bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the interplay between targeted motivation interventions and motivational teaching practices in mathematics classrooms
Authors: Gaspard Hanna , Parrisius Cora , Nagengast Benjamin , Trautwein Ulrich
Published: November 2022

Prior research has shown that brief motivation interventions, such as interventions targeting students’ perceptions concerning relevance of the learning material, can have long-lasting effects on students’ motivation and performance. However, the educational contexts in which these interventions have been implemented have their own motivational affordances, such as the extent to which teachers support students’ perceptions of relevance in regular classes. According to the seed-and-soil hypothesis for the effectiveness of psychological interventions, such interventions can be seen like a “seed” that needs to be implemented in a supportive educational context (i.e., the “soil”) in order to work. Therefore, in this study we examined the interplay between a one-time relevance intervention implemented in mathematics classrooms and the mathematics teacher’s relevance support as perceived by the students before and after the intervention. Data stemmed from a cluster-randomized controlled trial with 79 ninth-grade mathematics classes (N = 1744 students) in which the intervention was implemented by the mathematics teacher or a master’s student, both trained for this purpose. Multilevel moderation models showed that both intervention conditions had larger effects when students perceived higher relevance support before or after the intervention, thus providing support for the seed-and-soil hypothesis. Furthermore, multilevel mediation models indicated a positive effect of the teacher condition on perceived relevance support at posttest compared with the control condition, which partly explained the positive effect of this intervention condition on utility value at follow-up. The results shed light on the contexts in which these interventions are most effective and the mechanisms through which they work.
PCSK9 Inhibition and Risk of Diabetes: Should We Worry?
Authors: Carugo Stefano , Sirtori Cesare R. , Corsini Alberto , Tokgozoglu Lale , Ruscica Massimiliano
Published: November 2022

Purpose of Review

Since the clinical benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors occurs in a setting of reducing low-density lipoprotein-cholesterol (LDL-C) to unprecedentedly low levels, it becomes of interest to investigate possible adverse effects pertaining to the risk of new-onset diabetes (NOD).

Recent Findings

While safety results reported in either meta-analyses or cardiovascular outcome trials FOURIER (with evolocumab) and ODYSSEY (with alirocumab) did not rise the incidence of NOD, Mendelian randomization analyses were almost concordant in showing an increased risk of NOD. This evidence was in line with post-marketing safety reports highlighting that evolocumab and alirocumab were primarily related to mild hyperglycaemia rather than diabetes, with most of the hyperglycaemic events occurring during the first 6 months of treatment.

Considering the different nature of genetic studies and of randomized controlled trials, with careful monitoring of patients, particularly in the earlier phases of treatment, and the identification of those more susceptible to develop NOD, treatment with PCSK9 inhibitors should be of minimal concern.
Comparison and Investigation of Exosomes from Human Amniotic Fluid Stem Cells and Human Breast Milk in Alleviating Neonatal Necrotizing Enterocolitis
Authors: Hu Xiaohan , Zhang Rui , Liang Hansi , An Jingnan , Yang Yuan , Huo Jie , Chen Zhenjiang , Quan Wei , Jiang Lu , Li Cancan , Li Jian , Li Fang , Xu Yunyun , Zhu Xueping
Published: November 2022

In view of the devastating impact of neonatal necrotizing enterocolitis (NEC) on newborns, the research on its intervention is particularly important. Although exosomes from human amniotic fluid stem cells (AFSC) and human breast milk (HBM) can protect against NEC, their mechanisms remain unclear. Here, we intend to compare the intervention effects of two types of exosomes on NEC mouse model and reveal their respective regulatory mechanisms. In general, both AFSC-derived exosomes (AFSC-exos) and HBM-derived exosomes (HBM- exos) can alleviate NEC- associated intestinal injury, significantly reduce NEC score, and reduce systemic and ileal inflammation and NEC related brain injury during experimental NEC. However, the mode and mechanism of action of the two sources of exosomes were not identical. In vivo, the number of ileal crypts was more significantly restored after HBM-exos intervention than AFSC-exos, and in vitro, HBM-exos preferentially inhibited the inflammatory response of intestinal epithelial cells (IECs), whereas AFSC-exos preferentially regulated the migration of IECs. Mechanistically, GO and KEGG analyses revealed the different therapeutic mechanisms of AFSC-exos and HBM-exos in NEC. Taken together, our results illustrate that AFSC-exos and HBM-exos reduce the severity of experimental NEC and intestinal damage through different mechanisms, supporting the potential of cell-free or breast milk free exosome therapy for NEC.

