bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma
Authors: Lei Wen , Zhao Ai , Liu Hui , Yang Chunmei , Wei Cheng , Guo Shanshan , Chen Zhilu , Guo Qunyi , Li Linjie , Zhao Mingzhe , Wu Gongqiang , Ouyang Guifang , Liu Ming , Zhang Jinyi , Gao Jimin , Qian Wenbin
Published: January 2024

Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106–4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.
Upregulated pexophagy limits the capacity of selective autophagy
Authors: Germain Kyla , So Raphaella W. L. , DiGiovanni Laura F. , Watts Joel C. , Bandsma Robert H. J. , Kim Peter K.
Published: January 2024

Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but whether these pathways can influence one another remains unknown. We address this question using pexophagy, the autophagic degradation of peroxisomes, as a model. We show in cells that upregulated pexophagy impairs the selective autophagy of both mitochondria and protein aggregates by exhausting the autophagy initiation factor, ULK1. We confirm this finding in cell models of the pexophagy-mediated form of Zellweger Spectrum Disorder, a disease characterized by peroxisome dysfunction. Further, we extend the generalizability of limited selective autophagy by determining that increased protein aggregate degradation reciprocally reduces pexophagy using cell models of Parkinson’s Disease and Huntington’s Disease. Our findings suggest that the degradative capacity of selective autophagy can become limited by an increase in one substrate.
Stress-induced vagal activity influences anxiety-relevant prefrontal and amygdala neuronal oscillations in male mice
Authors: Okonogi Toya , Kuga Nahoko , Yamakawa Musashi , Kayama Tasuku , Ikegaya Yuji , Sasaki Takuya
Published: January 2024

The vagus nerve crucially affects emotions and psychiatric disorders. However, the detailed neurophysiological dynamics of the vagus nerve in response to emotions and its associated pathological changes remain unclear. In this study, we demonstrated that the spike rates of the cervical vagus nerve change depending on anxiety behavior in an elevated plus maze test, and these changes were eradicated in stress-susceptible male mice. Furthermore, instantaneous spike rates of the vagus nerve were negatively and positively correlated with the power of 2–4 Hz and 20–30 Hz oscillations, respectively, in the prefrontal cortex and amygdala. The oscillations also underwent dynamic changes depending on the behavioral state in the elevated plus maze, and these changes were no longer observed in stress-susceptible and vagotomized mice. Chronic vagus nerve stimulation restored behavior-relevant neuronal oscillations with the recovery of altered behavioral states in stress-susceptible mice. These results suggested that physiological vagal-brain communication underlies anxiety and mood disorders.
Tunable and parabolic piezoelectricity in hafnia under epitaxial strain
Authors: Cheng Hao , Jiao Peijie , Wang Jian , Qing Mingkai , Deng Yu , Liu Jun-Ming , Bellaiche Laurent , Wu Di , Yang Yurong
Published: January 2024

Piezoelectrics are a class of functional materials that have been extensively used for application in modern electro-mechanical and mechatronics technologies. The sign of longitudinal piezoelectric coefficients is typically positive but recently a few ferroelectrics, such as ferroelectric polymer poly(vinylidene fluoride) and van der Waals ferroelectric CuInP2S6, were experimentally found to have negative piezoelectricity. Here, using first-principles calculation and measurements, we show that the sign of the longitudinal linear piezoelectric coefficient of HfO2 can be tuned from positive to negative via epitaxial strain. Nonlinear and even parabolic piezoelectric behaviors are further found at tensile epitaxial strain. This parabolic piezoelectric behavior implies that the polarization decreases when increasing the magnitude of either compressive or tensile longitudinal strain, or, equivalently, that the strain increases when increasing the magnitude of electric field being either parallel or antiparallel to the direction of polarization. The unusual piezoelectric effects are from the chemical coordination of the active oxygen atoms. These striking piezoelectric features of positive and negative sign, as well as linear and parabolical behaviors, expand the current knowledge in piezoelectricity and broaden the potential of piezoelectric applications towards electro-mechanical and communications technology.
Steeper size spectra with decreasing phytoplankton biomass indicate strong trophic amplification and future fish declines
Authors: Atkinson Angus , Rossberg Axel G. , Gaedke Ursula , Sprules Gary , Heneghan Ryan F. , Batziakas Stratos , Grigoratou Maria , Fileman Elaine , Schmidt Katrin , Frangoulis Constantin
Published: January 2024

Under climate change, model ensembles suggest that declines in phytoplankton biomass amplify into greater reductions at higher trophic levels, with serious implications for fisheries and carbon storage. However, the extent and mechanisms of this trophic amplification vary greatly among models, and validation is problematic. In situ size spectra offer a novel alternative, comparing biomass of small and larger organisms to quantify the net efficiency of energy transfer through natural food webs that are already challenged with multiple climate change stressors. Our global compilation of pelagic size spectrum slopes supports trophic amplification empirically, independently from model simulations. Thus, even a modest (16%) decline in phytoplankton this century would magnify into a 38% decline in supportable biomass of fish within the intensively-fished mid-latitude ocean. We also show that this amplification stems not from thermal controls on consumers, but mainly from temperature or nutrient controls that structure the phytoplankton baseline of the food web. The lack of evidence for direct thermal effects on size structure contrasts with most current thinking, based often on more acute stress experiments or shorter-timescale responses. Our synthesis of size spectra integrates these short-term dynamics, revealing the net efficiency of food webs acclimating and adapting to climatic stressors.
VESPA: an optimized protocol for accurate metabarcoding-based characterization of vertebrate eukaryotic endosymbiont and parasite assemblages
Authors: Owens Leah A. , Friant Sagan , Martorelli Di Genova Bruno , Knoll Laura J. , Contreras Monica , Noya-Alarcon Oscar , Dominguez-Bello Maria G. , Goldberg Tony L.
Published: January 2024

