bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task
Authors: Lamontagne Steven J. , Gilbert Jessica R. , Zabala Paloma K. , Waldman Laura R. , Zarate Carlos A. , Ballard Elizabeth D.
Published: November 2023

Background

An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks.

Methods

Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30–58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects.

Results

Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline.

Conclusions

Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.

Clinicaltrials.gov identifier: NCT02543983, NCT00397111.
Arming Slaves in Early Modern Maritime Asia
Authors: McManus Stuart M.
Published: November 2023

While there are large literatures on both Islamic slave soldiers and the phenomenon of “arming slaves” in the Atlantic world, military slavery in early modern Asia is still poorly understood. Using a variety of Chinese, Latin, Spanish, and Portuguese sources, this article will argue that enslaved labour was frequently directed towards violence across early modern Asia, colonial or otherwise. At the same time, the phenomenon was far from uniform in the vast expanse of land and sea between East Africa and Japan. Rather, it is better to speak of a series of analogous regimes of bondage that interacted with each other across large distances, with the line between enslaved soldiers, mercenaries, and run-of-the-mill trader-raiders being vanishingly thin at times. Finally, all this existed within the context of military infrastructure in the broadest sense of the word that included fortresses, factories, and even war elephants.
Regimes of Bondage: The Encounter between Early Modern European and Asian Slaveries
Authors: McManus Stuart M , Ehalt Rômulo
Published: November 2023

This special issue focuses on the broader context and interconnectedness of different slave regimes in early modern Asia. Various transnational commercial and imperial projects influenced the waxing and waning of individual slave regimes, while internal and interpersonal conditions within polities also played important roles. The well-known European seaborne empires of Spain, Portugal, the Netherlands, and England were major drivers of this early modern slavery, but they coexisted and competed with other groups of trader-raiders. These included merchants from the Islamicate world and Chinese coastal regions, which connected Southeast Asia, Japan, Korea, and other regions. These extensive markets linked different regions together, such as the Malabar Coast with East Africa, the Arabian Peninsula, and the Red Sea. While the focus is on the Iberian expansion and its impact on the slave trade, this special issue acknowledges that slavery in Asia should be understood as a result of multiple overlapping and interacting regimes. Each article examines a particular regime while emphasizing its interactions with neighboring regions during the early modern period. The main focus is on the encounters between different slave regimes facilitated by early modern commercial networks. The history of slavery in early modern Asia involved clashes and cross-pollination between disparate slave systems. A further contribution relates to the terminology used to define and understand slavery in non-European contexts, which is still a subject of debate. The concept of “regimes of bondage” is adopted as an umbrella term to encompass the various forms of coerced, subaltern, and dependent labor in Asia during this period. Finally, by using local categories and sources, including European and non-European language materials, the special issue aims to recover marginalized perspectives and highlight the complexity and challenges of studying slavery in Asia.
Evaluation of a combined detection of SARS-CoV-2 and its variants using real-time allele-specific PCR strategy: an advantage for clinical practice
Authors: Chaves-Blanco Lucía , de Salazar Adolfo , Fuentes Ana , Viñuela Laura , Perez-Florido Javier , Dopazo Joaquín , García Federico
Published: November 2023

This study aimed to assess the ability of a real-time reverse transcription polymerase chain reaction (RT-PCR) with multiple targets to detect SARS-CoV-2 and its variants in a single test. Nasopharyngeal specimens were collected from patients in Granada, Spain, between January 2021 and December 2022. Five allele-specific RT-PCR kits were used sequentially, with each kit designed to detect a predominant variant at the time. When the Alpha variant was dominant, the kit included the HV69/70 deletion, E and N genes. When Delta replaced Alpha, the kit incorporated the L452R mutation in addition to E and N genes. When Omicron became dominant, L452R was replaced with the N679K mutation. Before incorporating each variant kit, a comparative analysis was carried out with SARS-CoV-2 whole genome sequencing (WGS). The results demonstrated that RT-PCR with multiple targets can provide rapid and effective detection of SARS-CoV-2 and its variants in a single test. A very high degree of agreement (96.2%) was obtained between the comparison of RT-PCR and WGS. Allele-specific RT-PCR assays make it easier to implement epidemiological surveillance systems for effective public health decision making.
The transformation of Mithraea in the Late Roman period
Authors: Walsh David
Published: November 2023

Discussions of mithraea tend to emphasize their uniformity. While it is true that many earlier mithraea do adhere to an established plan, there are a notable number of mithraea dating from the late 3rd c. onward that do not. This article discusses these various atypical mithraea, how such alterations to the standard mithraeum plan might have impacted on Mithraic rituals, and how this might have affected the experiences of the participants. It also explores why such changes occurred, observing that while in some instances this may have been to accommodate alterations to ritual practices, in others it was likely due to more mundane issues, such as limitations on space and environmental factors. The article concludes by reflecting on the implications this has for the identification of mithraea in the archaeological record.
Sharing Collective Memories on Campus While Sharing History Gets Tricky
Authors: Hong Ji Yeon
Published: November 2023

