bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the Work of Theologians in the Pandemic's Wake
Authors: Cox Kathryn Lilla , King Jason
Published: May 2023

This article focuses on what the pandemic reveals about theological work in the academy and imagines a way forward. Too often, theologians are ground down, isolated workers, overworked, and strapped for time. They constantly must choose between progress in the guild and their familial and communal relationships. This false choice starves theologians of meaning and purpose, and, in such scarcity, inflames pursuit of status. However, a communal conception of theological academic work could mitigate some of these frictions. To imagine this possibility, we draw upon our collective experiences of working in Benedictine institutions that also argue for communal approaches to living, learning, and experiencing God. We draw ideas from the Rule of Benedict as a model for life-giving community that we think can be resituated in academic life.
Fundamental time scales of bubble fragmentation in homogeneous isotropic turbulence
Authors: Gaylo Declan B. , Hendrickson Kelli , Yue Dick K.P.
Published: May 2023

We investigate the fundamental time scales that characterise the statistics of fragmentation under homogeneous isotropic turbulence for air–water bubbly flows at moderate to large bubble Weber numbers,

$We$

. We elucidate three time scales:

$\tau _r$

, the characteristic age of bubbles when their subsequent statistics become stationary;

$\tau _\ell$

, the expected lifetime of a bubble before further fragmentation; and

$\tau _c$

, the expected time for the air within a bubble to reach the Hinze scale, radius

$a_H$

, through the fragmentation cascade. The time scale

$\tau _\ell$

is important to the population balance equation (PBE),

$\tau _r$

is critical to evaluating the applicability of the PBE no-hysteresis assumption, and

$\tau _c$

provides the characteristic time for fragmentation cascades to equilibrate. By identifying a non-dimensionalised average speed

$\bar {s}$

at which air moves through the cascade, we derive

$\tau _c=C_\tau \varepsilon ^{-1/3} a^{2/3} (1-(a_{max}/a_H)^{-2/3})$

, where

$C_\tau =1/\bar {s}$

and

$a_{max}$

is the largest bubble radius in the cascade. While

$\bar {s}$

is a function of PBE fragmentation statistics, which depend on the measurement interval

$T$

,

$\bar {s}$

itself is independent of

$T$

for

$\tau _r \ll T \ll \tau _c$

. We verify the

$T$

-independence of

$\bar {s}$

and its direct relationship to

$\tau _c$

using Monte Carlo simulations. We perform direct numerical simulations (DNS) at moderate to large bubble Weber numbers,

$We$

, to measure fragmentation statistics over a range of

$T$

. We establish that non-stationary effects decay exponentially with

$T$

, independent of

$We$

, and provide

$\tau _r=C_{r} \varepsilon ^{-1/3} a^{2/3}$

with

$C_{r}\approx 0.11$

. This gives

$\tau _r\ll \tau _\ell$

, validating the PBE no-hysteresis assumption. From DNS, we measure

$\bar {s}$

and find that for large Weber numbers (

$We>30$

),

$C_{\tau }\approx 9$

. In addition to providing

$\tau _c$

, this obtains a new constraint on fragmentation models for PBE.
The role of a pre-wetting layer in resolving the contact line paradox of thin films in infinite elastic domains
Authors: Zigelman Anna , Breitman Peter , Gat Amir D.
Published: May 2023

Hydraulic fracturing for oil and gas production from shale formations, as well as natural geological phenomena, involve the propagation of thin viscous films within elastic media. For viscous fluids, stress diverges as the thickness of the film tends to zero, arresting the propagation of the film, and thus implying the contact line paradox. For free-surface films, this paradox is resolved by considering a precursor film, leading to Tanner's law. This approach was extended recently for viscous films between a thin elastic plate and a rigid solid, allowing calculation of the film propagation rate. In this work, we examine the effect of a pre-wetting layer on the rate of propagation of a viscous flow within an infinitely deep and long domain. We analyse the linear and nonlinear dynamic problems, and perform a self-similarity analysis. We find that peeling front propagation scales as time to the power of

$1/9$

and

$1/3$

for thin and thick pre-wetting layer limits, respectively. Our results contribute to the understanding of the contact line paradox in elastic media and the crucial role of the pre-wetting layer in resolving it.
Stabilise and symmetrise the deformation of buckling metamaterial for tunable vibration bandgaps
Authors: Liu Encai , Fang Xin , Zhu Peidong , Wen Jihong
Published: May 2023

Mechanical metamaterials have attracted extensive attention. This paper reports a metamaterial with tunable elastic wave bandgaps based on bistable buckling structure. First, we find that deformation of two symmetric buckling shells is intrinsically asymmetric, which blocks the realisation of robust tunability. Based on an analytical model, we clarify that the mechanisms for this intrinsic asymmetricity are the bifurcations on force–deformation curves. Then we propose a superposition method of buckling shells, which can realise the symmetric deformation for robust tunable stiffness. Using this variable-stiffness oscillator, we design a metamaterial sandwich beam, and numerically and experimentally demonstrate its tunable bandgap for vibration suppression. This paper presents the unusual deformation process of buckling elements widely used for constructing metamaterials, and provides a robust way to realise metamaterials with tunable vibration bandgaps.
Temporal patterns of energy intake identified by the latent class analysis in relation to prevalence of overweight and obesity in Iranian adults
Authors: Jayedi Ahmad , Shafiei Neyestanak Mahdi , Djafarian Kurosh , Shab-Bidar Sakineh
Published: May 2023

