bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of heavy subaqueous spherical pendulums
Authors: Gold Thomas , Reiterer Kevin , Worf Dominik , Kaiblinger Norbert , Khosronejad Ali , Habersack Helmut , Sindelar Christine
Published: January 2024

We present a systematic study to investigate the fluid–structure interaction (FSI) of subaqueous spherical pendulums with several solid-to-fluid mass ratios

$m^*\in [1.14, 14.95]$

and corresponding Reynolds numbers of up to

$\textit {Re}\sim 10^4$

. A digital object tracking (DOT) method was employed to track the oscillating pendulum spheres whereas the time-resolved 3-D particle tracking velocimetry (tr-3D-PTV) was used to measure the flow field around the spheres. The data obtained from the coupling of the two measuring techniques provide novel insights into the dynamics of pendulum sphere oscillations, instantaneous pressure fluctuations related to vortex shedding around the spheres and the way they are influenced by the vortex and wake interactions. Namely, we show that during the downward motion of the pendulum spheres, vortex rings are shed off the spheres which, in turn, induce short-lived propulsion and, subsequently, distinct deceleration. Further, we used the measured data to improve an existing basic model of pendulum motion, which has significant discrepancies for the period and peak amplitude predictions. We did this by incorporating a vortex-induced drag term and a wake interaction term into the equation. Finally, the improved equations are shown to be capable of predicting the subaqueous pendulum dynamics with high accuracy, for the investigated range of

$m^*$

. The study thus extends the current understanding of basic fluid dynamic mechanisms such as added mass, nonlinear drag, vortex and pressure dynamics.
Analytical models for pressure-driven Stokes flow through superhydrophobic and liquid-infused tubes and annular pipes
Authors: Zimmermann Sebastian , Schönecker Clarissa
Published: January 2024

Analytical expressions for the velocity field and the effective slip length of pressure-driven Stokes flow through slippery pipes and annuli with rotationally symmetrical longitudinal slits are derived. Specifically, the developed models incorporate a finite local slip length and constant shear stress along the slits, and thus go beyond the assumption of perfect slip employed commonly for superhydrophobic surfaces. Thereby, they provide the possibility to assess the influence of both the viscosity of the air or other fluid that is modelled to fill the slits as well as the influence of the micro-geometry of these slits. First, expressions for tubes and annular pipes with superhydrophobic or slippery walls are provided. Second, these solutions are combined to a tube-within-a circular-pipe scenario, where one fluid domain provides a slip to the other. This scenario is interesting as an application to achieve stable fluid–fluid interfaces. With respect to modelling, it illustrates the specification of the local slip length depending on a linked flow field. The comparison of the analytically calculated solutions with numerical simulations shows excellent agreement. The results of this paper thus represent an important instrument for the design and optimization of slippage along surfaces in circular geometries.
Liquid inertia versus bubble cloud buoyancy in circular plunging jet experiments
Authors: Dev Narendra , John Soundar Jerome J. , Scolan Hélène , Matas Jean-Philippe
Published: January 2024

When a liquid jet plunges into a pool, it can generate a bubble-laden jet flow underneath the surface. This common and simple phenomenon is investigated experimentally for circular jets to illustrate and quantify the role played by the net gas/liquid void fraction on the maximum bubble penetration depth. It is first shown that an increase in either the impact diameter or the jet fall height to diameter ratio at constant impact momentum leads to a reduction in the bubble cloud size. By measuring systematically the local void fraction using optical probes in the biphasic jet, it is then demonstrated that this effect is a direct consequence of the increase in air content within the cloud. A simple momentum balance model, including only inertia and the buoyancy force, is shown to predict the bubble cloud depth without any fitting parameters. Finally, a Froude number based on the bubble terminal velocity, the cloud depth and also the net void fraction is introduced to propose a simple criterion for the threshold between the inertia-dominated and buoyancy-dominated regimes.
Capillary rise in sharp corners: not quite universal
Authors: Wu Katie , Duprat C. , Stone H.A.
Published: January 2024

We study the capillary rise of viscous liquids into sharp corners formed by two surfaces whose geometry is described by power laws

$h_i(x) = c_i x^n$

,

$i = 1,2$

, where

$c_2 > c_1$

for

$n \geq 1$

. Prior investigations of capillary rise in sharp corners have shown that the meniscus altitude increases with time as

$t^{1/3}$

, a result that is universal, i.e. applies to all corner geometries. The universality of the phenomenon of capillary rise in sharp corners is revisited in this work through the analysis of a partial differential equation for the evolution of a liquid column rising into power-law-shaped corners, which is derived using lubrication theory. Despite the lack of geometric similarity of the liquid column cross-section for

$n>1$

, there exist a scaling and a similarity transformation that are independent of

$c_i$

and

$n$

, which gives rise to the universal

$t^{1/3}$

power law for capillary rise. However, the prefactor, which corresponds to the tip altitude of the self-similar solution, is a function of

