bluuebunny/crossref_metadata_2025 huggingface dataset:
Tiller Number1 encodes an ankyrin repeat protein that controls tillering in bread wheat
Authors: Dong Chunhao , Zhang Lichao , Zhang Qiang , Yang Yuxin , Li Danping , Xie Zhencheng , Cui Guoqing , Chen Yaoyu , Wu Lifen , Li Zhan , Liu Guoxiang , Zhang Xueying , Liu Cuimei , Chu Jinfang , Zhao Guangyao , Xia Chuan , Jia Jizeng , Sun Jiaqiang , Kong Xiuying , Liu Xu
Published: February 2023

Wheat (Triticum aestivum L.) is a major staple food for more than one-third of the world’s population. Tiller number is an important agronomic trait in wheat, but only few related genes have been cloned. Here, we isolate a wheat mutant, tiller number1 (tn1), with much fewer tillers. We clone the TN1 gene via map-based cloning: TN1 encodes an ankyrin repeat protein with a transmembrane domain (ANK-TM). We show that a single amino acid substitution in the third conserved ankyrin repeat domain causes the decreased tiller number of tn1 mutant plants. Resequencing and haplotype analysis indicate that TN1 is conserved in wheat landraces and modern cultivars. Further, we reveal that the expression level of the abscisic acid (ABA) biosynthetic gene TaNCED3 and ABA content are significantly increased in the shoot base and tiller bud of the tn1 mutants; TN1 but not tn1 could inhibit the binding of TaPYL to TaPP2C via direct interaction with TaPYL. Taken together, we clone a key wheat tiller number regulatory gene TN1, which promotes tiller bud outgrowth probably through inhibiting ABA biosynthesis and signaling.
A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells
Authors: Turkalo Timothy K. , Maffia Antonio , Schabort Johannes J. , Regalado Samuel G. , Bhakta Mital , Blanchette Marco , Spierings Diana C. J. , Lansdorp Peter M. , Hockemeyer Dirk
Published: February 2023

Alternative Lengthening of Telomeres (ALT) is an aberrant DNA recombination pathway which grants replicative immortality to approximately 10% of all cancers. Despite this high prevalence of ALT in cancer, the mechanism and genetics by which cells activate this pathway remain incompletely understood. A major challenge in dissecting the events that initiate ALT is the extremely low frequency of ALT induction in human cell systems. Guided by the genetic lesions that have been associated with ALT from cancer sequencing studies, we genetically engineered primary human pluripotent stem cells to deterministically induce ALT upon differentiation. Using this genetically defined system, we demonstrate that disruption of the p53 and Rb pathways in combination with ATRX loss-of-function is sufficient to induce all hallmarks of ALT and results in functional immortalization in a cell type-specific manner. We further demonstrate that ALT can be induced in the presence of telomerase, is neither dependent on telomere shortening nor crisis, but is rather driven by continuous telomere instability triggered by the induction of differentiation in ATRX-deficient stem cells.
Tunable superconductivity and its origin at KTaO3 interfaces
Authors: Liu Changjiang , Zhou Xianjing , Hong Deshun , Fisher Brandon , Zheng Hong , Pearson John , Jiang Jidong Samuel , Jin Dafei , Norman Michael R. , Bhattacharya Anand
Published: February 2023

What causes Cooper pairs to form in unconventional superconductors is often elusive because experimental signatures that connect to a specific pairing mechanism are rare. Here, we observe distinct dependences of the superconducting transition temperature Tc on carrier density n2D for electron gases formed at KTaO3 (111), (001) and (110) interfaces. For the (111) interface, a remarkable linear dependence of Tc on n2D is observed over a range of nearly one order of magnitude. Further, our study of the dependence of superconductivity on gate electric fields reveals the role of the interface in mediating superconductivity. We find that the extreme sensitivity of superconductivity to crystallographic orientation can be explained by pairing via inter-orbital interactions induced by an inversion-breaking transverse optical phonon and quantum confinement. This mechanism is also consistent with the dependence of Tc on n2D. Our study may shed light on the pairing mechanism in other superconducting quantum paraelectrics.
Engraftment of allogeneic iPS cell-derived cartilage organoid in a primate model of articular cartilage defect
Authors: Abe Kengo , Yamashita Akihiro , Morioka Miho , Horike Nanao , Takei Yoshiaki , Koyamatsu Saeko , Okita Keisuke , Matsuda Shuichi , Tsumaki Noriyuki
Published: February 2023