We aimed to identify temporal patterns of energy intake and investigate their association with adiposity. We performed a cross-sectional study of 775 adults in Iran. Information about eating occasions across the day was collected by three 24-h dietary recalls. Latent class analysis (LCA) was used to identify temporal eating patterns based on whether or not an eating occasion occurred within each hour of the day. We applied binary logistic regression to estimate the OR and 95 % CI of overweight and obesity (defined as BMI of 25–29·9 and ≥ 30 kg/m2, respectively) across temporal eating patterns while controlling for potential confounders. LCA grouped participants into three exclusive sub-groups named ‘Conventional’, ‘Earlier breakfast’ and ‘Later lunch’. The ‘Conventional’ class was characterised by high probability of eating occasions at conventional meal times. ‘Earlier breakfast’ class was characterised by high probability of a breakfast eating occasion 1 h before the conventional pattern and a dinner eating occasion 1 h after the conventional pattern, and the ‘Later lunch’ class was characterised by a high probability of a lunch eating occasion 1 h after the conventional pattern. Participants in the ‘Earlier breakfast’ pattern had a lower likelihood of obesity (adjusted OR: 0·56, 95 % CI: 0·35, 0·95) as compared with the ‘Conventional’ pattern. There was no difference in the prevalence of obesity or overweight between participants in the ‘Later lunch’ and the ‘Conventional’ patterns. We found an inverse association between earlier eating pattern and the likelihood of obesity, but reverse causation may be a plausible explanation.
The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K2, in healthy subjects
Authors: Du Fan , Yan Min , Duan Lili , Xie Guolong , Yao Xiuhua , Hu Wenjing , Liu Yu , Meng Min , Chen Jiepeng , Shao Di
Published: May 2023

Menaquinone-7 (MK-7), a multipotent vitamin K2, possesses a wide range of biological activities, a precise curative effect and excellent safety. A simple and rapid LC-APCI-MS/MS method for the determination of MK-7 in human plasma with single liquid–liquid extraction (LLE) extraction and 4·5-min analysis time has been developed and validated. Four per cent bovine serum albumin (BSA) was used as surrogate matrix for standard curves and endogenous baseline subtraction. This method was reproducible and reliable and was used to analyse of MK-7 in human plasma. The endogenous circadian rhythm and bioavailability of MK-7 were investigated in two randomised single-dose, open, one-way clinical trials (Study I and Study II). A total of five healthy male subjects were enrolled in Study I and 12 healthy male subjects in Study II. Single-dose (1 mg) of MK-7 was given to each subject under fasting condition, and all eligible subjects were given a restricting VK2 diet for 4 d prior to drug administration and during the trial. The experiment results of Study I demonstrated that endogenous MK-7 has no circadian rhythm in individuals. Both studies showed MK-7 are absorbed with peak plasma concentrations at about 6 h after intake and has a very long half-life time.
Irrigation pumps in late colonial Taiwan: Farmers’ utilization of technology and the transition to rice cultivation
Authors: Tsuru Shuntaro
Published: May 2023

This article describes how Taiwanese farmers adopted irrigation pumps to enhance their livelihoods under the shifting relationship of sugar and rice production in late colonial Taiwan. I argue that farmers utilized commercial technologies to make a living and prosper within the established order of Japanese colonial rule. With allocated procurement districts granting exclusive purchasing rights over sugarcane, sugar companies maintained substantial influence over sugarcane cultivation. However, with the proliferation of Penglai rice and new agricultural implements, the situation of the farmers changed substantially. Serious problems in the sugar industry due to economic depression and the rising price of rice in the 1930s led farmers to shift from sugarcane to rice cultivation by introducing a variety of pumps. Those with the means installed new motor pumps, while others independently constructed wind pumps by combining newly introduced parts with older techniques. Despite a prohibition by the colonial government, farmers continued installing pumps until the government established a planned economy in preparation for war. Moreover, distribution of pump capacity through both sales and sharing shows that Taiwanese farmers sought to maintain an informal yet significant cohesion throughout the process of agricultural commercialization. By focusing on the social dynamics surrounding agricultural technologies, this article challenges simplistic portrayals of technology transfer from Japan to the colonies.
The Uses and Abuses of Legal Pluralism: A View from the Sideline
Authors: Herzog Tamar
Published: May 2023

This text takes issue with how present day debates regarding legal pluralism affect our vision of the past, as well as limit the horizons of possibilities in the future. It suggests that the genealogy of these debates determined what would be seen, and what ignored, and that, as a result, it has privileged some aspects, while forgetting the importance of others.
Self-reported quality of life before, during, and after pregnancy in women with CHD
Authors: Wedlund Frida , Hlebowicz Joanna
Published: May 2023

Background:

Adults with CHD are a growing patient group and childbirth is a relatively new phenomenon. EQ-5D is commonly used to measure health-related quality of life. We sought to investigate EQ-5D status before, during, and after pregnancy in women with CHD.

Methods:

We identified 128 pregnancies in 86 CHD women giving birth in Skåne County during 2009–2021. Repeated measures ANOVA was performed to test for differences between the five EQ-5D domains, EQ-VAS, and EQ-index over time points before, the second trimester, the third trimester, and after pregnancy.