$n$

, and it is shown to be bounded and monotonically decreasing as

$n\to \infty$

. Accordingly, the profile of the interface radius as a function of altitude is also independent of

$c_i$

and exhibits slight variations with

$n$

. Theoretical results are compared against experimental measurements of the time evolution of the tip altitude and of profiles of the interface radius as a function of altitude.
Social cognition, emotion regulation and social competence in classical galactosemia patients without intellectual disability
Authors: Hermans Merel E. , Geurtsen Gert J. , Hollak Carla E.M. , Janssen Mirian C.H. , Langendonk Janneke G. , Merckelbach Valerie L.V. , Oussoren Esmee , Oostrom Kim J. , Bosch Annet M.
Published: January 2024

Objective:

Classical galactosemia (CG) is an inborn error of galactose metabolism. Many CG patients suffer from long-term complications including poor cognitive functioning. There are indications of social dysfunction but limited evidence in the literature. Therefore, this study aims to improve our understanding of social competence in CG by investigating social cognition, neurocognition and emotion regulation.

Methods:

A comprehensive (neuro)psychological test battery, including self and proxy questionnaires, was administered to CG patients without intellectual disability. Social cognition was assessed by facial emotion recognition, Theory of Mind and self-reported empathy. Standardised results were compared to normative data of the general population.

Results:

Data from 23 patients (aged 8–52) were included in the study. On a group level, CG patients reported satisfaction with social roles and no social dysfunction despite the self-report of lower social skills. They showed deficits in all aspects of social cognition on both performance tests (emotion recognition and Theory of Mind) and self-report questionnaires (empathy). Adults had a lower social participation than the general population. Parents reported lower social functioning, less adaptive emotion regulation and communication difficulties in their children. Individual differences in scores were present.

Conclusion:

This study shows that CG patients without intellectual disability are satisfied with their social competence, especially social functioning. Nevertheless, deficits in social cognition are present in a large proportion of CG patients. Due to the large variability in scores and discrepancies between self- and proxy-report, an individually tailored, comprehensive neuropsychological assessment including social cognition is advised in all CG patients. Treatment plans need to be customised to the individual patient.
The end of an era
Authors: Bowler Peter J.
Published: January 2024

These volumes conclude a series initiated in 1974, marking almost fifty years of effort by a huge cohort of scholars. This review is thus a valedictory for the whole series as well as an account of what we have learned from the most recent volumes about Darwin's final years (1879–82). The project was begun by Frederick Burckhardt, who shared the editorial role for the early volumes with Sydney Smith and a rolling sequence of assistant editors and advisers who eventually comprised a significant fraction of the leading members of what used to be called the ‘Darwin industry’. Smith passed away in 1988 (volume 7 notes his legacy). Burkardt too left this world in 2007 – volume 16, part 1 includes an obituary, but his name has been retained and Cambridge University Press still ask that the series be cited as ‘Burkhardt et al.’ Duncan Porter took over for volumes 8–15, again with a sequence of fellow editors and assistants, after which James Secord became head of the project through its final years. The dedications of successive volumes record the efforts of individual scholars who have aided the teams and the involvement of the many institutions and foundations that have leant moral and material support over the years. For those of us with Cambridge connections, the University Library will not seem the same without the presence of the team it supported.
Nesting biology and nest structure of the exotic bee Megachile sculpturalis
Authors: Bogo Gherardo , Fisogni Alessandro , Iannone Antonio , Grillenzoni Francesca-Vittoria , Corvucci Francesca , Bortolotti Laura
Published: January 2024

From the 1990s, the Southeast Asia native giant resin bee Megachile sculpturalis (Smith, 1853) was introduced first to North America, and then to many countries in Europe. Despite increasing studies on its invasive potential and geographical expansion, information on nesting behaviour of this species is still extremely scarce. To increase knowledge on the nesting biology of M. sculpturalis, we studied multiple aspects of nesting and pollen provisioning in three consecutive years in artificial nests in Bologna, Italy. We observed 166 bees visiting nests, and followed individual nesting behaviour and success of 41 adult females. We measured cavity diameter in 552 nests and characterised the structure in 100 of them. More than 95% of nest diameters ranged between 0.6 and 1.2 cm, overlapping with several sympatric species of cavity-nesting hymenopterans in the study area. Most nests had a first chamber from the entrance of variable length without brood, followed by an average of about two brood cells with a mean length of 2.85 ± 0.13 cm each. The pollen stored in brood cells was almost monofloral, belonging to the ornamental plant Styphnolobium japonicum (L.) Schott. We estimated that a single female should visit ≈180 flowers to collect enough pollen for a single brood cell. These results fill knowledge gaps on the nesting biology and nest structure of the exotic M. sculpturalis, and they are discussed in relation to possible competition with native bees for nesting sites and foraging resources.
Collateral effects of Coping Power on caregiver symptoms of depression and long-term changes in child behavior
Authors: Saavedra Lissette M. , Lochman John E. , Morgan-López Antonio A. , McDaniel Heather L. , Bradshaw Catherine P. , Powell Nicole P. , Qu Lixin , Budavari Alexa , Yaros Anna C.
Published: January 2024

