bluuebunny/crossref_metadata_2025_split huggingface dataset:
A20 Restrains Thymic Regulatory T Cell Development
Authors: Fischer Julius Clemens , Otten Vera , Kober Maike , Drees Christoph , Rosenbaum Marc , Schmickl Martina , Heidegger Simon , Beyaert Rudi , van Loo Geert , Li Xian Chang , Peschel Christian , Schmidt-Supprian Marc , Haas Tobias , Spoerl Silvia , Poeck Hendrik 
Published: August 2017

Abstract
Maintaining immune tolerance requires the production of Foxp3-expressing regulatory T (Treg) cells in the thymus. Activation of NF-κB transcription factors is critically required for Treg cell development, partly via initiating Foxp3 expression. NF-κB activation is controlled by a negative feedback regulation through the ubiquitin editing enzyme A20, which reduces proinflammatory signaling in myeloid cells and B cells. In naive CD4+ T cells, A20 prevents kinase RIPK3-dependent necroptosis. Using mice deficient for A20 in T lineage cells, we show that thymic and peripheral Treg cell compartments are quantitatively enlarged because of a cell-intrinsic developmental advantage of A20-deficient thymic Treg differentiation. A20-deficient thymic Treg cells exhibit reduced dependence on IL-2 but unchanged rates of proliferation and apoptosis. Activation of the NF-κB transcription factor RelA was enhanced, whereas nuclear translocation of c-Rel was decreased in A20-deficient thymic Treg cells. Furthermore, we found that the increase in Treg cells in T cell–specific A20-deficient mice was already observed in CD4+ single-positive CD25+ GITR+ Foxp3− thymic Treg cell progenitors. Treg cell precursors expressed high levels of the tumor necrosis factor receptor superfamily molecule GITR, whose stimulation is closely linked to thymic Treg cell development. A20-deficient Treg cells efficiently suppressed effector T cell–mediated graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, suggesting normal suppressive function. Holding thymic production of natural Treg cells in check, A20 thus integrates Treg cell activity and increased effector T cell survival into an efficient CD4+ T cell response.
CXCL12–CXCR4 Axis Is Required for Contact-Mediated Human B Lymphoid and Plasmacytoid Dendritic Cell Differentiation but Not T Lymphoid Generation
Authors: Minami Hirohito , Nagaharu Keiki , Nakamori Yoshiki , Ohishi Kohshi , Shimojo Naoshi , Kageyama Yuki , Matsumoto Takeshi , Sugimoto Yuka , Tawara Isao , Masuya Masahiro , Miwa Hiroshi , Katayama Naoyuki 
Published: August 2017

Abstract
We investigated the involvement of CXCL12–CXCR4 interactions in human lymphohematopoiesis by coculture with telomerized human stromal cells. CXCR4 expression was low in CD34+CD38−CD45RA−CD10−CD7−CD19− immature hematopoietic stem/precursor cells (HSPCs) but higher in CD34+CD38−CD45RA+CD10+CD7+/−CD19− early lymphoid precursors and even higher in CD34+CD38+CD45RA+CD10+CD7−CD19+ pro-B cells. Inhibition of the effect of stromal cell–produced CXCL12 by an anti-CXCR4–blocking Ab suppressed the generation of CD45RA+CD10−CD7+CD19− early T lymphoid precursors (ETPs) and CD45RA+CD10+CD7−CD19+/− B lymphoid precursors on stromal cells, but it did not affect the generation of ETPs in conditioned medium of stromal cell cultures. Replating assays showed that contact with stromal cells was critical for HSPC-derived CD45RA+CD10+CD7−CD19− B lineage–biased precursors to differentiate into CD19+ pro-B cells, which was suppressed by the anti-CXCR4 Ab. Conversely, HSPC-derived ETPs possessed T and B lymphoid and monocytic differentiation potential; stromal cell contact was not required for their growth but rather promoted B lymphoid differentiation. The anti-CXCR4 Ab did not affect the growth of ETPs in conditioned medium, but it suppressed their B lymphoid differentiation on stromal cells. CD14−CD11c−HLA-DR+CD123highCD303+ plasmacytoid dendritic cells developed from HSPCs and ETPs exclusively in contact with stromal cells, which was suppressed by the anti-CXCR4 Ab. These data indicate that CXCL12 plays an essential role in stromal cell contact–mediated B lymphoid and plasmacytoid dendritic cell differentiation from immature hematopoietic and early T lymphoid precursors with a multilineage differentiation potential, but it does not participate in contact-independent generation of early T lymphoid precursors.
POEMS SYNDROME: AN UPDATE
Authors: Nozza Andrea 
Published: August 2017

