bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconfigurable transmissive metasurface with a combination of scissor and rotation actuators for independently controlling beam scanning and polarization conversion
Authors: Lor Chhunheng , Phon Ratanak , Lim Sungjoon 
Published: March 2024

AbstractPolarization conversion and beam scanning metasurfaces are commonly used to reduce polarization mismatch and direct electromagnetic waves in a specific direction to improve the strength of a wireless signal. However, identifying suitable active and mechanically reconfigurable metasurfaces for polarization conversion and beam scanning is a considerable challenge, and the reported metasurfaces have narrow scanning ranges, are expensive, and cannot be independently controlled. In this paper, we propose a reconfigurable transmissive metasurface combined with a scissor and rotation actuator for independently controlling beam scanning and polarization conversion functions. The metasurface is constructed with rotatable unit cells (UCs) that can switch the polarization state between right-handed (RHCP) and left-handed circular polarization (LHCP) by flipping the UCs to reverse their phase variation. Moreover, independent beam scanning is achieved using the scissor actuator to linearly change the distance between the UCs. Numerical and experimental results confirm that the proposed metasurface can perform beam scanning in the range of 28° for both the positive and negative regions of a radiation pattern (RHCP and LHCP beams) at an operational frequency of 10.5 GHz.
DNA methylation of IFI44L as a potential blood biomarker for childhood-onset systemic lupus erythematosus
Authors: Wang Jingwei , Dang Xiqiang , Wu Xiaochuan , Xiang Zhongyuan , Li Yongzhen , Fu Yaqian , Shen Tian 
Published: March 2024

Abstract
Background
IFN-induced protein 44-like (IFI44L) promoter methylation has been demonstrated to serve as an effective blood diagnostic biomarker for adult-onset SLE. However, its utility as a diagnostic marker for childhood-onset SLE (cSLE) remains to be verified.

Methods
Initially, we conducted a differential analysis of gene methylation and mRNA expression patterns in cSLE whole blood samples obtained from the public GEO database to determine IFI44L gene expression and assess the methylation status at its CpG sites. Subsequently, we collected clinical whole blood samples from 49 cSLE patients and 12 healthy children, employing an HRM-qPCR-based IFI44L methylation detection technique to evaluate its diagnostic efficacy in pediatric clinical practice.

Results
A total of 26 hypomethylated, highly expressed genes in cSLE were identified by intersecting differentially expressed genes (DEGs) and differentially methylation genes (DMGs). GO enrichment analysis for these 26 genes indicated a robust association with type I IFN. Among the overlapping genes, IFI44L exhibited the most pronounced differential expression and methylation. In subsequent clinical validation experiments, IFI44L methylation was confirmed as an effective blood-based diagnostic biomarker for cSLE, achieving an AUC of 0.867, a sensitivity of 0.753, and a specificity of 1.000.

Conclusions
IFI44L methylation is a promising blood biomarker for cSLE.

Impact

IFI44L promoter methylation was reported to serve as a highly sensitive and specific diagnostic marker for adult-onset SLE. However, the diagnostic efficacy of IFI44L in childhood-onset SLE (cSLE) still remains to be confirmed. In this study, we utilized bioinformatics analysis and conducted clinical experiments to demonstrate that IFI44L methylation can also serve as a promising blood biomarker for cSLE. The findings of this study can facilitate the diagnosis of cSLE and broaden our understanding of its molecular mechanisms, with a particular focus on those related to type I interferons.
Monitoring Activity and Gait in Children (MAGIC) using digital health technologies
Authors: Di Junrui , Tuttle Pirinka Georgiev , Adamowicz Lukas , Lin Wenyi , Zhang Hao , Psaltos Dimitrios , Selig Jessica , Bai Jiawei , Karahanoglu F. Isik , Sheriff Paul , Seelam Vijitha , Williams Bunmi , Ghafoor Sana , Demanuele Charmaine , Santamaria Mar , Cai Xuemei 
Published: March 2024

Abstract
Background
Digital health technologies (DHTs) can collect gait and physical activity in adults, but limited studies have validated these in children. This study compared gait and physical activity metrics collected using DHTs to those collected by reference comparators during in-clinic sessions, to collect a normative accelerometry dataset, and to evaluate participants’ comfort and their compliance in wearing the DHTs at-home.