A large body of research demonstrates positive impacts of the Coping Power Program as a preventive intervention for youth behavioral outcomes, but potential collateral effects for caregivers is less known. The current study examined whether the youth-focused Coping Power Program can have a secondary impact on caregiver self-reported symptoms of depression and in turn result in longer-term impacts on child disruptive behavior problems including aggression, conduct problems and hyperactivity. Data from 360 youth/caregiver pairs across 8 waves of data (grades 4 through 10) were analyzed. We used two methodological approaches to (a) assess indirect effects in the presence of potential bidirectionality using timepoint-to-timepoint dynamic effects under Autoregressive Latent Trajectory modeling and (b) estimate scale scores in the presence of measurement non-invariance. Results showed that individually delivered Coping Power (ICP) produced greater direct effects on conduct problems and indirect effects on general externalizing and hyperactivity (through reductions in caregiver self-reported symptoms of depression), compared to group Coping Power (GCP). In comparison to GCP, ICP produced similar direct effects on reductions in caregiver depression. Child-focused prevention interventions can have an indirect impact on caregiver depression, which later shows improvements in longer-term reductions for child disruptive problems.
Longitudinal coupling of emotional wellbeing in parent-adolescent dyads: Evaluating the role of daily life positive affect socialization processes
Authors: Griffith Julianne M. , Hankin Benjamin L.
Published: January 2024

This study evaluated the role of bidirectional micro- and macro- level positive affect-related processes in the longitudinal coupling of depressive symptoms in parent-adolescent dyads. Using a measurement-burst design, including dyadic experience sampling methods (ESM) and monthly follow-ups over one year, this work investigated associations between (1) parental depressive symptoms and anhedonia and parental daily-life enhancing and dampening responses to youth positive affect; (2) parental daily-life enhancing and dampening and trajectories of youth positive affect, negative affect, and depressive symptoms across one year; and (3) youth developmental trajectories and prospective parental daily-life enhancing and dampening, and parental depressive symptoms and anhedonia at one-year follow-up. Participants included 146 early adolescents (52.1% girls, 47.9% boys; Mage[SD] = 12.71[.86]) and 139 parents (78.7% mothers; Mage[SD] = 44.11[5.08]). Parental enhancing and dampening were measured using a dyadic ESM procedure at baseline and 12-months. Youth completed monthtly questionnaires assessing depressive symptoms and trait positive and negative affect across 12 months. Parents reported on depressive symptoms and anhedonia at baseline and 12-months. Results showed that parental anhedonia negatively related to parental daily-life enhancing, and youths’ perceptions of their parents’ enhancing and dampening reciprocally related to youth emotional development across one year, with downstream implications for parents’ own symptoms of depression.
Effects of Dignity Therapy on individuals with amyotrophic lateral sclerosis: Case studies
Authors: Meira Mariana do Valle , Silva Rudval Souza da , Chochinov Harvey Max , Medeiros Maria Olivia Sobral Fraga de , Ferreira Marilaine Matos de Menezes , de Góes Salvetti Marina
Published: January 2024

Objectives

To analyze the effects of Dignity Therapy (DT) on the physical, existential, and psychosocial symptoms of individuals with amyotrophic lateral sclerosis (ALS).

Methods

This is a mixed-methods case study research that used the concurrent triangulation strategy to analyze the effects of DT on 3 individuals with ALS. Data collection included 3 instances of administering validated scales to assess multiple physical symptoms, anxiety, depression, spiritual well-being, and the Patient Dignity Inventory (PDI), followed by the implementation of DT and a semi-structured interview.

Results

The scale results indicate that DT led to an improvement in the assessment of physical, social, emotional, spiritual, and existential symptoms according to the score results. It is worth noting that the patient with a recent diagnosis showed higher scores for anxiety and depression after DT. Regarding the PDI, the scores indicate improvements in the sense of dignity in all 3 cases, which aligns with the positive verbal reports after the implementation of DT.

Significance of results

This study allowed us to analyze the effects of DT on the physical, existential, and psychosocial symptoms of individuals with ALS, suggesting the potential benefits of this approach for this group of patients. Participants reported positive effects regarding pain and fatigue, could reflect on their life trajectories, and regained their value and meaning.
Pearl Millet Crop Biophysical Parameter Retrieval From Space Borne Polarimetric SAR Data Using Machine Learning
Authors: Thulasiraman Dharanya , Haldar Dipanwita , Kumar Shashi , Ramathilagam Arun Balaji , Patel N. R.
Published: January 2024