POEMS syndrome is a rare, chronic and disabling condition. The causes of this condition remain unknown; however, chronic overproduction of pro-inflammatory cytokines appears to be a major contributor. Early diagnosis is essential to start treatment before the clinical condition of the patient becomes compromised.A complete evaluation of the disease at its onset is essential for treatment decision. In localized disease, curative doses of radiation (50 Gy) is the recommended therapy. On the other hand, patients with disseminated disease should be given systemic therapy. Treatment-related morbidity can be minimized by an effective induction therapy that modifies the cytokine status, improving clinical condition and control disease severity before mobilization and transplantation. Patients not suitable for hematopoietic stem cell transplantation (HSCT) are usually treated with alkylator-based therapy. Novel agents may also offer benefits to patients with a poor performance status or renal dysfunction, and induce transplantation eligibility. Given the biological characteristics of POEMS, immunomodulatory effects and the absence of neurotoxicity, lenalidomide appears to be an effective therapy for the treatment of POEMS, both as short induction therapy before PBSCT and in non-transplant eligible patients, as it showed high response rate and long lasting responses.At present, however, guidelines for the diagnosis and treatment of POEMS are not available and appear advocated. Keywords: POEMS, plasma cell dyscrasia; Osteosclerosis; neuropathy
Boosting Efficiency to 22.73%: Unraveling the Role of Solvent Environment in Low‐Dimensional Perovskites Through Competitive Bonding Interactions
Authors: Xu Kaiqin , Xing Zhi , Li Dengxue , Du Canqiang , Gao Yang , Hu Xiaotian , Hu Ting , Chen Yiwang 
Published: October 2024

AbstractIt is reported that the solvent environment exerts a significant influence on the property of perovskite precursor solution and resultant film, which is more pronounced in more complex low‐dimensional perovskites. Four solvent additives with varying basicity are introduced to instigate a tug‐of‐war among bonding interactions, thereby exploring the systematic effect of the solvent environment on the growth of quantum wells and the photoelectric properties of the resultant low‐dimensional perovskite films. A governing principle that diverges significantly from those previously documented for three‐dimensional perovskites is elucidated in low‐dimensional perovskites. When coordination interactions predominate in the solvent environment, the emergence of a two‐dimensional GA2PbI4 transitional phase is fostered to facilitate subsequent transformation into the desirable ACI phase, and the perovskite crystallization kinetics is retarded to improve the film quality. Hence, the highest power conversion efficiency (PCE) of 22.73% is obtained for GA(MA)nPbnI3n+1 (n = 5) based solar cells with a p‐i‐n structure. The PCE achieved in this work is a record among the reported low‐dimensional perovskite solar cells.
Electrode Droplet Microarray (eDMA): An Impedance Platform for Label‐Free Parallel Monitoring of Cellular Drug Response in Nanoliter Droplets
Authors: Zhou Meijun , Urrutia Gomez Joaquin E. , Mandsberg Nikolaj K. , Liu Sida , Schmidt Sabine , Meier Matthias , Levkin Pavel A. , Jahnke Heinz‐Georg , Popova Anna 
Published: October 2024

AbstractLabel‐free real‐time monitoring of cellular behavior using impedance spectroscopy is important for drug development and toxicological assessments. Parallelization and miniaturization of such experiments are essential for increasing throughput and enabling experiments with low abundant stem or primary cells. Traditional methods are not miniaturized and require large volumes of reagents and number of cells, limiting their suitability for cost effective high‐throughput screening of cells of limited availability. Here, the fabrication, optimization, and application of a bioelectrical signaling monitoring system – electrode droplet microarray (eDMA) are demonstrated. The eDMA platform is based on preparation of a hydrophilic‐superhydrophobic patterns covering an array of individually addressable microelectrodes, which confines cells to individual microelectrodes, allowing for parallel, real‐time, and label‐free detection of cellular responses to drug treatments in nanoliter droplets. The real‐time monitoring of cytotoxic effect of an anticancer drug is demonstrated over 48 h with real‐time calculation of the half‐inhibitory concentration (IC50) values through impedance spectroscopy. This demonstrates eDMA's ability to dynamically assess responses to various drugs in parallel at any given time point, which is crucial for functional personalized oncology. Specifically, the platform can be employed for monitoring anticancer drug toxicity using limited patient samples, where the miniaturization provided by eDMA is essential.
Nanozyme‐Shelled Microcapsules for Targeting Biofilm Infections in Confined Spaces
Authors: Tran Hong Huy , Jaruchotiratanasakul Nadasinee , Xiang Zhenting , Pandey Nil Kanatha , Oh Min Jun , Liu Yuan , Ren Zhi , Babeer Alaa , Zdilla Michael J. , Cormode David P. , Karabucak Bekir , Lee Daeyeon , Steager Edward B. , Koo Hyun 
Published: October 2024