Protocols for characterizing taxonomic assemblages by deep sequencing of short DNA barcode regions (metabarcoding) have revolutionized our understanding of microbial communities and are standardized for bacteria, archaea, and fungi. Unfortunately, comparable methods for host-associated eukaryotes have lagged due to technical challenges. Despite 54 published studies, issues remain with primer complementarity, off-target amplification, and lack of external validation. Here, we present VESPA (Vertebrate Eukaryotic endoSymbiont and Parasite Analysis) primers and optimized metabarcoding protocol for host-associated eukaryotic community analysis. Using in silico prediction, panel PCR, engineered mock community standards, and clinical samples, we demonstrate VESPA to be more effective at resolving host-associated eukaryotic assemblages than previously published methods and to minimize off-target amplification. When applied to human and non-human primate samples, VESPA enables reconstruction of host-associated eukaryotic endosymbiont communities more accurately and at finer taxonomic resolution than microscopy. VESPA has the potential to advance basic and translational science on vertebrate eukaryotic endosymbiont communities, similar to achievements made for bacterial, archaeal, and fungal microbiomes.
Direct observation of strong surface reconstruction in partially reduced nickelate films
Authors: Yang Chao , Pons Rebecca , Sigle Wilfried , Wang Hongguang , Benckiser Eva , Logvenov Gennady , Keimer Bernhard , van Aken Peter A.
Published: January 2024

The polarity of a surface can affect the electronic and structural properties of oxide thin films through electrostatic effects. Understanding the mechanism behind these effects requires knowledge of the atomic structure and electrostatic characteristics at the surface. In this study, we use annular bright-field imaging to investigate the surface structure of a Pr0.8Sr0.2NiO2+x (0 < x < 1) film. We observe a polar distortion coupled with octahedral rotations in a fully oxidized Pr0.8Sr0.2NiO3 sample, and a stronger polar distortion in a partially reduced sample. Its spatial depth extent is about three unit cells from the surface. Additionally, we use four-dimensional scanning transmission electron microscopy (4D-STEM) to directly image the local atomic electric field surrounding Ni atoms near the surface and discover distinct valence variations of Ni atoms, which are confirmed by atomic-resolution electron energy-loss spectroscopy (EELS). Our results suggest that the strong surface reconstruction in the reduced sample is closely related to the formation of oxygen vacancies from topochemical reduction. These findings provide insights into the understanding and evolution of surface polarity at the atomic level.
Motion and teleportation of polar bubbles in low-dimensional ferroelectrics
Authors: Prokhorenko S. , Nahas Y. , Govinden V. , Zhang Q. , Valanoor N. , Bellaiche L.
Published: January 2024

Electric bubbles are sub-10nm spherical vortices of electric dipoles that can spontaneously form in ultra-thin ferroelectrics. While the static properties of electric bubbles are well established, little to nothing is known about the dynamics of these particle-like structures. Here, we reveal pathways to realizing both the spontaneous and controlled dynamics of electric bubbles in ultra-thin Pb(Zr0.4Ti0.6)O3 films. In low screening conditions, we find that electric bubbles exhibit thermally-driven chaotic motion giving rise to a liquid-like state. In the high screening regime, we show that bubbles remain static but can be continuously displaced by a local electric field. Additionally, we predict and experimentally demonstrate the possibility of bubble teleportation - a process wherein a bubble is transferred to a new location via a single electric field pulse of a PFM tip. Finally, we attribute the discovered phenomena to the hierarchical structure of the energy landscape.
Gasdermin E dictates inflammatory responses by controlling the mode of neutrophil death
Authors: Ma Fengxia , Ghimire Laxman , Ren Qian , Fan Yuping , Chen Tong , Balasubramanian Arumugam , Hsu Alan , Liu Fei , Yu Hongbo , Xie Xuemei , Xu Rong , Luo Hongbo R.
Published: January 2024

Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil lytic pyroptotic death. The tightly regulated GSDME cleavage and activation in aging neutrophils are mediated by proteinase-3 and caspase-3, leading to pyroptosis. GSDME deficiency does not alter neutrophil overall survival rate; instead, it specifically precludes pyroptosis and skews neutrophil death towards apoptosis, thereby attenuating inflammatory responses due to augmented efferocytosis of apoptotic neutrophils by macrophages. In a clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion of GSDME reduces pulmonary inflammation, facilitates inflammation resolution, and alleviates lung injury. Thus, by controlling the mode of neutrophil death, GSDME dictates host inflammatory outcomes, providing a potential therapeutic target for infectious and inflammatory diseases.
Online legal driving behavior monitoring for self-driving vehicles
Authors: Yu Wenhao , Zhao Chengxiang , Wang Hong , Liu Jiaxin , Ma Xiaohan , Yang Yingkai , Li Jun , Wang Weida , Hu Xiaosong , Zhao Ding
Published: January 2024