The potential of single date fully Polarimetric RADARSAT‐2 data in retrieving crop biophysical parameters using Machine Learning techniques was investigated. Various polarimetric parameters along with coherent and incoherent decomposition techniques were assessed for its sensitivity toward crop parameters like Wet and Dry Biomass, Crop Height, Leaf Area Index and Vegetation Water Content. A set of 39 polarimetric observables extracted from the Quad‐Pol data were used for regression analysis. In this study two Machine Learning techniques Random Forest Regression (RFR) and Multiple Linear Regression (MLR) models were assessed for the prediction of Wet Biomass (gm−2) and Height (cm). The most significant (6 out of 39) variables were applied for prediction. The results revealed that RFR algorithm performed better than MLR. The coefficient of determination (R2) and root‐mean‐square‐error of estimating wet biomass and height were 0.646, 655.65 (gm−2) and 0.71, 14.5 (cm) respectively in RFR and 0.566, 683.86 (gm−2) and 0.65, 16.14 (cm) respectively in MLR. Thus this study explored the effective application of quad‐pol data for assessing sensitivity and accurate retrieval of parameters using optimum PolSAR observables.
Systematic Underestimation of Canopy Conductance Sensitivity to Drought by Earth System Models
Authors: Green J. K. , Zhang Y. , Luo X. , Keenan T. F.
Published: January 2024

The response of vegetation canopy conductance (gc) to changes in moisture availability () is a major source of uncertainty in climate projections. While vegetation typically reduces stomatal conductance during drought, accurately modeling how and to what degree stomata respond to changes in moisture availability at global scales is particularly challenging, because no global scale gc observations exist. Here, we leverage a collection of satellite, reanalysis and station‐based near‐surface air and surface temperature estimates, which are physically and statistically linked to due to the local cooling effect of gc through transpiration, to develop a novel emergent constraint of in an ensemble of Earth System Models (ESMs). We find that ESMs systematically underestimate by ∼33%, particularly in grasslands, croplands, and savannas in semi‐arid and bordering regions of the Central United States, Central Europe, Southeastern South America, Southern Africa, Eastern Australia, and parts of East Asia. We show that this underestimation occurs because ESMs inadequately reduce gc when soil moisture decreases. As gc controls carbon, water and energy fluxes, the misrepresentation of modeled contributes to biases in ESM projections of gross primary production, transpiration, and temperature during droughts. Our results suggest that the severity and duration of droughts may be misrepresented in ESMs due to the impact of sustained gc on both soil moisture dynamics and the biosphere‐atmosphere feedbacks that affect local temperatures and regional weather patterns.
Dimethyl Sulfide Emissions From a Peatland Result More From Organic Matter Degradation Than Sulfate Reduction
Authors: Lehnert Ann‐Sophie , Cooper Rebecca E. , Ignatz Rebecca , Ruecker Alexander , Gomes‐Alves Eliane , Küsel Kirsten , Pohnert Georg , Trumbore Susan E.
Published: January 2024

Volatile sulfur compounds (VSCs) contribute to acid rain, cloud formation, and albedo, and thus influence the climate. Their global emissions are quite uncertain, especially contributions from freshwater wetlands. We investigated the processes leading to hydrogen sulfide (H2S), methanethiol (MeSH), and dimethyl sulfide (Me2S) emissions in a slightly acidic peatland and found multiple indications that organic matter degradation rather than sulfate reduction is the main driver for Me2S emissions in this system. Evidence includes: the lack of labeled Me234S production after addition of Na234SO4 despite high emissions of Me34SH and H234S, and increased emission rates when soils were amended with organic substrates containing thiol groups (H2S emissions), methylthiols (MeSH), and dimethyl sulfonio groups (Me2S). VSC precursors were identified from an Untargeted Metabolomics data set from the same soil. The abundance of sulfur cycling microbes like Acidobacteria SD 1 and Desulfosporosinus correlated with VSC emissions. We conclude that organic matter degradation is more important than sulfate reduction as a source of Me2S in our peatland system, and potentially also in other organic and wetland soils.
NELF and PAF1C complexes are core transcriptional machineries controlling colon cancer stemness
Authors: Aoki Koji , Nitta Akari , Igarashi Ayumi
Published: January 2024

Mutations in APC, found in 80% of colon caner, enhance β-catenin stabilization, which is the initial step of colonic tumorigenesis. However, the core transcriptional mechanism underlying the induction of colon cancer stemness by stable β-catenin remains unclear. Here, we found that inducible inhibition of β-catenin suppressed elongation of Pol II and RNA polymerase-associated factor 1 complex (PAF1C) around the transcription start site (TSS) of LGR5. Moreover, stable β-catenin enhanced the formation of active Pol II complex cooperatively with CDC73 and CDK9 by facilitating the recruitment of DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF) complexes to the Pol II complex. Subsequently, stable β-catenin facilitated the formation of the Pol II–DSIF–PAF1C complex, suggesting that stable β-catenin induces cancer stemness by stimulating active Pol II complex through NELF and PAF1C. Furthermore, NELF or PAF1C inhibition recapitulated the changes in cancer stemness-related gene expression induced by the inhibition of stable β-catenin and suppressed colon cancer stemness. Additionally, the chemical inhibition of CDK12 (a downstream transcription CDK of PAF1C) suppressed colon cancer stemness. These results suggest that NELF and PAF1C are the core transcriptional machineries that control expression of colon cancer stemness-inducing genes and may be therapeutic targets for colon cancer.
RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism
Authors: Gu Xinyu , Li Penghui , Gao Xiaohui , Ru Yi , Xue Chen , Zhang Shujun , Liu Yafeng , Hu Xinjun
Published: January 2024