During the past century, protest has become a shared experience around the world, as citizens across the continents have taken to the streets to demand political, social, and economic changes. In Asia—from China to India, Thailand to Myanmar—people have organized mass demonstrations to express their dissatisfaction with colonial and state governments and their policies. Often, people shared news and supported protests in neighboring countries, using it as an opportunity to mobilize and coordinate their efforts for protest and leading to a growing sense of regional solidarity. Solidarity is possible despite differences in culture, history, and language because the citizens in the region share universal values.
The direct and indirect economic consequences of climate damage in poor countries
Authors: Knight John
Published: November 2023

The predictions of the adverse effects of greenhouse gas emissions on climate change are now accepted. Somewhat less attention has been given to the economic, social, and political consequences. The three interact: the former will have social and political effects, which in turn will harm economies and economic well-being. This analysis of poor countries draws on much recent evidence and various projections. Climate damage contributes to internal political instability and conflict. There is a risk that poor countries will be driven down economically, so reducing the capacity of their governments: some will become fragile states. Internal migration is likely to become a central policy issue. However, international migration will also grow. Climate damage will drag countries into both cooperation and conflict with each other. The effects on sending countries, contiguous countries, and destination countries are examined. This scenario presented is predictive but should be taken as a warning.
How does evidence-based medicine training affect medical students’ views on traditional, complementary, and alternative medicine and the conspiracy theories about COVID-19: a nationwide study
Authors: Coşkun Özlem , Kıyak Yavuz Selim , Budakoğlu Işıl İrem
Published: November 2023

Aim:

It was aimed to explore the relationship between evidence-based medicine (EBM) training and medical students’ views on traditional, complementary, and alternative medicine (TCAM) and their views on conspiracies about COVID-19.

Background:

Medical students constitute the future workforce of primary health care services. The relationship between EBM training and their views on conspiracies about COVID-19 is critical to explore for providing a better primary health care. The relationship EBM training and medical students’ views on TCAM is also important in this regard.

Methods:

This is a cross-sectional study. Turkish medical students were surveyed about EBM training, TCAM, and COVID-19 conspiracies. The electronic survey form consisted of five parts: Demographic characteristics, views and self-perceived knowledge about TCAM and the methods, views on the origin of SARS-COV-2, participation in EBM training, and views on TCAM training. A total of 49 medical schools provided response. Along with descriptive statistics, Chi-square test was utilized.

Findings:

Among 2577 participants, 24.0% of them believed SARS-COV-2 was artificially designed. The students who have participated in EBM training via both lecture and small group discussions have a less positive view on TCAM than both the students who have not participated in any EBM training (p < 0.05) and the students who participated in only-lectures (p < 0.05). There was a significant association between EBM training and whether believing COVID-19 (SARS-COV-2) has been designed purposefully by some people or it has emerged naturally χ2 (1) = 17.21 p < 0.001. The odds of thinking COVID-19 emerged naturally was 1.85 times higher (95% CI: 1.38-2.47) if the students have participated in EBM training via both lectures and small group discussions than if they have not participated in any EBM training. EBM training affects medical students in terms of beliefs on COVID-19 conspiracies.
On the Non-Discrimination Principles in Digital Trade
Authors: Suh Jeongmeen , Lee Joohyoung , Roh Jaeyoun
Published: November 2023

What do the provisions on the non-discrimination principle (the principles) in digital trade mean under trade agreements, especially in the absence of a clear international consensus on the subject of the principles? To answer this question, this study first identifies the issues related to the application of the principles in digital trade and presents a theoretical framework to explain how the principles can affect digital trade despite such issues. Using various data sources, such as digital trade flows, the inclusion of the principles in digital trade agreements, and digital trade barriers, we empirically test the hypotheses constructed from our theoretical framework. We find that inclusion of the principles in the trade agreements is more likely to increase digital trade flows. Moreover, though digital trade barriers decrease digital trade flows, this negative effect can be mitigated when the principles are more clearly defined in the trade agreements.
Emotion dysregulation and family functioning moderate family caregiving burden during the pandemic
Authors: Kim Dahee , Russell Beth S. , Park Crystal L. , Fendrich Michael
Published: November 2023

Objectives

Since the onset of COVID-19 pandemic, additional risk factors affecting family caregivers’ mental health have arisen. Therefore, personal stress coping strategies and family dynamics became important factors in reducing the impact of the pandemic on family caregivers’ mental health. The present research aimed to estimate the association between COVID-19 stressors and family caregiving burden. Moreover, moderating effects of emotion dysregulation and family functioning on this association were investigated.

Methods

This study analyzed data collected in April 2021 from 154 family caregivers (Mage = 38.79, SDage = 9.36, range = 22–64) recruited through Amazon’s Mechanical Turk (MTurk). The impact of COVID-19 stressors on family caregiving burden was tested, and moderating impacts of emotion dysregulation and family functioning were also investigated.

Results

Both COVID-19 stress exposure and stress appraisal were positively associated with family caregiving burden. Emotion dysregulation and problematic family functioning were also positively associated with family caregiving burden. A significant moderating effect of emotion dysregulation was found, such that family caregivers with higher emotion dysregulation were likely to feel more caregiving burden when they experienced more COVID-19 stressors.

