bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics of Patients With Kabuki Syndrome at a Single Tertiary Children's Hospital
Authors: Dortenzio Victoria , Barbaric Lidija , Rosenfeld Elizabeth , Dechene Elizabeth T. , Gilbert Melissa A. , Dulik Matthew C. , Rippert Alyssa L. , Izumi Kosuke 
Published: February 2025

ABSTRACTKabuki syndrome (KS) is a multisystem disorder characterized by facial dysmorphic features, growth delays, skeletal anomalies, and variable intellectual disability (ID) due to pathogenic variants in KMT2D and KDM6A. Significant phenotypic variability has been reported in patients with KS. To further characterize the variability observed in the genomic sequencing era, comprehensive genotypic and phenotypic information from 36 patients with KS and likely pathogenic or pathogenic KMT2D or KDM6A variants at the Children's Hospital of Philadelphia (CHOP) was collected. Dysmorphic features, growth restriction, and developmental delays were commonly reported, as expected. Hyperinsulinism (HI) was seen more frequently than in previously published cohorts. Patients diagnosed with HI were more likely to require neonatal intensive care unit admission and feeding tube(s). Intellectual disability was variable in severity and less frequent than previously reported. This study highlights the wide phenotypic spectrum of KS and expands our knowledge of the diagnostic process for KS. This study is limited by potential ascertainment bias as CHOP is a HI Center of Excellence, however, our cohort is unique as many were ascertained with disease‐agnostic testing. Screening for hyperinsulinism, including consideration of diagnostic fast, at time of KS diagnosis is warranted to prevent long‐term neurologic effects of untreated hypoglycemia.
Mapping reactive astrogliosis in Parkinson's brain with astroglial tracers BU99008 and Deprenyl: New insights from a multi‐marker postmortem study
Authors: Rocha Filipa M. , Roy Avishek , Varshney Mukesh , Kumar Amit 
Published: February 2025

AbstractBACKGROUNDDespite significant astrocytic involvement in Parkinson's disease (PD), the knowledge regarding the role of reactive astrogliosis is still at the surface level; largely due to lack of specific biomarkers to track these processes. Novel astroglial PET‐tracers BU99008 and Deprenyl, hold immense potential for visualizing reactive astrogliosis in PD. However, they have not been thoroughly investigated in PD.METHODSWe employed a multi‐marker approach and performed in vitro radioligand binding and autoradiography studies with 3H‐BU99008 and 3H‐Deprenyl together with astrocytic immunofluorescence and morphometric analyses in the frontal cortex, temporal cortex, caudate and putamen brain regions of PD (n = 4) and control (n = 7) cases.RESULTS AND DISCUSSION3H‐BU99008 and 3H‐Deprenyl showed distinct binding behavior and displayed a diverse array of binding sites (single or multiple) in PD and control brains. Importantly, 3H‐BU99008 and 3H‐Deprenyl autoradiography studies captured pronounced reactive astrogliosis in PD brain regions, corroborated by marked changes in astrocytic markers, morphology, and cellular processes.Highlights
Astroglial tracers BU99008 and Deprenyl displayed a range of binding sites with different levels of affinity and proportions (%) in healthy control (CN) and Parkinson's disease (PD) brains.
Astroglial tracers BU99008 and Deprenyl showed a highly specific (permanent) high‐affinity (HA) binding site in the nanomolar range, which might be consistent across different pathologies.
Astroglial tracers BU99008 and Deprenyl highlighted distinct tracer binding behavior, indicating that they might be targeting different subpopulations or specific states of astrocytes in CN and PD brains.
Astroglial tracers BU99008 and Deprenyl captured prominent reactive astrogliosis at the advanced/end stages of PD, substantiated by a significant increase in intercellular adhesion molecule 1 (ICAM‐1)–positive reactive astrocytes and marked changes in astrocytic morphology and processes.
The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20‐year dementia risk
Authors: Duggan Michael R. , Paterson Clare , Lu Yifei , Biegel Hannah , Dark Heather E. , Cordon Jenifer , Bilgel Murat , Kaneko Naoto , Shibayama Masaki , Kato Shintaro , Furuichi Makio , Waga Iwao , Hiraga Keita , Katsuno Masahisa , Nishita Yukiko , Otsuka Rei , Davatzikos Christos , Erus Guray , Loupy Kelsey , Simpson Melissa , Lewis Alexandria , Moghekar Abhay , Palta Priya , Gottesman Rebecca F. , Resnick Susan M. , Coresh Josef , Williams Stephen A. , Walker Keenan A. 
Published: February 2025