Induced pluripotent stem cells (iPSCs) are a promising resource for allogeneic cartilage transplantation to treat articular cartilage defects that do not heal spontaneously and often progress to debilitating conditions, such as osteoarthritis. However, to the best of our knowledge, allogeneic cartilage transplantation into primate models has never been assessed. Here, we show that allogeneic iPSC-derived cartilage organoids survive and integrate as well as are remodeled as articular cartilage in a primate model of chondral defects in the knee joints. Histological analysis revealed that allogeneic iPSC-derived cartilage organoids in chondral defects elicited no immune reaction and directly contributed to tissue repair for at least four months. iPSC-derived cartilage organoids integrated with the host native articular cartilage and prevented degeneration of the surrounding cartilage. Single-cell RNA-sequence analysis indicated that iPSC-derived cartilage organoids differentiated after transplantation, acquiring expression of PRG4 crucial for joint lubrication. Pathway analysis suggested the involvement of SIK3 inactivation. Our study outcomes suggest that allogeneic transplantation of iPSC-derived cartilage organoids may be clinically applicable for the treatment of patients with chondral defects of the articular cartilage; however further assessment of functional recovery long term after load bearing injuries is required.
Four-dimensional trapped ion mobility spectrometry lipidomics for high throughput clinical profiling of human blood samples
Authors: Lerner Raissa , Baker Dhanwin , Schwitter Claudia , Neuhaus Sarah , Hauptmann Tony , Post Julia M. , Kramer Stefan , Bindila Laura
Published: February 2023

Lipidomics encompassing automated lipid extraction, a four-dimensional (4D) feature selection strategy for confident lipid annotation as well as reproducible and cross-validated quantification can expedite clinical profiling. Here, we determine 4D descriptors (mass to charge, retention time, collision cross section, and fragmentation spectra) of 200 lipid standards and 493 lipids from reference plasma via trapped ion mobility mass spectrometry to enable the implementation of stringent criteria for lipid annotation. We use 4D lipidomics to confidently annotate 370 lipids in reference plasma samples and 364 lipids in serum samples, and reproducibly quantify 359 lipids using level-3 internal standards. We show the utility of our 4D lipidomics workflow for high-throughput applications by reliable profiling of intra-individual lipidome phenotypes in plasma, serum, whole blood, venous and finger-prick dried blood spots.
Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis
Authors: Grotzinger Andrew D. , Mallard Travis T. , Liu Zhaowen , Seidlitz Jakob , Ge Tian , Smoller Jordan W.
Published: February 2023

Recent work in imaging genetics suggests high levels of genetic overlap within cortical regions for cortical thickness (CT) and surface area (SA). We model this multivariate system of genetic relationships by applying Genomic Structural Equation Modeling (Genomic SEM) and parsimoniously define five genomic brain factors underlying both CT and SA along with a general factor capturing genetic overlap across all brain regions. We validate these factors by demonstrating the generalizability of the model to a semi-independent sample and show that the factors align with biologically and functionally relevant parcellations of the cortex. We apply Stratified Genomic SEM to identify specific categories of genes (e.g., neuronal cell types) that are disproportionately associated with pleiotropy across specific subclusters of brain regions, as indexed by the genomic factors. Finally, we examine genetic associations with psychiatric and cognitive correlates, finding that broad aspects of cognitive function are associated with a general factor for SA and that psychiatric associations are null. These analyses provide key insights into the multivariate genomic architecture of two critical features of the cerebral cortex.
Fluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats
Authors: Han Haobo , Xing Jiakai , Chen Wenqi , Jia Jiaxin , Li Quanshun
Published: February 2023

In rheumatoid arthritis (RA), insufficient apoptosis of macrophages and excessive generation of pro-inflammatory cytokines are intimately connected, accelerating the development of disease. Here, a fluorinated polyamidoamine dendrimer (FP) is used to deliver miR-23b to reduce inflammation by triggering the apoptosis of as well as inhibiting the inflammatory response in macrophages. Following the intravenous injection of FP/miR-23b nanoparticles in experimental RA models, the nanoparticles show therapeutic efficacy with inhibition of inflammatory response, reduced bone and cartilage erosion, suppression of synoviocyte infiltration and the recovery of mobility. Moreover, the nanoparticles accumulate in the inflamed joint and are non-specifically captured by synoviocytes, leading to the restoration of miR-23b expression in the synovium. The miR-23b nanoparticles target Tab2, Tab3 and Ikka to regulate the activation of NF-κB pathway in the hyperplastic synovium, thereby promoting anti-inflammatory and anti-proliferative responses. Additionally, the intravenous administration of FP/miR-23b nanoparticles do not induce obvious systemic toxicity. Overall, our work demonstrates that the combination of apoptosis induction and inflammatory inhibition could be a promising approach in the treatment of RA and possibly other autoimmune diseases.
Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport
Authors: Bojarskaite Laura , Vallet Alexandra , Bjørnstad Daniel M. , Gullestad Binder Kristin M. , Cunen Céline , Heuser Kjell , Kuchta Miroslav , Mardal Kent-Andre , Enger Rune
Published: February 2023

Perivascular spaces are important highways for fluid and solute transport in the brain enabling efficient waste clearance during sleep. However, the underlying mechanisms augmenting perivascular flow in sleep are unknown. Using two-photon imaging of naturally sleeping male mice we demonstrate sleep cycle-dependent vascular dynamics of pial arteries and penetrating arterioles: slow, large-amplitude oscillations in NREM sleep, a vasodilation in REM sleep, and a vasoconstriction upon awakening at the end of a sleep cycle and microarousals in NREM and intermediate sleep. These vascular dynamics are mirrored by changes in the size of the perivascular spaces of the penetrating arterioles: slow fluctuations in NREM sleep, reduction in REM sleep and an enlargement upon awakening after REM sleep and during microarousals in NREM and intermediate sleep. By biomechanical modeling we demonstrate that these sleep cycle-dependent perivascular dynamics likely enhance fluid flow and solute transport in perivascular spaces to levels comparable to cardiac pulsation-driven oscillations.
Magnetically boosted 1D photoactive microswarm for COVID-19 face mask disruption
Authors: Kim Jeonghyo , Mayorga-Martinez Carmen C. , Pumera Martin
Published: February 2023