Graphical Abstract
Innovation Despite Backsliding—the Importance of the Events of 7th August 2020 for Polish LGBTQIA Youth
Authors: Sobczak Michał
Published: November 2022

In this paper, I analysed the events of 7th August 2020 in Warsaw, when 48 people were detained by the Polish police who brutally raided solidarity demonstration with non-binary activist Margot Szutowicz. The aim of the paper is to explore queer activism in Poland on microsociological level using Gabriel Tarde imitation theory. I tried to show how individual experience of resistance gave rise to new, innovative forms of activism which became a social phenomenon. In my research, I used in-depth interviews with some of detainees and over 180 diaries/memoirs of Polish LGBTQIA people.
On the initial-boundary value problem for a non-local elliptic-hyperbolic system related to the short pulse equation
Authors: Coclite Giuseppe Maria , di Ruvo Lorenzo
Published: November 2022

In this paper, we prove the well-posedness of the initial-boundary value problem for a non-local elliptic-hyperbolic system related to the short pulse equation. Our arguments are based on energy estimates and passing to the limit in a vanishing viscosity approximation of the problem.
National landscape assessment of academic medical center support for expanded access to investigational products
Authors: Gravelin Misty , Adamo Joan E. , Ellison Sharon , Segear Erika , Parrish Amanda B. , Deeter Christine , Hamill Jennifer , Rigan Laurie , Mashour George A. , Weatherwax Kevin J.
Published: November 2022

Expanded access (EA) provides a pathway for the clinical use of investigational products (drugs, biologics, and medical devices) for patients who are without satisfactory therapeutic options and for whom a clinical trial is not available. Academic medical centers (AMCs) are likely to encounter EA requests, but it is unknown what support is available at these institutions for physicians seeking EA for patients. Methods: A landscape assessment was conducted at AMCs, focused on those within the Clinical and Translational Science Awards (CTSA) consortium. Results: Forty-seven responses were evaluated including 42 CTSA hubs. The large majority (43 of 47 respondents) reported using single-patient EA, while 37 reported multi-patient industry sponsored EA and 37 reported multi-patient investigator-initiated EA. Only half reported central tracking of EA requests. Support was available at 89% of sites for single-patient EA but less often for multi-patient EA. Types of support varied and were focused largely on the initial submission to the FDA. Conclusion: Use of and support for EA is widespread at AMCs, with support focused on single-patient requests. Gaps in support are common for activities after initial submission, such as FDA reporting and data collection.
Association of the coronavirus disease 2019 (COVID-19) pandemic with the incidence of healthcare-associated infections in California hospitals
Authors: Parriott Andrea M. , Kazerouni N. Neely , Epson Erin E.
Published: November 2022

Objective:

To assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of central-line–associated bloodstream infections (CLABSIs), Clostridioides difficile infections (CDIs), and methicillin-resistant Staphyloccocus aureus (MRSA) bloodstream infections (BSIs) in California acute-care hospitals.

Design:

Retrospective cohort and before-and-after study.

Methods:

We compared standardized infection ratios (SIRs) for CLABSI, CDI, and MRSA BSI from the second half of 2020 to the second half of 2019. We performed interrupted time-series (ITS) analyses for these infections to assess departures from long-term trends. We also examined the association between the proportion of facility beds that were occupied by COVID-19 patients in May and June of 2020 and the incidence of infections using negative binomial models. In addition, we compared standardized antimicrobial administration ratios (SAARs) for the second halves of 2019 and 2020.

Results:

We detected substantial and significant increases in the SIRs for CLABSI and MRSA BSI from 2019 to 2020. For the ITS analysis, CLABSI and had significant positive values for the pandemic onset level-change parameters, and CLABSI and MRSA BSI had significant positive values for the postinterruption slope-change parameters. We also detected a positive association between facility COVID-19 patient occupancy and CLABSI and MRSA BSI incidence. We did not detect associations with the onset of the pandemic or COVID-19 patient occupancy and CDI. The SAAR for all antibacterial drugs decreased slightly, but the SAAR for drugs with a high risk for CDI increased slightly.

Conclusions:

This study adds to a body of literature documenting increases in CLABSI and MRSA BSI incidence during the pandemic.
Vestibular neuronitis in a child with coronavirus disease 2019 infection and review of the literature
Authors: Goulioumis A , Angelopoulou M , Athanasopoulos M , Kourelis K
Published: November 2022

Objective

This article presents the case of an adolescent with asymptomatic coronavirus disease 2019 infection who had vestibular neuronitis symptoms.

Method and results

The new coronavirus disease 2019 demonstrates neurotropic properties, apart from airway symptoms. Early in the pandemic, coronavirus disease 2019 infection had been associated with olfactory disturbances. Accumulative evidence supports that both the infection with coronavirus disease 2019 and the vaccination against the virus may induce a condition of vestibular hypofunction, known as vestibular neuronitis. Coronavirus disease 2019 may directly affect the vestibular organs and ganglia, or indirectly damage them via immune-mediated mechanisms. In most cases, complete recovery is achieved with the typical therapeutic approaches for vestibular neuronitis, consisting of supportive measures and corticosteroids.

Conclusion

Physicians may expect an increased incidence of vestibular neuronitis during the coronavirus disease 2019 pandemic. Conversely, coronavirus disease 2019 infection should be considered in patients with sudden vestibular symptoms.
Proxy‐Based Preformed Phosphate Estimates Point to Increased Biological Pump Efficiency as Primary Cause of Last Glacial Maximum CO2 Drawdown
Authors: Vollmer T. D. , Ito T. , Lynch‐Stieglitz J.
Published: November 2022