AbstractINTRODUCTIONThere is an unmet need for tools to quantify dementia risk during its multi‐decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow‐up periods and are specific to Alzheimer's disease.METHODSUsing high‐throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST).RESULTSIn addition to outperforming existing plasma biomarkers, the dSST predicted mid‐life dementia risk over a 20‐year follow‐up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.68–0.70, dSST+age 0.75–0.81). In a separate cohort, the dSST was associated with longitudinal declines across multiple cognitive domains, accelerated brain atrophy, and elevated measures of neuropathology (as evidenced by positron emission tomography and plasma biomarkers).DISCUSSIONThe dSST is a cost‐effective, scalable, and minimally invasive protein‐based prognostic aid that can quantify risk up to two decades before dementia onset.Highlights
The Dementia SomaSignal Test (dSST) predicts 20‐year dementia risk across two independent cohorts.
dSST outperforms existing plasma biomarkers in predicting multi‐decade dementia risk.
dSST predicts cognitive decline and accelerated brain atrophy in a third cohort.
dSST is a prognostic aid that can predict dementia risk over two decades.
Remote cognitive tests predict neurodegenerative biomarkers in the Insight 46 cohort
Authors: Giovane Martina Del , Giunchiglia Valentina , Cai Ziyuan , Leoni Marguerite , Street Rebecca , Lu Kirsty , Wong Andrew , Popham Maria , Nicholas Jennifer M. , Trender William , Hellyer Peter J. , Parker Thomas D. , Murray‐Smith Heidi , Cash David M. , Barnes Josephine , Sudre Carole H. , Malhotra Paresh A. , Crutch Sebastian J. , Richards Marcus , Hampshire Adam , Schott Jonathan M. 
Published: February 2025

AbstractBACKGROUNDAlzheimer's disease‐related biomarkers detect pathology years before symptoms emerge, when disease‐modifying therapies might be most beneficial. Remote cognitive testing provides a means of assessing early cognitive changes. We explored the relationship between neurodegenerative biomarkers and cognition in cognitively normal individuals.METHODSWe remotely deployed 13 computerized Cognitron tasks in 255 Insight 46 participants. We generated amyloid load and positivity, white matter hyperintensity volume (WMHV), whole brain and hippocampal volumes at age 73, plus rates of change over 2 years. We examined the relationship between Cognitron, biomarkers, and standard neuropsychological tests.RESULTSSlower response time on a delayed recognition task predicted amyloid positivity (odds ratio [OR] = 1.79, confidence interval [CI]: 1.15, 2.95), and WMHV (1.23, CI: 1.00, 1.56). Brain and hippocampal atrophy rates correlated with poorer visuospatial performance (b = ‐0.42, CI: ‐0.80, ‐0.05) and accuracy on immediate recognition (b = ‐0.01, CI: ‐0.012, ‐0.001), respectively. Standard tests correlated with Cognitron composites (rho = 0.50, p < 0.001).DISCUSSIONRemote computerized testing correlates with standard supervised assessments and holds potential for studying early cognitive changes associated with neurodegeneration.Highlights
70% of the Online 46 cohort performed a set of remote online cognitive tasks.
Response time and accuracy on a memory task predicted amyloid status and load (SUVR).
Accuracy on memory and spatial span tasks correlated with longitudinal atrophy rate.
The Cognitron tasks correlated with standard supervised cognitive tests.
Online cognitive testing can help identify early AD‐related memory deficits.
Breaking the Limitation of Laminar Flow in Thrombolytic Therapy with Reconfigurable Vortex‐Like Nanobot Swarms
Authors: Yang Tingxin , Si Tieyan , Wu Yingjie , Liu Jinhong , Dai Luru , Lin Xiankun , Xuan Mingjun , Leng Xiaoping , He Qiang 
Published: February 2025

AbstractLaminar blood flow represents the normal physiological state of blood circulation, but it also acts as a natural physiological barrier for the effective diffusion of drugs to the lesion site. Here, we report a bioinspired strategy in which reconfigurable vortex‐like swarms of magnetic swimming nanobots actively disrupt the laminar flow to deliver drugs in a manner similar to how bacteria seek food. The drug was released from the cavity of biodegradable, submicron pentosan flask‐like nanobots, aggregates as the dynamic rotating drug fluid under a rotating magnetic field. The vortex‐like nanobot swarm successfully overcame the laminar barrier near the thrombus in a rat inferior vena cava stenosis thrombosis model, which was observed by ultrasound blood flow imaging. Furthermore, the clinical feasibility of nanobots swarm for enhancing thrombolytic efficacy through drug aggregation after breaking the laminar flow was further confirmed in a rat deep vein thrombosis model. This bionic active targeting approach overcomes the laminar flow barrier and restricts the release of drugs by the swarm‐induced vortex fluid to facilitate targeted drug delivery, which is expected to be an innovative method to enhance drug delivery efficiency.
Highly Threatened Status for the Relict Populations of Ectoparasitic Copepod Salmincola californiensis in Japan
Authors: Hasegawa Ryota , Uemura Yohsuke , Yamashita Yasunori , Inoshita Makoto , Koizumi Itsuro 
Published: February 2025