The recent COVID-19 pandemic has resulted in the massive discard of pandemic-related plastic wastes, causing serious ecological harm and a high societal burden. Most single-use face masks are made of synthetic plastics, thus their careless disposal poses a direct threat to wildlife as well as potential ecotoxicological effects in the form of microplastics. Here, we introduce a 1D magnetic photoactive microswarm capable of actively navigating, adhering to, and accelerating the degradation of the polypropylene microfiber of COVID-19 face masks. 1D microrobots comprise an anisotropic magnetic core (Fe3O4) and photocatalytic shell (Bi2O3/Ag), which enable wireless magnetic maneuvering and visible-light photocatalysis. The actuation of a programmed rotating magnetic field triggers a fish schooling-like 1D microswarm that allows active interfacial interactions with the microfiber network. The follow-up light illumination accelerates the disruption of the polypropylene microfiber through the photo-oxidative process as corroborated by morphological, compositional, and structural analyses. The active magnetic photocatalyst microswarm suggests an intriguing microrobotic solution to treat various plastic wastes and other environmental pollutants.
Tight genetic linkage of genes causing hybrid necrosis and pollinator isolation between young species
Authors: Li Chaobin , Binaghi Marta , Pichon Vivien , Cannarozzi Gina , Brandão de Freitas Loreta , Hanemian Mathieu , Kuhlemeier Cris
Published: February 2023

The mechanisms of reproductive isolation that cause phenotypic diversification and eventually speciation are a major topic of evolutionary research. Hybrid necrosis is a post-zygotic isolation mechanism in which cell death develops in the absence of pathogens. It is often due to the incompatibility between proteins from two parents. Here we describe a unique case of hybrid necrosis due to an incompatibility between loci on chromosomes 2 and 7 between two pollinator-isolated Petunia species. Typical immune responses as well as endoplasmic reticulum stress responses are induced in the necrotic line. The locus on chromosome 2 encodes ChiA1, a bifunctional GH18 chitinase/lysozyme. The enzymatic activity of ChiA1 is dispensable for the development of necrosis. We propose that the extremely high expression of ChiA1 involves a positive feedback loop between the loci on chromosomes 2 and 7. ChiA1 is tightly linked to major genes involved in the adaptation to different pollinators, a form of pre-zygotic isolation. This linkage of pre- and post-zygotic barriers strengthens reproductive isolation and probably contributes to rapid diversification and speciation.
Dynamic crystallography reveals spontaneous anisotropy in cubic GeTe
Authors: Kimber Simon A. J. , Zhang Jiayong , Liang Charles H. , Guzmán-Verri Gian G. , Littlewood Peter B. , Cheng Yongqiang , Abernathy Douglas L. , Hudspeth Jessica M. , Luo Zhong-Zhen , Kanatzidis Mercouri G. , Chatterji Tapan , Ramirez-Cuesta Anibal J. , Billinge Simon J. L.
Published: February 2023

Cubic energy materials such as thermoelectrics or hybrid perovskite materials are often understood to be highly disordered1,2. In GeTe and related IV–VI compounds, this is thought to provide the low thermal conductivities needed for thermoelectric applications1. Since conventional crystallography cannot distinguish between static disorder and atomic motions, we develop the energy-resolved variable-shutter pair distribution function technique. This collects structural snapshots with varying exposure times, on timescales relevant for atomic motions. In disagreement with previous interpretations3–5, we find the time-averaged structure of GeTe to be crystalline at all temperatures, but with anisotropic anharmonic dynamics at higher temperatures that resemble static disorder at fast shutter speeds, with correlated ferroelectric fluctuations along the <100>c direction. We show that this anisotropy naturally emerges from a Ginzburg–Landau model that couples polarization fluctuations through long-range elastic interactions6. By accessing time-dependent atomic correlations in energy materials, we resolve the long-standing disagreement between local and average structure probes1,7–9 and show that spontaneous anisotropy is ubiquitous in cubic IV–VI materials.
Unidirectional scattering with spatial homogeneity using correlated photonic time disorder
Authors: Kim Jungmin , Lee Dayeong , Yu Sunkyu , Park Namkyoo
Published: February 2023

