflammasome activation and pyroptotic cell death are known to contribute to the pathogenesis of cardiovascular diseases, such as myocardial ischemia-reperfusion (I/R) injury, although the underlying regulatory mechanisms remain poorly understood. Here we report that expression levels of the E3 ubiquitin ligase membrane-associated RING finger protein 2 (MARCH2) were elevated in ischemic human hearts or mouse hearts upon I/R injury. Genetic ablation of MARCH2 aggravated myocardial infarction and cardiac dysfunction upon myocardial I/R injury. Single-cell RNA-seq analysis suggested that loss of MARCH2 prompted activation of NLRP3 inflammasome in cardiomyocytes. Mechanistically, phosphoglycerate mutase 5 (PGAM5) was found to act as a novel regulator of MAVS-NLRP3 signaling by forming liquid-liquid phase separation condensates with MAVS and fostering the recruitment of NLRP3. MARCH2 directly interacts with PGAM5 to promote its K48-linked polyubiquitination and proteasomal degradation, resulting in reduced PGAM5–MAVS co-condensation, and consequently inhibition of NLRP3 inflammasome activation and cardiomyocyte pyroptosis. AAV-based re-introduction of MARCH2 significantly ameliorated I/R-induced mouse heart dysfunction. Altogether, our findings reveal a novel mechanism where MARCH2-mediated ubiquitination negatively regulates the PGAM5/MAVS/NLRP3 axis to protect against cardiomyocyte pyroptosis and myocardial I/R injury.
People quasi-randomly assigned to farm rice are more collectivistic than people assigned to farm wheat
Authors: Talhelm Thomas , Dong Xiawei
Published: February 2024

The rice theory of culture argues that the high labor demands and interdependent irrigation networks of paddy rice farming makes cultures more collectivistic than wheat-farming cultures. Despite prior evidence, proving causality is difficult because people are not randomly assigned to farm rice. In this study, we take advantage of a unique time when the Chinese government quasi-randomly assigned people to farm rice or wheat in two state farms that are otherwise nearly identical. The rice farmers show less individualism, more loyalty/nepotism toward a friend over a stranger, and more relational thought style. These results rule out confounds in tests of the rice theory, such as temperature, latitude, and historical events. The differences suggest rice-wheat cultural differences can form in a single generation.
Chemoenzymatic indican for light-driven denim dyeing
Authors: Bidart Gonzalo Nahuel , Teze David , Jansen Charlotte Uldahl , Pasutto Eleonora , Putkaradze Natalia , Sesay Anna-Mamusu , Fredslund Folmer , Lo Leggio Leila , Ögmundarson Olafur , Sukumara Sumesh , Qvortrup Katrine , Welner Ditte Hededam
Published: February 2024

Blue denim, a billion-dollar industry, is currently dyed with indigo in an unsustainable process requiring harsh reducing and alkaline chemicals. Forming indigo directly in the yarn through indican (indoxyl-β-glucoside) is a promising alternative route with mild conditions. Indican eliminates the requirement for reducing agent while still ending as indigo, the only known molecule yielding the unique hue of blue denim. However, a bulk source of indican is missing. Here, we employ enzyme and process engineering guided by techno-economic analyses to develop an economically viable drop-in indican synthesis technology. Rational engineering of PtUGT1, a glycosyltransferase from the indigo plant, alleviated the severe substrate inactivation observed with the wildtype enzyme at the titers needed for bulk production. We further describe a mild, light-driven dyeing process. Finally, we conduct techno-economic, social sustainability, and comparative life-cycle assessments. These indicate that the presented technologies have the potential to significantly reduce environmental impacts from blue denim dyeing with only a modest cost increase.
Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation
Authors: Kirchberger Stefanie , Shoeb Mohamed R. , Lazic Daria , Wenninger-Weinzierl Andrea , Fischer Kristin , Shaw Lisa E. , Nogueira Filomena , Rifatbegovic Fikret , Bozsaky Eva , Ladenstein Ruth , Bodenmiller Bernd , Lion Thomas , Traver David , Farlik Matthias , Schöfer Christian , Taschner-Mandl Sabine , Halbritter Florian , Distel Martin
Published: February 2024

