bluuebunny/crossref_metadata_2025 huggingface dataset:
Stressful life events, psychosocial health and general health in preschool children before age 4
Authors: Luo Jie , van Grieken Amy , Zhou Shuang , Fang Yuan , Raat Hein
Published: November 2022

Background

The impact of stressful life events (SLEs) in early childhood is often ignored. We aimed to examine longitudinal associations between SLEs and psychosocial and general health in preschool children.

Methods

Twelve SLEs occurring before the age of 24 months were assessed and categorized by frequency (no events, 1–2 SLEs, and > 2 SLEs) and overall tension (no events, low, and high) (n = 1431). Psychosocial and general health were measured three times at the age of 24, 36 and 45 months. The associations were examined by logistic regression models using generalized estimating equations to handle repeated measurements.

Results

Half (48.4%) of the families experienced SLEs, and 23.8% perceived high-tension SLEs before the children were aged 24 months. Gender differences were observed in the association between SLEs and psychosocial health. Compared to girls without SLEs, girls who experienced > 2 SLEs [OR = 3.31, 95% confidence interval (CI) 2.05–5.35] or high-tension SLEs (OR = 3.01, 95% CI 2.07–4.39) had higher odds of psychosocial problems from 24 to 45 months. The odds ratios in boys were 2.10 (95% CI 1.36–3.24) and 1.47 (95% CI 1.06–2.03), respectively. Moreover, only girls’ risk of psychosocial problems increased after experiencing 1–2 SLEs (OR = 2.15, 95% CI 1.54–3.00) or low-tension SLEs (OR = 1.90, 95% CI 1.31–2.74). Regarding general health, children who experienced > 2 SLEs (OR = 1.96, 95% CI 1.21–3.18) and high-tension SLEs (OR = 1.60, 95% CI 1.12–2.28) had higher odds of poor general health from 24 to 45 months.

Conclusions

The findings emphasized that young children’s psychosocial and general health can be impacted by experiencing SLEs in early childhood. Attention and adequate support for families experiencing SLEs are needed to minimize the potential negative effect of SLEs on child health, particularly in girls.
Quantitative 3D orientation analysis of particles and voids to differentiate hand-built pottery forming techniques using X-ray microtomography and neutron tomography
Authors: Gait John , Bajnok Katalin , Szilágyi Veronika , Szenti Imre , Kukovecz Ákos , Kis Zoltán
Published: November 2022

This article describes the quantitative analysis of the 3D orientation of objects (i.e. particles and voids) within pottery fabrics to differentiate two categories of pottery hand-building primary forming techniques, specifically percussion-building and coil-building, comparing the use of two independent non-destructive imaging modalities, X-ray microtomography (µ-CT) and neutron tomography (NT). For this purpose, series of experimental organic-tempered vessels and coil sections were analysed. For both imaging modalities, two separate systems were employed for quantitatively describing both the orientation of individual objects, as well as the collective preferential alignment of objects within samples, utilising respectively polar and azimuth angles within a spherical coordinate system, and projected sizes within a positive Cartesian coordinate system. While the former provided full descriptions of the orientations of objects within 3D space, the latter, through a ratio dubbed here the ‘Orientation Index’ (OI), gave a simple numerical value with which the investigated samples were differentiated according to forming technique. Both imaging modalities were able to differentiate between coil-built and percussion-built vessels with a high degree of confidence, with the strength of these findings additionally demonstrated through extensive statistical modelling using Monte Carlo simulations. Despite differences in resolution and differences in the attenuation of X-rays and neutrons, µ-CT and NT were shown to provide comparable results. The findings presented here broadly agree with earlier studies; however, the quantitative and three-dimensional nature of the results enables more subtle features to be identified, while additionally, in principle, the non-destructive nature of both imaging techniques facilitates such structural analysis without recourse to invasive sampling.
Attenuation of Mild Steel-Acid Corrosion Using Exfoliated Graphite Oxide-Polymer Composite: Synthesis, Characterization, Electrochemical, and Response Surface Method Approach
Authors: Raj Aishwarya , Kumari Preethi , Lavanya M. , Vishwanath T. , Suvarna Aishwarya M.
Published: November 2022

This work deals with the study of the anticorrosion behavior of a biopolymer, namely Guar Gum (GG) and its composite on mild steel (MS) in sulfamic acid (SA) solution using electrochemical techniques. GG was found to be a potential inhibitor relatively at its higher concentration and showed maximum inhibition efficiency (IE) of 74% at 3 g/L (3000 ppm). To improve its IE, exfoliated graphite oxide (xGO)/GG polymer composite was prepared, and its inhibition property was assessed in 1 M SA solution at different temperatures by weight loss method (WL). The chemical structure of xGO/GG polymer composite was examined by FT-IR, and the morphology was inspected by optical microscopy, scanning electron microscopy study, and energy dispersive spectroscopy technique. xGO/GG polymer composite emerged as an efficient corrosion inhibitor for MS as marked from the outcomes of the electrochemical investigations and showed improved IE of 93% at 0.6 g/L (600 ppm) when compared to GG. Experimental results found by WL measurements are used to evaluate the thermodynamic parameters at various temperatures. Further, a Box-Behnken composite design with three factors and three levels has been used to minimize the experimental conditions. The IE was enhanced with the increase in the inhibitor concentration as observed from the main effect plot. The maximum IE of 84.21% was projected by the response surface method (RSM) with temperature (A = 30 °C), inhibitor concentration (B = 600 ppm), and time (C = 1 h).
Assessment of mouthguards worn by Irish children playing contact sports: an observational cross-sectional cohort study
Authors: Shore Elaine , O’Connell Anne C.
Published: November 2022