Defined traffic laws must be respected by all vehicles when driving on the road, including self-driving vehicles without human drivers. Nevertheless, the ambiguity of human-oriented traffic laws, particularly compliance thresholds, poses a significant challenge to the implementation of regulations on self-driving vehicles, especially in detecting illegal driving behaviors. To address these challenges, here we present a trigger-based hierarchical online monitor for self-assessment of driving behavior, which aims to improve the rationality and real-time performance of the monitoring results. Furthermore, the general principle to determine the ambiguous compliance threshold based on real driving behaviors is proposed, and the specific outcomes and sensitivity of the compliance threshold selection are analyzed. In this work, the effectiveness and real-time capability of the online monitor were verified using both Chinese human driving behavior datasets and real vehicle field tests, indicating the potential for implementing regulations in self-driving vehicles for online monitoring.
Efficient and stable visible-light-driven Z-scheme overall water splitting using an oxysulfide H2 evolution photocatalyst
Authors: Lin Lihua , Ma Yiwen , Vequizo Junie Jhon M. , Nakabayashi Mamiko , Gu Chen , Tao Xiaoping , Yoshida Hiroaki , Pihosh Yuriy , Nishina Yuta , Yamakata Akira , Shibata Naoya , Hisatomi Takashi , Takata Tsuyoshi , Domen Kazunari
Published: January 2024

So-called Z-scheme systems permit overall water splitting using narrow-bandgap photocatalysts. To boost the performance of such systems, it is necessary to enhance the intrinsic activities of the hydrogen evolution photocatalyst and oxygen evolution photocatalyst, promote electron transfer from the oxygen evolution photocatalyst to the hydrogen evolution photocatalyst, and suppress back reactions. The present work develop a high-performance oxysulfide photocatalyst, Sm2Ti2O5S2, as an hydrogen evolution photocatalyst for use in a Z-scheme overall water splitting system in combination with BiVO4 as the oxygen evolution photocatalyst and reduced graphene oxide as the solid-state electron mediator. After surface modifications of the photocatalysts to promote charge separation and redox reactions, this system is able to split water into hydrogen and oxygen for more than 100 hours with a solar-to-hydrogen energy conversion efficiency of 0.22%. In contrast to many existing photocatalytic systems, the water splitting activity of the present system is only minimally reduced by increasing the background pressure to 90 kPa. These results suggest characteristics suitable for applications under practical operating conditions.
Stretchable and negative-Poisson-ratio porous metamaterials
Authors: Zhang Xiaoyu , Sun Qi , Liang Xing , Gu Puzhong , Hu Zhenyu , Yang Xiao , Liu Muxiang , Sun Zejun , Huang Jia , Wu Guangming , Zu Guoqing
Published: January 2024

Highly stretchable porous materials are promising for flexible electronics but their fabrication is a great challenge. Herein, several kinds of highly stretchable conductive porous elastomers with low or negative Poisson’s ratios are achieved by uniaxial, biaxial, and triaxial hot-pressing strategies. The reduced graphene oxide/polymer nanocomposite elastomers with folded porous structures obtained by uniaxial hot pressing exhibit high stretchability up to 1200% strain. Furthermore, the meta-elastomers with reentrant porous structures combining high biaxial (or triaxial) stretchability and negative Poisson’s ratios are achieved by biaxial (or triaxial) hot pressing. The resulting elastomer-based wearable strain sensors exhibit an ultrawide response range (0-1200%). The materials can be applied for smart thermal management and electromagnetic interference shielding, which are achieved by regulating the porous microstructures via stretching. This work provides a versatile strategy to highly stretchable and negative-Poisson-ratio porous materials with promising features for various applications such as flexible electronics, thermal management, electromagnetic shielding, and energy storage.
Neurocognitive correlates of semantic memory navigation in Parkinson’s disease
Authors: Toro-Hernández Felipe Diego , Migeot Joaquín , Marchant Nicolás , Olivares Daniela , Ferrante Franco , González-Gómez Raúl , González Campo Cecilia , Fittipaldi Sol , Rojas-Costa Gonzalo M. , Moguilner Sebastian , Slachevsky Andrea , Chaná Cuevas Pedro , Ibáñez Agustín , Chaigneau Sergio , García Adolfo M.
Published: January 2024

Cognitive studies on Parkinson’s disease (PD) reveal abnormal semantic processing. Most research, however, fails to indicate which conceptual properties are most affected and capture patients’ neurocognitive profiles. Here, we asked persons with PD, healthy controls, and individuals with behavioral variant frontotemporal dementia (bvFTD, as a disease control group) to read concepts (e.g., ‘sun’) and list their features (e.g.,hot). Responses were analyzed in terms of ten word properties (including concreteness, imageability, and semantic variability), used for group-level comparisons, subject-level classification, and brain-behavior correlations. PD (but not bvFTD) patients produced more concrete and imageable words than controls, both patterns being associated with overall cognitive status. PD and bvFTD patients showed reduced semantic variability, an anomaly which predicted semantic inhibition outcomes. Word-property patterns robustly classified PD (but not bvFTD) patients and correlated with disease-specific hypoconnectivity along the sensorimotor and salience networks. Fine-grained semantic assessments, then, can reveal distinct neurocognitive signatures of PD.
Bringing immunofocusing into focus
Authors: Musunuri Sriharshita , Weidenbacher Payton A. B. , Kim Peter S.
Published: January 2024