Significance of results

The current research highlighted the role of emotion regulation in reducing the negative impact of COVID-19 stressors on family caregiving burden. The research also emphasizes the need for intervention programs to improve emotion regulation strategies to decrease family caregiving burden during the pandemic.
Origins of Uncertainty in the Response of the Summer North Pacific Subtropical High to CO2 Forcing
Authors: Lu Kezhou , He Jie , Simpson Isla R.
Published: November 2023

The variability of the summer North Pacific Subtropical High (NPSH) has substantial socioeconomic impacts. However, state‐of‐the‐art climate models significantly disagree on the response of the NPSH to anthropogenic warming. Inter‐model spread in NPSH projections originates from models' inconsistency in simulating tropical precipitation changes. This inconsistency in precipitation changes is partly due to inter‐model spread in tropical sea surface temperature (SST) changes, but it can also occur independently of uncertainty in SST changes. Here, we show that both types of precipitation uncertainty influence the NPSH via the Matsuno‐Gill wave response, but their relative impact varies by region. Through the modulation of low cloud fraction, inter‐model spread of the NPSH can have a further impact on extra‐tropical land surface temperature. The teleconnection between tropical precipitation and the NPSH is examined through a series of numerical experiments.
The Role of Small to Moderate Volcanic Eruptions in the Early 19th Century Climate
Authors: Fang Shih‐Wei , Sigl Michael , Toohey Matthew , Jungclaus Johann , Zanchettin Davide , Timmreck Claudia
Published: November 2023

Small‐to‐moderate volcanic eruptions can lead to significant surface cooling when they occur clustered, as observed in recent decades. In this study, based on new high‐resolution ice‐core data from Greenland, we produce a new volcanic forcing data set that includes several small‐to‐moderate eruptions not included in prior reconstructions and investigate their climate impacts of the early 19th century through ensemble simulations with the Max Planck Institute Earth System Model. We find that clustered small‐to‐moderate eruptions produce significant additional global surface cooling (∼0.07 K) during the period 1812–1820, superposing with the cooling by large eruptions in 1809 (unidentified location) and 1815 (Tambora). This additional cooling helps explain the reconstructed long‐lasting cooling after the large eruptions, but simulated regional impacts cannot be confirmed with reconstructions due to a low signal‐to‐noise ratio. This study highlights the importance of small‐to‐moderate eruptions for climate simulations as their impacts can be comparable with that of solar irradiance changes.
Diagnosing the Linear Periodicity Dynamics of ENSO for Its Two Spatiotemporal Modes
Authors: Ren Hong‐Li , Wang Run
Published: November 2023

The El Niño–Southern Oscillation (ENSO) is mainly manifested as the quasi‐biennial (QB) and low‐frequency (LF) coupled modes centered at different longitudes. Based on the recharge oscillator framework, we propose a new method to diagnose the linear periodicity dynamics of spatiotemporally diverse ENSOs, for example, the two coupled modes, to which the traditional Wyrtki index method is ineligible. This method is applied to reanalysis data sets and models and validated by comparisons with the Wyrtki index, which shows that the periodicity of the LF mode is dominated by the thermocline feedback (TH) and effectively reproduced by models, whereas the periodicity of the QB mode is equally driven by the TH and zonal advective feedback (ZA) and poorly simulated in most models due to the insufficient ZA simulations. The new method provides an effective tool for a deeper understanding of the multi‐timescale nature of diverse ENSOs and improving their representations in future models.
Triple‐Dip La Niña in 2020–23: North Pacific Atmosphere Drives 2nd Year La Niña
Authors: Iwakiri Tomoki , Imada Yukiko , Takaya Yuhei , Kataoka Takahito , Tatebe Hiroaki , Watanabe Masahiro
Published: November 2023

La Niña persisted from 2020 to 2023, but its mechanisms are still unclear. In this study, atmosphere and ocean reanalysis and 100‐member initialized forecasts using a state‐of‐the‐art climate model were analyzed to identify factors contributing to the persistence of the first‐ to second‐year La Niña during 2020–2022. We found that North Pacific high pressure anomalies in the winter of 2020/2021 forced a negative phase of the Pacific meridional mode through the following spring, forming the broader structure of La Niña. The resultant broader La Niña pattern slowed down the recharge‐discharge process by Ekman transport, persisting La Niña. Ensemble forecast sensitivity analysis revealed that the meridional extent of La Niña explains its forecast spread, reaffirming the importance of La Niña spatial pattern. Advancing predictive understanding of 2020–2022 multi‐year La Niña can help to improve the extended seasonal forecast.
Bridging the Gap Between Experimental and Natural Fabrics: Modeling Ice Stream Fabric Evolution and its Comparison With Ice‐Core Data
Authors: Richards Daniel H. , Pegler Samuel S. , Piazolo Sandra , Stoll Nicolas , Weikusat Ilka
Published: November 2023