Methods
The MAGIC (Monitoring Activity and Gait in Children) study was an analytical validation study which enrolled 40, generally healthy participants aged 3–17 years. Gait and physical activity were collected using DHTs in a clinical setting and continuously at-home.

Results
Overall good to excellent agreement was observed between gait metrics extracted with a gait algorithm from a lumbar-worn DHT compared to ground truth reference systems. Majority of participants either “agreed” or “strongly agreed” that wrist and lumbar DHTs were comfortable to wear at home, respectively, with 86% (wrist-worn DHT) and 68% (lumbar-worn DHT) wear-time compliance. Significant differences across age groups were observed in multiple gait and activity metrics obtained at home.

Conclusions
Our findings suggest that gait and physical activity data can be collected from DHTs in pediatric populations with high reliability and wear compliance, in-clinic and in home environments.

Trial registration
ClinicalTrials.gov: NCT04823650

Impact

Digital health technologies (DHTs) have been used to collect gait and physical activity in adult populations, but limited studies have validated these metrics in children.

The MAGIC study comprehensively validates the performance and feasibility of DHT-measured gait and physical activity in the pediatric population.

Our findings suggest that reliable gait and physical activity data can be collected from DHTs in pediatric populations, with both high accuracy and wear compliance both in-clinic and in home environments.

The identified across-age-group differences in gait and activity measurements highlighted their potential clinical value.
Exploring knowledge and implementation gaps of activity-based therapy in centers lacking specialized spinal cord injury services: understanding therapists’ perspectives
Authors: Cesca Nicole , Lin Chantal , Abu-Jurji Zeina , Wexler Aaron , Mark Jonas , McCullum Shane , Kamran Rija , Chan Brian , Musselman Kristin E. 
Published: March 2024

Abstract
Study design
Qualitative exploratory

Objectives
Rehabilitation following spinal cord injury (SCI) is a life-long process involving healthcare in a variety of settings, including facilities lacking SCI-specific services (i.e., non-SCI-specialized centers). Activity-based therapy (ABT) is a neurorestorative approach involving intensive, task-specific movement practice below the injury level. This study explored the existing knowledge, perceptions, and implementation of ABT among physical and occupational therapists working in non-SCI-specialized centers.

Setting
Canadian hospitals and community clinics

Design/methods
Semi-structured interviews were conducted with Canadian therapists who worked at non-SCI-specialized centers and treated at least one patient with SCI within the last 18 months. The Theoretical Domains Framework was used to develop interview questions that queried therapists’ experiences in delivering SCI rehabilitation, their understanding of ABT and experience with its implementation. Interviews were audio-recorded, transcribed verbatim and analyzed using interpretive description.

Results
Four physical therapists and three occupational therapists, from diverse settings (i.e., acute care, inpatient rehabilitation, long-term care, outpatient rehabilitation, rural outpatient clinic) participated. Three themes were identified: (1) Available knowledge, resources and therapy time in non-SCI-specialized centers challenge ABT implementation, (2) How current therapy practices in non-SCI-specialized centers align with ABT and (3) Desire for ABT knowledge. Although participants were not familiar with the term ABT, it was identified that they were unknowingly incorporating some components of ABT into their practice. Participants expressed a keenness to learn more about ABT.