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer-related mortality worldwide. Nop2/Sun domain family member 5 (NSUN5), a conserved RNA 5-methylcytosine methyltransferase, is conventionally recognized as oncogenic. However, its role in HCC development remains unknown. In this study, we observed a remarkable upregulation of NSUN5 expression in both tumor tissues from patients with HCC, establishing a correlation with unfavorable clinical outcomes. NSUN5 knockdown and overexpression significantly inhibited and promoted HCC cell proliferation, respectively. Additionally, employing a combination of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RIP-seq techniques, we identified zinc finger BED domain-containing protein 3 (ZBED3) as a novel downstream target of NSUN5. Additionally, we found that the overexpression of ZBED3 counteracted the tumor-suppressing effect of NSUN5 knockdown and simultaneously reversed the inhibition of the Wnt/β-catenin signaling pathway. In summary, we elucidated the oncogenic role of NSUN5 in HCC development and identified the ZBED3/Wnt/β-catenin signaling pathway as its downstream target. This study provides a novel therapeutic target for further development in HCC treatment.
PIWI-interacting RNA-YBX1 inhibits proliferation and metastasis by the MAPK signaling pathway via YBX1 in triple-negative breast cancer
Authors: Wu Linyu , Huang Shanshan , Tian Wenwen , Liu Peng , Xie Yi , Qiu Yu , Li Xing , Tang Yuhui , Zheng Shaoquan , Sun Yuying , Tang Hailin , Du Wei , Tan Weige , Xie Xinhua
Published: January 2024

Breast cancer is the second leading cause of death in women worldwide, with triple-negative breast cancer (TNBC) having the worst prognosis. Although there are numerous studies on TNBC, there is no effective treatment for it, and it is still a major problem today. Studies on PIWI-interacting RNAs (piRNAs) are increasing and investigating the mechanism of piRNAs in the proliferation and metastasis of TNBC may lead to new potential treatment targets. Here, we identified a novel piRNA, piR-YBX1, which was downregulated in TNBC compared to matched normal breast tissue. Overexpression of piR-YBX1 significantly inhibited the proliferation, migration, invasion ability of TNBC cells both in vivo and in vitro. Mechanistically, piR-YBX1 could bind directly to mRNA of Y-box binding protein 1 (YBX1) and overexpression of piR-YBX1 downregulated YBX1 in both mRNA and protein levels, while the function of piR-YBX1 could be partly rescued by overexpression of YBX1. In addition, YBX1 could bind to RAF1 which is the key molecule in the MAPK signaling pathway, and overexpression of piR-YBX1 inhibited the p-MEK and p-ERK1/2, which can be reverted by YBX1. In conclusion, our findings discovered that the piR-YBX1/YBX1/MAPK axis suppresses the proliferation and metastasis of TNBC and therefore piR-YBX1 has the potential to be an effective therapeutic agent for breast cancer.
Decoding the spatiotemporal regulation of transcription factors during human spinal cord development
Authors: Shi Yingchao , Huang Luwei , Dong Hao , Yang Meng , Ding Wenyu , Zhou Xiang , Lu Tian , Liu Zeyuan , Zhou Xin , Wang Mengdi , Zeng Bo , Sun Yinuo , Zhong Suijuan , Wang Bosong , Wang Wei , Yin Chonghai , Wang Xiaoqun , Wu Qian
Published: January 2024

The spinal cord is a crucial component of the central nervous system that facilitates sensory processing and motor performance. Despite its importance, the spatiotemporal codes underlying human spinal cord development have remained elusive. In this study, we have introduced an image-based single-cell transcription factor (TF) expression decoding spatial transcriptome method (TF-seqFISH) to investigate the spatial expression and regulation of TFs during human spinal cord development. By combining spatial transcriptomic data from TF-seqFISH and single-cell RNA-sequencing data, we uncovered the spatial distribution of neural progenitor cells characterized by combinatorial TFs along the dorsoventral axis, as well as the molecular and spatial features governing neuronal generation, migration, and differentiation along the mediolateral axis. Notably, we observed a sandwich-like organization of excitatory and inhibitory interneurons transiently appearing in the dorsal horns of the developing human spinal cord. In addition, we integrated data from 10× Visium to identify early and late waves of neurogenesis in the dorsal horn, revealing the formation of laminas in the dorsal horns. Our study also illuminated the spatial differences and molecular cues underlying motor neuron (MN) diversification, and the enrichment of Amyotrophic Lateral Sclerosis (ALS) risk genes in MNs and microglia. Interestingly, we detected disease-associated microglia (DAM)-like microglia groups in the developing human spinal cord, which are predicted to be vulnerable to ALS and engaged in the TYROBP causal network and response to unfolded proteins. These findings provide spatiotemporal transcriptomic resources on the developing human spinal cord and potential strategies for spinal cord injury repair and ALS treatment.
LDLR is an entry receptor for Crimean-Congo hemorrhagic fever virus
Authors: Xu Zhi-Sheng , Du Wen-Tian , Wang Su-Yun , Wang Mo-Yu , Yang Yi-Ning , Li Yu-Hui , Li Zhen-Qi , Zhao Li-Xin , Yang Yan , Luo Wei-Wei , Wang Yan-Yi
Published: January 2024