Neutrophils are evolutionarily conserved innate immune cells playing pivotal roles in host defense. Zebrafish models have contributed substantially to our understanding of neutrophil functions but similarities to human neutrophil maturation have not been systematically characterized, which limits their applicability to studying human disease. Here we show, by generating and analysing transgenic zebrafish strains representing distinct neutrophil differentiation stages, a high-resolution transcriptional profile of neutrophil maturation. We link gene expression at each stage to characteristic transcription factors, including C/ebp-β, which is important for late neutrophil maturation. Cross-species comparison of zebrafish, mouse, and human samples confirms high molecular similarity of immature stages and discriminates zebrafish-specific from pan-species gene signatures. Applying the pan-species neutrophil maturation signature to RNA-sequencing data from human neuroblastoma patients reveals association between metastatic tumor cell infiltration in the bone marrow and an overall increase in mature neutrophils. Our detailed neutrophil maturation atlas thus provides a valuable resource for studying neutrophil function at different stages across species in health and disease.
Finite-momentum Cooper pairing in proximitized altermagnets
Authors: Zhang Song-Bo , Hu Lun-Hui , Neupert Titus
Published: February 2024

Finite-momentum Cooper pairing is an unconventional form of superconductivity that is widely believed to require finite magnetization. Altermagnetism is an emerging magnetic phase with highly anisotropic spin-splitting of specific symmetries, but zero net magnetization. Here, we study Cooper pairing in metallic altermagnets connected to conventional s-wave superconductors. Remarkably, we find that the Cooper pairs induced in the altermagnets acquire a finite center-of-mass momentum, despite the zero net magnetization in the system. This anomalous Cooper-pair momentum strongly depends on the propagation direction and exhibits unusual symmetric patterns. Furthermore, it yields several unique features: (i) highly orientation-dependent oscillations in the order parameter, (ii) controllable 0-π transitions in the Josephson supercurrent, (iii) large-oblique-angle Cooper-pair transfer trajectories in junctions parallel with the direction where spin splitting vanishes, and (iv) distinct Fraunhofer patterns in junctions oriented along different directions. Finally, we discuss the implementation of our predictions in candidate materials such as RuO2 and KRu4O8.
Deaggregation of mutant Plasmodium yoelii de-ubiquitinase UBP1 alters MDR1 localization to confer multidrug resistance
Authors: Xu Ruixue , Lin Lirong , Jiao Zhiwei , Liang Rui , Guo Yazhen , Zhang Yixin , Shang Xiaoxu , Wang Yuezhou , Wang Xu , Yao Luming , Liu Shengfa , Deng Xianming , Yuan Jing , Su Xin-zhuan , Li Jian
Published: February 2024

Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine. Mechanistically, the double mutations are shown to impair UBP1 cytoplasmic aggregation and de-ubiquitinating activity, leading to increased ubiquitination levels and altered protein localization, from the parasite digestive vacuole to the plasma membrane, of the P. yoelii multidrug resistance transporter 1 (MDR1). The MDR1 on the plasma membrane enhances the efflux of substrates/drugs out of the parasite cytoplasm to confer multidrug resistance, which can be reversed by inhibition of MDR1 transport. This study reveals a previously unknown drug-resistant mechanism mediated by UBP1 through altered MDR1 localization and substrate transport direction in a mouse model, providing a new malaria treatment strategy.
Q586B2 is a crucial virulence factor during the early stages of Trypanosoma brucei infection that is conserved amongst trypanosomatids
Authors: Stijlemans Benoit , De Baetselier Patrick , Van Molle Inge , Lecordier Laurence , Hendrickx Erika , Romão Ema , Vincke Cécile , Baetens Wendy , Schoonooghe Steve , Hassanzadeh-Ghassabeh Gholamreza , Korf Hannelie , Wallays Marie , Pinto Torres Joar E. , Perez-Morga David , Brys Lea , Campetella Oscar , Leguizamón María S. , Claes Mathieu , Hendrickx Sarah , Mabille Dorien , Caljon Guy , Remaut Han , Roelants Kim , Magez Stefan , Van Ginderachter Jo A. , De Trez Carl
Published: February 2024