Upwelling deep waters in the Southern Ocean release biologically sequestered carbon into the atmosphere, contributing to the relatively high atmospheric CO2 levels during interglacial climate periods. Paleoceanographic evidence suggests this “CO2 leak” was lessened during the last glacial maximum (LGM), potentially due to increased stratification, weaker and equatorward‐shifted winds, and/or enhanced biological carbon export. The collective influences of these mechanisms on the ocean's biological pump efficiency and amount of atmospheric CO2 can be quantified by determining preformed phosphate of deep waters. We quantify preformed PO4 (Ppre,AOU) and preformed () of LGM bottom waters using a compilation of published paleo‐temperature, nutrient and oxygen estimates from benthic foraminifera. Our results show that preformed phosphate of the Pacific and Indian deep oceans was reduced by about −0.53 ± 0.13 μM and suggest that much (64 ± 28 ppmv) of the Glacial‐Interglacial CO2 drawdown resulted from changes in the ocean's biological pump efficiency. Once carbonate compensation is accounted for, this can explain the entire CO2 drawdown (87 ± 40 ppmv). Preformed shows similar results. The reconstructed LGM Ppre,AOU and oxygen are qualitatively consistent with the changes produced by a suite of numerical sensitivity experiments that roughly simulate three proposed mechanisms for an increase in LGM biological pump efficiency: an increase in biological activity, a decrease in wind‐driven upwelling, and an increase in stratification in the Southern Ocean.
Effects of Water Source and Technology on Energy Use and Environmental Impacts of Rice Production in Northern Iran
Authors: Jamali Mohsen , Bakhshandeh Esmaeil , Emadi Mostafa
Published: November 2022

To assess the sustainability of rice production systems, it is essential to quantify its impact on the environment and energy flow. To analyze the energy flow and greenhouse gas emissions, a total of 200 paddy fields were selected based on the water source utilized for irrigation (river as the surface water source and well as the underground water source), transplanting methods (traditional and mechanical) and grain yield (low‐ and high‐yielding rice cultivars) based on a factorial experimental design (2 × 2 × 2 = 8 conditions). Data were collected in 2020 from 200 rice growers in northern Iran, using a face‐to‐face questionnaire survey. Results showed that the highest total energy use efficiency (EUE) (5.26 GJ ha−1) was observed under the surface water source + traditional + low‐yielding rice system. Although the total EUE in surface water source was higher than that in groundwater source (4.98 vs. 2.90). Water consumption by high‐yielding rice cultivars was higher, as compared to the low‐yielding ones. Electricity (35.2%) and nitrogen fertilizer (31.5%) inputs were the highest energy input for the groundwater and surface water sources, respectively. Average shares of the renewable and non‐renewable energies used in agroecosystems were 25.70% and 74.30% respectively, while the shares of the direct and indirect energies were 60.36% and 39.64%, respectively. The calculated global warming potential value in the paddy fields of northern Iran ranged from 878 to 2,666 kg eqCO2 ha−1. Amongst the studied conditions, the surface water source + traditional + high‐yielding rice system had the highest carbon efficiency and carbon sustainability index level. Overall, surface water source conditions were found to be a more environmentally‐friendly approach in northern Iran. These results, thus, demonstrated that there is a huge potential for improving energy efficiency in the studied conditions, especially for high‐yielding rice cultivars irrigated by surface water sources. These findings could help decision‐makers to better understand the linkage between various conditions, which is a prerequisite to any planning effort for future management strategies at national and international levels.
High‐Resolution Observation of Heater‐Induced Daytime Plasma Fluctuations at Arecibo
Authors: Henderson Brian S. , Sultan Peter J. , Sulzer Michael P. , Levine Edlyn V.
Published: November 2022

Ionospheric heating is known to induce density and temperature irregularities in the ionospheric plasma, which have been observed by various in‐situ and radar techniques. Analysis of incoherent scatter radar (ISR) plasma line spectra offers high resolution reconstruction of ionospheric features, but the plasma line profile is frequently difficult to reconstruct at altitudes where the heater is generating Langmuir turbulence and thus creating additional signals in the ISR spectrum. This work presents a novel, automated method based on Gabor filter image analysis to reconstruct plasma line spectra recorded with the coded long‐pulse technique. The method permits the unsupervised reconstruction of the Langmuir frequency with resolution in frequency (sub‐kHz) and altitude (∼300 m) typical of the coded long‐pulse technique even in regions directly coupling to the heater. The technique is applied to ISR data from the June 2019 Arecibo Observatory heating experiment, demonstrating the formation of field‐aligned irregularities of magnitude ∼0.5% in the Langmuir frequency during daytime conditions and spatial scale perpendicular to the magnetic field (fluctuation periodicity of several kilometers, corresponding to k ≈ 1 km−1) consistent with the patches of depletions of free electrons previously observed by in‐situ methods. Additionally, the method allows observation of the formation and evolution of the bunches over the course of several hours. Additional F‐layer irregularities were found in the ambient ionosphere in regions away from the heater coupling altitude. The automated nature of this technique offers the potential for precision analysis of Arecibo's ISR data archives for a variety of ionospheric physics applications.
Storm‐Time Magnetopause: Pressure Balance
Authors: Grygorov K. , Němeček Z. , Šafránková J. , Šimůnek J. , Gutynska O.
Published: November 2022