Results:

Mean age at estimated childbirth was 30.3 (± 4.7) years; 56.25% of births were vaginal deliveries and 43.75% were Caesarean sections. The cohort consisted of patients with double outlet right ventricle (4.7%), transposition (Mustard/Senning 2.3%, arterial switch 4.7%), aortic anomalies (19.5%), Fallot’s anomaly (16.4%), single ventricle (3.9%), shunt lesions (11.7%), cardiomyopathies (4.7%), coronary anomalies (1.6%), arrythmias (0.8%), and valve lesions: aortic (19.5%), mitral (5.5%), and pulmonary (4.7%). The women reported significantly worse mobility (p = 0.007) and higher pain/discomfort (p = 0.049) at trimester 3 compared to before pregnancy. The women had lower EQ-5D index during trimester 3 compared to after pregnancy (p = 0.004). We saw worse mobility during Tri 2 comparing multiparity with primiparity (p = 0.046). Looking at delivery mode, we noted significantly higher anxiety/depression before pregnancy (p =0.023) in women that had a Caesarean section.

Conclusions:

In this study, women with CHD reported worse mobility and a higher pain level during Tri 3, although the overall health-related quality of life is acceptably high.
To what extent do institutional arrangements shape the excludability of resource systems? Lessons from French farms
Authors: Kassis Grâce
Published: May 2023

The question of the impact of institutional arrangements on the nature of goods is insufficiently addressed in the literature. By the nature of goods, we refer to the economic taxonomy of goods, meaning their privateness is defined according to their degrees of excludability and subtractability. This paper aims to fill this research gap by examining whether institutional arrangements developed for the management of private goods can reduce the degrees of excludability of these goods. To this end, we analyse four collective farmland management projects in the Isère department in France. We adapt the tool of property as a bundle of rights in order to characterize the impact of these projects on the nature of farmland. Our results show that the distribution of land rights, as well as the rules designed to define land rights, influence the degree of excludability of farmland. We discuss the impact of these findings on public policy-making.
Effect of Combined Subsurface Structures and Steps on Hyporheic Exchange
Authors: Tajari M. , Omid M. H. , Dehghani A. A. , Ghameshlou A. N. , Boano F.
Published: May 2023

The deployment of artificial structures in streambeds has been proposed as a way to enhance 21 hyporheic exchange, and numerical models can be used to quantify their effects. In this study, combinations of different structures—that is, boxes, steps and a new type of subsurface structure (L‐shaped structure)—were considered to evaluate their potential applicability on river restoration. Flow‐3D and COMSOL were applied to simulate surface and subsurface flow, respectively. The performance of the structures was evaluated on the basis of hyporheic flow and residence time distributions. For the structure sizes here considered, results showed for steps (single step, combination of two steps) and L‐shaped structures (single L‐shaped structure, combination of two L‐shaped structures) most hyporheic flowpaths return to the stream after 5 and 2.5 hr, respectively. Instead, shorter residence times (<0.25 hr) were found for boxes (single box, combination of two boxes). For combinations of steps and permeable boxes, the values of hyporheic flow per unit width are higher (0.35 and 0.3 m2/hr, respectively) than for the combination of L‐shaped (0.06 m2/hr). As a result, the combinations of steps and boxes are more effective in increasing hyporheic flow. However, when subsurface structures are combined with steps the resulting hyporheic exchange is dominated by the steps. Therefore, the combined use of in‐stream and subsurface structures separately may increase their benefits for hyporheic exchange, but when steps are the other subsurface structures provide minor advantages.
Reconstructing the Unsaturated Flow Equation From Sparse and Noisy Data: Leveraging the Synergy of Group Sparsity and Physics‐Informed Deep Learning
Authors: Song Wenxiang , Shi Liangsheng , Hu Xiaolong , Wang Yanling , Wang Lijun
Published: May 2023

Data‐driven scientific discovery methods have been developed and applied to discover governing equations from data, involving the attempt to discover the unsaturated flow equation in soils from data. However, an important but unresolved problem is how to reconstruct the unsaturated flow equation from highly noisy and scarce discrete data. In this study, we present a new deep‐learning framework: DeepGS (deep‐learning‐based group sparsity framework), that leverages the synergy of group sparsity and physics‐informed deep learning (PIDL) to reconstruct the latent governing equation for unsaturated flow. In particular, we design a strategy that decomposes the identification of the unsaturated flow equation into two tasks: the determination of the partial differential equation structure and the reconstruction of the nonlinear coefficients. The tasks can be seamlessly handled by group sparse regression and the PIDL approach. Through the training, it realizes the simultaneous reconstruction of soil moisture dynamics and unsaturated flow governing equation. A series of comprehensive numerical experiments are conducted to determine the optimal architecture and test its performance. The results show the efficacy and robustness of DeepGS, which significantly outperform previous methods. We also conclude that accurately reconstructing soil moisture dynamics and spatiotemporal derivatives from noisy and scarce data play a critical role in governing equation discovery. This study further demonstrates the potential of discovering the governing equation for unsaturated flow from data in more complex scenarios, where rich and accurate soil moisture observations are generally intractable to access.
How Does Tropical Cyclone Genesis Frequency Respond to a Changing Climate?
Authors: Zhao Jiuwei , Wang Fang , Zhan Ruifen , Guo Yipeng , Huang Xin , Liu Chao
Published: May 2023