Conclusion
Current knowledge and implementation of ABT in non-SCI-specialized centers is limited. Tailoring ABT education to therapists at non-SCI-specialized centers may increase ABT implementation.
VDR and deubiquitination control neuronal oxidative stress and microglial inflammation in Parkinson’s disease
Authors: Zheng Zihui , Chen Miao , Feng Shengliang , Zhao Huanhuan , Qu Tiange , Zhao Xudong , Ruan Qinli , Li Lei , Guo Jun 
Published: March 2024

AbstractClose correlation between vitamin D (VitD) deficiency and Parkinson’s Disease (PD) risk, VitD as an adjuvant treatment promising to improve PD progression. However, VitD excessive intake could induce hypercalcemia and renal damage. Therefore, upregulation of vitD receptor (VDR) is considered a compensatory strategy to overcome VitD insufficiency and alleviate PD symptoms. In this study, we discovered that VDR played antioxidative roles in dopaminergic neurons by decreasing reactive oxygen species (ROS) and maintaining mitochondrial membrane potential. Further, we newly identified VDR downstream events in C. elegans, including glutathione S-transferase (gst) and forkhead box transcription factor class O (daf-16) mediated oxidative stress resistance. VDR upregulation also mitigated microglial activation through inhibition of NLRP3/caspase-1-mediated inflammation and membrane permeabilization. These findings highlight the multifaceted protective effects of VDR in both neurons and microglia against the development of PD. Importantly, we discovered a novel deubiquitinase DUB3, whose N-terminal catalytic domain interacted with the C-terminal ligand-binding domain of VDR to reduce VDR ubiquitination. Identification of DUB3 as an essential player in the deubiquitinating mechanism of VDR provides valuable insights into VDR regulation and its potential as a therapeutic target for PD.
Osteocyte mitochondria regulate angiogenesis of transcortical vessels
Authors: Liao Peng , Chen Long , Zhou Hao , Mei Jiong , Chen Ziming , Wang Bingqi , Feng Jerry Q. , Li Guangyi , Tong Sihan , Zhou Jian , Zhu Siyuan , Qian Yu , Zong Yao , Zou Weiguo , Li Hao , Zhang Wenkan , Yao Meng , Ma Yiyang , Ding Peng , Pang Yidan , Gao Chuan , Mei Jialun , Zhang Senyao , Zhang Changqing , Liu Delin , Zheng Minghao , Gao Junjie 
Published: March 2024

AbstractTranscortical vessels (TCVs) provide effective communication between bone marrow vascular system and external circulation. Although osteocytes are in close contact with them, it is not clear whether osteocytes regulate the homeostasis of TCVs. Here, we show that osteocytes maintain the normal network of TCVs by transferring mitochondria to the endothelial cells of TCV. Partial ablation of osteocytes causes TCV regression. Inhibition of mitochondrial transfer by conditional knockout of Rhot1 in osteocytes also leads to regression of the TCV network. By contrast, acquisition of osteocyte mitochondria by endothelial cells efficiently restores endothelial dysfunction. Administration of osteocyte mitochondria resultes in acceleration of the angiogenesis and healing of the cortical bone defect. Our results provide new insights into osteocyte-TCV interactions and inspire the potential application of mitochondrial therapy for bone-related diseases.
The AMPK-related kinase NUAK1 controls cortical axons branching by locally modulating mitochondrial metabolic functions
Authors: Lanfranchi Marine , Yandiev Sozerko , Meyer-Dilhet Géraldine , Ellouze Salma , Kerkhofs Martijn , Dos Reis Raphael , Garcia Audrey , Blondet Camille , Amar Alizée , Kneppers Anita , Polvèche Hélène , Plassard Damien , Foretz Marc , Viollet Benoit , Sakamoto Kei , Mounier Rémi , Bourgeois Cyril F. , Raineteau Olivier , Goillot Evelyne , Courchet Julien 
Published: March 2024