Recently, there has been increasing interest in the temporal degree of freedom in photonics due to its analogy with spatial axes, causality and open-system characteristics. In particular, the temporal analogues of photonic crystals have allowed the design of momentum gaps and their extension to topological and non-Hermitian photonics. Although recent studies have also revealed the effect of broken discrete time-translational symmetry in view of the temporal analogy of spatial Anderson localization, the broad intermediate regime between time order and time uncorrelated disorder has not been examined. Here we theoretically investigate the inverse design of photonic time disorder to achieve optical functionalities in spatially homogeneous platforms. By developing the structure factor and order metric using causal Green’s functions for disorder in the time domain, we propose an engineered time scatterer, which provides unidirectional scattering with controlled scattering amplitudes. We also show that the order-to-disorder transition in the time domain allows the manipulation of scattering bandwidths, which makes resonance-free temporal colour filtering possible. Our work could advance optical functionalities without spatial patterning.
In-depth virological and immunological characterization of HIV-1 cure after CCR5Δ32/Δ32 allogeneic hematopoietic stem cell transplantation
Authors: Jensen Björn-Erik Ole , Knops Elena , Cords Leon , Lübke Nadine , Salgado Maria , Busman-Sahay Kathleen , Estes Jacob D. , Huyveneers Laura E. P. , Perdomo-Celis Federico , Wittner Melanie , Gálvez Cristina , Mummert Christiane , Passaes Caroline , Eberhard Johanna M. , Münk Carsten , Hauber Ilona , Hauber Joachim , Heger Eva , De Clercq Jozefien , Vandekerckhove Linos , Bergmann Silke , Dunay Gábor A. , Klein Florian , Häussinger Dieter , Fischer Johannes C. , Nachtkamp Kathrin , Timm Joerg , Kaiser Rolf , Harrer Thomas , Luedde Tom , Nijhuis Monique , Sáez-Cirión Asier , Schulze zur Wiesch Julian , Wensing Annemarie M. J. , Martinez-Picado Javier , Kobbe Guido
Published: February 2023

Despite scientific evidence originating from two patients published to date that CCR5Δ32/Δ32 hematopoietic stem cell transplantation (HSCT) can cure human immunodeficiency virus type 1 (HIV-1), the knowledge of immunological and virological correlates of cure is limited. Here we characterize a case of long-term HIV-1 remission of a 53-year-old male who was carefully monitored for more than 9 years after allogeneic CCR5Δ32/Δ32 HSCT performed for acute myeloid leukemia. Despite sporadic traces of HIV-1 DNA detected by droplet digital PCR and in situ hybridization assays in peripheral T cell subsets and tissue-derived samples, repeated ex vivo quantitative and in vivo outgrowth assays in humanized mice did not reveal replication-competent virus. Low levels of immune activation and waning HIV-1-specific humoral and cellular immune responses indicated a lack of ongoing antigen production. Four years after analytical treatment interruption, the absence of a viral rebound and the lack of immunological correlates of HIV-1 antigen persistence are strong evidence for HIV-1 cure after CCR5Δ32/Δ32 HSCT.
A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans
Authors: Topalovic Uros , Barclay Sam , Ling Chenkai , Alzuhair Ahmed , Yu Wenhao , Hokhikyan Vahagn , Chandrakumar Hariprasad , Rozgic Dejan , Jiang Wenlong , Basir-Kazeruni Sina , Maoz Sabrina L. , Inman Cory S. , Stangl Matthias , Gill Jay , Bari Ausaf , Fallah Aria , Eliashiv Dawn , Pouratian Nader , Fried Itzhak , Suthana Nanthia , Markovic Dejan
Published: February 2023

Advances in technologies that can record and stimulate deep brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and restricted full-duplex bidirectional capability. In this study, we developed a wearable bidirectional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans and, consequently, bridge decades of neuroscientific findings across species.
NLRC3 is a potential prognostic biomarker that is correlated with immune cell infiltration in lung adenocarcinoma
Authors: Zhuo Yingchen , Li Xueqian , Feng Weiyi
Published: February 2023

The NLR family CARD domain containing 3 (NLRC3) gene has been reported to have a crucial effect on immunity, inflammation, and tumorigenesis. However, the clinical relevance of NLRC3 in lung adenocarcinoma (LUAD) remains unclear. This study analyzed both RNA sequencing data and corresponding clinical outcomes obtained from public databases to identify (i) NLRC3 as a tumor suppressor in LUAD and (ii) its predictive value for the likelihood of patient responsiveness to immunotherapy. The results showed that NLRC3 expression was reduced in LUAD and was lower in advanced-stage tumors. Additionally, reduced NLRC3 expression was correlated with worse patient prognosis. The protein level of NLRC3 was also observed to have prognostic significance. Moreover, downregulation of NLRC3 was found to suppress the chemotaxis and infiltration of antitumor lymphocyte subpopulations as well as natural killer cells. Mechanistic analysis indicated that NLRC3 may be involved in immune infiltration by regulating chemokines and their receptors in LUAD. Furthermore, NLRC3 functions as a molecular switch in macrophages, whereby it mediates the polarization of M1 macrophages. Patients with high NLRC3 expression were also found to exhibit a more promising response to immunotherapy. In conclusion, NLRC3 could serve as a potential prognostic biomarker for LUAD, help predict the immunotherapeutic response of patients, and guide personalized strategies for the treatment of LUAD.
Efficient plasma electron accelerator driven by linearly chirped multi-10-TW laser pulses
Authors: Grigoriadis A. , Andrianaki G. , Tazes I. , Dimitriou V. , Tatarakis M. , Benis E. P. , Papadogiannis N. A.
Published: February 2023