Global tropical cyclone (TC) genesis frequency (TCGF) has been documented to decrease or increase linearly in a changing climate. However, our numerical experiments show that the global TCGF exhibits a parabolic relation with spatio‐uniform climate changes in sea surface temperature (SST) from −15 K to 5 K relative to the present climate, with the peak in the 5 K‐cooler climate. The parabolic relation is found in all TC basins except the eastern North Pacific where TCGF keeps increasing with the changing climate. TCGF can be expressed as the product of the frequency of TC seeds and the TC survival rate (SR). Further analysis shows that this parabolic structure in the global TCGF depends on TC seeds rather than the TC SR. The TC SR exhibits an increasing trend with the SST increase, while TC seeds show a consistent change with TCGF, which might be linked to the changes in low‐level relative humidity.
Function Model Based on Nonlinear Transient Rheology of Rocks: An Analysis of Decadal GNSS Time Series After the 2011 Tohoku‐oki Earthquake
Authors: Dhar Sambuddha , Muto Jun
Published: May 2023

The postseismic Global Navigation Satellite System (GNSS) time series after the 2011 Tohoku‐oki earthquake is often empirically explained by one or more logarithmic and exponential decay functions. However, a function model with these decay functions struggles to illuminate various deformation mechanisms. Here, we propose a new function model incorporating laboratory‐derived constitutive laws (power‐law flow and velocity‐strengthening friction) utilized in mechanical postseismic models of the last decade. We demonstrated that our function model accurately predicts the decade‐long time series of inland GNSS stations, including coastal areas where significant postseismic uplift continues now. Moreover, it decomposes them into displacements due to viscoelastic relaxation and afterslip, similar to results produced by previous stress‐dependent postseismic models of the 2011 Tohoku‐oki earthquake. This physics‐based function model is an effective tool to ease the process of forecasting long‐term GNSS time series by dividing them into two dominant mechanisms at the plate interface and the surrounding viscoelastic mantle.
The hydrocortisone-responsive urinary metabolome of premature infants
Authors: Torgerson Dara , Guardado Miguel , Steurer Martina , Chapin Cheryl , Hernandez Ryan D. , Ballard Philip L.
Published: May 2023

Background

Extremely premature infants are at risk for circulatory collapse or respiratory failure that are often treated with hydrocortisone (HC); however, there is no information on the metabolic consequences of this therapy.

Methods

Longitudinal urine samples from infants <28 weeks gestation in the Trial of Late Surfactant were analyzed by untargeted UHPLC:MS/MS. Fourteen infants who received a tapering course of HC beginning at 3 mg/kg/day for ≥9 days were compared to 14 matched control infants. A secondary cross-sectional analysis by logistic regression used urines from 314 infants.

Results

Of 1145 urinary metabolites detected, abundance of 219, representing all the major biochemical pathways, changed at p < 0.05 in the HC-treated group with 90% decreasing; 3 cortisol derivatives increased ~2-fold with HC therapy. Only 11% of regulated metabolites remained responsive at the lowest HC dose. Regulated metabolites included two steroids and thiamin that are associated with lung inflammation in infants. HC responsiveness was confirmed in 57% of metabolites by cross-sectional analysis.

Conclusions

HC treatment of premature infants influenced in a dose-dependent manner abundance of 19% of identified urinary metabolites of diverse biochemical systems, primarily reducing concentrations. These findings indicate that exposure to HC reversibly impacts the nutritional status of premature infants.

Impact

Hydrocortisone treatment of premature infants with respiratory failure or circulatory collapse alters levels of a subset of urinary metabolites representing all major biochemical pathways.

This is the first description of the scope, magnitude, timing and reversibility of metabolomic changes in infants in response to hydrocortisone, and it confirms corticosteroid regulation of three biochemicals that are associated with lung inflammatory status.

The findings indicate a dose-dependency of hydrocortisone for metabolomic and anti-inflammatory effects, that prolonged therapy may lower the supply of many nutrients, and that monitoring concentrations of cortisol and inflammation markers may be a useful clinical approach during corticosteroid therapy.
DNA polymerase gamma variants and hepatotoxicity during maintenance therapy of childhood acute lymphoblastic leukemia: is there a causal relationship?
Authors: Harju Tekla , Hurme-Niiranen Anri , Suo-Palosaari Maria , Nygaard Nielsen Stine , Hinttala Reetta , Schmiegelow Kjeld , Uusimaa Johanna , Harila Arja , Niinimäki Riitta
Published: May 2023

Hepatotoxicity is a frequent complication during maintenance therapy of acute lymphoblastic leukemia (ALL) with 6-mercaptopurine and methotrexate. Elevated levels of methylated 6-mercaptopurine metabolites (MeMP) are associated with hepatotoxicity. However, not all mechanisms are known that lead to liver failure in patients with ALL. Variants in the POLG gene, which encodes the catalytic subunit of mitochondrial DNA polymerase gamma (POLG1), have been related to drug-induced hepatotoxicity, for example, by sodium valproate. The association of common POLG variants with hepatotoxicity during maintenance therapy was studied in 34 patients with childhood ALL. Of the screened POLG variants, four different variants were detected in 12 patients. One patient developed severe hepatotoxicity without elevated MeMP levels and harbored a heterozygous POLG p.G517V variant, which was not found in the other patients.
Loss of function of FIP200 in human pluripotent stem cell-derived neurons leads to axonal pathology and hyperactivity
Authors: Wen Jianbin , Zellner Andreas , Braun Nils Christian , Bajaj Thomas , Gassen Nils Christian , Peitz Michael , Brüstle Oliver
Published: May 2023