Fabrics, also known as textures or crystallographic preferred orientations, reveal information about the deformation history of the flow of polycrystalline materials, including glacial ice, olivine in the mantle, and feldspar and quartz in the crust. Ice fabrics can have an order‐of‐magnitude effect on the ease of flow in ice sheets. However, due to the choice of ice core drill site locations, the outputs of fabric models have mostly been compared to observations from the least dynamic regions of the ice sheet (ice divides). Recently, fabric data from an active ice stream have become available from ice cores drilled at the East Greenland Ice‐core Project (EGRIP). In this work, we present a novel approach that combines satellite‐derived velocity data with the fabric evolution model SpecCAF, a continuum model based on dominant dislocation creep. We directly compare model output to ice‐core observations from EGRIP, allowing us to examine the quantitative predictions of calibrated fabric models alongside those of active ice streams for the first time. As the model is calibrated against laboratory experiments, it provides a surrogate to compare the evolution of fabrics under laboratory and natural conditions. The predictions show good qualitative agreement with the observed fabric patterns and orientations, suggesting that a fabric between a girdle and horizontal maximum, orientated perpendicular to the flow direction, is the characteristic ice stream fabric. A discrepancy in fabric strength is attributed to the lower strain rates of ice sheets compared to laboratory experiments, revealing a significant strain‐rate dependence in the processes controlling fabric evolution.
Stratospheric Climate Anomalies and Ozone Loss Caused by the Hunga Tonga‐Hunga Ha'apai Volcanic Eruption
Authors: Wang Xinyue , Randel William , Zhu Yunqian , Tilmes Simone , Starr Jon , Yu Wandi , Garcia Rolando , Toon Owen B. , Park Mijeong , Kinnison Douglas , Zhang Jun , Bourassa Adam , Rieger Landon , Warnock Taran , Li Jianghanyang
Published: November 2023

The Hunga Tonga‐Hunga Ha'apai (HTHH) volcanic eruption in January 2022 injected unprecedented amounts of water vapor (H2O) and a moderate amount of the aerosol precursor sulfur dioxide (SO2) into the Southern Hemisphere (SH) tropical stratosphere. The H2O and aerosol perturbations have persisted during 2022 and early 2023 and dispersed throughout the atmosphere. Observations show large‐scale SH stratospheric cooling, equatorward shift of the Antarctic polar vortex and slowing of the Brewer‐Dobson circulation. Satellite observations show substantial ozone reductions over SH winter midlatitudes that coincide with the largest circulation anomalies. Chemistry‐climate model simulations forced by realistic HTHH inputs of H2O and SO2 qualitatively reproduce the observed evolution of the H2O and aerosol plumes over the first year, and the model exhibits stratospheric cooling, circulation changes and ozone effects similar to observed behavior. The agreement demonstrates that the observed stratospheric changes are caused by the HTHH volcanic influences.
Spatiotemporal cellular dynamics and molecular regulation of tooth root ontogeny
Authors: Rao Pengcheng , jing Junjun , Fan Yi , Zhou Chenchen
Published: November 2023

Tooth root development involves intricate spatiotemporal cellular dynamics and molecular regulation. The initiation of Hertwig’s epithelial root sheath (HERS) induces odontoblast differentiation and the subsequent radicular dentin deposition. Precisely controlled signaling pathways modulate the behaviors of HERS and the fates of dental mesenchymal stem cells (DMSCs). Disruptions in these pathways lead to defects in root development, such as shortened roots and furcation abnormalities. Advances in dental stem cells, biomaterials, and bioprinting show immense promise for bioengineered tooth root regeneration. However, replicating the developmental intricacies of odontogenesis has not been resolved in clinical treatment and remains a major challenge in this field. Ongoing research focusing on the mechanisms of root development, advanced biomaterials, and manufacturing techniques will enable next-generation biological root regeneration that restores the physiological structure and function of the tooth root. This review summarizes recent discoveries in the underlying mechanisms governing root ontogeny and discusses some recent key findings in developing of new biologically based dental therapies.
Genomic DNA-based measurable residual disease monitoring in pediatric acute myeloid leukemia: unselected consecutive cohort study
Authors: Zaliova Marketa , Zuna Jan , Winkowska Lucie , Janotova Iveta , Skorepova Justina , Lukes Julius , Meyer Claus , Marschalek Rolf , Novak Zbynek , Domansky Jiri , Stary Jan , Sramkova Lucie , Trka Jan
Published: November 2023

Measurable residual disease (MRD) monitoring in childhood acute myeloid leukemia (AML) is used to assess response to treatment and for early detection of imminent relapse. In childhood AML, MRD is typically evaluated using flow cytometry, or by quantitative detection of leukemia-specific aberrations at the mRNA level. Both methods, however, have significant limitations. Recently, we demonstrated the feasibility of MRD monitoring in selected subgroups of AML at the genomic DNA (gDNA) level. To evaluate the potential of gDNA-based MRD monitoring across all AML subtypes, we conducted a comprehensive analysis involving 133 consecutively diagnosed children. Integrating next-generation sequencing into the diagnostic process, we identified (presumed) primary genetic aberrations suitable as MRD targets in 97% of patients. We developed patient-specific quantification assays and monitored MRD in 122 children. The gDNA-based MRD monitoring via quantification of primary aberrations with a sensitivity of at least 10−4 was possible in 86% of patients; via quantification with sensitivity of 5 × 10−4, of secondary aberrations, or at the mRNA level in an additional 8%. Importantly, gDNA-based MRD exhibited independent prognostic value at early time-points in patients stratified to intermediate-/high-risk treatment arms. Our study demonstrates the broad applicability, feasibility, and clinical significance of gDNA-based MRD monitoring in childhood AML.
Wavefront control of subcycle vortex pulses via carrier-envelope-phase tailoring
Authors: Lin Yu-Chieh , Midorikawa Katsumi , Nabekawa Yasuo
Published: November 2023