Human African trypanosomiasis or sleeping sickness, caused by the protozoan parasite Trypanosoma brucei, is characterized by the manipulation of the host’s immune response to ensure parasite invasion and persistence. Uncovering key molecules that support parasite establishment is a prerequisite to interfere with this process. We identified Q586B2 as a T. brucei protein that induces IL-10 in myeloid cells, which promotes parasite infection invasiveness. Q586B2 is expressed during all T. brucei life stages and is conserved in all Trypanosomatidae. Deleting the Q586B2-encoding Tb927.6.4140 gene in T. brucei results in a decreased peak parasitemia and prolonged survival, without affecting parasite fitness in vitro, yet promoting short stumpy differentiation in vivo. Accordingly, neutralization of Q586B2 with newly generated nanobodies could hamper myeloid-derived IL-10 production and reduce parasitemia. In addition, immunization with Q586B2 delays mortality upon a challenge with various trypanosomes, including Trypanosoma cruzi. Collectively, we uncovered a conserved protein playing an important regulatory role in Trypanosomatid infection establishment.
Mesoscopic fluctuations in entanglement dynamics
Authors: Lim Lih-King , Lou Cunzhong , Tian Chushun
Published: February 2024

Understanding fluctuation phenomena plays a dominant role in the development of many-body physics. The time evolution of entanglement is essential to a broad range of subjects in many-body physics, ranging from exotic quantum matter to quantum thermalization. Stemming from various dynamical processes of information, fluctuations in entanglement evolution differ conceptually from out-of-equilibrium fluctuations of traditional physical quantities. Their studies remain elusive. Here we uncover an emergent random structure in the evolution of the many-body wavefunction in two classes of integrable—either interacting or noninteracting—lattice models. It gives rise to out-of-equilibrium entanglement fluctuations which fall into the paradigm of mesoscopic fluctuations of wave interference origin. Specifically, the entanglement entropy variance obeys a universal scaling law in each class, and the full distribution displays a sub-Gaussian upper and a sub-Gamma lower tail. These statistics are independent of both the system’s microscopic details and the choice of entanglement probes, and broaden the class of mesoscopic universalities. They have practical implications for controlling entanglement in mesoscopic devices.
Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review
Authors: Kingsmore Stephen F. , Nofsinger Russell , Ellsworth Kasia
Published: February 2024

Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, and net healthcare costs were reduced by $14,265 per child tested by URGS, RGS, or RES. URGS outperformed RGS and RES with faster time to diagnosis, and higher rate of diagnosis and clinical utility. Diagnostic and clinical outcomes will improve as methods evolve, costs decrease, and testing is implemented within precision medicine delivery systems attuned to ICU needs. URGS, RGS, and RES are currently performed in <5% of the ~200,000 children likely to benefit annually due to lack of payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition of possible genetic diseases, and current formatting as tests rather than as a rapid precision medicine delivery system. The gap between actual and optimal outcomes in children in ICUs is currently increasing since expanded use of URGS, RGS, and RES lags growth in those likely to benefit through new therapies. There is sufficient evidence to conclude that URGS, RGS, or RES should be considered in all children with diseases of uncertain etiology at ICU admission. Minimally, diagnostic URGS, RGS, or RES should be ordered early during admissions of critically ill infants and children with suspected genetic diseases.
Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A
Authors: Mahheidari Naimeh , Kamalabadi-Farahani Mohammad , Nourani Mohammad Reza , Atashi Amir , Alizadeh Morteza , Aldaghi Niloofar , Salehi Majid
Published: February 2024

A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.
Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics
Authors: Liu Gary W. , Pickett Matthew J. , Kuosmanen Johannes L. P. , Ishida Keiko , Madani Wiam A. M. , White Georgia N. , Jenkins Joshua , Park Sanghyun , Feig Vivian R. , Jimenez Miguel , Karavasili Christina , Lal Nikhil B. , Murphy Matt , Lopes Aaron , Morimoto Joshua , Fitzgerald Nina , Cheah Jaime H. , Soule Christian K. , Fabian Niora , Hayward Alison , Langer Robert , Traverso Giovanni
Published: February 2024

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.
Pan-chloroplast genomes for accession-specific marker development in Hibiscus syriacus
Authors: Go Sangjin , Koo Hyunjin , Jung Minah , Hong Seongmin , Yi Gibum , Kim Yong-Min
Published: February 2024