FIP200 plays important roles in homeostatic processes such as autophagy and signaling pathways such as focal adhesion kinase (FAK) signaling. Furthermore, genetic studies suggest an association of FIP200 mutations with psychiatric disorders. However, its potential connections to psychiatric disorders and specific roles in human neurons are not clear. We set out to establish a human-specific model to study the functional consequences of neuronal FIP200 deficiency. To this end, we generated two independent sets of isogenic human pluripotent stem cell lines with homozygous FIP200KO alleles, which were then used for the derivation of glutamatergic neurons via forced expression of NGN2. FIP200KO neurons exhibited pathological axonal swellings, showed autophagy deficiency, and subsequently elevated p62 protein levels. Moreover, monitoring the electrophysiological activity of neuronal cultures on multi-electrode arrays revealed that FIP200KO resulted in a hyperactive network. This hyperactivity could be abolished by glutamatergic receptor antagonist CNQX, suggesting a strengthened glutamatergic synaptic activation in FIP200KO neurons. Furthermore, cell surface proteomic analysis revealed metabolic dysregulation and abnormal cell adhesion-related processes in FIP200KO neurons. Interestingly, an ULK1/2-specific autophagy inhibitor could recapitulate axonal swellings and hyperactivity in wild-type neurons, whereas inhibition of FAK signaling was able to normalize the hyperactivity of FIP200KO neurons. These results suggest that impaired autophagy and presumably also disinhibition of FAK can contribute to the hyperactivity of FIP200KO neuronal networks, whereas pathological axonal swellings are primarily due to autophagy deficiency. Taken together, our study reveals the consequences of FIP200 deficiency in induced human glutamatergic neurons, which might, in the end, help to understand cellular pathomechanisms contributing to neuropsychiatric conditions.
Single-cell transcriptomics of the ocular anterior segment: a comprehensive review
Authors: Ahsanuddin Sofia , Wu Albert Y.
Published: May 2023

Elucidating the cellular and genetic composition of ocular tissues is essential for uncovering the pathophysiology of ocular diseases. Since the introduction of single-cell RNA sequencing (scRNA-seq) in 2009, vision researchers have performed extensive single-cell analyses to better understand transcriptome complexity and heterogeneity of ocular structures. This technology has revolutionized our ability to identify rare cell populations and to make cross-species comparisons of gene expression in both steady state and disease conditions. Importantly, single-cell transcriptomic analyses have enabled the identification of cell-type specific gene markers and signalling pathways between ocular cell populations. While most scRNA-seq studies have been conducted on retinal tissues, large-scale transcriptomic atlases pertaining to the ocular anterior segment have also been constructed in the past three years. This timely review provides vision researchers with an overview of scRNA-seq experimental design, technical limitations, and clinical applications in a variety of anterior segment-related ocular pathologies. We review open-access anterior segment-related scRNA-seq datasets and illustrate how scRNA-seq can be an indispensable tool for the development of targeted therapeutics.
Global transportation infrastructure exposure to the change of precipitation in a warmer world
Authors: Liu Kai , Wang Qianzhi , Wang Ming , Koks Elco E.
Published: May 2023

Transportation infrastructures are generally designed to have multi-decadal service lives. Transport infrastructure design, however, is largely based on historical conditions. Yet, in the face of global warming, we are likely going to experience more intense and frequent extreme events, which may put infrastructure at severe risk. In this study, we comprehensively analyze the exposure of road and railway infrastructure assets to changes in precipitation return periods globally. Under ~2 degrees of warming in mid-century (RCP 8.5 scenario), 43.6% of the global transportation assets are expected to experience at least a 25% decrease in design return period of extreme rainfall (a 33% increase in exceedance probability), which may increase to 69.9% under ~4 degrees of warming by late-21st century. To accommodate for such increases, we propose to incorporate a safety factor for climate change adaptation during the transportation infrastructure design process to ensure transportation assets will maintain their designed risk level in the future. Our results show that a safety factor of 1.2 would work sufficient for most regions of the world for quick design process calculations following the RCP4.5 path.
Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy
Authors: Dong Yu , Gao Qian , Chen Yong , Zhang Zhao , Du Yanhua , Liu Yuan , Zhang Guangxiong , Li Shengli , Wang Gaoyang , Chen Xiang , Liu Hong , Han Leng , Ye Youqiong
Published: May 2023

Circular RNAs (circRNAs) play important roles in the regulation of cancer. However, the clinical implications and regulatory networks of circRNAs in cancer patients receiving immune checkpoint blockades (ICB) have not been fully elucidated. Here, we characterize circRNA expression profiles in two independent cohorts of 157 ICB-treated advanced melanoma patients and reveal overall overexpression of circRNAs in ICB non-responders in both pre-treatment and early during therapy. Then, we construct circRNA-miRNA-mRNA regulatory networks to reveal circRNA-related signaling pathways in the context of ICB treatment. Further, we construct an ICB-related circRNA signature (ICBcircSig) score model based on progression-free survival-related circRNAs to predict immunotherapy efficacy. Mechanistically, the overexpression of ICBcircSig circTMTC3 and circFAM117B could increase PD-L1 expression via the miR-142-5p/PD-L1 axis, thus reducing T cell activity and leading to immune escape. Overall, our study characterizes circRNA profiles and regulatory networks in ICB-treated patients, and highlights the clinical utility of circRNAs as predictive biomarkers of immunotherapy.
Reconfigurable signal modulation in a ferroelectric tunnel field-effect transistor
Authors: Zhu Zhongyunshen , Persson Anton E. O. , Wernersson Lars-Erik
Published: May 2023