The carrier-envelope phase (CEP) of an ultrashort laser pulse is becoming more crucial to specify the temporal characteristic of the pulse’s electric field when the pulse duration becomes shorter and attains the subcycle regime; here, the pulse duration of the intensity envelope is shorter than one cycle period of the carrier field oscillation. When this subcycle pulse involves a structured wavefront as is contained in an optical vortex (OV) pulse, the CEP has an impact on not only the temporal but also the spatial characteristics owing to the spatiotemporal coupling in the structured optical pulse. However, the direct observation of the spatial effect of the CEP control has not yet been demonstrated. In this study, we report on the measurement and control of the spatial wavefront of a subcycle OV pulse by adjusting the CEP. To generate subcycle OV pulses, an optical parametric amplifier delivering subcycle Gaussian pulses and a Sagnac interferometer as a mode converter were integrated and provided an adequate spectral adaptability. The pulse duration of the generated OV pulse was 4.7 fs at a carrier wavelength of 1.54 µm. To confirm the wavefront control with the alteration of the CEP, we developed a novel $$f$$
f
-2$$f$$
f
interferometer that exhibited spiral fringes originating from the spatial interference between the subcycle OV pulse and the second harmonic of the subcycle Gaussian pulse producing a parabolic wavefront as a reference; this resulted in the successful observation of the rotation of spiral interference fringes during CEP manipulation.
Antisecretory factor in breastmilk is associated with reduced incidence of sepsis in preterm infants
Authors: Gustafsson Anna , Johansson Ewa , Henckel Ewa , Olin Axel , Rodriguez Lucie , Brodin Petter , Lange Stefan , Bohlin Kajsa
Published: November 2023

Background

Antisecretory Factor (AF) is a protein present in breastmilk that regulates inflammatory processes. We aimed to investigate the level of AF in mothers’ own milk (MOM) in relation to sepsis and other neonatal morbidities in preterm infants.

Methods

Samples of breastmilk and infant plasma were collected at 1, 4, and 12 weeks after birth from 38 mothers and their 49 infants born before 30 weeks gestation. AF-compleasome in MOM was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) and inflammatory markers in infant plasma by a panel of 92 inflammatory proteins. Neonatal treatments and outcomes were recorded.

Results

The level of AF in MOM week 1 was lower for infants with later sepsis compared to no sepsis (p = 0.005). Corrected for nutritional intake of MOM, higher levels of AF decreased the risk for sepsis, OR 0.24. AF in MOM week 1 was negatively correlated to inflammatory proteins in infant plasma week 4, markedly IL-8, which was also associated with infant sepsis. Overall, higher AF levels in MOM was associated with fewer major morbidities of prematurity.

Conclusion

Mother’s milk containing high levels of antisecretory factor is associated with reduced risk for sepsis and inflammation in preterm infants.

Impact

High level of antisecretory factor (AF) in mothers’ own milk is associated with less risk for later sepsis in preterm infants.

Receiving mothers’ milk with low AF levels during the first week after birth is correlated with more inflammatory proteins in infant’s plasma 2–4 weeks later.

Human breastmilk has anti-inflammatory properties, and antisecretory factor in mothers’ own milk is a component of potential importance for infants born preterm.

The findings suggest that food supplementation with AF to mothers of preterm infants to increase AF-levels in breastmilk may be a means to decrease the risk of inflammatory morbidities of prematurity.
3D-printed TCP-HA scaffolds delivering MicroRNA-302a-3p improve bone regeneration in a mouse calvarial model
Authors: Limlawan Pirawish , Insin Numpon , Marger Laurine , Freudenreich Mélanie , Durual Stéphane , Vacharaksa Anjalee
Published: November 2023

Objective

To demonstrate hydroxyapatite nanoparticles modified with cationic functional molecules. 3-aminopropyltriethoxysilane (HA-NPs-APTES) carrying microRNA-302a-3p (miR) in the 3D-printed tricalcium phosphate/Hydroxyapatite (TCP/HA) scaffold can increase healing of the critical-sized bone defect.

Materials and methods

3D-printed TCP/HA were modified with HA-NPs-APTES by two methods (M1, M2). The dispersion of particles was visualized by fluorescent microscopy. Biocompatibility of the scaffolds was tested by alizarin assay. Delivery of miR to the cells and osteogenic gene expression were evaluated by qPCR. After selecting best method (M2), scaffolds, scaffolds+HA-NPs-APTES with or without miR were implanted in 4 mm mouse calvarium defect (n = 4 per group). After 2,4 and 6 weeks, bone regeneration were evaluated by microCT and histology sections.

Results

Both M1 and M2 scaffolds were biocompatible with cell adhesion on its surface. M2 scaffold showed significant increase of miR, suggesting successful delivery, resulted in downregulation of its target mRNA COUP-TFII, and upregulation of RUNX2 mRNA. Calvarium defect with M2 scaffold also showed significantly higher BV/TV and higher number of filled spaces at all time points. Histomorphometry demonstrated new bone formed at the center of the HA-NPs-APTES-miR scaffold earlier than controls.