Crimean-Congo hemorrhagic fever virus (CCHFV) is the most widespread tick-born zoonotic bunyavirus that causes severe hemorrhagic fever and death in humans. CCHFV enters the cell via clathrin-mediated endocytosis which is dependent on its surface glycoproteins. However, the cellular receptors that are required for CCHFV entry are unknown. Here we show that the low density lipoprotein receptor (LDLR) is an entry receptor for CCHFV. Genetic knockout of LDLR impairs viral infection in various CCHFV-susceptible human, monkey and mouse cells, which is restored upon reconstitution with ectopically-expressed LDLR. Mutagenesis studies indicate that the ligand binding domain (LBD) of LDLR is necessary for CCHFV infection. LDLR binds directly to CCHFV glycoprotein Gc with high affinity, which supports virus attachment and internalization into host cells. Consistently, a soluble sLDLR–Fc fusion protein or anti-LDLR blocking antibodies impair CCHFV infection into various susceptible cells. Furthermore, genetic knockout of LDLR or administration of an LDLR blocking antibody significantly reduces viral loads, pathological effects and death following CCHFV infection in mice. Our findings suggest that LDLR is an entry receptor for CCHFV and pharmacological targeting of LDLR may provide a strategy to prevent and treat Crimean-Congo hemorrhagic fever.
Role of MnS in the intergranular corrosion and depassivation of sensitized Type 304 stainless steel
Authors: Ida Noriyuki , Nishimoto Masashi , Muto Izumi , Sugawara Yu
Published: January 2024

During polarization in 1 M NaCl (pH 5.4), intergranular corrosion of sensitized re-sulfurized Type 304 stainless steel occurred after pit initiation at MnS inclusions. Intergranular corrosion occurred when the pitting corrosion reached a Cr-depleted region along the sensitized grain boundaries. During depassivation under open-circuit conditions in 1 M NaCl (pH 1.0), MnS dissolution occurred as the first step, and the second step was the initiation of intergranular corrosion. Finally, dissolution of the steel matrix occurred. The role of MnS in the initiation of intergranular corrosion and depassivation of sensitized steel is discussed.
Machine Learning in the Parkinson’s disease smartwatch (PADS) dataset
Authors: Varghese Julian , Brenner Alexander , Fujarski Michael , van Alen Catharina Marie , Plagwitz Lucas , Warnecke Tobias
Published: January 2024

The utilisation of smart devices, such as smartwatches and smartphones, in the field of movement disorders research has gained significant attention. However, the absence of a comprehensive dataset with movement data and clinical annotations, encompassing a wide range of movement disorders including Parkinson’s disease (PD) and its differential diagnoses (DD), presents a significant gap. The availability of such a dataset is crucial for the development of reliable machine learning (ML) models on smart devices, enabling the detection of diseases and monitoring of treatment efficacy in a home-based setting. We conducted a three-year cross-sectional study at a large tertiary care hospital. A multi-modal smartphone app integrated electronic questionnaires and smartwatch measures during an interactive assessment designed by neurologists to provoke subtle changes in movement pathologies. We captured over 5000 clinical assessment steps from 504 participants, including PD, DD, and healthy controls (HC). After age-matching, an integrative ML approach combining classical signal processing and advanced deep learning techniques was implemented and cross-validated. The models achieved an average balanced accuracy of 91.16% in the classification PD vs. HC, while PD vs. DD scored 72.42%. The numbers suggest promising performance while distinguishing similar disorders remains challenging. The extensive annotations, including details on demographics, medical history, symptoms, and movement steps, provide a comprehensive database to ML techniques and encourage further investigations into phenotypical biomarkers related to movement disorders.
Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease
Authors: Shiraishi Kazushige , Morley Michael P. , Jones Dakota L. , Zhao Gan , Weiner Aaron I. , Basil Maria C. , Cantu Edward , Ferguson Laura T. , Oyster Michele , Babu Apoorva , Ying Yun , Zhou Su , Li Shanru , Vaughan Andrew E. , Morrisey Edward E.
Published: January 2024