Hibiscus syriacus L. is a renowned ornamental plant. We constructed 95 chloroplast genomes of H. syriacus L. cultivars using a short-read sequencing platform (Illumina) and a long-read sequencing platform (Oxford Nanopore Technology). The following genome assembly, we delineate quadripartite structures encompassing large single-copy, small single-copy, and inverted repeat (IRa and IRb) regions, from 160,231 bp to 161,041 bp. Our comprehensive analyses confirmed the presence of 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes in the pan-chloroplast genome, consistent with prior research on the H. syriacus chloroplast genome. Subsequent pangenome analysis unveiled widespread genome sequence conservation alongside unique cultivar-specific variant patterns consisting of 193 single-nucleotide polymorphisms and 61 insertions or deletions. The region containing intra-species variant patterns, as identified in this study, has the potential to develop accession-specific molecular markers, enhancing precision in cultivar classification. These findings are anticipated to drive advancements in breeding strategies, augment biodiversity, and unlock the agricultural potential inherent in H. syriacus.
High-quality genome assembly of a C. crossoptilon and related functional and genetics data resources
Authors: Wu Siwen , Wang Kun , Dou Tengfei , Yuan Sisi , Wu Dong-Dong , Ge Changrong , Jia Junjing , Su Zhengchang
Published: February 2024

There are four species in the Crossoptilon genus inhibiting at from very low to very high altitudes across China, and they are in varying levels of danger of extinction. To better understand the genetic basis of adaptation to high altitudes and genetic changes due to bottleneck, we assembled the genome (~1.02 Gb) of a white eared pheasant (WT) (Crossoptilon crossoptilon) inhibiting at high altitudes (3,000~7,000 m) in northwest of Yunnan province, China, using a combination of Illumina short reads, PacBio long reads and Hi-C reads, with a contig N50 of 19.63 Mb and only six gaps. To further provide resources for gene annotation as well as functional and population genetics analyses, we sequenced transcriptomes of 20 major tissues of the WT individual and re-sequenced another 10 WT individuals and a blue eared pheasant (Crossoptilon auritum) individual inhabiting at intermediate altitudes (1,500~3,000 m). Our assembled WT genome, transcriptome data, and DNA sequencing data can be valuable resources for studying the biology, evolution and developing conservation strategies of these endangered species.
Synergistic activity of Limosilactobacillus reuteri KUB-AC5 and water-based plants against Salmonella challenge in a human in vitro gut model
Authors: Mok Kevin , Honwichit Orranich , Funnuam Thanyakan , Charoensiddhi Suvimol , Nitisinprasert Sunee , Nielsen Dennis Sandris , Nakphaichit Massalin
Published: February 2024

A synbiotic is a combination of live microorganisms and specific substrates that are selectively utilized by host microorganisms, resulting in health benefits for the host. Previous studies have demonstrated the protective effects of L. reuteri KUB-AC5 against Salmonella infection in chicken and mouse models. The probiotic activity of L. reuteri KUB-AC5 in these hosts was influenced by nutritional supplements. Water-based plants contain significant amounts of carbohydrates, particularly dietary fiber and proteins, making them potential prebiotic substrates. In this study, four water-based plants (Ulva rigida, Caulerpa lentillifera, Wolffia globosa, and Gracillaria fisheri) were screened for their ability to support the growth of L. reuteri KUB-AC5. Under monoculture testing, U. rigida exhibited the highest capacity to support the growth of L. reuteri KUB-AC5 and the production of organic acids, including acetic acid, lactic acid, and propionic acid (p ≤ 0.05). In co-culture experiments, the synbiotic combination of U. rigida and L. reuteri KUB-AC5 demonstrated the potential to eliminate Salmonella Typhimurium DMST 48437 when inoculated at 104 CFU/mL within 9 h. The synbiotic activities of U. rigida and L. reuteri KUB-AC5 were further investigated using an in vitro human gut model. Compared to the probiotic treatment, the synbiotic combination of L. reuteri KUB-AC5 and U. rigida showed significantly higher levels of L. reuteri KUB-AC5 (5.1 log copies/mL) and a reduction of S. Typhimurium by 0.8 log (CFU/ml) after 24 h (p ≤ 0.05). Synbiotic treatment also significantly promoted the production of short-chain fatty acids (SCFAs), including butyric acid, propionic acid, and acetic acid, compared to prebiotic and probiotic treatments alone (p ≤ 0.05). Furthermore, the synbiotic formulation modulated the in vitro simulated gut microbiome, enhancing putatively beneficial gut microbes, including lactobacilli, Faecalibacterium, and Blautia. Our findings demonstrated that L. reuteri KUB-AC5, in combination with U. rigida, exhibited synergistic activity, as indicated by increased viability, higher anti-pathogenicity toward Salmonella, and the ability to modulate the gut microbiome.
Association of adverse childhood experiences with anemia in older Chinese: Guangzhou Biobank Cohort Study
Authors: He Shao Yi , Zhang Wei Sen , Jiang Chao Qiang , Jin Ya Li , Lam Tai Hing , Cheng Kar Keung , Xu Lin
Published: February 2024