Reconfigurable transistors are an emerging device technology adding new functionalities while lowering the circuit architecture complexity. However, most investigations focus on digital applications. Here, we demonstrate a single vertical nanowire ferroelectric tunnel field-effect transistor (ferro-TFET) that can modulate an input signal with diverse modes including signal transmission, phase shift, frequency doubling, and mixing with significant suppression of undesired harmonics for reconfigurable analogue applications. We realize this by a heterostructure design in which a gate/source overlapped channel enables nearly perfect parabolic transfer characteristics with robust negative transconductance. By using a ferroelectric gate oxide, our ferro-TFET is non-volatilely reconfigurable, enabling various modes of signal modulation. The ferro-TFET shows merits of reconfigurability, reduced footprint, and low supply voltage for signal modulation. This work provides the possibility for monolithic integration of both steep-slope TFETs and reconfigurable ferro-TFETs towards high-density, energy-efficient, and multifunctional digital/analogue hybrid circuits.
Central medial thalamic nucleus dynamically participates in acute itch sensation and chronic itch-induced anxiety-like behavior in male mice
Authors: Li Jia-Ni , Wu Xue-Mei , Zhao Liu-Jie , Sun Han-Xue , Hong Jie , Wu Feng-Ling , Chen Si-Hai , Chen Tao , Li Hui , Dong Yu-Lin , Li Yun-Qing
Published: May 2023

Itch is an annoying sensation consisting of both sensory and emotional components. It is known to involve the parabrachial nucleus (PBN), but the following transmission nodes remain elusive. The present study identified that the PBN-central medial thalamic nucleus (CM)-medial prefrontal cortex (mPFC) pathway is essential for itch signal transmission at the supraspinal level in male mice. Chemogenetic inhibition of the CM-mPFC pathway attenuates scratching behavior or chronic itch-related affective responses. CM input to mPFC pyramidal neurons is enhanced in acute and chronic itch models. Specifically chronic itch stimuli also alter mPFC interneuron involvement, resulting in enhanced feedforward inhibition and a distorted excitatory/inhibitory balance in mPFC pyramidal neurons. The present work underscores CM as a transmit node of the itch signal in the thalamus, which is dynamically engaged in both the sensory and affective dimensions of itch with different stimulus salience.
Cortico-cortical feedback engages active dendrites in visual cortex
Authors: Fişek Mehmet , Herrmann Dustin , Egea-Weiss Alexander , Cloves Matilda , Bauer Lisa , Lee Tai-Ying , Russell Lloyd E. , Häusser Michael
Published: May 2023

Sensory processing in the neocortex requires both feedforward and feedback information flow between cortical areas1. In feedback processing, higher-level representations provide contextual information to lower levels, and facilitate perceptual functions such as contour integration and figure–ground segmentation2,3. However, we have limited understanding of the circuit and cellular mechanisms that mediate feedback influence. Here we use long-range all-optical connectivity mapping in mice to show that feedback influence from the lateromedial higher visual area (LM) to the primary visual cortex (V1) is spatially organized. When the source and target of feedback represent the same area of visual space, feedback is relatively suppressive. By contrast, when the source is offset from the target in visual space, feedback is relatively facilitating. Two-photon calcium imaging data show that this facilitating feedback is nonlinearly integrated in the apical tuft dendrites of V1 pyramidal neurons: retinotopically offset (surround) visual stimuli drive local dendritic calcium signals indicative of regenerative events, and two-photon optogenetic activation of LM neurons projecting to identified feedback-recipient spines in V1 can drive similar branch-specific local calcium signals. Our results show how neocortical feedback connectivity and nonlinear dendritic integration can together form a substrate to support both predictive and cooperative contextual interactions.
The temporal precision of audiovisual integration is associated with longitudinal fall incidents but not sensorimotor fall risk in older adults
Authors: O’Dowd Alan , Hirst Rebecca J. , Setti Annalisa , Donoghue Orna A. , Kenny Rose Anne , Newell Fiona N.
Published: May 2023

Sustained multisensory integration over long inter-stimulus time delays is typically found in older adults, particularly those with a history of falls. However, the extent to which the temporal precision of audio-visual integration is associated with longitudinal fall or fall risk trajectories is unknown. A large sample of older adults (N = 2319) were grouped into longitudinal trajectories of self-reported fall incidents (i.e., decrease, stable, or increase in number) and, separately, their performance on a standard, objective measure of fall risk, Timed Up and Go (TUG; stable, moderate decline, severe decline). Multisensory integration was measured once as susceptibility to the Sound-Induced Flash Illusion (SIFI) across three stimulus onset asynchronies (SOAs): 70 ms, 150 ms and 230 ms. Older adults with an increasing fall number showed a significantly different pattern of performance on the SIFI than non-fallers, depending on age: For adults with increasing incidents of falls, those aged 53–59 years showed a much smaller difference in illusion susceptibility at 70 ms versus 150 ms than those aged 70 + years. In contrast, non-fallers showed a more comparable difference between these SOA conditions across age groups. There was no association between TUG performance trajectories and SIFI susceptibility. These findings suggests that a fall event is associated with distinct temporal patterns of multisensory integration in ageing and have implications for our understanding of the mechanisms underpinning brain health in older age.
The association between food desert severity, socioeconomic status, and metabolic state during pregnancy in a prospective longitudinal cohort
Authors: Wood Elizabeth K. , Stamos Gayle , Mitchell A J , Gonoud Rose , Horgan Angela M. , Nomura Olivia , Young Anna , Nigg Joel T. , Gustafsson Hanna C. , Sullivan Elinor L.
Published: May 2023