The magnetopause is treated as a boundary where the pressure of the incoming solar wind is balanced by the pressure of the geomagnetic field and the plasma pressure inside the magnetopause is often neglected. However, published studies of pressure balance at the magnetopause reveal an excess of the magnetosheath pressure. Moreover, our survey of about 50,000 THEMIS magnetopause crossings shows that about 1% of them exhibits even larger magnetic field in the magnetosheath than in the magnetosphere. A subsequent analysis of crossings observed in the subsolar region under a southward interplanetary magnetic field shows the pressure of the dense cold ion population as an important component of the total magnetospheric pressure. This component is too cold to be registered by standard ion analyzers but its density can reach 300 cm−3. The second effect connected with a presence of cold plasma population is a reduction of the reconnection rate that slows down the transport of the magnetic flux down the tail and leads to magnetic pile‐up in the subsolar magnetosheath.
A Statistical Study of Nighttime Ionospheric NmF2 Enhancement at Middle‐to‐High Latitudes in the Northern Hemisphere
Authors: Zhao Ling‐Xin , Zhang Qing‐He , Xu Tong , Xing Zan‐Yang , Balan N. , Wang Yong , Ma Yu‐Zhang , Gao Dong‐Xing
Published: November 2022

The electron density in the ionosphere usually continuously decreases during nighttime due to the vanishing of sunlit ionization. However, it sometimes increases unexpectedly, which has been called nighttime ionospheric enhancement. Previous researches studied this type of phenomenon mainly in the low‐to‐middle latitude regions. Here, we investigate the nighttime ionospheric NmF2 enhancement at middle‐to‐high latitudes in the northern hemisphere (NH) during solar cycles 23–24 by analyzing the ionosonde observations at Chilton (51.1°N, 359.4°E, geomagnetic 48.5°N), Juliusruh (54.6°N, 13.4°E, 51.7°N), Tromsø (69.9°N, 19.6°E, 66.9°N), and Qaanaaq (77.5°N, 290.8°E, 84.3°N), as well as comparing with the Empirical Canadian High Arctic Ionospheric Model (E‐CHAIM). The observations show that the nighttime NmF2 enhancement occurs mainly in the winter solstice months (November–February), and the occurrence rate and relative amplitude of the enhancement are inversely related to solar activity. The observed results are in good agreement with the results obtained from E‐CHAIM. Furthermore, the model shows the spatial distribution of the enhancement at the middle‐to‐high latitudes in NH in winter, most obvious in geomagnetic latitude between 50°N and 65°N, and have longitudinal minima centered at 30°W and maxima centered at 120°W and 75°E. From these results, this unique phenomenon at middle latitude is explained probably by the plasma flux from the higher altitudes (e.g., topside ionosphere and plasmasphere) diffusing downward into the ionospheric F2 layer. However, at polar regions, under the influence of the abundant high‐density structures such as polar cap patches, auroral blob, particle precipitation, etc., the F region plasma density enhancement becomes more complicated.
Sensitivity of Heavy Convective Precipitation Simulations to Changes in Land‐Atmosphere Exchange Processes Over China
Authors: Zhang Xia , Chen Liang , Ma Zhuguo , Zheng Ziyan , Meng Yanan
Published: November 2022

Heavy precipitation and associated flood hazards can cause enormous socioeconomic losses. The advances in atmospheric modeling enable great promise in accurately predicting precipitation. However, the representation of land‐atmosphere exchange processes in atmospheric models and its impacts on precipitation evolution remain high uncertainties. This study investigated the sensitivity of convective precipitation to land‐atmosphere exchanges and examined the improvements in precipitation simulations by a dynamic vegetation‐type‐dependent exchange scheme. We conducted 3‐km‐resolution convection‐permitting modeling for three heavy precipitation events that occurred over areas with different dominant land‐cover types. The results showed that land‐atmosphere exchange efficiency significantly altered the precipitation intensity as well as the onset and peak time of precipitation but hardly affected the precipitation pattern. Strong exchange simulations could agree better with the observed precipitation in the 21 July 2012 Beijing and the 19 June 2010 Jiangxi heavy precipitation events occurring over humid and semihumid zones, while weak exchange simulations could attain higher consistencies with the observations in the 30 July 2012 Ningxia heavy precipitation event occurring over arid and semiarid zones. As a more physical alternative, the dynamic exchange simulations could achieve the closest agreement with the field observations, especially the intensity and location of the heaviest rainfall. The dynamic scheme modifies land‐atmosphere exchange efficiency to match local land cover conditions and could provide promising applications in heavy precipitation modeling studies.
Impacts of Cloud‐Processing on Ice Nucleation of Soot Particles Internally Mixed With Sulfate and Organics
Authors: Gao Kunfeng , Kanji Zamin A.
Published: November 2022