The temporal rearrangement of the spectral components of an ultrafast and intense laser pulse, i.e., the chirp of the pulse, offers significant possibilities for controlling its interaction with matter and plasma. In the propagation of ultra-strong laser pulses within the self-induced plasma, laser pulse chirp can play a major role in the dynamics of wakefield and plasma bubble formation, as well as in the electron injection and related electron acceleration. Here, we experimentally demonstrate the control of the generation efficiency of a relativistic electron beam, with respect to maximum electron energy and current, by accurately varying the chirp value of a multi-10-TW laser pulse. We explicitly show that positively chirped laser pulses, i.e., pulses with instantaneous frequency increasing with time, accelerate electrons in the order of 100 MeV much more efficiently in comparison to unchirped or negatively chirped pulses. Corresponding Particle-In-Cell simulations strongly support the experimental results, depicting a smoother plasma bubble density distribution and electron injection conditions that favor the maximum acceleration of the electron beam, when positively chirped laser pulses are used. Our results, aside from extending the validity of similar studies reported for PW laser pulses, provide the ground for understanding the subtle dynamics of an efficient plasma electron accelerator driven by chirped laser pulses.
Beneficial behavioral effects of chronic cerebral dopamine neurotrophic factor (CDNF) infusion in the N171-82Q transgenic model of Huntington’s disease
Authors: Stepanova P. , Kumar D. , Cavonius K. , Korpikoski J. , Sirjala J. , Lindholm D. , Voutilainen M. H.
Published: February 2023

Huntington’s disease (HD) is a progressive inherited neurological disease characterized by the degeneration of basal ganglia and the accumulation of mutant huntingtin (mHtt) aggregates in specific brain areas. Currently, there is no treatment for halting the progression of HD. Cerebral dopamine neurotrophic factor (CDNF) is a novel endoplasmic reticulum located protein with neurotrophic factor properties that protects and restores dopamine neurons in rodent and non-human primate models of Parkinson’s disease. Our recent study showed that CDNF improves motor coordination and protects NeuN positive cells in a Quinolinic acid toxin rat model of HD. Here we have investigated the effect of chronic intrastriatal CDNF administration on behavior and mHtt aggregates in the N171-82Q mouse model of HD. Data showed that CDNF did not significantly decrease the number of mHtt aggregates in most brain regions studied. Notably, CDNF significantly delayed the onset of symptoms and improved motor coordination in N171-82Q mice. Furthermore, CDNF increased BDNF mRNA level in hippocampus in vivo in the N171-82Q model and BDNF protein level in cultured striatal neurons. Collectively our results indicate that CDNF might be a potential drug candidate for the treatment of HD.
Long-term visual acuity outcome of pediatric uveitis patients presenting with severe visual impairment
Authors: Tungsattayathitthan Usanee , Rattanalert Narisa , Sittivarakul Wantanee
Published: February 2023

This study investigated the long-term visual acuity (VA) outcome in the eyes of children with uveitis and severe visual impairment (SVI; VA ≤ 20/200) at presentation. Fifty-one children [57 eyes; median age, 11 years; 51% female; median follow-up period, 36 months (interquartile range 14.9–64.4)] aged ≤ 16 years with uveitis managed at our tertiary center from January 2010 to July 2020 were reviewed. Uveitis mainly manifested as unilateral (74.5%), chronic course (82.4%), and panuveitis (43.1%). Ocular toxoplasmosis and toxocariasis were the most common diagnoses (9.8% each). At least one ocular complication at presentation was observed in 93% of the eyes. Overall, the mean logMAR VA improved from 1.8 at presentation to 1.2 at 5 years (P < 0.001). Common causes of poor vision included retinal detachment, atrophic bulbi, and optic atrophy. Predictive factors associated with less VA improvement over the follow-up period included preschool age of uveitis onset (P < 0.001), ocular symptoms duration before uveitis diagnosis ≥ 1 month (P = 0.004), and non-anterior uveitis (P = 0.047). The long-term VA outcome in uveitis-affected eyes with SVI at presentation was unfavorable. Younger age at uveitis onset, delayed presentation, and uveitis involving the posterior segment were associated with poorer VA outcome.
Frequency-specific brain network architecture in resting-state fMRI
Authors: Kajimura Shogo , Margulies Daniel , Smallwood Jonathan
Published: February 2023

The analysis of brain function in resting-state network (RSN) models, ascertained through the functional connectivity pattern of resting-state functional magnetic resonance imaging (rs-fMRI), is sufficiently powerful for studying large-scale functional integration of the brain. However, in RSN-based research, the network architecture has been regarded as the same through different frequency bands. Thus, here, we aimed to examined whether the network architecture changes with frequency. The blood oxygen level-dependent (BOLD) signal was decomposed into four frequency bands—ranging from 0.007 to 0.438 Hz—and the clustering algorithm was applied to each of them. The best clustering number was selected for each frequency band based on the overlap ratio with task activation maps. The results demonstrated that resting-state BOLD signals exhibited frequency-specific network architecture; that is, the networks finely subdivided in the lower frequency bands were integrated into fewer networks in higher frequency bands rather than reconfigured, and the default mode network and networks related to perception had sufficiently strong architecture to survive in an environment with a lower signal-to-noise ratio. These findings provide a novel framework to enable improved understanding of brain function through the multiband frequency analysis of ultra-slow rs-fMRI data.
Modulation of transcription factor dynamics allows versatile information transmission
Authors: Givré Alan , Colman-Lerner Alejandro , Ponce Dawson Silvina
Published: February 2023