AbstractBacterial infections in irregular and branched confinements pose significant therapeutic challenges. Despite their high antimicrobial efficacy, enzyme‐mimicking nanoparticles (nanozymes) face difficulties in achieving localized catalysis at distant infection sites within confined spaces. Incorporating nanozymes into microrobots enables the delivery of catalytic agents to hard‐to‐reach areas, but poor nanoparticle dispersibility and distribution during fabrication hinder their catalytic performance. To address these challenges, a nanozyme‐shelled microrobotic platform is introduced using magnetic microcapsules with collective and adaptive mobility for automated navigation and localized catalysis within complex confinements. Using double emulsions produced from microfluidics as templates, iron oxide and silica nanoparticles are assembled into 100‐µm microcapsules, which self‐organize into multi‐unit, millimeter‐size assemblies under rotating magnetic fields. These microcapsules exhibit high peroxidase‐like activity, efficiently catalyzing hydrogen peroxide to generate reactive oxygen species (ROS). Notably, microcapsule assemblies display remarkable collective navigation within arched and branched confinements, reaching the targeted apical regions of the tooth canal with high accuracy. Furthermore, these nanozyme‐shelled microrobots perform rapid catalysis in situ and effectively kill biofilms on contact via ROS generation, enabling localized antibiofilm action. This study demonstrates a facile method of integrating nanozymes onto a versatile microrobotic platform to address current needs for targeted therapeutic catalysis in complex and confined microenvironments.
Ultra‐Broadband Emission in Bi/Ge Co‐Doped Silica Glass and Fiber via Bismuth Coordination Engineering
Authors: Li Xin , Tian Jinmin , Shao Chongyun , Guo Mengting , Chen Yinggang , Yu Chunlei , Hu Lili 
Published: October 2024

AbstractBismuth (Bi) and Germanium (Ge) co‐doped silica glass and fiber, as advanced gain media with broadband near‐infrared (NIR) emission and amplification, have promise for extending communication bandwidth. However, efficiently modulating the NIR emissions of bismuth to cover the C+L communication bands remain a significant challenge. In the study, a high‐temperature and high‐pressure reduction treatment on Bi/Ge co‐doped silica glass is employed to tailor the coordination environment around bismuth active center. This method facilitated the creation of new bismuth NIR luminescence centers, resulting in the luminescence spectrum with a peak position at 1550 nm and a FWHM exceeding 350 nm. The changes in the bismuth coordination environment are elucidated using HRTEM, photoluminescence decay, temperature‐dependent emission, EXAFS and CW‐EPR. Furthermore, the feasibility of this method in Bi/Ge co‐doped silica fiber is validated, and obtained >5 dB amplification in the range of 1400–1700 nm. This coordination engineering method holds significant potential for widespread application in Bi/Ge co‐doped silica glass and optical fiber is believed. It presents a promising prospect for expanding communication bandwidth by effectively modulating the NIR emissions of bismuth to cover the S to U communication band.
Essential(ly forgotten) workers: Latine youth farmworkers during the COVID‐19 pandemic
Authors: Arnold Taylor J. , Morrison Sharon D. , Romero Michelle Y. Martin , Echeverria Sandra E. , Zapata Sylvia , Quandt Sara A. , Torres‐Lara Fabiola , Arvizu Jose A. Robles , Arcury Thomas A. 
Published: October 2024