Soot particles are one of the major aerosol components (in particle number concentration) in the troposphere and can impact cirrus formation. Depending on their physicochemical properties, soot particles can nucleate ice in the cirrus regime via pore condensation and freezing (PCF) at a lower ice saturation threshold than that of the homogeneous freezing of solution droplets. Soot aerosol undergoing multiple cloud cycles can change its porosity and surface wettability, thus modulating its PCF ability. In this study, organic‐rich and ‐lean size‐selected propane flame soot particles were coated with different thicknesses of sulfuric acid (H2SO4) and exposed to thermodynamic conditions under 228 K and relative humidity with respect to water 104% to simulate contrail formation. Ice‐activated soot particles from the mimicked contrail were sublimated before being tested for ice nucleation (IN) at T ≤ 233 K. Additionally, soot particle size and mass distribution as well as morphology were characterized. The results demonstrate that the increase in mesopore availability induced by cloud‐processing plays a key role in regulating soot IN. All cloud‐processed soot become more compacted, however, only if more PCF relevant mesopores are generated, can the compacted soot exhibit promoted IN. If a H2SO4 coating and/or enriched organics occupy the pore volume, inhibition of PCF is observed for the cloud‐processed soot. Notably, a thick H2SO4 coating enhances the PCF of 400 nm organic‐lean soot particles because the partially engulfed but collapsed soot‐core may have new mesopores produced by compaction. Therefore, the mesopore abundance plays the key role in evaluating aged soot IN ability.
Development and Evaluation of E3SM‐MOSAIC: Spatial Distributions and Radiative Effects of Nitrate Aerosol
Authors: Wu Mingxuan , Wang Hailong , Easter Richard C. , Lu Zheng , Liu Xiaohong , Singh Balwinder , Ma Po‐Lun , Tang Qi , Zaveri Rahul A. , Ke Ziming , Zhang Rudong , Emmons Louisa K. , Tilmes Simone , Dibb Jack E. , Zheng Xue , Xie Shaocheng , Leung L. Ruby
Published: November 2022

Nitrate aerosol plays an important role in affecting regional air quality as well as Earth's climate. However, it is not well represented or even neglected in many global climate models. In this study, we couple the Model for Simulating Aerosol Interactions and Chemistry (MOSAIC) module with the four‐mode version of the Modal Aerosol Module (MAM4) in DOE's Energy Exascale Earth System Model version 2 (E3SMv2) to simulate nitrate aerosol and its radiative effects. We find that nitrate aerosol simulated by E3SMv2‐MAM4‐MOSAIC is sensitive to the treatment of gaseous HNO3 transfer to/from interstitial particles related to accommodation coefficients of HNO3 () on dust and non‐dust particles. We compare three different treatments of HNO3 transfer: (a) a treatment (MTC_SLOW) that uses a low in the mass transfer coefficient (MTC) calculation; (b) a dust‐weighted MTC treatment (MTC_WGT) that uses a high on non‐dust particles; and (c) a dust‐weighted MTC treatment that also splits coarse mode aerosols into the coarse dust and sea salt sub‐modes in MOSAIC (MTC_SPLC). MTC_WGT and MTC_SPLC increase the global annual mean (2005–2014) nitrate burden from 0.096 (MTC_SLOW) to 0.237 and 0.185 Tg N, respectively, mostly in the coarse mode. MTC_WGT and MTC_SPLC also produce stronger nitrate direct radiative forcing (−0.048 and −0.051 W m−2, respectively) and indirect forcing (−0.33 and −0.35 W m−2, respectively) than MTC_SLOW (−0.021 and −0.24 W m−2). MTC_WGT and MTC_SPLC improve nitrate surface concentrations over remote oceans based on limited observations and vertical profiles of nitrate concentrations against aircraft measurements below 400 hPa.
Atypical Sotos syndrome caused by a novel splice site variant
Authors: Minatogawa Mari , Tsuji Taichi , Inaba Mie , Kawakami Noriaki , Mizuno Seiji , Kosho Tomoki
Published: November 2022

Sotos syndrome is usually caused by haploinsufficiency of NSD1; it is characterized by overgrowth, craniofacial features, and learning disabilities. We describe a boy with Sotos syndrome caused by a splicing variant (c.4378+5G>A). The clinical manifestations included severe connective tissue involvement, including joint hypermobility, progressive scoliosis, pectus deformity, and skin hyperextensibility; no overgrowth was observed.
Tunable valley band and exciton splitting by interlayer orbital hybridization
Authors: Wang Dan , Zou Xiaolong
Published: November 2022

Magnetic proximity effect has been demonstrated to be an effective routine to introduce valley splitting in two-dimensional van der Waals heterostructures. However, the control of its strength and the induced valley splitting remains challenging. In this work, taking heterobilayers combining monolayer MSe2 (M = Mo or W) with room-temperature ferromagnetic VSe2 as examples, we demonstrate that the valley splitting for both band edges and excitons can be modulated by the tuning of the interlayer orbital hybridization, achieved by inclusion of different amounts of exact Hartree exchange potential via hybrid functionals. Besides, we show such tuning of orbital hybridization could be experimentally realized by external strain and electric field. The calculations suggest that large valley band splitting about 30 meV and valley exciton splitting over 150 meV can be induced in monolayer MSe2. Our work reveals a way to control proximity effects and provides some guidance for the design of optoelectronic and valleytronic devices.
Direct activation of a bacterial innate immune system by a viral capsid protein
Authors: Zhang Tong , Tamman Hedvig , Coppieters ’t Wallant Kyo , Kurata Tatsuaki , LeRoux Michele , Srikant Sriram , Brodiazhenko Tetiana , Cepauskas Albinas , Talavera Ariel , Martens Chloe , Atkinson Gemma C. , Hauryliuk Vasili , Garcia-Pino Abel , Laub Michael T.
Published: November 2022

Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages1–3. Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRelSJ46, a fused toxin–antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRelSJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRelSJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin–antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a ‘Red Queen conflict’5, revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts6–10, our results reveal a deeply conserved facet of immunity.
NETome: A model to Decode the Human Genome and Proteome of Neutrophil Extracellular Traps
Authors: Scieszka David , Lin Yi-Han , Li Weizhong , Choudhury Saibyasachi , Yu Yanbao , Freire Marcelo
Published: November 2022