Maintenance of the cellular boundary between airway and alveolar compartments during homeostasis and after injury is essential to prohibit pathological plasticity which can reduce respiratory function. Lung injury and disease can induce either functional alveolar epithelial regeneration or dysplastic formation of keratinized epithelium which does not efficiently contribute to gas exchange. Here we show that Sox2 preserves airway cell identity and prevents fate changes into either functional alveolar tissue or pathological keratinization following lung injury. Loss of Sox2 in airway epithelium leads to a loss of airway epithelial identity with a commensurate gain in alveolar and basal cell identity, in part due to activation of Wnt signaling in secretory cells and increased Trp63 expression in intrapulmonary basal-like progenitors. In idiopathic pulmonary fibrosis, loss of SOX2 expression correlates with increased WNT signaling activity in dysplastic keratinized epithelium. SOX2-deficient dysplastic epithelial cells are also observed in COVID-19 damaged lungs. Thus, Sox2 provides a molecular barrier that suppresses airway epithelial plasticity to prevent acquisition of alveolar or basal cell identity after injury and help guide proper epithelial fate and regeneration.
Shared genetic architectures of educational attainment in East Asian and European populations
Authors: Chen Tzu-Ting , Kim Jaeyoung , Lam Max , Chuang Yi-Fang , Chiu Yen-Ling , Lin Shu-Chin , Jung Sang-Hyuk , Kim Beomsu , Kim Soyeon , Cho Chamlee , Shim Injeong , Park Sanghyeon , Ahn Yeeun , Okbay Aysu , Jang Hyemin , Kim Hee Jin , Seo Sang Won , Park Woong-Yang , Ge Tian , Huang Hailiang , Feng Yen-Chen Anne , Lin Yen-Feng , Myung Woojae , Chen Chia-Yen , Won Hong-Hee
Published: January 2024

Educational attainment (EduYears), a heritable trait often used as a proxy for cognitive ability, is associated with various health and social outcomes. Previous genome-wide association studies (GWASs) on EduYears have been focused on samples of European (EUR) genetic ancestries. Here we present the first large-scale GWAS of EduYears in people of East Asian (EAS) ancestry (n = 176,400) and conduct a cross-ancestry meta-analysis with EduYears GWAS in people of EUR ancestry (n = 766,345). EduYears showed a high genetic correlation and power-adjusted transferability ratio between EAS and EUR. We also found similar functional enrichment, gene expression enrichment and cross-trait genetic correlations between two populations. Cross-ancestry fine-mapping identified refined credible sets with a higher posterior inclusion probability than single population fine-mapping. Polygenic prediction analysis in four independent EAS and EUR cohorts demonstrated transferability between populations. Our study supports the need for further research on diverse ancestries to increase our understanding of the genetic basis of educational attainment.
Bright and stable near-infrared lead-free perovskite light-emitting diodes
Authors: Yuan Fanglong , Folpini Giulia , Liu Tianjun , Singh Utkarsh , Treglia Antonella , Lim Jia Wei Melvin , Klarbring Johan , Simak Sergei I. , Abrikosov Igor A. , Sum Tze Chien , Petrozza Annamaria , Gao Feng
Published: January 2024

Long-wavelength near-infrared light-emitting diodes (NIR LEDs) with peak emission wavelengths beyond 900 nm are of critical importance for various applications including night vision, biomedical imaging, sensing and optical communications. However, the low radiance and poor operational stability of state-of-the-art long-wavelength NIR LEDs based on soft materials remain the most critical factors limiting their practical applications. Here we develop NIR LEDs emitting beyond 900 nm with improved performance through the rational manipulation of p doping in all-inorganic tin perovskites (CsSnI3) by retarding and controlling the crystallization process of perovskite precursors in tin-rich conditions. The resulting NIR LEDs exhibit a peak emission wavelength at 948 nm, high radiance of 226 W sr−1 m−2 and long operational half-lifetime of 39.5 h at a high constant current density of 100 mA cm−2. Our demonstration of efficient and stable NIR LEDs operating at high current densities may also open up new opportunities towards electrically pumped lasers.
Distinct baseline immune characteristics associated with responses to conjugated and unconjugated pneumococcal polysaccharide vaccines in older adults
Authors: Ravichandran Sathyabaarathi , Erra-Diaz Fernando , Karakaslar Onur E. , Marches Radu , Kenyon-Pesce Lisa , Rossi Robert , Chaussabel Damien , Nehar-Belaid Djamel , LaFon David C. , Pascual Virginia , Palucka Karolina , Paust Silke , Nahm Moon H. , Kuchel George A. , Banchereau Jacques , Ucar Duygu
Published: January 2024