Conclusion

TCP/HA scaffold modified with HA-NPs-APTES facilitated delivery of miR and enhanced bone regeneration.
Izod impact resistance of 3D printed discontinuous fibrous composites with Bouligand structure
Authors: Guan Lizhi , Peng Weixiang , Wen Rachel Ng Jing , Fan Jingbo , Le Ferrand Hortense
Published: November 2023

The Bouligand structure found in the dactyl club of mantis shrimps is known for its impact resistance. However, Bouligand-inspired reinforced composites with 3D shapes and impact resistance characteristics have not yet been demonstrated. Herein, direct ink writing was used to 3D print composites reinforced with glass microfibers assembled into Bouligand structures with controllable pitch angles. The energy absorption levels of the Bouligand composites under impact were found to surpass those of composites with unidirectional microfiber alignment. Additionally, the Bouligand composites with a pitch angle of 40° exhibited a maximum energy absorption of 2.4 kJ/m2, which was 140% higher than that of the unidirectional composites. Furthermore, the characterization of the topography of the fractured surface, supplemented with numerical simulations, revealed a combination of crack twisting and crack bridging mechanisms. Flexural tests conducted on the composites with a pitch angle of 40° revealed that these composites had the strongest properties, including a flexural strength of 36.9 MPa, a stiffness of 2.26 GPa, and energy absorption of 8 kJ/m2. These findings are promising for the microstructural design of engineered composites using direct ink writing for applications in aerospace, transportation, and defense.
Paired single-cell multi-omics data integration with Mowgli
Authors: Huizing Geert-Jan , Deutschmann Ina Maria , Peyré Gabriel , Cantini Laura
Published: November 2023

The profiling of multiple molecular layers from the same set of cells has recently become possible. There is thus a growing need for multi-view learning methods able to jointly analyze these data. We here present Multi-Omics Wasserstein inteGrative anaLysIs (Mowgli), a novel method for the integration of paired multi-omics data with any type and number of omics. Of note, Mowgli combines integrative Nonnegative Matrix Factorization and Optimal Transport, enhancing at the same time the clustering performance and interpretability of integrative Nonnegative Matrix Factorization. We apply Mowgli to multiple paired single-cell multi-omics data profiled with 10X Multiome, CITE-seq, and TEA-seq. Our in-depth benchmark demonstrates that Mowgli’s performance is competitive with the state-of-the-art in cell clustering and superior to the state-of-the-art once considering biological interpretability. Mowgli is implemented as a Python package seamlessly integrated within the scverse ecosystem and it is available at http://github.com/cantinilab/mowgli.
The unusual quadruple bonding of nitrogen in ThN
Authors: Fei Zejie , Wang Jia-Qi , Tang Rulin , Lu Yuzhu , Han Changcai , Wang Yongtian , Hong Jing , Dong Changwu , Hu Han-Shi , Xiong Xiao-Gen , Ning Chuangang , Liu Hongtao , Li Jun
Published: November 2023

Nitrogen has five valence electrons and can form a maximum of three shared electron-pair bonds to complete its octet, which suggests that its maximum bond order is three. With a joint anion photoelectron spectroscopy and quantum chemistry investigation, we report herein that nitrogen presents a quadruple bonding interaction with thorium in ThN. The quadruple Th≣N bond consists of two electron-sharing Th-N π bonds formed between the Th-6dxz/6dyz and N 2px/2py orbitals, one dative Th←N σ bond and one weak Th←N σ bonding interaction formed between Th-6dz2 and N 2s/2pz orbitals. The ThC molecule has also been investigated and proven to have a similar bonding pattern as ThN. Nonetheless, due to one singly occupied σ-bond, ThC is assigned a bond order of 3.5. Moreover, ThC has a longer bond length as well as a lower vibrational frequency in comparison with ThN.
All electromagnetic scattering bodies are matrix-valued oscillators
Authors: Zhang Lang , Monticone Francesco , Miller Owen D.
Published: November 2023

Scattering theory is the basis of all linear optical and photonic devices, whose spectral response underpins wide-ranging applications from sensing to energy conversion. Unlike the Shannon theory for communication channels, or the Fano theory for electric circuits, understanding the limits of spectral wave scattering remains a notoriously challenging open problem. We introduce a mathematical scattering representation that inherently embeds fundamental principles of causality and passivity into its elemental degrees of freedom. We use this representation to reveal strong constraints in the mathematical structure of scattered fields, and to develop a general theory of the maximum radiative heat transfer in the near field, resolving a long-standing open question. Our approach can be seamlessly applied to high-interest applications across nanophotonics, and appears extensible to general classical and quantum scattering theory.
Autophagy drives the conversion of developmental neural stem cells to the adult quiescent state
Authors: Calatayud-Baselga Isabel , Casares-Crespo Lucía , Franch-Ibáñez Carmina , Guijarro-Nuez José , Sanz Pascual , Mira Helena
Published: November 2023