AbstractThe cellular mechanisms underlying axonal morphogenesis are essential to the formation of functional neuronal networks. We previously identified the autism-linked kinase NUAK1 as a central regulator of axon branching through the control of mitochondria trafficking. However, (1) the relationship between mitochondrial position, function and axon branching and (2) the downstream effectors whereby NUAK1 regulates axon branching remain unknown. Here, we report that mitochondria recruitment to synaptic boutons supports collateral branches stabilization rather than formation in mouse cortical neurons. NUAK1 deficiency significantly impairs mitochondrial metabolism and axonal ATP concentration, and upregulation of mitochondrial function is sufficient to rescue axonal branching in NUAK1 null neurons in vitro and in vivo. Finally, we found that NUAK1 regulates axon branching through the mitochondria-targeted microprotein BRAWNIN. Our results demonstrate that NUAK1 exerts a dual function during axon branching through its ability to control mitochondrial distribution and metabolic activity.
Universal control of a bosonic mode via drive-activated native cubic interactions
Authors: Eriksson Axel M. , Sépulcre Théo , Kervinen Mikael , Hillmann Timo , Kudra Marina , Dupouy Simon , Lu Yong , Khanahmadi Maryam , Yang Jiaying , Castillo-Moreno Claudia , Delsing Per , Gasparinetti Simone 
Published: March 2024

AbstractLinear bosonic modes offer a hardware-efficient alternative for quantum information processing but require access to some nonlinearity for universal control. The lack of nonlinearity in photonics has led to encoded measurement-based quantum computing, which relies on linear operations but requires access to resourceful (’nonlinear’) quantum states, such as cubic phase states. In contrast, superconducting microwave circuits offer engineerable nonlinearities but suffer from static Kerr nonlinearity. Here, we demonstrate universal control of a bosonic mode composed of a superconducting nonlinear asymmetric inductive element (SNAIL) resonator, enabled by native nonlinearities in the SNAIL element. We suppress static nonlinearities by operating the SNAIL in the vicinity of its Kerr-free point and dynamically activate nonlinearities up to third order by fast flux pulses. We experimentally realize a universal set of generalized squeezing operations, as well as the cubic phase gate, and exploit them to deterministically prepare a cubic phase state in 60 ns. Our results initiate the experimental field of polynomial quantum computing, in the continuous-variables notion originally introduced by Lloyd and Braunstein.
Late-stage guanine C8–H alkylation of nucleosides, nucleotides, and oligonucleotides via photo-mediated Minisci reaction
Authors: Xie Ruoqian , Li Wanlu , Ge Yuhua , Zhou Yutong , Xiao Guolan , Zhao Qin , Han Yunxi , Li Yangyan , Chen Gang 
Published: March 2024

AbstractChemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction. Addition of catechol to assist the formation of alkyl radicals via in situ generated boronic acid catechol ester derivatives (BACED) markedly enhances the yields especially for the reaction of less stable primary alkyl radicals, and is the key to success for the post-synthetic alkylation of ONs. This method features excellent chemoselectivity, no necessity for pre-protection, wide range of substrate scope, various free radical precursors, and little strand lesion. Downstream applications in disease treatment and diagnosis, or as biochemical probes to study biological processes after linking with suitable fluorescent compounds are expected.
An evolutionary mechanism to assimilate new nutrient sensors into the mTORC1 pathway
Authors: Liu Grace Y. , Jouandin Patrick , Bahng Raymond E. , Perrimon Norbert , Sabatini David M. 
Published: March 2024

AbstractAnimals sense and respond to nutrient availability in their environments, a task coordinated in part by the mTOR complex 1 (mTORC1) pathway. mTORC1 regulates growth in response to nutrients and, in mammals, senses specific amino acids through specialized sensors that bind the GATOR1/2 signaling hub. Given that animals can occupy diverse niches, we hypothesized that the pathway might evolve distinct sensors in different metazoan phyla. Whether such customization occurs, and how the mTORC1 pathway might capture new inputs, is unknown. Here, we identify the Drosophila melanogaster protein Unmet expectations (CG11596) as a species-restricted methionine sensor that directly binds the fly GATOR2 complex in a fashion antagonized by S-adenosylmethionine (SAM). We find that in Dipterans GATOR2 rapidly evolved the capacity to bind Unmet and to thereby repurpose a previously independent methyltransferase as a SAM sensor. Thus, the modular architecture of the mTORC1 pathway allows it to co-opt preexisting enzymes to expand its nutrient sensing capabilities, revealing a mechanism for conferring evolvability on an otherwise conserved system.
An optofluidic antenna for enhancing the sensitivity of single-emitter measurements
Authors: Morales-Inostroza Luis , Folz Julian , Kühnemuth Ralf , Felekyan Suren , Wieser Franz-Ferdinand , Seidel Claus A. M. , Götzinger Stephan , Sandoghdar Vahid 
Published: March 2024