Purpose

Traumatic dental injuries occur during participation in sports. Prevention of these injuries by wearing a mouthguard (MG) is desirable, especially in a paediatric population. There are several types of MG available, and their effectiveness depends on device design. The aim of this study was to examine the features of MG worn by children playing a contact sport (Gaelic football), and to determine whether these MG fulfilled recommendations for adequate dentoalveolar protection.

Methods

A cross-sectional observational cohort study design was developed. Dentists were trained and calibrated in assessing MGs, both qualitatively (retention, extension, integrity) and quantitatively (thickness). A convenience sample of male and female subjects aged 9–16 years was selected for MG assessment via their sports clubs. Data were collected anonymously and analysed using descriptive and comparative statistics.

Results

One hundred and six children presented with their MG for assessment. Two-thirds were wearing mouth-formed MG (N = 71, 66.96%). Only four were wearing custom MG (3.77%). Most MG had inadequate retention (N = 86, 81.13%) and labial extension (N = 89, 83.96%), with a significant relationship between MG type and retention. Mouthguard thickness varied widely at each site. Mouth-formed MG were significantly thicker than both stock and custom MG.

Conclusions

Mouth-formed MG were the most common type followed by stock MG. Most MG did not have appropriate retention or labial extension. Parents and coaches need to be aware of MG features that maximise protection. If mouth-formed MG are provided in this age group, education on how to adapt them is essential. Paediatric dentists should check MG routinely for appropriate fit.
Understanding and Control of Activation Process of Lithium-Rich Cathode Materials
Authors: Lin Tongen , Seaby Trent , Hu Yuxiang , Ding Shanshan , Liu Ying , Luo Bin , Wang Lianzhou
Published: November 2022

Lithium-rich materials (LRMs) are among the most promising cathode materials toward next-generation Li-ion batteries due to their extraordinary specific capacity of over 250 mAh g−1 and high energy density of over 1 000 Wh kg−1. The superior capacity of LRMs originates from the activation process of the key active component Li2MnO3. This process can trigger reversible oxygen redox, providing extra charge for more Li-ion extraction. However, such an activation process is kinetically slow with complex phase transformations. To address these issues, tremendous effort has been made to explore the mechanism and origin of activation, yet there are still many controversies. Despite considerable strategies that have been proposed to improve the performance of LRMs, in-depth understanding of the relationship between the LRMs’ preparation and their activation process is limited. To inspire further research on LRMs, this article firstly systematically reviews the progress in mechanism studies and performance improving attempts. Then, guidelines for activation controlling strategies, including composition adjustment, elemental substitution and chemical treatment, are provided for the future design of Li-rich cathode materials. Based on these investigations, recommendations on Li-rich materials with precisely controlled Mn/Ni/Co composition, multi-elemental substitution and oxygen vacancy engineering are proposed for designing high-performance Li-rich cathode materials with fast and stable activation processes.

Graphical abstract

The “Troika” of composition adjustment, elemental substitution, and chemical treatment can drive the Li-rich cathode towards stabilized and accelerated activation.
Climate change vulnerability and smallholder farmers’ adaptive responses in the semi-arid Far North Region of Cameroon
Authors: Njoya Hamza Moluh , Matavel Custodio Efraim , Msangi Haji Athumani , Wouapi Hervé Alain Napi , Löhr Katharina , Sieber Stefan
Published: November 2022

Climate change and variability contribute to exacerbating poverty and social unrest in poor countries. Therefore, it becomes important to assess vulnerability and adaptation measures to raise awareness and monitoring of climate change adaptation policy for better decision-making. This research examines how farmers perceive their vulnerability and how they respond to climate change in the semi-arid Far North Region of Cameroon. Using both quantitative and qualitative approaches, data on perceptions with regards to vulnerability and adaptation responses to climate change related hazards were collected based on expert opinions, individual farmers’ interviews, and focus group discussion. The qualitative data were triangulated with direct observations in the field. The results reveal that farmers are mostly concerned about drought and decrease in rainfall. Thus, they have mainly implemented behavioral and locally-made options such as short-cycle varieties, terrace farming, half-moon, and bunds, among others, to overcome water shortages. Nevertheless, these measures were not solely driven by vulnerability; the socioeconomic context might play a role. Moreover, farmers perceive a limited capacity to adapt to climate change, which suggests that the government and policy-makers should focus, not only on implementing planned adaptation strategies, but also on the improvement and promotion of farmers’ autonomous adaptation strategies.
STM study on the vortex states and Majorana zero-modes in FeSe-based high-Tc superconductors
Authors: Wang Xu , Chen Chen , Zhang Tianzhen , Zhang Tong , Feng Donglai
Published: November 2022