Cells detect changes in their environment and generate responses, often involving changes in gene expression. In this paper we use information theory and a simple transcription model to analyze whether the resulting gene expression serves to identify extracellular stimuli and assess their intensity when they are encoded in the amplitude, duration or frequency of pulses of a transcription factor’s nuclear concentration (or activation state). We find, for all cases, that about three ranges of input strengths can be distinguished and that maximum information transmission occurs for fast and high activation threshold promoters. The three input modulation modes differ in the sensitivity to changes in the promoters parameters. Frequency modulation is the most sensitive and duration modulation, the least. This is key for signal identification: there are promoter parameters that yield a relatively high information transmission for duration or amplitude modulation and a much smaller value for frequency modulation. The reverse situation cannot be found with a single promoter transcription model. Thus, pulses of transcription factors can selectively activate the “frequency-tuned” promoter while prolonged nuclear accumulation would activate promoters of all three modes simultaneously. Frequency modulation is therefore highly selective and better suited than the other encoding modes for signal identification without requiring other mediators of the transduction process.
Multiple metrics assessment method for a reliable evaluation of corneal suturing skills
Authors: Dormegny Lea , Neumann Nicole , Lejay Anne , Sauer Arnaud , Gaucher David , Proust François , Chakfe Nabil , Bourcier Tristan
Published: February 2023

This study aimed to evaluate the efficiency of a multiple metrics assessment method to differentiate between surgeons of differing experience while performing a corneal suturing task. Volunteer ophthalmologists were assigned to three groups (senior [SG], junior [JG] and novice [NG]) according to their experience in corneal suturing. All participants performed three sessions of corneal wound closure by three stitches. Suturing and participant posture were recorded with cameras, and assessed by two blind assessors for stitch quality (using Zhang score) and ergonomics (using Rapid Upper Limb Assessment [RULA] score). Task duration was recorded. Objective analyses of stitches geometry and instrument position were carried out. We included 24 participants: 5 in the SG, 8 in the JG and 11 in the NG. Stitch quality was significantly better and time to perform the procedure significantly lower in more experienced groups (p < 0.001 and p = 0.002, respectively). SG participants better respected regular distance and parallelism between stitches compared to others (p = 0.01). Instrument position was similar between groups, although SG participants minimized their back-and-forth movements compared to NG participants. Ergonomics assessment was similar. Multiple metrics assessment efficiently determined how to differentiate between novices and experienced surgeons on corneal suturing skills, providing hints for future training studies.
Mindfulness training reduces slippery slope effects in moral decision-making and moral judgment
Authors: Du Wei , Yu Hongbo , Liu Xinghua , Zhou Xiaolin
Published: February 2023

Extant research has demonstrated the positive intrapersonal effects of mindfulness training. However, the cognitive mechanisms underlying the effects of mindfulness training on interpersonal processes are less clear. Here, we combined a randomized control mindfulness training design with computational approach to moral decision-making and moral judgments. Participants were randomly assigned to a Training group (N = 32) who received an 8-week mindfulness training or a Control group (N = 26) who waited for the same period of time. Before and after the 8-week period, participants completed a moral decision-making task, where they made tradeoff between money for themselves and unpleasant electric shocks to another person, and a moral judgment task, where they evaluated the blameworthiness of someone else’s choices in the same moral decision-making task. Trait mindfulness, as measured by the Five-Facet Mindfulness Questionnaire, significantly increased from the pre- to post-training session for the Training group, but not the Control group, demonstrating the effectiveness of the mindfulness manipulation. For the Control group, participants’ moral preference in both the decision-making task and the judgment task declined over time, exhibiting a “slippery slope” effect. In contrast, for the Training group, mindfulness training prevented moral preferences from declining. Computational modeling revealed that mindfulness training specifically reduced the increase in the weights of money over time in both the decision-making and judgment tasks, thereby curbing the “slippery slope” effects. These findings provide a cognitive account of the prosocial effects of mindfulness training on moral decision-making and moral judgments.
Exploring the impact of COVID-19 on newborn neurodevelopment: a pilot study
Authors: Ayesa-Arriola Rosa , Castro Quintas Águeda , Ortiz-García de la Foz Víctor , Miguel Corredera Margarita , San Martín González Nerea , Murillo-García Nancy , Neergaard Karl , Fañanás Saura Lourdes , de las Cuevas-Terán Isabel
Published: February 2023