To examine the association of adverse childhood experiences (ACEs) with anemia among older people. 24,116 participants aged 50 years or above were recruited. Multivariable linear and logistic regression was used to assess the associations of self-reported ACEs number with hemoglobin concentrations (g/dL) and presence of anemia. Older individuals with two or more ACEs, versus no ACEs, showed lower hemoglobin concentrations (β =  − 0.08 g/dL, 95% confidence intervals (CI) − 0.12 to − 0.03) and higher odds of anemia (odds ratio = 1.26, 95% CI 1.01–1.59). A more pronounced association between ACEs and anemia in the lower education group was found, while the association became non-significant in those with higher education (P for ACEs-education interaction = 0.02). ACEs was associated with anemia in older people, and the association was stronger in those with lower education, highlighting the significance of early-life psychological stressors assessment and consideration of education background in geriatric care.
Assessing the association between tea intake and risk of dental caries and periodontitis: a two-sample Mendelian randomization study
Authors: Jin Bilun , Chen Heng , Liu Peiqi , Wang Yijie , Guo Yi , Wang Chenxu , Jia Yue , Zou Rui , Niu Lin
Published: February 2024

Tea is an indispensable beverage in people’s daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P < 5.0 × 10–8). Mendelian randomization (MR) was performed to investigate the potential causality between tea intake and caries and periodontitis. Multivariable Mendelian randomization (MVMR) analyses were utilized to estimate causal effects of tea intake on risk of caries and periodontitis after adjusting for smoking, body mass index (BMI), and socioeconomic factors. The results showed that higher tea intake was suggestively associated with fewer natural teeth (β = − 0.203; 95% CI = 0.680 to 0.980; P = 0.029) and higher risk of periodontitis (OR = 1.622; 95% CI = 1.194 to 2.205; P = 0.002). After Bonferroni correction, the causality of tea intake on periodontitis remained significant. The significance of periodontitis disappeared after adjusting for the socioeconomic factors in MVMR (OR = 1.603; 95% CI = 0.964 to 2.666; P = 0.069). Tea intake had no association with risk of caries. Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Our results provide insight into the potential relationship between tea intake and oral diseases from a dietary lifestyle perspective, which may help prevent oral diseases.
An improved V-Net lung nodule segmentation model based on pixel threshold separation and attention mechanism
Authors: Ma Xiaopu , Song Handing , Jia Xiao , Wang Zhan
Published: February 2024

Accurate labeling of lung nodules in computed tomography (CT) images is crucial in early lung cancer diagnosis and before nodule resection surgery. However, the irregular shape of lung nodules in CT images and the complex lung environment make it much more challenging to segment lung nodules accurately. On this basis, we propose an improved V-Net segmentation method based on pixel threshold separation and attention mechanism for lung nodules. This method first offers a data augment strategy to solve the problem of insufficient samples in 3D medical datasets. In addition, we integrate the feature extraction module based on pixel threshold separation into the model to enhance the feature extraction ability under different thresholds on the one hand. On the other hand, the model introduces channel and spatial attention modules to make the model pay more attention to important semantic information and improve its generalization ability and accuracy. Experiments show that the Dice similarity coefficients of the improved model on the public datasets LUNA16 and LNDb are 94.9% and 81.1% respectively, and the sensitivities reach 92.7% and 76.9% respectively. which is superior to most existing UNet architecture models and comparable to the manual level segmentation results by medical technologists.
Protective effect of microbisporicin (NAI-107) against vancomycin resistant Enterococcus faecium infection in a Galleria mellonella model
Authors: Hofkens Nele , Gestels Zina , Abdellati Saïd , Gabant Philippe , Rodriguez-Villalobos Hector , Martin Anandi , Kenyon Chris , Manoharan-Basil Sheeba Santhini
Published: February 2024