The Majorana fermions/quasi-particles obey non-Abelian statistics and play an essential role in topological quantum computing. Theoretically, they can be realized as a zero-energy excitation in the vortex core of topological superconductors, called Majorana zero mode (MZM). However, the coexisting low-energy bound states in vortex cores often bring difficulties for identifying MZM. In this review, we summarized recent STM studies on the vortex states of electron-doped FeSe-based superconductors such as (Li,Fe)OHFeSe and single-layer FeSe/SrTiO3. Zero-bias conductance peaks (ZBCP) are observed in the unpinned vortex cores of (Li,Fe)OHFeSe. It displays nearly quantized conductance and distinct spatial distributions with respect to nonzero bound states, which indicates their nontrivial origin. Meanwhile, single-layer FeSe/SrTiO3 film only has conventional Caroli-de Gennes-Matricon (CdGM) bound states without zero-energy mode, reflecting the characteristics of s-wave superconductor. These results not only provide strong evidence of MZM, but also shed light on its origin in FeSe-based superconductors.
Distribution of daily protein intake across meals and all-cause mortality in community-dwelling older adults
Authors: Estrada-deLeón Daniela B. , Struijk Ellen A. , Caballero Francisco Félix , Yévenes-Briones Humberto , Banegas José Ramón , Rodríguez-Artalejo Fernando , Lopez-Garcia Esther
Published: November 2022

Recent findings suggest that the distribution of protein intake throughout the day has an impact on various health outcomes in older adults, independently of the amount consumed. We evaluated the association between the distribution of dietary protein intake across meals and all-cause mortality in community-dwelling older adults. Data from 3225 older adults aged ≥ 60 years from the Seniors-ENRICA-1 cohort were examined. Habitual dietary protein consumption was collected in 2008–2010 and in 2012 through a validated diet history. Protein distribution across meals was calculated for each participant as the coefficient of variation (CV) of protein intake per meal, in sex-specific tertiles. Vital status was obtained from the National Death Index up to 30 January 2020. Cox proportional hazards regression was performed to determine the hazard ratios (HR) and their 95 % CI for the association between the distribution of daily protein intake across meals and all-cause mortality. Over a median follow-up of 10·6 years, 591 deaths occurred. After adjustment for potential confounders, the CV of total protein intake was not associated with all-cause mortality (HR and 95 % CI in the second and third tertile v. the lowest tertile: 0·94 (0·77, 1·15) and 0·88 (0·72, 1·08); Ptrend = 0·22). Similarly, the HR of all-cause mortality when comparing extreme tertiles of CV for types of protein were 0·89 (0·73, 1·10) for animal-protein intake and 1·02 (0·82, 1·25) for plant-protein intake. Dietary protein distribution across meals was not associated with all-cause mortality, regardless of protein source and amount, among older adults. Further studies should investigate whether this picture holds for specific causes of death.
A narrative review on food neophobia throughout the lifespan: relationships with dietary behaviours and interventions to reduce it
Authors: Karaağaç Yasemin , Bellikci-Koyu Ezgi
Published: November 2022

Food neophobia is defined as the unwillingness to taste new foods and the avoidance of unfamiliar foods. This eating behaviour is a complex issue, and both genetic and environmental factors play a role in it. The aim of this review is to understand its relationships with dietary behaviours throughout the lifespan and to examine the impact of interventions on food neophobia. A literature search was performed using the PubMed, Web of Science, Cochrane Library and ScienceDirect databases. As a result of the screening, a total of 139 studies, seven of which were intervention studies, were included in this review. According to current evidence, food neophobia is negatively associated with the acceptance of not only novel/unfamiliar foods but also familiar foods. Many studies have shown that food neophobia is negatively associated with the hedonics and consumption of core foods, especially vegetables and fruits. Individuals with higher levels of food neophobia are less familiar with many foods, but familiarity is a prominent motivator in food choices for these individuals. Therefore, it may be considered a barrier limiting diet quality and this trend is similar for both children and adults. However, food neophobia is not an unchangeable personality trait. Intervention studies have pointed out that educational programmes and food-related activities that increase familiarity and exposure to foods and create positive attitudes towards and positive experiences with foods can reduce food neophobia. The results highlight that people with high food neophobia need more support to improve their diets and the quality of dietary behaviour.
PRECLASSIC PLACEMAKING AT YAXNOHCAH, MEXICO: A VIEW FROM THE GRAZIA AND HELENA COMPLEXES
Authors: Vázquez López Verónica A. , Reese-Taylor Kathryn , Flores Esquivel F.C. Atasta
Published: November 2022