Poor metabolic health during pregnancy is associated with health concerns for pregnant individuals and their offspring. Lower socioeconomic status (SES) is one risk factor for poor metabolic health, and may be related to limited access to healthful and affordable foods (e.g., living in a food desert). This study evaluates the respective contributions of SES and food desert severity on metabolic health during pregnancy. The food desert severity of 302 pregnant individuals was determined using the United States Department of Agriculture Food Access Research Atlas. SES was measured using total household income adjusted for household size, years of education, and amount of reserve savings. Information about participants’ glucose concentrations one hour following an oral glucose tolerance test during the second trimester was extracted from medical records and percent adiposity during the second trimester was assessed using air displacement plethysmography. Information about participants’ nutritional intake during the second trimester was obtained by trained nutritionists via three unannounced 24-h dietary recalls. Structural equation models showed that lower SES predicted higher food desert severity (β = − 0.20, p = 0.008) and higher adiposity (β = − 0.27, p = 0.016) and consumption of a more pro-inflammatory diet (β = − 0.25, p = 0.003) during the second trimester of pregnancy. Higher food desert severity also predicted higher percent adiposity during the second trimester (β = 0.17, p = 0.013). Food desert severity significantly mediated the relationship between lower SES and higher percent adiposity during the second trimester (βindirect = − 0.03, 95% CI [− 0.079, − 0.004]). These findings indicate that access to healthful and affordable foods is a mechanism by which SES contributes to adiposity during pregnancy and may inform interventions intended to improve metabolic health during pregnancy.
A neural network based global traveltime function (GlobeNN)
Authors: Taufik Mohammad H. , Waheed Umair bin , Alkhalifah Tariq A.
Published: May 2023

Global traveltime modeling is an essential component of modern seismological studies with a whole gamut of applications ranging from earthquake source localization to seismic velocity inversion. Emerging acquisition technologies like distributed acoustic sensing (DAS) promise a new era of seismological discovery by allowing a high-density of seismic observations. Conventional traveltime computation algorithms are unable to handle virtually millions of receivers made available by DAS arrays. Therefore, we develop GlobeNN—a neural network based traveltime function that can provide seismic traveltimes obtained from the cached realistic 3-D Earth model. We train a neural network to estimate the traveltime between any two points in the global mantle Earth model by imposing the validity of the eikonal equation through the loss function. The traveltime gradients in the loss function are computed efficiently using automatic differentiation, while the P-wave velocity is obtained from the vertically polarized P-wave velocity of the GLAD-M25 model. The network is trained using a random selection of source and receiver pairs from within the computational domain. Once trained, the neural network produces traveltimes rapidly at the global scale through a single evaluation of the network. As a byproduct of the training process, we obtain a neural network that learns the underlying velocity model and, therefore, can be used as an efficient storage mechanism for the huge 3-D Earth velocity model. These exciting features make our proposed neural network based global traveltime computation method an indispensable tool for the next generation of seismological advances.
Applying novel economic simple green sample preparation procedures on natural and industrial specimens for chromatographic determination of insecticidal residues
Authors: Hegazy Amira M. , Mahmoud Hamada M. , Elsayed Mohamed A. , Ali Nouruddin W. , Abdelfatah Rehab M.
Published: May 2023

Spraying a tertiary blend of the insecticides (hexythiazox, imidacloprid, and thiamethoxam), on tomato fruits, is a routine in agriculture-attentive countries. A simple green sample preparation technique was developed and applied to the field samples. Specific HP-TLC and RP-HPLC methodologies are established to estimate the residual insecticides and applied to the prepared field specimens. In the planner chromatographic methodology, methanol:chloroform:glacial acetic acid:triethyl amine (8.5:1.5:0.2:0.1, v/v) is recommended as a mobile system. The other one is columnar chromatography; acetonitrile: water (20:80, v/v), pH 2.8, is recommended as a mobile system. The validation parameters were examined following the ICH rules. The means percentages and standard deviations of the accuracy of the HP-TLC method for the determined compounds were 99.66 ± 0.974, 99.41 ± 0.950, and 99.89 ± 0.983, correspondingly. The values were 99.24 ± 0.921, 99.69 ± 0.681, and 99.20 ± 0.692, correspondingly, when they were determined by the RP-HPLC method. The relative standard deviation percentages of the methods’ repeatability and intermediate precision ranged from 0.389 to 0.920. Both methods were highly specific having resolution factors of ≥ 1.78 and selectivity factors of ≥ 1.71. They were applied to the field samples perfectly.
Machine learning based on computational fluid dynamics enables geometric design optimisation of the NeoVAD blades
Authors: Nissim Lee , Karnik Shweta , Smith P. Alex , Wang Yaxin , Frazier O. Howard , Fraser Katharine H.
Published: May 2023