Immunofocusing is a strategy to create immunogens that redirect humoral immune responses towards a targeted epitope and away from non-desirable epitopes. Immunofocusing methods often aim to develop “universal” vaccines that provide broad protection against highly variant viruses such as influenza virus, human immunodeficiency virus (HIV-1), and most recently, severe acute respiratory syndrome coronavirus (SARS-CoV-2). We use existing examples to illustrate five main immunofocusing strategies—cross-strain boosting, mosaic display, protein dissection, epitope scaffolding, and epitope masking. We also discuss obstacles for immunofocusing like immune imprinting. A thorough understanding, advancement, and application of the methods we outline here will enable the design of high-resolution vaccines that protect against future viral outbreaks.
Chromosome-level genome assembly of humpback grouper using PacBio HiFi reads and Hi-C technologies
Authors: Liu Jinxiang , Sun Huibang , Tang Lei , Wang Yujue , Wang Zhigang , Mao Yunxiang , Huang Hai , Zhang Quanqi
Published: January 2024

The humpback grouper (Cromileptes altivelis), a medium-sized coral reef teleost, is a naturally rare species distributed in the tropical waters of the Indian and Pacific Oceans. It has high market value, but artificial reproduction and breeding remain limited and need to be improved. Here, we assembled the genome with 1.08 Gb, with a contig N50 of 43.78 Mb. A total of 96.59% of the assembly anchored to 24 pseudochromosomes using Hi-C technology. It contained 24,442 protein-coding sequences, of which 99.3% were functionally annotated. The completeness of the assembly was estimated to be 97.3% using BUSCO. The phylogenomic analysis suggested that humpback grouper should be classified into the genus Epinephelus rather than Cromileptes. The comparative genomic analysis revealed that the gene families related to circadian entrainment were significantly expanded. The high-quality reference genome provides useful genomic tools for exploiting the genomic resource of humpback grouper and supports the functional genomic study of this species in the future.
Genetic diversity, morphological traits, quality traits and antioxidants potentiality of Coccinia grandis germplasm under rainfed semi-arid region
Authors: Yadav Lalu Prasad , Gangadhara K. , Apparao V. V. , Yadav Vikas , Mishra D. S. , Singh A. K. , Rane Jagdish , Kaushik Prashant , Janani P. , Kumar Raj , Verma A. K. , Kumar Sanjay , Malhotra S. K. , Shekhawat Neelam
Published: January 2024

The present study was conducted to evaluate the genetic variability for morphological and qualitative traits of Coccinia for development of trait specific lines at ICAR-Central Horticultural Experiment Station (CIAH-RS), Panchmahals (Godhra), Gujarat during 2020–2022. In this study, we evaluated 26 gynoecious accessions to assess the genetic divergence through principal component and cluster analysis. The experiment was carried out in a randomized complete block design with three replications under rainfed semi-arid conditions. High values of PCV and GCV were observed for variables such as NFFP (25.13 and 22.20), PL (23.14 and 20.69), FD (24.01 and 21.46), AFW (22.98 and 20.13), NFPY (26.38 and 24.40), FYP (37.57 and 31.29), FY (35.55 and 33.20), AsC (28.65 and 27.73), Ac (24.32 and 21.06), TSS (37.23 and 35.94), DPPHL (20.71 and 20.38), FRAPL (21.08 and 20.92), TPF(20.81 and 20.45) respectively. High heritability coupled with high genetic advance as per cent of mean was observed for vine length (VL), internodal length (IL), number of female flowers per plant (NFFP), fruit length (FL), peduncle length (PL), fruit diameter (FD), average fruit weight (AFW), number of fruit per plant per year (NFPY), fruit yield per plant (FYP), fruit yield (FY), ascorbic acid (AsC), acidity (Ac), total soluble solids (TSS), total phenols in leaves TPL), total flavonoids in leaves TFL, CUPRAC in leaves (CUPRACL), DPPH in leaves (DPPHL), FRAP in leaves (FRAPL), Total phenols in fruits (TPF), Total flavonoids in fruits (TFF), CUPRAC in fruits (CUPRACF) and DPPH in fruits (DPPHF). The FYP exhibited a significant positive correlation with variables like VL (0.6833), IL (0.2991), NFFP (0.8107), FD (0.5245), AFW (0.6766), NFPY (0.7659), ASC (0.4611), TSS (0.5004) and TPF (0.4281). The estimates of genetic parameters revealed scope for further improvement of fruit yield by selection. Of the eight principal components, PC-I through PC-VIII had eigen values greater than 1 and it accounts 85.02% of the total variation for 26 gynoecious accessions of Ivy gourd. The eigen values of PC-I comprised 5.775% of total variation followed by PC-II (4.250%), PC-III (3.175%), PC-IV (2.588%), PC-V (1.828%), PC-VI (1.447%), PC-VII (1.179%) and PC-VIII (1.013%).The cluster VI and cluster I having highest mean values for most of traits under study. Thus, genotypes from the distinct cluster like cluster VI and I for should be used for selection of parents and varietal improvement for further breeding programme in ivy gourd.
Susceptibility to radiation adverse effects in veterans with Gulf War illness and healthy civilians
Authors: Golomb Beatrice Alexandra , Berg Brinton Keith , Han Jun Hee
Published: January 2024