Archaeological excavations at Yaxnohcah have revealed a long sequence of sedentary occupation, from 1000 b.c. to a.d. 1400, with dynamic periods of growth occurring during the Middle (1000–400 b.c.) and Late Preclassic (400 b.c.–a.d. 200). Two of these complexes, Grazia and Helena, serve as case studies that reveal the transformative processes of this period, illustrating site evolution on a larger scale. The Grazia platform probably began as a residential area in the Middle Preclassic and acquired an increasingly public character throughout subsequent modifications, culminating in the construction of a triadic temple platform and a ballcourt. A long sequence of fire rituals and altars show the importance of the Grazia complex as a center for collective ritual. Helena also features Middle Preclassic domestic constructions, but was transformed into a ballcourt platform during the transition to the Late Preclassic. Both cases show that Yaxnohcah was founded as a widespread, loosely integrated settlement in the Middle Preclassic and evolved into a formally and centralized network of communities with their respective nodal centers in the Late Preclassic period. Placemaking and the rise of monumentality played an important role in this transformation and reflect the particular forms of community integration.
MIDDLE PRECLASSIC HYDRAULIC PLANNING AT NIXTUN-CH'ICH', PETEN, GUATEMALA
Authors: Pugh Timothy W. , Rice Prudence M. , Chan Nieto Evelyn M. , Meranda Marie L. , Milley David S.
Published: November 2022

Nixtun-Ch'ich', on the western edge of Lake Peten Itza in Peten, northern Guatemala, features an axis urbis and an urban grid dating to the Middle Preclassic period (800–500 b.c.). New research reveals that Middle Preclassic constructions—five circular or oval artificial pools and planned surface drainage—facilitated or impeded the movement of water. Large limestone rubble lines at least two of the pools (aguadas) in the city's core; two pools lie on the axis urbis, demonstrating that they were central ceremonial constructions. The gridded streets facilitated drainage: they consistently slope from west to east and from the center to north and south. In some areas seeing intense water flow, the streets divide into waterways and pedestrian-ways and/or were given special paving. Many scholars argue that water management contributed to the power of despotic kings, but no evidence of such rulers exists among the Middle Preclassic Maya. Nonetheless, we believe that such systems emerged in the Middle Preclassic. Nixtun-Ch'ich' appears to have been cooperative in its organization and its water management system was a public good.
New Insights Into Cyclone Impacts on Sea Ice in the Atlantic Sector of the Arctic Ocean in Winter
Authors: Aue Lars , Vihma Timo , Uotila Petteri , Rinke Annette
Published: November 2022

Based on the ERA5 reanalysis, we report on statistically significant impacts of transient cyclones on sea ice concentration (SIC) in the Atlantic sector of the Arctic Ocean in winter under “New Arctic” conditions (2000–2020). This includes a pattern of reduced SIC prior to and during cyclones for the whole study domain, while a regional difference between increased SIC in the Barents Sea and reduced SIC in the Greenland Sea is found as the net effect from 3 days prior to 5 days after the cyclone passage. Generally, locally low to medium SIC conditions combined with intense cyclones drive highest SIC changes. There are indications that both thermodynamic and dynamic effects contribute to the SIC changes, but a detailed quantification is required in future research. We provide evidence that cyclone impacts on SIC have amplified compared to the “Old Arctic” (1979–1999), particularly in the Barents Sea.
Pathways of Influence Between Northern Hemisphere Blocking and Stratospheric Polar Vortex Variability
Authors: Yessimbet Kamilya , Shepherd Theodore G. , Ossó Albert C. , Steiner Andrea K.
Published: November 2022

We apply a causal inference‐based framework to test and quantify previously suggested causal relationships between Northern Hemisphere blocking, upward wave‐activity fluxes and stratospheric polar vortex (SPV) variability using reanalysis data. We show that the influence of blocking on the polar vortex is entirely mediated by upward wave‐activity fluxes, as the classical view would suggest. However, the causal pathway is not completely straightforward. In contrast to the vortex‐weakening effect of European blocking, the vortex‐strengthening effect of west Pacific blocking on lower stratospheric wave‐activity fluxes is only partially mediated by upper tropospheric wave‐activity fluxes. In addition, only two‐thirds of the effect of upper tropospheric wave‐activity fluxes on polar vortex variability is mediated by lower stratospheric wave‐activity fluxes. We also show that sudden stratospheric warmings are not entirely explainable in terms of upward wave‐activity fluxes. These findings help clarify the pathways of influence between blocking and SPV variability.
Downgoing Plate‐Buoyancy Driven Retreat of North Sulawesi Trench: Transition of a Passive Margin Into a Subduction Zone
Authors: Dong Miao , Lü ChuanChuan , Zhang Jian , Hao Tianyao
Published: November 2022

The transition of a passive continental margin into a subduction zone remains a hypothesis because few geological cases have been reported. The North Sulawesi subduction zone is a 5–9 myr system in Southeast Asia that has evolved from a passive continental margin and has long been overlooked by studies of passive to active margin transitions. Here we compare geophysical evidence from the region with our numerical simulation results. We find that the initial subduction of North Sulawesi relies on horizontal stress, where the trench retreat depends on the negative buoyancy of the oceanic lithosphere. Furthermore, less space available for subduction leads to reduced mantle flow caused by subduction and slower trench retreat. These new dynamical constraints indicate that the negative buoyancy of the oceanic plate is a key factor for the trench retreat, even though subduction initiated was induced.
Terahertz structured light: nonparaxial Airy imaging using silicon diffractive optics
Authors: Ivaškevičiūtė-Povilauskienė Rusnė , Kizevičius Paulius , Nacius Ernestas , Jokubauskis Domas , Ikamas Kęstutis , Lisauskas Alvydas , Alexeeva Natalia , Matulaitienė Ieva , Jukna Vytautas , Orlov Sergej , Minkevičius Linas , Valušis Gintaras
Published: November 2022