The COVID-19 pandemic can seize the opportunity to explore the hypothesis of prenatal exposure to viral infections increases the risk for neurodevelopmental disorders. Advancing our knowledge in this regard would improve primary prevention of mental disorders in children. For this pilot study, six-week-old infants born to mothers exposed (n = 21) or unexposed (n = 21) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were assessed in Santander-Cantabria (Spain) using the Neonatal Behavioral Assessment Scale (NBAS). Groups comparisons were performed to explore the effects that infection and timing of exposure (in terms of the three trimesters of pregnancy). The infants’ competencies and performances on the NBAS were generally similar in the exposed and unexposed to SARS-CoV-2 groups. The most significant difference found was a less optimally response to cuddliness (item on the state regulation domain) particularly in infants born to mothers exposed in the third trimester of pregnancy, and in pull-to-sit (item on the motor system domain). Although our interpretations must be careful, these preliminary results highlight the possible association between prenatal SARS-CoV-2 exposure and poorer development in motor skills and infant interactive behavior. Further longitudinal studies are needed to explore these relationships and disentangle the biological mechanisms implicated.
Influence of surgical position and registration methods on clinical accuracy of navigation systems in brain tumor surgery
Authors: Furuse Motomasa , Ikeda Naokado , Kawabata Shinji , Park Yangtae , Takeuchi Koji , Fukumura Masao , Tsuji Yuichiro , Kimura Seigo , Kanemitsu Takuya , Yagi Ryokichi , Nonoguchi Naosuke , Kuroiwa Toshihiko , Wanibuchi Masahiko
Published: February 2023

The aim of this study was to evaluate the influence of skin distortion due to surgical positioning on the clinical accuracy of the navigation system. The distance errors were measured in four fiducial markers (anterior, posterior, right, and left of the head) after the registration of the navigation system. The distance errors were compared between the surface-merge registration (SMR) method using preoperative imaging and the automatic intraoperative registration (AIR) method using intraoperative imaging. The comparison of the distance errors were performed in various surgical positions. The AIR method had the significant accuracy in the lateral markers than the SMR method (lateral position, 3.8 mm vs. 8.95 mm; p < 0.0001; prone position, 4.5 mm vs. 13.9 mm; p = 0.0001; 5.2 mm vs. 11.5 mm; p = 0.0070). The smallest distance errors were obtained close to the surgical field in the AIR method (3.25–3.85 mm) and in the forehead in the SMR method (3.3–8.1 mm). The AIR method was accurate and recommended for all the surgical positions if intraoperative imaging was available. The SMR method was only recommended for the supine position, because skin distortion was frequently observed in the lateral region.
Enduring musician advantage among former musicians in prosodic pitch perception
Authors: Toh Xin Ru , Tan Shen Hui , Wong Galston , Lau Fun , Wong Francis C. K.
Published: February 2023

Musical training has been associated with various cognitive benefits, one of which is enhanced speech perception. However, most findings have been based on musicians taking part in ongoing music lessons and practice. This study thus sought to determine whether the musician advantage in pitch perception in the language domain extends to individuals who have ceased musical training and practice. To this end, adult active musicians (n = 22), former musicians (n = 27), and non-musicians (n = 47) were presented with sentences spoken in a native language, English, and a foreign language, French. The final words of the sentences were either prosodically congruous (spoken at normal pitch height), weakly incongruous (pitch was increased by 25%), or strongly incongruous (pitch was increased by 110%). Results of the pitch discrimination task revealed that although active musicians outperformed former musicians, former musicians outperformed non-musicians in the weakly incongruous condition. The findings suggest that the musician advantage in pitch perception in speech is retained to some extent even after musical training and practice is discontinued.
Voluntary running-induced activation of ventral hippocampal GABAergic interneurons contributes to exercise-induced hypoalgesia in neuropathic pain model mice
Authors: Minami Kohei , Kami Katsuya , Nishimura Yukihide , Kawanishi Makoto , Imashiro Kyosuke , Kami Takuma , Habata Shogo , Senba Emiko , Umemoto Yasunori , Tajima Fumihiro
Published: February 2023

The exact mechanism of exercise-induced hypoalgesia (EIH) in exercise therapy to improve chronic pain has not been fully clarified. Recent studies have suggested the importance of the ventral hippocampus (vHPC) in inducing chronic pain. We investigated the effects of voluntary running (VR) on FosB+cells and GABAergic interneurons (parvalbumin-positive [PV+] and somatostatin-positive [SOM+]) in the vHPC-CA1 in neuropathic pain (NPP) model mice. VR significantly improved thermal hyperalgesia in the NPP model. The number of the FosB+cells was significantly higher in partial sciatic nerve ligation-sedentary mice than in Sham and Naive mice, whereas VR significantly suppressed the FosB+cells in the vHPC-CA1. Furthermore, VR significantly increased the proportion of activated PV+and SOM+interneurons in the vHPC-CA1, and tracer experiments indicated that approximately 24% of neurons projecting from the vHPC-CA1 to the basolateral nucleus of amygdala were activated in NPP mice. These results indicate that feedforward suppression of the activated neurons via VR-induced activation of GABAergic interneurons in the vHPC-CA1 may be a mechanism to produce EIH effects, and suggested that disappearance of negative emotions such as fear and anxiety by VR may play a critical role in improving chronic pain.
Socioeconomic inequality in awareness, treatment and control of diabetes among adults in India: Evidence from National Family Health Survey of India (NFHS), 2019–2021
Authors: Maiti Suraj , Akhtar Shamrin , Upadhyay Ashish Kumar , Mohanty Sanjay K.
Published: February 2023