ABSTRACTMany species have been threatened over the past century because of anthropogenic disturbances. Parasites are among the most vulnerable groups because they rely on host organisms, many of which are now endangered. While many studies have argued and evaluated the risk of parasite extinction, empirical evidence is still lacking, especially from aquatic ecosystems. Here, we show the highly threatened status of relict populations of the ectoparasitic copepod Salmincola californiensis in Japan. S. californiensis attaches to the branchial cavities of freshwater salmonids of the genus Oncorhynchus spp., and only four local populations have been reported from disparate regions of Japan, isolated probably due to range contractions after glacial periods. Through citizen‐led field surveys, we found no copepod infections in half of the S. californiensis populations previously reported, suggesting that local extinction has occurred within the last 50–60 years. The upstream reaches of the Kiso River and the Naka River harboured the only sustained populations, though the Kiso population may also have experienced population decline. Our results indicate that parasites can quickly decline over a large geographic scale, especially at range margins. When focal parasites are visible, citizen science is an effective approach for identifying the distributional range of rare parasites and aiding their conservation.
Diruthenium(II,II) Complex Assemblies Showing Electrical Conduction via π‐Stacked 2‐Pyrenecarboxylate Moiety
Authors: Takaki Ren , Iguchi Hiroaki , Qu Liyuan , Pirillo Jenny , Kusaka Shinpei , Hijikata Yuh , Tanaka Hisaaki , Matsuda Wakana , Seki Shu , Matsuda Ryotaro 
Published: February 2025

AbstractThrough‐space electrical conduction in paddlewheel‐type homovalent dinuclear complexes remains poorly understood, despite the numerous reports on these complexes. Herein, the electrical conduction of new Ru2(II,II) complexes with 2‐pyrenecarboxylate (pyrCOO−) ligands, [Ru2(pyrCOO)4X2] ⋅ n(X) (where X=DMF (Ru‐DMF), NMP (Ru‐NMP), DMA (Ru‐DMA)), was investigated. The dimensionality of π‐stacking interactions between discrete molecules in Ru‐DMA is higher (two‐dimensional) than in Ru‐DMF and Ru‐NMP (stair‐like one‐dimensional). Nevertheless, Ru‐DMF, which contains a slight amount of organic radicals, exhibited the highest electrical conductivity. This suggests that the large overlap and high dimensionality of π‐stacking interactions among the complexes, along with a slight organic radical impurity, contribute to the increased electrical conductivity.
The Relationships, Employment, Autonomy, and Life Satisfaction (REALS) Measures for Autistic Adults and Adults With Other Intellectual and Developmental Disabilities: Psychometric Testing of the Self‐Report and Proxy Versions
Authors: Conner Caitlin M. , Yu Lan , MacKenzie Kristen T. , Zeglen Katharine N. , Rutenberg Elizabeth L. , Pilkonis Paul A. , Eack Shaun M. , Mazefsky Carla A. 
Published: February 2025

ABSTRACTResearch and clinical work demonstrate that adults with intellectual and developmental disabilities (IDDs; including autistic adults and adults with other IDDs) struggle with key outcomes in adult life, including social relationships, employment, autonomy, and life satisfaction. However, few validated measures exist to measure these outcomes in adults with IDDs. The Relationships, Employment, Autonomy, and Life Satisfaction (REALS) Measures were created using methods developed by the Patient‐Reported Outcomes Measurement Information System (PROMIS) to assess these outcomes. Large item pools were generated for the four domains, and, in field testing, 875 adults with IDDs (90% autistic; 18.4% with intellectual disability or a non‐autism IDD) and 911 proxy reporters (caregivers; 79% autistic; 48.3% with intellectual disability or a non‐autism IDD) completed 108 and 74 items, respectively, using response options capturing frequency, level of support needed, and satisfaction. The structure and item content of the REALS Measures were determined through an iterative process using both classical test theory and item response theory analyses. The final versions include 19 self‐report and 14 proxy‐report measures, with a range of 3 to 14 items each. The measures have excellent psychometric properties, high precision, and acceptable respondent burden. Thus, they are applicable for service provision, clinical, and research arenas for autistic adults and adults with other IDDs, though additional testing in IDD is warranted and evidence supporting self‐report use in IDD is more limited.
Analysis of Blood Absorption Components by UPLC‐Q‐TOF‐MS/MS From Anemarrhenae Rhizoma Before and After Salt Processing
Authors: Ya‐zhu Wang , Xiao‐ting Wang , Shu‐qing Tian , Hui Gao 
Published: February 2025