Structured light – electromagnetic waves with a strong spatial inhomogeneity of amplitude, phase, and polarization – has occupied far-reaching positions in both optical research and applications. Terahertz (THz) waves, due to recent innovations in photonics and nanotechnology, became so robust that it was not only implemented in a wide variety of applications such as communications, spectroscopic analysis, and non-destructive imaging, but also served as a low-cost and easily implementable experimental platform for novel concept illustration. In this work, we show that structured nonparaxial THz light in the form of Airy, Bessel, and Gaussian beams can be generated in a compact way using exclusively silicon diffractive optics prepared by femtosecond laser ablation technology. The accelerating nature of the generated structured light is demonstrated via THz imaging of objects partially obscured by an opaque beam block. Unlike conventional paraxial approaches, when a combination of a lens and a cubic phase (or amplitude) mask creates a nondiffracting Airy beam, we demonstrate simultaneous lensless nonparaxial THz Airy beam generation and its application in imaging system. Images of single objects, imaging with a controllable placed obstacle, and imaging of stacked graphene layers are presented, revealing hence potential of the approach to inspect quality of 2D materials. Structured nonparaxial THz illumination is investigated both theoretically and experimentally with appropriate extensive benchmarks. The structured THz illumination consistently outperforms the conventional one in resolution and contrast, thus opening new frontiers of structured light applications in imaging and inverse scattering problems, as it enables sophisticated estimates of optical properties of the investigated structures.
Spectral control of nonclassical light pulses using an integrated thin-film lithium niobate modulator
Authors: Zhu Di , Chen Changchen , Yu Mengjie , Shao Linbo , Hu Yaowen , Xin C. J. , Yeh Matthew , Ghosh Soumya , He Lingyan , Reimer Christian , Sinclair Neil , Wong Franco N. C. , Zhang Mian , Lončar Marko
Published: November 2022

Manipulating the frequency and bandwidth of nonclassical light is essential for implementing frequency-encoded/multiplexed quantum computation, communication, and networking protocols, and for bridging spectral mismatch among various quantum systems. However, quantum spectral control requires a strong nonlinearity mediated by light, microwave, or acoustics, which is challenging to realize with high efficiency, low noise, and on an integrated chip. Here, we demonstrate both frequency shifting and bandwidth compression of heralded single-photon pulses using an integrated thin-film lithium niobate (TFLN) phase modulator. We achieve record-high electro-optic frequency shearing of telecom single photons over terahertz range (±641 GHz or ±5.2 nm), enabling high visibility quantum interference between frequency-nondegenerate photon pairs. We further operate the modulator as a time lens and demonstrate over eighteen-fold (6.55 nm to 0.35 nm) bandwidth compression of single photons. Our results showcase the viability and promise of on-chip quantum spectral control for scalable photonic quantum information processing.
Thin ceramic PZT dual- and multi-frequency pMUT arrays for photoacoustic imaging
Authors: Zheng Qincheng , Wang Haoran , Yang Hao , Jiang Huabei , Chen Zhenfang , Lu Yao , Feng Philip X.-L. , Xie Huikai
Published: November 2022

Miniaturized ultrasonic transducer arrays with multiple frequencies are key components in endoscopic photoacoustic imaging (PAI) systems to achieve high spatial resolution and large imaging depth for biomedical applications. In this article, we report on the development of ceramic thin-film PZT-based dual- and multi-frequency piezoelectric micromachined ultrasonic transducer (pMUT) arrays and the demonstration of their PAI applications. With chips sized 3.5 mm in length or 10 mm in diameter, square and ring-shaped pMUT arrays incorporating as many as 2520 pMUT elements and multiple frequencies ranging from 1 MHz to 8 MHz were developed for endoscopic PAI applications. Thin ceramic PZT with a thickness of 9 μm was obtained by wafer bonding and chemical mechanical polishing (CMP) techniques and employed as the piezoelectric layer of the pMUT arrays, whose piezoelectric constant d31 was measured to be as high as 140 pm/V. Benefiting from this high piezoelectric constant, the fabricated pMUT arrays exhibited high electromechanical coupling coefficients and large vibration displacements. In addition to electrical, mechanical, and acoustic characterization, PAI experiments with pencil leads embedded into an agar phantom were conducted with the fabricated dual- and multi-frequency pMUT arrays. Photoacoustic signals were successfully detected by pMUT elements with different frequencies and used to reconstruct single and fused photoacoustic images, which clearly demonstrated the advantages of using dual- and multi-frequency pMUT arrays to provide comprehensive photoacoustic images with high spatial resolution and large signal-to-noise ratio simultaneously.
Effects of stress on neural processing of combat-related stimuli in deployed soldiers: an fMRI study
Authors: Lorenz Robert C. , Butler Oisin , Willmund Gerd , Wesemann Ulrich , Zimmermann Peter , Gallinat Jürgen , Kühn Simone
Published: November 2022