Diabetes is a growing epidemic and a major threat to most of the households in India. Yet, there is little evidence on the extent of awareness, treatment, and control (ATC) among adults in the country. In this study, we estimate the prevalence and ATC of diabetes among adults across various sociodemographic groups and states of India. We used data on 2,078,315 individuals aged 15 years and over from the recent fifth round, the most recent one, of the National Family Health Survey (NFHS-5), 2019–2021, that was carried out across all the states of India. Diabetic individuals were identified as those who had random blood glucose above 140 mg/dL or were taking diabetes medication or has doctor-diagnosed diabetes. Diabetic individuals who reported diagnosis were labelled as aware, those who reported taking medication for controlling blood glucose levels were labelled as treated and those whose blood glucose levels were < 140 mg/dL were labelled as controlled. The estimates of prevalence of diabetes, and ATC were age-sex adjusted and disaggregated by household wealth quintile, education, age, sex, urban–rural residence, caste, religion, marital status, household size, and state. Concentration index was used to quantify socioeconomic inequalities and multivariable logistic regression was used to estimate the adjusted differences in those outcomes. We estimated diabetes prevalence to be 16.1% (15.9–16.1%). Among those with diabetes, 27.5% (27.1–27.9%) were aware, 21.5% (21.1–21.7%) were taking treatment and 7% (6.8–7.1%) had their diabetes under control. Across the states of India, the adjusted rates of awareness varied from 14.4% (12.1–16.8%) to 54.4% (40.3–68.4%), of treatment from 9.3% (7.5–11.1%) to 41.2% (39.9–42.6%), and of control from 2.7% (1.6–3.7%) to 11.9% (9.7–14.0%). The age-sex adjusted rates were lower (p < 0.001) among the poorer and less educated individuals as well as among males, residents of rural areas, and those from the socially backward groups Among individuals with diabetes, the richest fifth were respectively 12.4 percentage points (pp) (11.3–13.4; p < 0.001), 10.5 pp (9.7–11.4; p < 0.001), and 2.3 pp (1.6–3.0; p < 0.001) more likely to be aware, getting treated, and having diabetes under control, than the poorest fifth. The concentration indices of ATC were 0.089 (0.085–0.092), 0.083 (0.079–0.085) and 0.017 (0.015–0.018) respectively. Overall, the ATC of diabetes is low in India. It is especially low the poorer and the less educated individuals. Targeted interventions and management can reduce the diabetes burden in India.
Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing
Authors: Alba-Pavón Piedad , Alaña Lide , Gutierrez-Jimeno Miriam , García-Obregón Susana , Imízcoz Teresa , Panizo Elena , González-Urdiales Paula , Echebarria-Barona Aizpea , Lopez Almaraz Ricardo , Zaldumbide Laura , Astigarraga Itziar , Patiño-García Ana , Villate Olatz
Published: February 2023

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans´ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.
Successful identification of the species of the semipetrified amber medicinal resin benzoin using molecular diagnostic technology
Authors: Feng Jian , He Qingqin , Xie Anzhen , Liu Yangyang
Published: February 2023

Benzoin is an incomplete lithified resin secreted from the trunk of the Styrax Linn. that is known as "semipetrified amber" and has been widely used in medicine due to its blood circulation-promoting and pain-relieving properties. However, the lack of an effective species identification method due to the numerous sources of benzoin resin and the difficulty of DNA extraction has led to the uncertainty of species of benzoin in the trade process. Here, we report the successful extraction of DNA from benzoin resin containing bark-like residues and the evaluation of commercially available benzoin species using molecular diagnostic techniques. By performing a BLAST alignment of ITS2 primary sequences and homology prediction analysis of ITS2 secondary structures, we found that commercially available benzoin species were derived from Styrax tonkinensis (Pierre) Craib ex Hart. and Styrax japonicus Sieb. et Zucc. of the genus Styrax Linn. In addition, some of the benzoin samples were mixed with plant tissues from other genera, accounting for 29.6%. Therefore, this study provides a new method to solve the problem of species identification of semipetrified amber benzoin using information from bark residues.
Estimability study on the age of toddlers’ gait development based on gait parameters
Authors: Tsuyuki Chisa , Hiraga Haruna , Sudo Motoki , Ueda Tomoya , Seo Kanako , Minatozaki Masayuki , Fukuda Yuko , Okuda Yasuyuki , Iwasaki Hiroyuki , Naito Hisashi , Lu Dajiang
Published: February 2023

In the first few years of toddlers’ locomotion, various gait parameters improve gradually and dynamically with gait development. Therefore, in this study, we hypothesized that the age of gait development, or the level of gait development with age as its indicator, can be estimated from several gait parameters related to gait development, and investigated its estimability. In total, 97 healthy toddlers aged about 1–3 years participated in the study. All five selected gait parameters showed a moderate or higher correlation with age, but the duration with a large change and the strength of the association with gait development varied for each gait parameter. Multiple regression analysis was performed using age as the objective variable and five selected gait parameters as explanatory variables, and an estimation model (R2 = 0.683, adjusted R2 = 0.665) was created. The estimation model was verified using a test dataset separate from the training dataset (R2 = 0.82, p < 0.001). It was suggested that the age of gait development could be estimated from gait alone. Gait analysis based on empirical observations may reduce the need for skilled observers and their potential variability.