The NeoVAD is a proposed paediatric axial-flow Left Ventricular Assist Device (LVAD), small enough to be implanted in infants. The design of the impeller and diffuser blades is important for hydrodynamic performance and haemocompatibility of the pump. This study aimed to optimise the blades for pump efficiency using Computational Fluid Dynamics (CFD), machine learning and global optimisation. Meshing of each design typically included 6 million hexahedral elements and a Shear Stress Transport turbulence model was used to close the Reynolds Averaged Navier–Stokes equations. CFD models of 32 base geometries, operating at 8 flow rates between 0.5 and 4 L/min, were created to match experimental studies. These were validated by comparison of the pressure-flow and efficiency-flow curves with those experimentally measured for all base prototype pumps. A surrogate model was required to allow the optimisation routine to conduct an efficient search; a multi-linear regression, Gaussian Process Regression and a Bayesian Regularised Artificial Neural Network predicted the optimisation objective at design points not explicitly simulated. A Genetic Algorithm was used to search for an optimal design. The optimised design offered a 5.51% increase in efficiency at design point (a 20.9% performance increase) as compared to the best performing pump from the 32 base designs. An optimisation method for the blade design of LVADs has been shown to work for a single objective function and future work will consider multi-objective optimisation.
Association of superficial macular vessel density with visual field progression in open-angle glaucoma with central visual field damage
Authors: Yoon Jooyoung , Lee Anna , Song Woo Keun , Kim Ko Eun , Kook Michael S.
Published: May 2023

Identifying the clinical relevance of superficial versus deep layer macular vessel density (mVD) in glaucoma is important for monitoring glaucoma patients. Our current retrospective longitudinal study investigated the association of superficial and deep layer mVD parameters with glaucomatous visual field (VF) progression in mild to moderate open-angle glaucoma (OAG) eyes with central visual field (CVF) damage. Serial optical coherence tomography (OCT) angiography-derived mVD measurements were obtained in 182 mild to moderate OAG eyes (mean deviation ≥ -10 decibels). Forty-eight eyes (26.4%) showed VF progression during a mean follow-up of 3.5 years. The parafoveal and perifoveal mVDs of both superficial and deep layers showed significantly faster reduction rates in the VF progressors than in the non-progressors according to linear mixed effects models (P < 0.05). Cox and linear regression analyses showed that greater reduction rates of both the superficial layer parafoveal and perifoveal mVDs, but not their deep layer counterparts, were significant predictors of VF progression and faster VF loss (P < 0.05). In conclusion, faster rates of change in superficial but not deep layer mVD parameters are significantly associated with subsequent VF progression and faster VF deterioration in mild to moderate OAG eyes with CVF damage.
Northernmost (Subarctic) and deepest record of Paleodictyon: paleoecological and biological implications
Authors: Miguez-Salas Olmo , Rodríguez-Tovar Francisco J. , Ekdale Allan A. , Kaiser Stefanie , Brandt Angelika , Gooday Andrew J.
Published: May 2023

Paleodictyon is one of the most iconic and widespread of trace fossils in the geological record. However, modern examples are less well known and restricted to deep-sea settings at relatively low latitudes. Here, we report the distribution of Paleodictyon at six abyssal sites near the Aleutian Trench. This study reveals for the first time the presence of Paleodictyon at Subarctic latitudes (51°–53°N) and at depths over 4500 m, although the traces were not observed at stations deeper than 5000 m suggesting that there is some bathymetric constraint for the trace maker. Two small Paleodictyon morphotypes were recognized (average mesh size of 1.81 cm), one having a central hexagonal pattern, the other being characterized by a non-hexagonal pattern. Within the study area, Paleodictyon shows no apparent correlation with local environmental parameters. Finally, based on a worldwide morphological comparison, we conclude that the new Paleodictyon specimens represent distinct ichnospecies that are associated with the relatively eutrophic conditions in this region. Their smaller size may reflect this more eutrophic setting in which sufficient food can be obtained from a smaller area in order to satisfy the energetic requirements of the tracemakers. If so, then Paleodictyon size may provide some assistance when interpreting paleoenvironmental conditions.
Ultraviolet exposure regulates skin metabolome based on the microbiome
Authors: Patra Vijaykumar , Bordag Natalie , Clement Yohann , Köfeler Harald , Nicolas Jean-Francois , Vocanson Marc , Ayciriex Sophie , Wolf Peter
Published: May 2023

Skin metabolites (< 1500 Da) play a critical role in barrier function, hydration, immune response, microbial invasion, and allergen penetration. We aimed to understand the global metabolic profile changes of the skin in relation to the microbiome and UV exposure and exposed germ-free (devoid of microbiome), disinfected mice (partially devoid of skin microbiome) and control mice with intact microbiome to immunosuppressive doses of UVB radiation. Targeted and untargeted lipidome and metabolome profiling was performed with skin tissue by high-resolution mass spectrometry. UV differentially regulated various metabolites such as alanine, choline, glycine, glutamine, and histidine in germ-free mice compared to control mice. Membrane lipid species such as phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin were also affected by UV in a microbiome-dependent manner. These results shed light on the dynamics and interactions between the skin metabolome, microbiome, and UV exposure and open new avenues for the development of metabolite- or lipid-based applications to maintain skin health.