ABSTRACTTo investigate the material basis for the increased efficacy of Anemarrhenae Rhizoma (AR) after salt processing, this study employed UPLC‐Q‐TOF‐MS/MS technology to analyze metabolites in both AR and salt‐processed AR (SAR) extracts, as well as in serum samples treated with these extracts. The results identified 54 chemical components in AR and SAR under both positive and negative ion modes, with 21 prototype components detected in the bloodstream. A comparative analysis of serum absorption levels revealed higher concentrations of neomangiferin, mangiferin, and other chemical constituents in the SAR group than in the AR group. Additionally, 29 differential metabolites were identified, with 12 unique to AR and 17 to SAR. These findings highlight significant alterations in the chemical composition of AR after salt processing and provide a scientific basis for understanding the enhanced efficacy of SAR. This study offers valuable insights for further research into the clinical efficacy of SAR and its applications.
State Influence on ESG Performance in Emerging Markets: A Study of Institutional Roles
Authors: Santos Jhunior Ronaldo de Oliveira , dos Santos Costa Lucas , Uchoa Mariana Torres , de Melo Gomes Victor Pessoa 
Published: February 2025

ABSTRACTThis study investigates how institutional factors, specifically the role of the State, influence corporate ESG performance in emerging markets. Using a dataset of 293 companies operating in sensitive industries from 2017 to 2021, the analysis employs panel data models to assess the impact of State Direct Dominance (SDD), State Indirect Intervention (SII), and State typologies. The results indicate that SDD negatively affects ESG scores, potentially due to increased bureaucracy. Conversely, SII, characterized by mechanisms such as policy incentives and governance support, positively influences ESG outcomes. Additionally, companies operating in predatory States exhibit significantly lower ESG performance, highlighting governance challenges in such environments. This study provides actionable insights for policymakers, managers, and investors to promote sustainable corporate practices in emerging economies. By emphasizing the nuanced impacts of State interventions, the research advances the understanding of institutional dynamics shaping ESG outcomes.
Carboxymethyl cellulose‐polylactic acid particles for inhibiting anoikis and enhancing wound healing efficacy of human mesenchymal stem cells
Authors: Lee Dong‐Hyun , Lee You Bin , Park Hyun Su , Jang Young‐Ju , Kim Youn Chul , Bhang Suk Ho 
Published: February 2025

AbstractAdult human mesenchymal stem cells (hMSCs) injection into the wound site promotes angiogenesis and the wound‐closing process by secreting various growth and immune‐modulating factors. However, lower cell attachment sites and the hypoxic microenvironment in the wound site limit their viability and engraftment rate, leading to programmed cell death, anoikis. We synthesized carboxymethyl cellulose‐coated polylactic acid (CMC‐PLA) particles to prevent anoikis by providing an attachable surface for hMSCs. In vitro experiments demonstrated enhanced viability and secretion of growth factors by hMSCs under severely hypoxic microenvironments, when CMC‐PLA particles provided attachment surfaces, compared to controls. Furthermore, in vivo experiments showed that CMC‐PLA particles injected with hMSCs improved collagen synthesis and wound closure more than those of the control groups. These findings suggest that CMC‐PLA particles effectively enhance the therapeutic potential of hMSCs by providing a supportive microenvironment, promoting cell survival, proliferation, and angiogenesis, thereby offering a promising approach for advanced wound healing therapies.
Design of Zn‐binding Peptide(s) from Protein Fragments
Authors: Kormaník Ján Michael , Herman Daniel , Andris Erik , Culka Martin , Gutten Ondrej , Kožíšek Milan , Bednárová Lucie , Srb Pavel , Veverka Václav , Rulíšek Lubomír 
Published: February 2025