AbstractBackgroundEssential workers across multiple industries faced a disproportionate burden of morbidity and mortality during the COVID‐19 pandemic. The effects were especially severe for agricultural and food processing workers, many of whom are members of the structurally vulnerable Latine community. Under current U.S. federal laws, children under 12 years old can legally work in agriculture, one of the most hazardous U.S. industries. Many of these working youth are Latine and experience health and educational inequities.MethodsUsing a community‐based participatory research approach and a qualitative design, we conducted semi‐structured in‐depth interviews in North Carolina in 2022, with service providers in health, education, and advocacy fields (n = 10) and Latine youth farmworkers aged 10–17 (n = 24). We used participatory qualitative analysis methods and a reflexive thematic analysis to understand and describe the work experiences of these youth during the first 2 years of the pandemic.ResultsAmidst precarious economic and school situations exacerbated by the COVID‐19 pandemic, many youths described an increased need to work to support their families. While aware and sometimes fearful of the added occupational health risks of COVID‐19, youth and their families felt they had few other options. Service providers and youth described minimal employer‐provided safety protocols or equipment, yet some workers organized their own attempts at safety protocols. Youth narratives imply limited knowledge of basic workplace safety requirements.ConclusionsStudy findings emphasize the urgent need to address structural vulnerabilities shaping workplace policies and norms to protect Latine youth farmworkers to support their healthy development.
Cerebellar Hypoplasia and Treatment Course of a Two‐Month‐Old Infant With KCNQ2 Epileptic Encephalopathy Due to a De Novo Variant and Review of the Literature
Authors: Cebeci Dilek , Cavdarli Busranur , Ozbudak Pinar , Arhan Ebru , Gucuyener Kivilcim , Demir Ercan 
Published: October 2024

ABSTRACTIn this paper, we report the treatment course, magnetic resonance imaging (MRI), and electroencephalography (EEG) findings of a two‐month‐old girl with KCNQ2 epileptic encephalopathy caused by a de novo variant. The patient started having seizures 2 days postnatally. Despite treatment with phenobarbital, phenytoin, levetiracetam, topiramate, clonazepam, vigabatrin, clobazam, and pyridoxine, she continued to have 10 or more seizures per day. EEG recordings showed multifocal epileptiform discharges with diffuse background slowing. MRI revealed left cerebellar hypoplasia. After lacosamide administration, the severity and frequency of seizures decreased by 80%. EEG recordings showed a significant improvement. A de novo heterozygous variant of c.1681C>A (p.Pro561Thr) in the KCNQ2 gene was detected. After carbamazepine add‐on treatment, the patient achieved seizure‐free status for about 2 years. This case demonstrates the efficacy of lacosamide against KCNQ2 epileptic encephalopathy. To our knowledge, this is the first report to document the association between cerebellar hypoplasia and KCNQ2 variants.
The Relationship between Framingham Stroke Risk Profile on Incident Dementia and Alzheimer's Disease: A 40‐Year Follow‐Up Study Highlighting Female Vulnerability
Authors: Yuan Jing , Tao Qiushan , Ang Ting Fang Alvin , Liu Chunyu , Devine Sherral , Auerbach Sanford H. , Mez Jesse , Farrer Lindsay A. , Qiu Wei Qiao , Au Rhoda 
Published: October 2024

ObjectiveSex differences in the association between cardiovascular risk factors and the incident all‐cause dementia and the subtype Alzheimer's disease (AD) risk are unclear.MethodsFramingham Heart Study (FHS) participants (n = 4,171, 54% women, aged 55 to 69 years) were included at baseline and followed up to 40 years. The Framingham Stroke Risk Profile (FSRP) was dichotomized into 2 levels (cutoff: 75th percentile of the FSRP z‐scores). Cause‐specific hazard models, with death as a competing event, and restricted mean survival time (RMST) model were used to analyze the association between FSRP levels and incident all‐cause dementia and AD. Interactions between FSRP and sex were estimated, followed by a sex‐stratified analysis to examine the sex modification effect.ResultsHigh FSRP was significantly associated with all‐cause dementia (hazard ratio [HR] = 1.25, robust 95% confidence interval [CI] = 1.21 to 1.29, p < 0.001) and AD (HR = 1.58, robust 95% CI = 1.57 to 1.59, p < 0.001) in cause‐specific hazard models. High FSRP was significantly associated with incident dementia (HR = 2.81, robust 95% CI = 2.75 to 2.87, p < 0.001) and AD (HR = 2.96, robust 95% CI = 2.36 to 3.71, p < 0.001) in women, but not in men. Results were consistent in the RMST models. Current diabetes and high systolic blood pressure as FSRP components were significantly associated with dementia and AD in women but not in men.InterpretationHigh FSRP in mid‐ to early late life is a critical risk factor for all‐cause dementia and AD, particularly in women. Sex‐specific interventions and further research to elucidate underlying mechanisms are warranted. ANN NEUROL 2024;96:1124–1134
Quantization‐Based Latin Hypercube Sampling for Dependent Inputs With an Application to Sensitivity Analysis of Environmental Models
Authors: Lambert Guerlain , Helbert Céline , Lauvernet Claire 
Published: October 2024