We evaluated whether veterans with Gulf War illness (VGWI) report greater ionizing radiation adverse effects (RadAEs) than controls; whether radiation-sensitivity is tied to reported chemical-sensitivity; and whether environmental exposures are apparent risk factors for reported RadAEs (rRadAEs). 81 participants (41 VGWI, 40 controls) rated exposure to, and rRadAEs from, four radiation types. The relations of RadAE-propensity (defined as the ratio of rRadAEs to summed radiation exposures) to Gulf War illness (GWI) presence and severity, and to reported chemical-sensitivity were assessed. Ordinal logistic regression evaluated exposure prediction of RadAE-propensity in the full sample, in VGWI, and stratified by age and chemical-sensitivity. RadAE-propensity was increased in VGWI (vs. controls) and related to GWI severity (p < 0.01) and chemical-sensitivity (p < 0.01). Past carbon monoxide (CO) exposure emerged as a strong, robust predictor of RadAE-propensity on univariable and multivariable analyses (p < 0.001 on multivariable assessment, without and with adjustment for VGWI case status), retaining significance in age-stratified and chemical-sensitivity-stratified replication analyses. Thus, RadAE-propensity, a newly-described GWI-feature, relates to chemical-sensitivity, and is predicted by CO exposure—both features reported for nonionizing radiation sensitivity, consistent with shared mitochondrial/oxidative toxicity across radiation frequencies. Greater RadAE vulnerability fits an emerging picture of heightened drug/chemical susceptibility in VGWI.
Cranial form differences in goats by breed and domestic status
Authors: Balcarcel A. M. , Geiger M. , Sánchez-Villagra M. R.
Published: January 2024

Domestic goats (Capra hircus) are globally represented by over 300 breeds, making them a useful model for investigating patterns of morphological change related to domestication. However, they have been little studied, likely due to their poor representation in museum collections and the difficulty in obtaining truly wild goat (Capra aegagrus, the bezoar) samples. Similar studies on other species reveal that domestication correlates with craniofacial alterations in domestics, which are non-uniform and often species-specific. Here, we use three-dimensional geometric morphometric methods (3DGMM) to describe and quantify cranial shape variation in wild (n = 21) versus domestic (n = 54) goats. We find that mean cranial shapes differ significantly between wild and domestic goats as well as between certain breeds. The detected differences are lower in magnitude than those reported for other domestic groups, possibly explained by the fewer directions of artificial selection in goat breeding, and their low global genetic diversity compared to other livestock. We also find tooth-row length reduction in the domestics, suggestive of rostral shortening—a prediction of the “domestication syndrome” (DS). The goat model thus expands the array—and combinations of—morphological changes observed under domestication, notably detecting alterations to the calvarium form which could be related to the ~ 15% brain size reduction previously reported for domestic compared to wild goats. The global success of domestic goats is due more to their ability to survive in a variety of harsh environments than to systematized human management. Nonetheless, their domestication has resulted in a clear disruption from the wild cranial form, suggesting that even low-intensity selection can lead to significant morphological changes under domestication.
In-situ fabrication of Cr doped FeNi LDH on commercial stainless steel for oxygen evolution reaction
Authors: Lv Yanhong , Deng Xinrong , Ding Jingjing , Zhou Yang
Published: January 2024

Commercial stainless steel has attracted increasing interest due to their rich content in transition metal elements and corrosion resistance properties. In this work, we design a facile and rapid route to in-situ fabricate the Cr doped FeNi layered double hydroxides nanosheets (LDHs) on modified stainless steel (Cr–FeNi LDH @ ESS) under ambient condition.The ultra small scaled 2D structure only around 20 nm diameter and metal ions with multivalent oxidation state were observed on the in situ fabricated LDHs, which provides high active area and active sites and thus promote excellent oxygen evolution reaction (OER). The Cr–FeNi LDH @ESS electrocatalysts exhibit an over potential of 280 mV at 10 mA cm−2 and achieves a Tafel slope of 44 mV dec−1 for OER in the 1.0 M KOH aqueous solution. We anticipate that the operating strategy of our system may promote the development of commercial non-precious productions as the efficient electrocatalysts for energy storage and conversion.
Bovine Herpes Virus Type 1 (BoHV-1) seroprevalence, risk factor and Bovine Viral Diarrhoea (BVD) co-infection analysis from Ireland
Authors: Barrett D. , Lane E. , Lozano J. M. , O’Keeffe K. , Byrne A. W.
Published: January 2024