Neurogenesis in the adult mammalian brain relies on the lifelong persistence of quiescent neural stem cell (NSC) reservoirs. Little is known about the mechanisms that lead to the initial establishment of quiescence, the main hallmark of adult stem cells, during development. Here we show that protein aggregates and autophagy machinery components accumulate in developmental radial glia-like NSCs as they enter quiescence and that pharmacological or genetic blockade of autophagy disrupts quiescence acquisition and maintenance. Conversely, increasing autophagy through AMPK/ULK1 activation instructs the acquisition of the quiescent state without affecting BMP signaling, a gatekeeper of NSC quiescence during adulthood. Selective ablation of Atg7, a critical gene for autophagosome formation, in radial glia-like NSCs at early and late postnatal stages compromises the initial acquisition and maintenance of quiescence during the formation of the hippocampal dentate gyrus NSC niche. Therefore, we demonstrate that autophagy is cell-intrinsically required to establish NSC quiescence during hippocampal development. Our results uncover an important role of autophagy in the transition of developmental NSCs into their dormant adult form, paving the way for studies directed at further understanding the mechanisms of stem cell niche formation and maintenance in the mammalian brain.
Cu-mediated enantioselective C–H alkynylation of ferrocenes with chiral BINOL ligands
Authors: Kuang Xin , Li Jian-Jun , Liu Tao , Ding Chang-Hua , Wu Kevin , Wang Peng , Yu Jin-Quan
Published: November 2023

A wide range of Cu(II)-catalyzed C–H activation reactions have been realized since 2006, however, whether a C–H metalation mechanism similar to Pd(II)-catalyzed C–H activation reaction is operating remains an open question. To address this question and ultimately develop ligand accelerated Cu(II)-catalyzed C–H activation reactions, realizing the enantioselective version and investigating the mechanism is critically important. With a modified chiral BINOL ligand, we report the first example of Cu-mediated enantioselective C–H activation reaction for the construction of planar chiral ferrocenes with high yields and stereoinduction. The key to the success of this reaction is the discovery of a ligand acceleration effect with the BINOL-based diol ligand in the directed Cu-catalyzed C–H alkynylation of ferrocene derivatives bearing an oxazoline-aniline directing group. This transformation is compatible with terminal aryl and alkyl alkynes, which are incompatible with Pd-catalyzed C–H activation reactions. This finding provides an invaluable mechanistic information in determining whether Cu(II) cleaves C–H bonds via CMD pathway in analogous manner to Pd(II) catalysts.
Extent of carbon nitride photocharging controls energetics of hydrogen transfer in photochemical cascade processes
Authors: Savateev Oleksandr , Nolkemper Karlo , Kühne Thomas D. , Shvalagin Vitaliy , Markushyna Yevheniia , Antonietti Markus
Published: November 2023

Graphitic carbon nitride is widely studied in organic photoredox catalysis. Reductive quenching of carbon nitride excited state is postulated in many photocatalytic transformations. However, the reactivity of this species in the turn over step is less explored. In this work, we investigate electron and proton transfer from carbon nitride that is photocharged to a various extent, while the negative charge is compensated either by protons or ammonium cations. Strong stabilization of electrons by ammonium cations makes proton-coupled electron transfer uphill, and affords air-stable persistent carbon nitride radicals. In carbon nitrides, which are photocharged to a smaller extent, protons do not stabilize electrons, which results in spontaneous charge transfer to oxidants. Facile proton-coupled electron transfer is a key step in the photocatalytic oxidative-reductive cascade – tetramerization of benzylic amines. The feasibility of proton-coupled electron transfer is modulated by adjusting the extent of carbon nitride photocharging, type of counterion and temperature.
The genomic epidemiology of shigellosis in South Africa
Authors: Stenhouse George E. , Keddy Karen H. , Bengtsson Rebecca J. , Hall Neil , Smith Anthony M. , Thomas Juno , Iturriza-Gómara Miren , Baker Kate S.
Published: November 2023

Shigellosis, a leading cause of diarrhoeal mortality and morbidity globally, predominantly affects children under five years of age living in low- and middle-income countries. While whole genome sequence analysis (WGSA) has been effectively used to further our understanding of shigellosis epidemiology, antimicrobial resistance, and transmission, it has been under-utilised in sub-Saharan Africa. In this study, we applied WGSA to large sub-sample of surveillance isolates from South Africa, collected from 2011 to 2015, focussing on Shigella flexneri 2a and Shigella sonnei. We find each serotype is epidemiologically distinct. The four identified S. flexneri 2a clusters having distinct geographical distributions, and antimicrobial resistance (AMR) and virulence profiles, while the four sub-Clades of S. sonnei varied in virulence plasmid retention. Our results support serotype specific lifestyles as a driver for epidemiological differences, show AMR is not required for epidemiological success in S. flexneri, and that the HIV epidemic may have promoted Shigella population expansion.
Stepwise differentiation of follicular helper T cells reveals distinct developmental and functional states
Authors: Podestà Manuel A. , Cavazzoni Cecilia B. , Hanson Benjamin L. , Bechu Elsa D. , Ralli Garyfallia , Clement Rachel L. , Zhang Hengcheng , Chandrakar Pragya , Lee Jeong-Mi , Reyes-Robles Tamara , Abdi Reza , Diallo Alos , Sen Debattama R. , Sage Peter T.
Published: November 2023