ABSTRACTNumerical models are essential for comprehending intricate physical phenomena in different domains. To handle their complexity, sensitivity analysis, particularly screening is crucial for identifying influential input parameters. Kernel‐based methods, such as the Hilbert‐Schmidt Independence Criterion (HSIC), are valuable for analyzing dependencies between inputs and outputs. Implementing HSIC requires data from the original model, which leads to the need of efficient sampling strategies to limit the number of costly numerical simulations. While, for independent input variables, existing sampling methods like Latin Hypercube Sampling (LHS) are effective in estimating HSIC with reduced variance, incorporating dependence is challenging. This article introduces a novel LHS variant, quantization‐based LHS (QLHS), which leverages Voronoi vector quantization to address dependent inputs. The method provides good coverage of the range of variations in the input variables. The article outlines expectation estimators based on QLHS in various dependency settings, demonstrating their unbiasedness. The method is applied to several models of growing complexities, first on simple examples to illustrate the theory, then on more complex environmental hydrological models, when the dependence is known or not, and with more and more interactive processes and factors. The last application is on the digital twin of a French vineyard catchment (Beaujolais region) to design a vegetative filter strip and reduce water, sediment, and pesticide transfers from the fields to the river. QLHS is used to compute HSIC measures and independence tests, demonstrating its usefulness, especially in the context of complex models.
Genetic Variants in METTL16 Affect the Risk of Non‐Syndromic Orofacial Clefts
Authors: Xu Xinze , Li Xiaofeng , Han Minxuan , Xing Changyue , Zhu Guirong , Cui Xing , Wang Lin , Lou Shu , Pan Yongchu 
Published: October 2024

ABSTRACTObjectiveN6‐methyladenosine (m6A) is the most prevalent modification of RNA in eukaryotes which is associated with many cellular processes and diseases. Here, our objective is to explore whether genetic variants in m6A modification genes are associated with the risk of non‐syndrome orofacial clefts (NSOCs).MethodsThe transmission disequilibrium test (TDT) was performed to calculate the association between single nucleotide polymorphisms (SNPs) in m6A modification genes and NSOCs risk in 944 case‐parent trios. The function of SNP was predicted by HaploReg, RegulomeDB and histone enrichment data. The expression quantitative trait locus (eQTL) analysis was examined using Genotype‐Tissue Expression (GTEx) and eQTLGen. The role of gene in the development of NSOCs was assessed with correlation and enrichment analysis based on gene expression data in mice craniofacial tissue and zebrafish embryo.ResultsWe identified that rs8078195 (A > C) in METTL16 was suggestively associated with the increased risk of NSOCs (OR = 1.32, p = 1.80E − 03). The region surrounding rs8078195 was subjected to deoxyribonuclease hypersensitivity and enriched with multiple histone modifications. In addition, it had a significant eQTL effect with METTL16 in skin tissue and human peripheral blood, which played an important role in NSOCs development. Bioinformatic analysis indicated that METTL16 contributed to the development of NSOCs probably by regulating cell cycle process.ConclusionsRs8078195 in METTL16 was associated with the occurrence of NSOCs.
The influence of eyelashes on electric field distribution and absorbed power density in the cornea under millimeter‐wave exposure
Authors: Foroughimehr Negin , Vilagosh Zoltan , Yavari Ali , Wood Andrew 
Published: October 2024

AbstractAs millimeter wave (MMW) technology, particularly in fifth‐generation (5G) devices, gains prominence, there is a crucial need for comprehensive electromagnetic (EM) models of ocular tissues to understand and characterize EM exposure conditions accurately. This study employs numerical modeling to investigate the interaction between MMW and the cornea, aiming to characterize EM field distributions and absorption within an anatomically accurate eye model while considering the influence of eyelashes. Using the finite‐difference time‐domain (FDTD) method, we conduct simulations of EM radiation interactions from 20.0 to 100.0 GHz with a human eye model. Moreover, we analyze the temperature distribution increase within the eye model using a thermal sensor in XFdtd, employing a scheme based on the finite difference (FD) method. Our findings reveal a nonuniform distribution of the EM field, particularly intensified in corneal regions adjacent to eyelashes and eyelids. Despite similar EM field patterns, the presence or absence of eyelashes has minimal impact on temperature differences. However, the study highlights increased radiation absorption by the eyelid's epidermis at 100.0 GHz, reducing the rise in the cornea's temperature.