AbstractMany single-molecule investigations are performed in fluidic environments, for example, to avoid unwanted consequences of contact with surfaces. Diffusion of molecules in this arrangement limits the observation time and the number of collected photons, thus, compromising studies of processes with fast or slow dynamics. Here, we introduce a planar optofluidic antenna (OFA), which enhances the fluorescence signal from molecules by about 5 times per passage, leads to about 7-fold more frequent returns to the observation volume, and significantly lengthens the diffusion time within one passage. We use single-molecule multi-parameter fluorescence detection (sm-MFD), fluorescence correlation spectroscopy (FCS) and Förster resonance energy transfer (FRET) measurements to characterize our OFAs. The antenna advantages are showcased by examining both the slow (ms) and fast (50 μs) dynamics of DNA four-way (Holliday) junctions with real-time resolution. The FRET trajectories provide evidence for the absence of an intermediate conformational state and introduce an upper bound for its lifetime. The ease of implementation and compatibility with various microscopy modalities make OFAs broadly applicable to a diverse range of studies.
Oxygen-independent organic photosensitizer with ultralow-power NIR photoexcitation for tumor-specific photodynamic therapy
Authors: Tang Yufu , Li Yuanyuan , Li Bowen , Song Wentao , Qi Guobin , Tian Jianwu , Huang Wei , Fan Quli , Liu Bin 
Published: March 2024

AbstractPhotodynamic therapy (PDT) is a promising cancer treatment but has limitations due to its dependence on oxygen and high-power-density photoexcitation. Here, we report polymer-based organic photosensitizers (PSs) through rational PS skeleton design and precise side-chain engineering to generate •O2− and •OH under oxygen-free conditions using ultralow-power 808 nm photoexcitation for tumor-specific photodynamic ablation. The designed organic PS skeletons can generate electron-hole pairs to sensitize H2O into •O2− and •OH under oxygen-free conditions with 808 nm photoexcitation, achieving NIR-photoexcited and oxygen-independent •O2− and •OH production. Further, compared with commonly used alkyl side chains, glycol oligomer as the PS side chain mitigates electron-hole recombination and offers more H2O molecules around the electron-hole pairs generated from the hydrophobic PS skeletons, which can yield 4-fold stronger •O2− and •OH production, thus allowing an ultralow-power photoexcitation to yield high PDT effect. Finally, the feasibility of developing activatable PSs for tumor-specific photodynamic therapy in female mice is further demonstrated under 808 nm irradiation with an ultralow-power of 15 mW cm−2. The study not only provides further insights into the PDT mechanism but also offers a general design guideline to develop an oxygen-independent organic PS using ultralow-power NIR photoexcitation for tumor-specific PDT.
Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Authors: Kasikova Lenka , Rakova Jana , Hensler Michal , Lanickova Tereza , Tomankova Jana , Pasulka Josef , Drozenova Jana , Mojzisova Katerina , Fialova Anna , Vosahlikova Sarka , Laco Jan , Ryska Ales , Dundr Pavel , Kocian Roman , Brtnicky Tomas , Skapa Petr , Capkova Linda , Kovar Marek , Prochazka Jan , Praznovec Ivan , Koblizek Vladimir , Taskova Alice , Tanaka Hisashi , Lischke Robert , Mendez Fernando Casas , Vachtenheim Jiri , Heinzelmann-Schwarz Viola , Jacob Francis , McNeish Iain A. , Halaska Michal J. , Rob Lukas , Cibula David , Orsulic Sandra , Galluzzi Lorenzo , Spisek Radek , Fucikova Jitka 
Published: March 2024

AbstractIntratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that – at odds with NSCLC – HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.