Neutrophils are the most abundant type of white blood cells in humans with biological roles relevant to inflammation, and fighting off infections. Neutrophil Extracellular Traps (NETs) act as enxogenous agents controlling invasion by bacteria, viruses, fungi, metabolic, and traumatic agents. Traditionally, studies have focused on elucidating molecular and cellular pathways preceding NET formation. Here, we developed a model to decode the human genome and proteome of developted NETs. Via in vitro system to differentiate HL-60 human myeloid cell line into neutrophil extracellular trap (ecTrap) producing cells, we isolated and captured ectrap derived DNA and proteins for shotgun sequencing. The genomic sequences revealed accurate delineation of gene composition including immune response genes and mitochondrial enrichment, while providing a reference database for future interrogation. Shotgun proteomics showed global proteins in differentiated cells with specific immune pathways when compared to undifferentiated counterparts. Coupled with omics’ approaches, we validated our system by functional assays and began to dissect host-microbial interactions. Our work provides a new understanding of the genomic and proteomic sequences, establishing the first human database deposition of neutrophil extracellular traps.
Evolving collaboration, dependencies, and use in the Rust Open Source Software ecosystem
Authors: Schueller William , Wachs Johannes , Servedio Vito D. P. , Thurner Stefan , Loreto Vittorio
Published: November 2022

Open Source Software (OSS) is widely spread in industry, research, and government. OSS represents an effective development model because it harnesses the decentralized efforts of many developers in a way that scales. As OSS developers work independently on interdependent modules, they create a larger cohesive whole in the form of an ecosystem, leaving traces of their contributions and collaborations. Data harvested from these traces enable the study of large-scale decentralized collaborative work. We present curated data on the activity of tens of thousands of developers in the Rust ecosystem and the evolving dependencies between their libraries. The data covers eight years of developer contributions to Rust libraries and can be used to reconstruct the ecosystem’s development history, such as growing developer collaboration networks or dependency networks. These are complemented by data on downloads and popularity, tracking dynamics of use, visibility, and success over time. Altogether the data give a comprehensive view of several dimensions of the ecosystem.
High-quality Japanese flounder genome aids in identifying stress-related genes using gene coexpression network
Authors: Xu Xi-wen , Zheng Weiwei , Yang Yingming , Hou Jilun , Chen Songlin
Published: November 2022

The Japanese flounder is one of the most economically important marine flatfish. However, due to the increased frequency of extreme weather events and high-density industrial farming, an increasing number of environmental stresses have become severe threats to the healthy development of the Japanese flounder culture industry. Herein, we produced a high-quality chromosome-scale Japanese flounder genome using PacBio Circular Consensus Sequencing technologies. The assembled Japanese flounder genome spanned 588.22 Mb with a contig N50 size of 24.35 Mb. In total, 105.89 Mb of repetitive sequences and 22,565 protein-coding genes were identified by genome annotation. In addition, 67 candidate genes responding to distinct stresses were identified by gene coexpression network analysis based on 16 published stress-related RNA-seq datasets encompassing 198 samples. A high-quality chromosome-scale Japanese flounder genome and candidate stress-related gene set will not only serve as key resources for genomics studies and further research on the underlying stress responsive molecular mechanisms in Japanese flounder but will also advance the progress of genetic improvement and comprehensive stress-resistant molecular breeding of Japanese flounder.
Systematic analysis of expression profiles and prognostic significance for MMDS-related iron–sulfur proteins in renal clear cell carcinoma
Authors: Yang Ling , Chen Yu-Xin , Li Ying-Ying , Liu Xiao-Juan , Jiang Yong-Mei , Mai Jia
Published: November 2022

Mitochondrial metabolism disorders play an important role in the occurrence and development of tumors, and iron–sulfur protein is an important molecule for maintaining the normal function of mitochondria. However, the relationship between the expression, prognostic value, and immune infiltration of MMDS-related iron–sulfur protein genes in kidney renal clear cell carcinoma (KIRC) remains unclear. Based on online databases bioinformatics analysis was performed to evaluate the expression differences, survival impacts, immune infiltration, and prognostic significance of multiple mitochondrial dysfunction syndrome (MMDS)-related iron–sulfur protein genes in KIRC patients. For example, the protein–protein interaction (PPI) network was constructed using STRING and GEPIA database; Survival impacts were constructed by TCGA database; Immune infiltration was analyzed using TIMER database. There were significant differences in the mRNA expression levels of ISCA1, ISCA2, C1ORF69 and NFU1 in KIRC among different tumor grades and individual cancer stages. Furthermore, KIRC with high transcription levels of ISCA1, ISCA2, C1ORF69 and NFU1 (p < 0.01) was significantly associated with long overall survival (OS) and disease-free survival (DFS). In addition, overexpression of four genes, NFU1, ISCA1, ISCA2, and C1ORF69 in KIRC indicated a better prognosis. Further studies showed that immune cells had a significantly positive correlation with iron–sulfur protein family genes, including CD8+ T cells, CD4+ T cells and B cells. More importantly, the results of immunohistochemistry showed that the expression of NFU1, ISCA1, ISCA2 and C1ORF69 in normal tissues was higher than that in renal clear cell carcinoma tissues. In this study, we systematically analyzed the expression and prognostic value of iron–sulfur protein family genes in KIRC. More importantly, NFU1, ISCA1, ISCA2, and C1ORF69 are expected to become potential therapeutic targets for KIRC, as well as potential prognostic markers for improving the survival rate and prognostic accuracy of KIRC.
Phase 1 safety trial of a natural product cocktail with antibacterial activity in human volunteers
Authors: Bruce Julie , Oyedemi Blessing , Parsons Nick , Harrison Freya
Published: November 2022