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged < 30 months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1130/5273; 95%CI: 20.32–22.53%). Univariable analysis suggested that BoHV-1 seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland declined in 2020 relative to 2018 (from 23.32 to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.
A method for phenotypic evaluation of grapevine resistance in relation to phenological development
Authors: Schumacher Stefan , Mertes Caroline , Kaltenbach Thomas , Bleyer Gottfried , Fuchs René
Published: January 2024

Fungus-resistant grapevine cultivars, so called PIWIs, are characterized by increased resistance to powdery mildew and downy mildew. However, in order to maintain the durability of resistance in these new grape cultivars, targeted fungicide treatments are recommended. For ideal schedule of these treatments, it is necessary to recognize the most sensitive organs of the grape. This study introduces a method for phenotypic evaluation of Plasmopara viticola resistance in grape clusters under controlled and standardized conditions during phenological development over the entire season. The approach was validated with the traditional cultivar Pinot Noir and the PIWIs Cabernet Cortis (Rpv3.3, Rpv10), Solaris (Rpv3.3, Rpv10) and Souvignier Gris (Rpv3.2). All cultivars were susceptible during the early stages of development up to flowering, and resistance levels increased as phenological development progressed. Cabernet Cortis and Solaris clusters were susceptible until fruit development (BBCH 71–73) when they became almost completely resistant. No differences between Souvignier Gris and Pinot Noir were detected until berries were pea-sized (BBCH 75) when P. viticola resistance of Souvignier Gris clusters increased significantly. Ontogenetic resistance in Pinot Noir was detected at berry touch (BBCH 77–79) and clusters of this cultivar were almost completely resistant at the beginning of ripening (BBCH 81–83). These results indicate that the approach presented is suitable for determining the resistance of grape cultivars at different stages of development. Consequently, in the future, fungicide applications can be adjusted more precisely to the resistance level of a grape cultivar during the growing season.
Enhanced matrix inference with Seq2seq models via diagonal sorting
Authors: Peng Wei , Wang Yisong , Wu Maonian
Published: January 2024

The effectiveness of sequence-to-sequence (seq2seq) models in natural language processing has been well-established over time, and recent studies have extended their utility by treating mathematical computing tasks as instances of machine translation and achieving remarkable results. However, our exploratory experiments have revealed that the seq2seq model, when employing a generic sorting strategy, is incapable of inferring on matrices of unseen rank, resulting in suboptimal performance. This paper aims to address this limitation by focusing on the matrix-to-sequence process and proposing a novel diagonal-based sorting. The method constructs a stable ordering structure of elements for the shared leading principal submatrix sections in matrices with varying ranks. We conduct experiments involving maximal independent sets and Sudoku laws, comparing seq2seq models utilizing different sorting methods. Our findings demonstrate the advantages of the proposed diagonal-based sorting in inference, particularly when dealing with matrices of unseen ranks. By introducing and advocating for this method, we enhance the suitability of seq2seq models for investigating the laws of matrix inclusion and exploring their potential in solving matrix-related tasks.
Statistical classification of treatment responses in mouse clinical trials for stratified medicine in oncology drug discovery
Authors: Savel Hélène , Meyer-Losic Florence , Proust-Lima Cécile , Richert Laura
Published: January 2024

Translational oncology research strives to explore a new aspect: identifying subgroups that exhibit treatment response even during pre-clinical phases. In this study, we focus on PDX models and their implementation in mouse clinical trials (MCT). Our primary objective was to identify subgroups with different treatment responses using Latent Class Mixed Model (LCMM).We used a public dataset and focused on one treatment, encorafenib, and two indications, melanoma and colorectal cancer, for which efficacy depends on a specific mutation BRAF V600E. One LCMM per indication was implemented to classify treatment responses at the PDX level, analyzing the growth kinetics of treated tumors and matched controls within the PDX models. A simulation study was carried out to explore the performance of LCMM in this context. For both applications, LCMM identified classes for which the higher the proportion of mutated BRAF V600E PDX models the greater the treatment effect, which is aligned with encorafenib use recommendations. The simulation study showed that LCMM could identify classes with large differences in treatment effects. LCMM is a suitable tool for MCT to explore treatment response subgroups of PDX. Once these subgroups are defined, characterization of their phenotypes/genotypes could be performed to explore treatment response predictors.
Three-dimensional fine crust-mantle structure imaging and structural characteristics of Bohai Sea
Authors: Ma Yong , Gao Lei , Dong Demiao
Published: January 2024

This study used the consistency-constrained double-difference tomography method to invert 3D fine structure models of Vp, Vs, Vp/Vs at depths above 60 km, and precise relocation parameters of earthquakes in the Bohai Sea. According to the results, the velocity structures of P-wave and S-wave in the Bohai Sea area were highly similar and demonstrated noticeable lateral non-uniformity. The crust beneath the Tanlu Fault displayed a clear stratification structure, with a continuous velocity transition in the middle of the crust. The intricate crustal structure beneath the Zhangpeng Fault displayed high-velocity bodies in the crust and low-velocity anomalous zones connected to the top of the mantle in the lower section of the crust. The structural pattern in the deep crust of the Bohai Sea controls the occurrence characteristics of the Zhangpeng Fault and the Tanlu Fault. The earthquakes in the Bohai Sea area were concentrated mainly in the southern part near the Zhangpeng Fault. There is a good correspondence between the relocated earthquakes and velocity structure. There are many significant differences in crustal structure between the north and south of the Bohai Strait, and there are obvious velocity anomalies in the middle and upper crust. The distribution shape of high Vp/Vs value indicates that mantle material migration has occurred at the bottom of the crust. This paper provided important reference for further research on the relationship between deep tectonic features and tectonic activity in the North China Craton.
Association of PFDeA exposure with hypertension (NHANES, 2013–2018)
Authors: Li Jie , Ye Suling , Zhao Zeyuan , Xue Zhao , Ren Shupeng , Guan Yue , Sun Chuang , Yao Qiying , Chen Liang
Published: January 2024