Pneumococcal infections cause serious illness and death among older adults. The capsular polysaccharide vaccine PPSV23 and conjugated alternative PCV13 can prevent these infections; yet, underlying immunological responses and baseline predictors remain unknown. We vaccinated 39 older adults (>60 years) with PPSV23 or PCV13 and observed comparable antibody responses (day 28) and plasmablast transcriptional responses (day 10); however, the baseline predictors were distinct. Analyses of baseline flow cytometry and bulk and single-cell RNA-sequencing data revealed a baseline phenotype specifically associated with weaker PCV13 responses, which was characterized by increased expression of cytotoxicity-associated genes, increased frequencies of CD16+ natural killer cells and interleukin-17-producing helper T cells and a decreased frequency of type 1 helper T cells. Men displayed this phenotype more robustly and mounted weaker PCV13 responses than women. Baseline expression levels of a distinct gene set predicted PPSV23 responses. This pneumococcal precision vaccinology study in older adults uncovered distinct baseline predictors that might transform vaccination strategies and initiate novel interventions.
Magnesium–ibogaine therapy in veterans with traumatic brain injuries
Authors: Cherian Kirsten N. , Keynan Jackob N. , Anker Lauren , Faerman Afik , Brown Randi E. , Shamma Ahmed , Keynan Or , Coetzee John P. , Batail Jean-Marie , Phillips Angela , Bassano Nicholas J. , Sahlem Gregory L. , Inzunza Jose , Millar Trevor , Dickinson Jonathan , Rolle C. E. , Keller Jennifer , Adamson Maheen , Kratter Ian H. , Williams Nolan R.
Published: January 2024

Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium–Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery–Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen’sd = 0.74) and 1 month (Pcorrected < 0.001,d = 2.20) after treatment and in PTSD (Pcorrected < 0.001,d = 2.54), depression (Pcorrected < 0.001,d = 2.80) and anxiety (Pcorrected < 0.001,d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration:NCT04313712.
Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial
Authors: Heinrich Michael C. , Jones Robin L. , George Suzanne , Gelderblom Hans , Schöffski Patrick , von Mehren Margaret , Zalcberg John R. , Kang Yoon-Koo , Razak Albiruni Abdul , Trent Jonathan , Attia Steven , Le Cesne Axel , Siontis Brittany L. , Goldstein David , Boye Kjetil , Sanchez Cesar , Steeghs Neeltje , Rutkowski Piotr , Druta Mihaela , Serrano César , Somaiah Neeta , Chi Ping , Reichmann William , Sprott Kam , Achour Haroun , Sherman Matthew L. , Ruiz-Soto Rodrigo , Blay Jean-Yves , Bauer Sebastian
Published: January 2024

INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N = 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing–based assay. ctDNA was detected in 280/362 (77%) samples with KIT mutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KIT exon 11 + 13/14 mutations (ripretinib, n = 21; sunitinib, n = 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KIT exon 11 + 17/18 mutations (ripretinib, n = 27; sunitinib, n = 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.
Women’s neuroplasticity during gestation, childbirth and postpartum
Authors: Paternina-Die María , Martínez-García Magdalena , Martín de Blas Daniel , Noguero Inés , Servin-Barthet Camila , Pretus Clara , Soler Anna , López-Montoya Gonzalo , Desco Manuel , Carmona Susana
Published: January 2024

Pregnancy is a unique neuroplastic period in adult life. This longitudinal study tracked brain cortical changes during the peripartum period and explored how the type of childbirth affects these changes. We collected neuroanatomic, obstetric and neuropsychological data from 110 first-time mothers during late pregnancy and early postpartum, as well as from 34 nulliparous women evaluated at similar time points. During late pregnancy, mothers showed lower cortical volume than controls across all functional networks. These cortical differences attenuated in the early postpartum session. Default mode and frontoparietal networks showed below-expected volume increases during peripartum, suggesting that their reductions may persist longer. Results also pointed to different cortical trajectories in mothers who delivered by scheduled C-section. The main findings were replicated in an independent sample of 29 mothers and 24 nulliparous women. These data suggest a dynamic trajectory of cortical decreases during pregnancy that attenuates in the postpartum period, at a different rate depending on the brain network and childbirth type.
Online monitoring of phytate content in plant residuals during wet-treatment
Authors: Widderich Niklas , Bubenheim Paul , Liese Andreas
Published: January 2024

The occurrence of organically bound phosphorus (P) as phytate in plant-based feeding material is a challenge for livestock farming due to limited utilization during the digestion by the animal. Its excretion into the environment through the manure pathway, poses a challenge, due to increased eutrophication and restrictions for P. Hence, while the routine supplementation of phytase enzymes in monogastric diets is common practice, metabolically triggering endogenous plant enzymes by wet-treatment prior to feeding can also lead to a better utilization of phytate bound P and increased digestibility by the animal. Nonetheless, traditional quantification of residual phytate content in plant material is both labor- and chemical-intense. The aim of this study is, therefore, to predict the remaining phytate content during wet-treatment through a straightforward and flexible methodological approach based on real-time analysis. For this, rye bran is used as a model substrate. A partial least squares regression algorithm relates the infrared spectra to the concentrations and predict the amount of P species that are transferred from the bran matrix to the liquid phase. By applying a mass balance for P and considering the effect of water compression, the amount of residual phytate content in rye bran at different time points of wet-treatment is determined. Results are compared to wet chemical methods, resulting in a RMSEP of 0.28 gphytate∙100 gbran−1. In addition, the study demonstrates the feasibility of this approach and provides insights into phytate degradation in plant residuals. The method holds the potential for further applications for the screening and investigation of feed material conditioning and also offers the possibility to employ various real-time analytical techniques for assessing phytate remnants in biological samples during wet-treatment.