New antibiotics are urgently needed to reduce the health burden of antibiotic-resistant bacterial infection. Natural products (NPs) derived from plants and animals are a current focus of research seeking to discover new antibacterial molecules with clinical potential. A cocktail of NPs based on a medieval remedy for eye infection eliminated biofilms of several highly antibiotic-resistant bacterial species in laboratory studies, and had a promising safety profile in vitro and in a mouse model. A necessary prelude to refining this remedy into a defined, synthetic mixture suitable for testing with wound infections is to firstly establish safety when applied to healthy human skin. We aimed to assess skin-related outcomes of the preparation in a sample of healthy volunteers. This prospective, single arm, non-randomised Phase I clinical trial consisted of a single patch test intervention with 48-h follow-up. Volunteers were staff, students and members of the public recruited from the University of Warwick and surrounding locality. Adults aged 18–79 years, with no history of severe immunity-related disease, diabetes, recent infection, or known pregnancy were eligible. A 100 µl application of a filter-sterilised NP mixture, comprising ground garlic, onion, white wine and bovine bile, was applied to skin on the upper arm and covered with a dressing. The primary outcome was skin-related adverse events over 48 h. Digital photographs were captured where bothersome, salve-related events were reported. 109 volunteers, aged 18–77 years, were recruited between June and July 2021. Sample mean age was 37.6 (SD 16.1) years, and 63 (58%) participants were female. Outcome data were obtained for 106/109 (97%); two participants were lost to follow-up and one removed the skin patch after nine hours due to a bothersome garlic odour. Twenty-one (19.8%) participants reported any patch-test related sign or symptom; of these 14 (13.2%) participants reported minor events related to the salve, including itchiness, redness, or garlic odour. No serious events were reported. We found no evidence of serious skin-related adverse events related to the NP preparation.

Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN10773579). Date registered: 08/01/2021.
Multiomics analysis couples mRNA turnover and translational control of glutamine metabolism to the differentiation of the activated CD4+ T cell
Authors: Matheson Louise S. , Petkau Georg , Sáenz-Narciso Beatriz , D’Angeli Vanessa , McHugh Jessica , Newman Rebecca , Munford Haydn , West James , Chakraborty Krishnendu , Roberts Jennie , Łukasiak Sebastian , Díaz-Muñoz Manuel D. , Bell Sarah E. , Dimeloe Sarah , Turner Martin
Published: November 2022

The ZFP36 family of RNA-binding proteins acts post-transcriptionally to repress translation and promote RNA decay. Studies of genes and pathways regulated by the ZFP36 family in CD4+ T cells have focussed largely on cytokines, but their impact on metabolic reprogramming and differentiation is unclear. Using CD4+ T cells lacking Zfp36 and Zfp36l1, we combined the quantification of mRNA transcription, stability, abundance and translation with crosslinking immunoprecipitation and metabolic profiling to determine how they regulate T cell metabolism and differentiation. Our results suggest that ZFP36 and ZFP36L1 act directly to limit the expression of genes driving anabolic processes by two distinct routes: by targeting transcription factors and by targeting transcripts encoding rate-limiting enzymes. These enzymes span numerous metabolic pathways including glycolysis, one-carbon metabolism and glutaminolysis. Direct binding and repression of transcripts encoding glutamine transporter SLC38A2 correlated with increased cellular glutamine content in ZFP36/ZFP36L1-deficient T cells. Increased conversion of glutamine to α-ketoglutarate in these cells was consistent with direct binding of ZFP36/ZFP36L1 to Gls (encoding glutaminase) and Glud1 (encoding glutamate dehydrogenase). We propose that ZFP36 and ZFP36L1 as well as glutamine and α-ketoglutarate are limiting factors for the acquisition of the cytotoxic CD4+ T cell fate. Our data implicate ZFP36 and ZFP36L1 in limiting glutamine anaplerosis and differentiation of activated CD4+ T cells, likely mediated by direct binding to transcripts of critical genes that drive these processes.
Integrative network analysis interweaves the missing links in cardiomyopathy diseasome
Authors: Chauhan Pankaj Kumar , Sowdhamini Ramanathan
Published: November 2022

Cardiomyopathies are progressive disease conditions that give rise to an abnormal heart phenotype and are a leading cause of heart failures in the general population. These are complex diseases that show co-morbidity with other diseases. The molecular interaction network in the localised disease neighbourhood is an important step toward deciphering molecular mechanisms underlying these complex conditions. In this pursuit, we employed network medicine techniques to systematically investigate cardiomyopathy’s genetic interplay with other diseases and uncover the molecular players underlying these associations. We predicted a set of candidate genes in cardiomyopathy by exploring the DIAMOnD algorithm on the human interactome. We next revealed how these candidate genes form association across different diseases and highlighted the predominant association with brain, cancer and metabolic diseases. Through integrative systems analysis of molecular pathways, heart-specific mouse knockout data and disease tissue-specific transcriptomic data, we screened and ascertained prominent candidates that show abnormal heart phenotype, including NOS3, MMP2 and SIRT1. Our computational analysis broadens the understanding of the genetic associations of cardiomyopathies with other diseases and holds great potential in cardiomyopathy research.
The effects of mindfulness meditation versus CBT for anxiety on emotional distress and attitudes toward seeking mental health treatment: a semi-randomized trial
Authors: Aisenberg-Shafran Daniela , Shturm Liav
Published: November 2022