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) is a series of artificial compounds which is associated with human health. However, there are few studies on the relationship between PFASs and hypertension. In this study, we examined the association between different kinds of PFASs and hypertension. Multivariable logistic regression and subgroup analysis were adopted to assess the associations between PFASs and hypertension. Spline smoothing plots and linear regression were used to assess the relationship between PFASs and blood pressure. We found a positive association between serum PFDeA concentrations and the prevalence of hypertension after fully adjusting confounders (OR = 1.2, P = 0.01), but other types of PFASs showed no positive results. Subgroup analysis stratified by ethnicity showed there was a stronger relationship among non-Hispanics than Hispanics. Serum PFDeA concentrations were positively associated with systolic pressure (β = 0.7, P< 0.01) and diastolic blood pressure (β = 0.8, P< 0.01) among non-Hispanics who did not take antihypertensive drugs. This study showed that PFDeA exposure was associated with hypertension in Americans who identify as non-Hispanic. There was a positive association between PFDeA and blood pressure in non-Hispanic Americans who did not take antihypertensive drugs.
Microfluidically frequency-reconfigurable compact self-quadruplexing tunable antenna with high isolation based on substrate integrated waveguide
Authors: Barik Rusan Kumar , Koziel Slawomir
Published: January 2024

This communication presents a novel concept of microfluidically frequency-reconfigurable self-quadruplexing tunable antenna for quad-band applications. At the initial design stage, a substrate-integrated square cavity is divided into four unequal quarter-mode cavity resonators by inserting an X-shaped slot on the top surface of the cavity. Applying four 50-Ω microstrip feed-lines to these four quarter-mode cavity resonators enables quad-band operation with self-quadruplexing capabilities. The feed lines are organized orthogonally and off-center, which leads to port isolation greater than 32.3 dB. An equivalent network model is developed to validate the proposed antenna. To realize frequency reconfigurability, two microfluidic channels corresponding to each port are created by engraving the bottom surface of the cavity. To create a reconfigurable self-quadruplexing antenna, the channels are either filled with air or dielectric liquids of higher permittivity, so that the design offers independent tunability of the operating frequencies. As a proof of concept, the prototype of a self-quadruplexing tunable antenna is fabricated and validated through measurements. The antenna prototype occupies a footprint area of 0.37λg2. The design exhibits frequency tuning ranges of 350 MHz (8.3%), 500 MHz (10.3%), 610 MHz (11.2%), and 845 MHz (14.1%) for the first, second, third, and fourth operating bands, respectively. In all bands and across the entire tuning range, the realized gains of the designed antenna exceed 4.05 dBi. The electromagnetic modeling responses agree extremely well with the measured characteristics.
Range of protein induced by vitamin K absence or antagonist-II levels in neonates at birth
Authors: Sameshima Tomohiro , Ashina Mariko , Fukuda Takuya , Kido Takumi , Abe Shinya , Watanabe Yuko , Sato Itsuko , Yano Yoshihiko , Tanimura Kenji , Nagase Hiroaki , Nozu Kandai , Fujioka Kazumichi
Published: January 2024

Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is avitamin K (VK) deficiency indicator in neonates. However, PIVKA-II detection frequency in neonatal blood at birth and the correlation between PIVKA-II and gestational age are unclear. We retrospectively analyzed infants admitted to our institution between June 1, 2018, and March 31, 2022, whose clinical and PIVKA-II data were available, and classified them into preterm and term infant groups. Overall incidence of PIVKA-II-positive cases (≥ 50 mAU/mL) was 42.8%, including 0.6% apparent VK deficiency (≥ 5000 mAU/mL), 3.1% experimental VK deficiency (1000–4999 mAU/mL), and 10.7% latent VK deficiency (200–999 mAU/mL) cases. Incidence of PIVKA-II-positive cases was significantly higher in the term group than in the preterm group (49.4% vs. 29.7%, p < 0.001). Gestational age correlated with PIVKA-II levels (r2 = 0.117, p < 0.0001). Median serum PIVKA-II levels and incidence of PIVKA-II-positive cases (≥ 50 mAU/mL, 16.4%) were lower at 5 days after birth than at birth, possibly reflecting the postnatal VK prophylaxis impact. Only one infant was diagnosed with VK deficiency bleeding (PIVKA-II levels, at birth: 10,567 mAU/mL; at day 5: 2418 mAU/mL). Thus, serum PIVKA-II levels after birth weakly correlated with gestational age. VK deficiency was more common in term infants than in preterm infants.
A Pregnancy and Childhood Epigenetics Consortium (PACE) meta-analysis highlights potential relationships between birth order and neonatal blood DNA methylation
Authors: Li Shaobo , Spitz Natalia , Ghantous Akram , Abrishamcar Sarina , Reimann Brigitte , Marques Irene , Silver Matt J. , Aguilar-Lacasaña Sofía , Kitaba Negusse , Rezwan Faisal I. , Röder Stefan , Sirignano Lea , Tuhkanen Johanna , Mancano Giulia , Sharp Gemma C. , Metayer Catherine , Morimoto Libby , Stein Dan J. , Zar Heather J. , Alfano Rossella , Nawrot Tim , Wang Congrong , Kajantie Eero , Keikkala Elina , Mustaniemi Sanna , Ronkainen Justiina , Sebert Sylvain , Silva Wnurinham , Vääräsmäki Marja , Jaddoe Vincent W. V. , Bernstein Robin M. , Prentice Andrew M. , Cosin-Tomas Marta , Dwyer Terence , Håberg Siri Eldevik , Herceg Zdenko , Magnus Maria C. , Munthe-Kaas Monica Cheng , Page Christian M. , Völker Maja , Gilles Maria , Send Tabea , Witt Stephanie , Zillich Lea , Gagliardi Luigi , Richiardi Lorenzo , Czamara Darina , Räikkönen Katri , Chatzi Lida , Vafeiadi Marina , Arshad S. Hasan , Ewart Susan , Plusquin Michelle , Felix Janine F. , Moore Sophie E. , Vrijheid Martine , Holloway John W. , Karmaus Wilfried , Herberth Gunda , Zenclussen Ana , Streit Fabian , Lahti Jari , Hüls Anke , Hoang Thanh T. , London Stephanie J. , Wiemels Joseph L.
Published: January 2024

Higher birth order is associated with altered risk of many disease states. Changes in placentation and exposures to in utero growth factors with successive pregnancies may impact later life disease risk via persistent DNA methylation alterations. We investigated birth order with Illumina DNA methylation array data in each of 16 birth cohorts (8164 newborns) with European, African, and Latino ancestries from the Pregnancy and Childhood Epigenetics Consortium. Meta-analyzed data demonstrated systematic DNA methylation variation in 341 CpGs (FDR adjusted P < 0.05) and 1107 regions. Forty CpGs were located within known quantitative trait loci for gene expression traits in blood, and trait enrichment analysis suggested a strong association with immune-related, transcriptional control, and blood pressure regulation phenotypes. Decreasing fertility rates worldwide with the concomitant increased proportion of first-born children highlights a potential reflection of birth order-related epigenomic states on changing disease incidence trends.
Automatically discovering ordinary differential equations from data with sparse regression
Authors: Egan Kevin , Li Weizhen , Carvalho Rui
Published: January 2024

Discovering nonlinear differential equations that describe system dynamics from empirical data is a fundamental challenge in contemporary science. While current methods can identify such equations, they often require extensive manual hyperparameter tuning, limiting their applicability. Here, we propose a methodology to identify dynamical laws by integrating denoising techniques to smooth the signal, sparse regression to identify the relevant parameters, and bootstrap confidence intervals to quantify the uncertainty of the estimates. We evaluate our method on well-known ordinary differential equations with an ensemble of random initial conditions, time series of increasing length, and varying signal-to-noise ratios. Our algorithm consistently identifies three-dimensional systems, given moderately-sized time series and high levels of signal quality relative to background noise. By accurately discovering dynamical systems automatically, our methodology has the potential to impact the understanding of complex systems, especially in fields where data are abundant, but developing mathematical models demands considerable effort.
Autotaxin–lysolipid signaling suppresses a CCL11–eosinophil axis to promote pancreatic cancer progression
Authors: Bhattacharyya Sohinee , Oon Chet , Diaz Luis , Sandborg Holly , Stempinski Erin S. , Saoi Michelle , Morgan Terry K. , López Claudia S. , Cross Justin R. , Sherman Mara H.
Published: January 2024

Lipids and their modifying enzymes regulate diverse features of the tumor microenvironment and cancer progression. The secreted enzyme autotaxin (ATX) hydrolyzes extracellular lysophosphatidylcholine to generate the multifunctional lipid mediator lysophosphatidic acid (LPA) and supports the growth of several tumor types, including pancreatic ductal adenocarcinoma (PDAC). Here we show that ATX suppresses the accumulation of eosinophils in the PDAC microenvironment. Genetic or pharmacologic ATX inhibition increased the number of intratumor eosinophils, which promote tumor cell apoptosis locally and suppress tumor progression. Mechanistically, ATX suppresses eosinophil accumulation via an autocrine feedback loop, wherein ATX–LPA signaling negatively regulates the activity of the AP-1 transcription factor c-Jun, in turn suppressing the expression of the potent eosinophil chemoattractant CCL11 (eotaxin-1). Eosinophils were identified in human PDAC specimens, and rare individuals with high intratumor eosinophil abundance had the longest overall survival. Together with recent findings, this study reveals the context-dependent, immune-modulatory potential of ATX–LPA signaling in cancer.