Severe trauma exposure may lead to symptoms of both posttraumatic stress disorder and depression. Neuroanatomical theories suggest that both disorders may share imbalances in fronto-limbic circuits. Longitudinal studies are necessary to better understand the impact of a stressful life situation on potential long-term fronto-limbic imbalances. Here we investigated soldiers neural processing of combat-related stimuli versus negative affective stimuli before and after the deployment in different war zones. In the final analysis we included 104 deployed soldiers (combat group) and 36 soldiers that were not deployed (control group). Behaviorally, we found a significant group by time interaction regarding depression symptom scores with an increase in the combat group. Depressive symptoms were subclinical. On the neural level, neither the whole brain analysis nor the region of interest (ROI) analyses including frontal and limbic ROIs revealed any significant results in the group by time interaction. However, extracted ROI values of the group by time interaction of amygdala and hippocampus were positively associated with the change in depression symptom scores in the combat group, but not in the control group. These results highlight the role of depression in individuals that experience stressful life situations. Future studies may need to investigate the role of depressive symptoms after trauma exposure with different tasks that may be particularly sensitive to changes due to depressive symptoms.
Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation
Authors: Dieci Maria Vittoria , Carbognin Luisa , Miglietta Federica , Canino Fabio , Giorgi Carlo Alberto , Cumerlato Enrico , Amato Ottavia , Massa Davide , Griguolo Gaia , Genovesi Elisa , Garufi Giovanna , Giannarelli Diana , Tornincasa Antonio , Trudu Lucia , Michieletto Silvia , Saibene Tania , Lo Mele Marcello , Fassan Matteo , Zarrilli Giovanni , Piacentini Federico , Bria Emilio , Guarneri Valentina
Published: November 2022

Background

The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted.

Methods

Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/− Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias.

Results

In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05).

Conclusions

We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/− Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.
SphK-produced S1P in somatic cells is indispensable for LH-EGFR signaling-induced mouse oocyte maturation
Authors: Yuan Feifei , Hao Xiaoqiong , Cui Yanying , Huang FuXin , Zhang Xiaodan , Sun Yanli , Hao Tiantian , Wang Zhijuan , Xia Wei , Su Youqiang , Zhang Meijia
Published: November 2022

Germ cell division and differentiation require intimate contact and interaction with the surrounding somatic cells. Luteinizing hormone (LH) triggers epidermal growth factor (EGF)-like growth factors to promote oocyte maturation and developmental competence by activating EGF receptor (EGFR) in somatic cells. Here, we showed that LH-EGFR signaling-activated sphingosine kinases (SphK) in somatic cells. The activation of EGFR by EGF increased S1P and calcium levels in cumulus-oocyte complexes (COCs), and decreased the binding affinity of natriuretic peptide receptor 2 (NPR2) for natriuretic peptide type C (NPPC) to release the cGMP-mediated meiotic arrest. These functions of EGF were blocked by the SphK inhibitor SKI-II, which could be reversed by the addition of S1P. S1P also activated the Akt/mTOR cascade reaction in oocytes and promoted targeting protein for Xklp2 (TPX2) accumulation and oocyte developmental competence. Specifically depleting Sphk1/2 in somatic cells reduced S1P levels and impaired oocyte meiotic maturation and developmental competence, resulting in complete female infertility. Collectively, SphK-produced S1P in somatic cells serves as a functional transmitter of LH-EGFR signaling from somatic cells to oocytes: acting on somatic cells to induce oocyte meiotic maturation, and acting on oocytes to improve oocyte developmental competence.
BNIP3 phosphorylation by JNK1/2 promotes mitophagy via enhancing its stability under hypoxia
Authors: He Yun-Ling , Li Jian , Gong Sheng-Hui , Cheng Xiang , Zhao Ming , Cao Yan , Zhao Tong , Zhao Yong-Qi , Fan Ming , Wu Hai-Tao , Zhu Ling-Ling , Wu Li-Ying
Published: November 2022

Mitophagy is an important metabolic mechanism that modulates mitochondrial quality and quantity by selectively removing damaged or unwanted mitochondria. BNIP3 (BCL2/adenovirus e1B 19 kDa protein interacting protein 3), a mitochondrial outer membrane protein, is a mitophagy receptor that mediates mitophagy under various stresses, particularly hypoxia, since BNIP3 is a hypoxia-responsive protein. However, the underlying mechanisms that regulate BNIP3 and thus mediate mitophagy under hypoxic conditions remain elusive. Here, we demonstrate that in hypoxia JNK1/2 (c-Jun N-terminal kinase 1/2) phosphorylates BNIP3 at Ser 60/Thr 66, which hampers proteasomal degradation of BNIP3 and drives mitophagy by facilitating the direct binding of BNIP3 to LC3 (microtubule-associated protein 1 light chain 3), while PP1/2A (protein phosphatase 1/2A) represses mitophagy by dephosphorylating BNIP3 and triggering its proteasomal degradation. These findings reveal the intrinsic mechanisms cells use to regulate mitophagy via the JNK1/2-BNIP3 pathway in response to hypoxia. Thus, the JNK1/2-BNIP3 signaling pathway strongly links mitophagy to hypoxia and may be a promising therapeutic target for hypoxia-related diseases.
An AI approach for managing financial systemic risk via bank bailouts by taxpayers
Authors: Petrone Daniele , Rodosthenous Neofytos , Latora Vito
Published: November 2022