Increasing antimicrobial resistance in Enterococcus faecium necessitates the search for novel treatment agents, such as bacteriocins. In this study, we conducted an in vivo assessment of five bacteriocins, namely Lacticin Z, Lacticin Q, Garvicin KS (ABC), Aureocin A53 and Microbisporicin (NAI-107), against vanB-resistant Enterococcus faecium using a Galleria mellonella model. Our in vitro experiments demonstrated the efficacy of all five bacteriocins against vanB-resistant E. faecium with only NAI-107 demonstrating in vivo efficacy. Notably, NAI-107 exhibited efficacy across a range of tested doses, with the highest efficacy observed at a concentration of 16 µg/mL. Mortality rates in the group treated with 16 µg/mL NAI-107 were lower than those observed in the linezolid-treated group. These findings strongly suggest that NAI-107 holds promise as a potential alternative therapeutic agent for treating infections caused by resistant E. faecium and warrants further investigation.
Acute mountain sickness predicts the emotional state of amateur mountaineers
Authors: Zeng Zhengyang , Zhou Yun , Li Lun
Published: February 2024

Research on amateur mountaineers is scarce, and this study aims to delve into the emotional experiences of ten amateur mountaineers during their ascent using the "Befindlichkeitsskala" (BFS) and Lake Louise Acute Mountain Sickness scoring system (LLS). These subjects were exposed to altitudes of 3140 m, 4300 m, and 5276 m, respectively. We found that LLS scores were negatively correlated with positive emotions (β = −27.54, p < 0.05) and positively correlated with negative emotions (β = 21.97, p < 0.05). At an altitude of 4300 m, individuals with AMS exhibited significant differences in depression, anger, excitement, and inactivity compared to climbers without AMS. Upon returning to 3140 m after completing the climb, significant differences were observed in emotions such as happiness, calmness, anger, excitement, and depression. Throughout the three-day climb, noteworthy differences emerged in activity, happiness, calmness, inactivity, positive emotions (p < 0.01), negative emotions, and overall emotional scores (p < 0.05). Our study suggests a decline in the emotional well-being of amateur climbers with increasing altitude, highlighting AMS as a pivotal predictive factor for emotional experiences while climbing.
Shear stiffening gel-enabled twisted string for bio-inspired robot actuators
Authors: Zhang Qingqing , Xue Yuxuan , Zhao Yafei , Zou Kehan , Yuan Wenbo , Tian Yuqing , Chen Jiaming , Chen Jiangcheng , Xi Ning
Published: February 2024

A rotary motor combined with fibrous string demonstrates excellent performance because it is powerful, lightweight, and prone to large strokes; however, the stiffness range and force-generating capability of twisted string transmission systems are limited. Here, we present a variable stiffness artificial muscle generated by impregnating shear stiffening gels (STGs) into a twisted string actuator (TSA). A high twisting speed produces a large impact force and causes shear stiffening of the STG, thereby improving the elasticity, stiffness, force capacity, and response time of the TSA. We show that at a twisting speed of 4186 rpm, the elasticity of an STG-TSA reached 30.92 N/mm, whereas at a low twisting speed of 200 rpm, it was only 10.51 N/mm. In addition, the STG-TSA exhibited a more prominent shear stiffening effect under a high stiffness load. Our work provides a promising approach for artificial muscles to coactivate with human muscles to effectively compensate for motion.
Optimizing SH-SY5Y cell culture: exploring the beneficial effects of an alternative media supplement on cell proliferation and viability
Authors: Kaya Zeynep Bengisu , Santiago-Padilla Valeria , Lim Melina , Boschen Suelen L. , Atilla Pergin , McLean Pamela J.
Published: February 2024

In the quest to unravel the mysteries of neurological diseases, comprehending the underlying mechanisms is supreme. The SH-SY5Y human neuroblastoma cell line serves as a crucial tool in this endeavor; however, the cells are known for its sensitivity and slow proliferation rates. Typically, this cell line is cultured with 10% Fetal Bovine Serum (FBS) supplement. Nu-Serum (NuS), a low-protein alternative to FBS, is promising to advance cell culture practices. Herein, we evaluated the substitution of NuS for FBS to test the hypothesis that an alternative serum supplement can aid and promote SH-SY5Y cell proliferation and differentiation. Our findings revealed that the NuS-supplemented group exhibited a notable increase in adhered cells compared to both the FBS and serum-free (SF) groups. Importantly, cell viability remained high in both sera treated groups, with the NuS-supplemented cells displaying significantly larger cell sizes compared to the SF-treated group. Furthermore, cell proliferation rates were higher in the NuS-treated group, and neuroblast-like morphology was observed earlier than FBS group. Notably, both FBS and NuS supported the differentiation of these cells into mature neurons. Our data supports NuS as an alternative for SH-SY5Y cell culture, with the potential to elevate the quality of research in the neuroscience field.