Follicular helper T (Tfh) cells are essential for the formation of high affinity antibodies after vaccination or infection. Although the signals responsible for initiating Tfh differentiation from naïve T cells have been studied, the signals controlling sequential developmental stages culminating in optimal effector function are not well understood. Here we use fate mapping strategies for the cytokine IL-21 to uncover sequential developmental stages of Tfh differentiation including a progenitor-like stage, a fully developed effector stage and a post-effector Tfh stage that maintains transcriptional and epigenetic features without IL-21 production. We find that progression through these stages are controlled intrinsically by the transcription factor FoxP1 and extrinsically by follicular regulatory T cells. Through selective deletion of Tfh stages, we show that these cells control antibody dynamics during distinct stages of the germinal center reaction in response to a SARS-CoV-2 vaccine. Together, these studies demonstrate the sequential phases of Tfh development and how they promote humoral immunity.
Occlusive membranes for guided regeneration of inflamed tissue defects
Authors: Choi Woojin , Mangal Utkarsh , Park Jin-Young , Kim Ji-Yeong , Jun Taesuk , Jung Ju Won , Choi Moonhyun , Jung Sungwon , Lee Milae , Na Ji-Yeong , Ryu Du Yeol , Kim Jin Man , Kwon Jae-Sung , Koh Won-Gun , Lee Sangmin , Hwang Patrick T. J. , Lee Kee-Joon , Jung Ui-Won , Cha Jae-Kook , Choi Sung-Hwan , Hong Jinkee
Published: November 2023

Guided bone regeneration aided by the application of occlusive membranes is a promising therapy for diverse inflammatory periodontal diseases. Symbiosis, homeostasis between the host microbiome and cells, occurs in the oral environment under normal, but not pathologic, conditions. Here, we develop a symbiotically integrating occlusive membrane by mimicking the tooth enamel growth or multiple nucleation biomineralization processes. We perform human saliva and in vivo canine experiments to confirm that the symbiotically integrating occlusive membrane induces a symbiotic healing environment. Moreover, we show that the membrane exhibits tractability and enzymatic stability, maintaining the healing space during the entire guided bone regeneration therapy period. We apply the symbiotically integrating occlusive membrane to treat inflammatory-challenged cases in vivo, namely, the open and closed healing of canine premolars with severe periodontitis. We find that the membrane promotes symbiosis, prevents negative inflammatory responses, and improves cellular integration. Finally, we show that guided bone regeneration therapy with the symbiotically integrating occlusive membrane achieves fast healing of gingival soft tissue and alveolar bone.
Autonomous nanorobots with powerful thrust under dry solid-contact conditions by photothermal shock
Authors: Gu Zhaoqi , Zhu Runlin , Shen Tianci , Dou Lin , Liu Hongjiang , Liu Yifei , Liu Xu , Liu Jia , Zhuang Songlin , Gu Fuxing
Published: November 2023

Nanorobotic motion on solid substrates is greatly hindered by strong nanofriction, and powerful nanomotors‒the core components for nanorobotic motion‒are still lacking. Optical actuation addresses power and motion control issues simultaneously, while conventional technologies with small thrust usually apply to fluid environments. Here, we demonstrate micronewton-thrust nanomotors that enable the autonomous nanorobots working like conventional robots with precise motion control on dry surfaces by a photothermal-shock technique. We build a pulsed laser-based actuation and trapping platform, termed photothermal-shock tweezers, for general motion control of metallic nanomaterials and assembled nanorobots with nanoscale precision. The thrust-to-weight ratios up to 107 enable nanomotors output forces to interact with external micro/nano-objects. Leveraging machine vision and deep learning technologies, we assemble the nanomotors into autonomous nanorobots with complex structures, and demonstrate multi-degree-of-freedom motion and sophisticated functions. Our photothermal shock-actuation concept fundamentally addresses the nanotribology challenges and expands the nanorobotic horizon from fluids to dry solid surfaces.
Stochastic chain termination in bacterial pilus assembly
Authors: Giese Christoph , Puorger Chasper , Ignatov Oleksandr , Bečárová Zuzana , Weber Marco E. , Schärer Martin A. , Capitani Guido , Glockshuber Rudi
Published: November 2023

Adhesive type 1 pili from uropathogenic Escherichia coli strains are filamentous, supramolecular protein complexes consisting of a short tip fibrillum and a long, helical rod formed by up to several thousand copies of the major pilus subunit FimA. Here, we reconstituted the entire type 1 pilus rod assembly reaction in vitro, using all constituent protein subunits in the presence of the assembly platform FimD, and identified the so-far uncharacterized subunit FimI as an irreversible assembly terminator. We provide a complete, quantitative model of pilus rod assembly kinetics based on the measured rate constants of FimD-catalyzed subunit incorporation. The model reliably predicts the length distribution of assembled pilus rods as a function of the ratio between FimI and the main pilus subunit FimA and is fully consistent with the length distribution of membrane-anchored pili assembled in vivo. The results show that the natural length distribution of adhesive pili formed via the chaperone-usher pathway results from a stochastic chain termination reaction. In addition, we demonstrate that FimI contributes to anchoring the pilus to the outer membrane and report the crystal structures of (i) FimI in complex with the assembly chaperone FimC, (ii) the FimI-FimC complex bound to the N-terminal domain of FimD, and (iii) a ternary complex between FimI, FimA and FimC that provides structural insights on pilus assembly termination and pilus anchoring by FimI.