Bank bailouts are controversial governmental decisions, putting taxpayers’ money at risk to avoid a domino effect through the network of claims between financial institutions. Yet very few studies address quantitatively the convenience of government investments in failing banks from the taxpayers’ standpoint. We propose a dynamic financial network framework incorporating bailout decisions as a Markov Decision Process and an artificial intelligence technique that learns the optimal bailout actions to minimise the expected taxpayers’ losses. Considering the European global systemically important institutions, we find that bailout decisions become optimal only if the taxpayers’ stakes exceed some critical level, endogenously determined by all financial network’s characteristics. The convenience to intervene increases with the network’s distress, taxpayers’ stakes, bank bilateral credit exposures and crisis duration. Moreover, the government should optimally keep bailing-out banks that received previous investments, creating moral hazard for rescued banks that could increase their risk-taking, reckoning on government intervention.
The endocannabinoid anandamide is an airway relaxant in health and disease
Authors: Simon Annika , von Einem Thomas , Seidinger Alexander , Matthey Michaela , Bindila Laura , Wenzel Daniela
Published: November 2022

Chronic obstructive airway diseases are a global medical burden that is expected to increase in the near future. However, the underlying mechanistic processes are poorly understood so far. Herein, we show that the endocannabinoid anandamide (AEA) induces prominent airway relaxation in vitro and in vivo. In contrast to 2-arachidonlyglycerol-induced airway relaxation, this is mediated by fatty acid amide hydrolase (FAAH)-dependent metabolites. In particular, we identify mouse and also human epithelial and airway smooth muscle cells as source of AEA-induced prostaglandin E2 production and cAMP as direct mediator of AEA-dependent airway relaxation. Mass spectrometry experiments demonstrate reduced levels of endocannabinoid-like compounds in lungs of ovalbumin-sensitized mice indicating a pathophysiological relevance of endocannabinoid signalling in obstructive airway disease. Importantly, AEA inhalation protects against airway hyper-reactivity after ovalbumin sensitization. Thus, this work highlights the AEA/FAAH axis as a critical regulator of airway tone that could provide therapeutic targets for airway relaxation.
Ciliary neurotrophic factor-mediated neuroprotection involves enhanced glycolysis and anabolism in degenerating mouse retinas
Authors: Do Rhee Kun , Wang Yanjie , ten Hoeve Johanna , Stiles Linsey , Nguyen Thao Thi Thu , Zhang Xiangmei , Vergnes Laurent , Reue Karen , Shirihai Orian , Bok Dean , Yang Xian-Jie
Published: November 2022

Ciliary neurotrophic factor (CNTF) acts as a potent neuroprotective cytokine in multiple models of retinal degeneration. To understand mechanisms underlying its broad neuroprotective effects, we have investigated the influence of CNTF on metabolism in a mouse model of photoreceptor degeneration. CNTF treatment improves the morphology of photoreceptor mitochondria, but also leads to reduced oxygen consumption and suppressed respiratory chain activities. Molecular analyses show elevated glycolytic pathway gene transcripts and active enzymes. Metabolomics analyses detect significantly higher levels of ATP and the energy currency phosphocreatine, elevated glycolytic pathway metabolites, increased TCA cycle metabolites, lipid biosynthetic pathway intermediates, nucleotides, and amino acids. Moreover, CNTF treatment restores the key antioxidant glutathione to the wild type level. Therefore, CNTF significantly impacts the metabolic status of degenerating retinas by promoting aerobic glycolysis and augmenting anabolic activities. These findings reveal cellular mechanisms underlying enhanced neuronal viability and suggest potential therapies for treating retinal degeneration.
Neutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A
Authors: Joulia Régis , Guerrero-Fonseca Idaira María , Girbl Tamara , Coates Jonathon A. , Stein Monja , Vázquez-Martínez Laura , Lynam Eleanor , Whiteford James , Schnoor Michael , Voehringer David , Roers Axel , Nourshargh Sussan , Voisin Mathieu-Benoit
Published: November 2022

Neutrophil diapedesis is an immediate step following infections and injury and is driven by complex interactions between leukocytes and various components of the blood vessel wall. Here, we show that perivascular mast cells (MC) are key regulators of neutrophil behaviour within the sub-endothelial space of inflamed venules. Using confocal intravital microscopy, we observe directed abluminal neutrophil motility along pericyte processes towards perivascular MCs, a response that created neutrophil extravasation hotspots. Conversely, MC-deficiency and pharmacological or genetic blockade of IL-17A leads to impaired neutrophil sub-endothelial migration and breaching of the pericyte layer. Mechanistically, identifying MCs as a significant cellular source of IL-17A, we establish that MC-derived IL-17A regulates the enrichment of key effector molecules ICAM-1 and CXCL1 in nearby pericytes. Collectively, we identify a novel MC-IL-17A-pericyte axis as modulator of the final steps of neutrophil diapedesis, with potential translational implications for inflammatory disorders driven by increased neutrophil diapedesis.
Activation and signaling mechanism revealed by GPR119-Gs complex structures
Authors: Qian Yuxia , Wang Jiening , Yang Linlin , Liu Yanru , Wang Lina , Liu Wei , Lin Yun , Yang Hong , Ma Lixin , Ye Sheng , Wu Shan , Qiao Anna
Published: November 2022