We designed zinc(II)‐binding peptide featuring the Cys2His2 zinc‐finger motif. Several tens of thousands of (His/Cys)‑Xn‑(His/Cys) protein fragments (n = 2 to 20) were extracted from the 3D protein structures deposited in Protein Data Bank. Based on geometrical constraints positioning two Cys (C) and two His (H) side chains at the vertices of a tetrahedron, approximately 22 000 sequences of the (H/C)‑Xi‑(H/C)‑Xj‑(H/C)‑Xk‑(H/C) type, satisfying Nmetal‑binding H = Nmetal‐binding C = 2, were processed. To prove the viability of the computational design experimentally, three peptides were synthesized and subjected to isothermal calorimetry (ITC) measurements to determine the binding constants of Zn2+, including the entropy and enthalpy terms. For the strongest Zn2+ ions binding peptide, P1, the dissociation constant was shown to be in the nanomolar range (KD = ~220 nM; corresponding to DGbind = ‑9.1 kcal·mol‑1). In addition, ITC showed that the [P1:Zn2+] complex forms in 1:1 stoichiometry and two protons are released upon binding, which suggests that the zinc coordination involves both cysteines. NMR experiments also indicated that the structure of the [P1:Zn2+] complex might be quite similar to the computationally predicted one. In summary, our proof‐of‐principle study highlights the usefulness of our computational protocol for designing novel metal‐binding peptides.
Structural and Functional Information of Human Hemoglobin Subunit μ
Authors: Han Hui , Liu Xichun , Wang Yanfei , Yu Lu , Gao Shu‐Qin , Lin Ying‐Wu 
Published: February 2025

AbstractThe human hemoglobin subunit μ (Hb‐μ) has been identified as a potential biomarker for α‐thalassemia. However, little structural and functional information is available for this subunit. Here, we have overexpressed and purified a double mutant of C49S/C104S Hb‐μ and solved its X‐ray crystal structure. It adopts a typical protein fold of the globins, similar to that of the α‐subunit. The structure also reveals that the protein undergoes self‐oxidation of Met62 in the heme distal site, producing the form of sulfoxide (Met‐SO). The property and function have also been studied by spectroscopy, which shows that the protein has considerable peroxidase activity due to the presence of a catalytic His‐Arg pair in the heme distal site. The structure‐function relationship of Hb‐μ obtained in this study may provide useful insights into Hb‐related diseases.
Immune profiling of the macroenvironment in colorectal cancer unveils systemic dysfunction and plasticity of immune cells
Authors: Ke Haoxian , Li Peisi , Li Zhihao , Zeng Xian , Zhang Chi , Luo Shuzhen , Chen Xiaofang , Zhou Xinlan , Dong Shichen , Chen Shaopeng , Huang Junfeng , Yuan Ming , Yu Runfeng , Ye Shubiao , Hu Tuo , Tang Zhonghui , Liu Dongbin , Wu Kui , Wu Xianrui , Lan Ping 
Published: February 2025

AbstractBackgroundTumour immune macroenvironment is comprised of tumour and surrounding organs responding to tumourigenesis and immunotherapy. The lack of comprehensive analytical methods hinders its application for prediction of survival and treatment response in colorectal cancer (CRC) patients.MethodsCytometry by time‐of‐flight (CyTOF) and RNA‐seq was applied to characterise immune cell heterogeneity in a discovery cohort including tumour, blood and intestinal architecture comprising epithelium, lamina propria, submucosa, muscularis propria of normal bowel and tumour–adjacent bowel tissues. Immunoprofiling was also validated by a validation cohort using single‐cell RNA sequencing, spatial transcription, CyTOF and multiplex immunofluorescent staining.ResultsBased on cell phenotype and transcription, we identify distinct immunotypes in the CRC macroenvironment including blood, tumour and different intestinal architecture, showing disturbed immune cell compositions, increasing expression of immunosuppressive markers and cell–cell interactions contributing to immunosuppressive regulation. Furthermore, we evaluate immune macroenvironment influencing factors including tertiary lymphoid structures (TLSs), consensus molecular subtypes (CMSs) and immune checkpoint inhibitors (ICIs). TLS presence fuels anti‐tumour immunity by promoting CD8+ T cell infiltration and altering activation or suppression of T cell systematically. TLS presence correlates with patient survival, intrinsic CMS and therapeutic efficacy of ICI. PD‐1 and CD69 expressed in effector memory CD8+ T cells from blood can predict TLS presence in the CRC macroenvironment, serving as potential biomarkers for stratifying CRC patients into immunotherapy.ConclusionsOur findings provide insights into the CRC immune macroenvironment, highlighting immune cell suppression and activation in tumourigenesis. Our study illustrates the potential utility of blood for predicting immunotherapy response.Key points
Distinct immunotypes are identified in the CRC macroenvironment.
TLS and immunotherapy exert influence on the immune macroenvironment.
TLS presence correlates with patient survival, CMS and therapeutic efficacy of ICI.
PD‐1 and CD69 expressed in CD8+ Tem from blood can predict TLS presence in the CRC macroenvironment.