Older adults often avoid seeking psychological treatment, thus challenging their ability to cope effectively with anxiety, stress, and depression. The current study aimed to compare the effects of a mindfulness intervention with cognitive behavioral therapy (CBT) on measures of emotional distress and attitudes toward seeking mental health treatment among older adults. Twenty-four seniors were assigned to three groups: (1) Mindfulness-based intervention for seniors (MBIS), (2) CBT for anxiety, or (3) a care-as-usual control group. Participants in the two intervention groups of eight weekly sessions were randomly assigned. Results showed that attitudes toward seeking psychological treatment and depression, anxiety, and worry levels were evaluated before and after the interventions. Following both interventions, participants considered the prospect of utilizing psychological treatment more positively, whereas no changes were observed in the control group. Interestingly, worry levels were eased only in the MBIS group, and anxiety levels were eased only in the CBT group. Our findings support the understanding that cognitive group interventions can effectively achieve their intended aim (decreasing worry or anxiety) and positively impact attitudes toward psychological treatment.

Trial registration: clinicaltrials, NCT04165005, 15/11/19.
Au@Ag nanostructures for the sensitive detection of hydrogen peroxide
Authors: Yeh I-Hsiu , Tadepalli Sirimuvva , Liu Keng-Ku
Published: November 2022

Hydrogen peroxide (H2O2) is an important molecule in biological and environmental systems. In living systems, H2O2 plays essential functions in physical signaling pathways, cell growth, differentiation, and proliferation. Plasmonic nanostructures have attracted significant research attention in the fields of catalysis, imaging, and sensing applications because of their unique properties. Owing to the difference in the reduction potential, silver nanostructures have been proposed for the detection of H2O2. In this work, we demonstrate the Au@Ag nanocubes for the label- and enzyme-free detection of H2O2. Seed-mediated synthesis method was employed to realize the Au@Ag nanocubes with high uniformity. The Au@Ag nanocubes were demonstrated to exhibit the ability to monitor the H2O2 at concentration levels lower than 200 µM with r2 = 0.904 of the calibration curve and the limit of detection (LOD) of 1.11 µM. In the relatively narrow range of the H2O2 at concentration levels lower than 40 µM, the LOD was calculated to be 0.60 µM with r2 = 0.941 of the calibration curve of the H2O2 sensor. This facile fabrication strategy of the Au@Ag nanocubes would provide inspiring insights for the label- and enzyme-free detection of H2O2.
CO2 conversion to formamide using a fluoride catalyst and metallic silicon as a reducing agent
Authors: Wang Ruopeng , Nakao Kaiki , Manaka Yuichi , Motokura Ken
Published: November 2022

Metallic silicon could be an inexpensive, alternative reducing agent for CO2 functionalization compared to conventionally used hydrogen or hydrosilanes. Here, metallic silicon recovered from solar panel production is used as a reducing agent for formamide synthesis. Various amines are converted to their corresponding amides with CO2 and H2O via an Si-H intermediate species in the presence of a catalytic amount of tetrabutylammonium fluoride. The reaction system exhibits a wide substrate scope for formamide synthesis. Spectroscopic analysis, including in situ Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), N2 adsorption/desorption analyses, and isotopic experiments reveal that the fluoride catalyst effectively oxidizes Si atoms on both surface and interior of the powdered silicon particles. The solid recovered after catalysis contained mesopores with a high surface area. This unique behavior of the fluoride catalyst in the presence of metallic silicon may be extendable to other reductive reactions, including those with complex substrates. Therefore, this study presents a potential strategy for the efficient utilization of abundant resources.
High-frequency chaotic bursts in laser diode with optical-feedback
Authors: Malica Tushar , Bouchez Guillaume , Wolfersberger Delphine , Sciamanna Marc
Published: November 2022

The diversity of observed nonlinear dynamics in laser diodes subjected to optical feedback shows promise as an excellent candidate for chaos-based commercial applications. Thus, works in the last decade have primarily focused on system performances, geometric configurations, and balancing their trade-offs. We demonstrate an optical feedback system operating on phase-conjugate feedback exhibiting state-of-the-art chaos bandwidth values reaching ≈ 30 GHz. We report numerous high-frequency, spatiotemporally complex, chaotic dynamics undocumented in the past four decades. We highlight the underlying physics involving a three-tier temporal interaction mechanism between laser relaxation oscillations, phase-conjugate feedback induced external cavity modes, and chaotic bursts repeating each delay time in the extended cavity. We show supporting real-time high-definition system outputs captured by modern large bandwidth oscilloscopes. The presented work shows to our knowledge, the highest bandwidth and complexity entropy to-date in an optical chaos from a single laser, thereby proving the unnecessary need for further complexity using cascading lasers.