Agonists selectively targeting cannabinoid receptor-like G-protein-coupled receptor (GPCR) GPR119 hold promise for treating metabolic disorders while avoiding unwanted side effects. Here we present the cryo-electron microscopy (cryo-EM) structures of the human GPR119-Gssignaling complexes bound to AR231453 and MBX-2982, two representative agonists reported for GPR119. The structures reveal a one-amino acid shift of the conserved proline residue of TM5 that forms an outward bulge, opening up a hydrophobic cavity between TM4 and TM5 at the middle of the membrane for its endogenous ligands-monounsaturated lipid metabolites. In addition, we observed a salt bridge between ICL1 of GPR119 and Gβs. Disruption of the salt bridge eliminates the cAMP production of GPR119, indicating an important role of Gβsin GPR119-mediated signaling. Our structures, together with mutagenesis studies, illustrate the conserved binding mode of the chemically different agonists, and provide insights into the conformational changes in receptor activation and G protein coupling.
Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter
Authors: Schulte Tim , Chaves-Sanjuan Antonio , Mazzini Giulia , Speranzini Valentina , Lavatelli Francesca , Ferri Filippo , Palizzotto Carlo , Mazza Maria , Milani Paolo , Nuvolone Mario , Vogt Anne-Cathrine , Vogel Monique , Palladini Giovanni , Merlini Giampaolo , Bolognesi Martino , Ferro Silvia , Zini Eric , Ricagno Stefano
Published: November 2022

AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-β amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57–73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-β architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah.
Somatic mutation distribution across tumour cohorts provides a signal for positive selection in cancer
Authors: Boström Martin , Larsson Erik
Published: November 2022

Cancer gene discovery is reliant on distinguishing driver mutations from a multitude of passenger mutations in tumour genomes. While driver genes may be revealed based on excess mutation recurrence or clustering, there is a need for orthogonal principles. Here, we take advantage of the fact that non-cancer genes, containing only passenger mutations under neutral selection, exhibit a likelihood of mutagenesis in a given tumour determined by the tumour’s mutational signature and burden. This relationship can be disrupted by positive selection, leading to a difference in the distribution of mutated cases across a cohort for driver and passenger genes. We apply this principle to detect cancer drivers independently of recurrence in large pan-cancer cohorts, and show that our method (SEISMIC) performs comparably to traditional approaches and can provide resistance to known confounding mutational phenomena. Being based on a different principle, the approach provides a much-needed complement to existing methods for detecting signals of selection.
CHD7 regulates otic lineage specification and hair cell differentiation in human inner ear organoids
Authors: Nie Jing , Ueda Yoshitomo , Solivais Alexander J. , Hashino Eri
Published: November 2022

Mutations in CHD7 cause CHARGE syndrome, affecting multiple organs including the inner ear in humans. We investigate how CHD7 mutations affect inner ear development using human pluripotent stem cell-derived organoids as a model system. We find that loss of CHD7 or its chromatin remodeling activity leads to complete absence of hair cells and supporting cells, which can be explained by dysregulation of key otic development-associated genes in mutant otic progenitors. Further analysis of the mutant otic progenitors suggests that CHD7 can regulate otic genes through a chromatin remodeling-independent mechanism. Results from transcriptome profiling of hair cells reveal disruption of deafness gene expression as a potential underlying mechanism of CHARGE-associated sensorineural hearing loss. Notably, co-differentiating CHD7 knockout and wild-type cells in chimeric organoids partially rescues mutant phenotypes by restoring otherwise severely dysregulated otic genes. Taken together, our results suggest that CHD7 plays a critical role in regulating human otic lineage specification and hair cell differentiation.
Compact artificial neuron based on anti-ferroelectric transistor
Authors: Cao Rongrong , Zhang Xumeng , Liu Sen , Lu Jikai , Wang Yongzhou , Jiang Hao , Yang Yang , Sun Yize , Wei Wei , Wang Jianlu , Xu Hui , Li Qingjiang , Liu Qi
Published: November 2022

Neuromorphic machines are intriguing for building energy-efficient intelligent systems, where spiking neurons are pivotal components. Recently, memristive neurons with promising bio-plausibility have been developed, but with limited reliability, bulky capacitors or additional reset circuits. Here, we propose an anti-ferroelectric field-effect transistor neuron based on the inherent polarization and depolarization of Hf0.2Zr0.8O2 anti-ferroelectric film to meet these challenges. The intrinsic accumulated polarization/spontaneous depolarization of Hf0.2Zr0.8O2 films implements the integration/leaky behavior of neurons, avoiding external capacitors and reset circuits. Moreover, the anti-ferroelectric neuron exhibits low energy consumption (37 fJ/spike), high endurance (>1012), high uniformity and high stability. We further construct a two-layer fully ferroelectric spiking neural networks that combines anti-ferroelectric neurons and ferroelectric synapses, achieving 96.8% recognition accuracy on the Modified National Institute of Standards and Technology dataset. This work opens the way to emulate neurons with anti-ferroelectric materials and provides a promising approach to building high-efficient neuromorphic hardware.