bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biallelic Loss-of-Function Variants in UBAP1L and Nonsyndromic Retinal Dystrophies
Authors: Ullah Ehsan , Lin Siying , Lu Jiaxiong , Bender Chelsea , Webster Andrew R. , Malka Samantha , Madhusudhan Savita , Rees Emma , Williams Denise , Agather Aime R. , Cukras Catherine A. , Hufnagel Robert B. , Chen Rui , Huryn Laryssa A. , Arno Gavin , Guan Bin 
Published: September 2024

ImportanceInherited retinal dystrophies (IRDs) present a challenge in clinical diagnostics due to their pronounced genetic heterogeneity. Despite advances in next-generation sequencing (NGS) technologies, a substantial portion of the genetic basis underlying IRDs remains elusive. Addressing this gap seems important for gaining insights into the genetic landscape of IRDs, which may help improve diagnosis and prognosis and develop targeted therapies in the future.ObjectiveTo provide a clinical and molecular characterization of 6 patients with IRDs with biallelic disease-causing variants in a novel candidate IRD disease gene.Design, Setting, and ParticipantsThis multicenter case series study included 6 patients with IRDs from 4 tertiary hospitals (in the US: National Eye Institute, National Institutes of Health Clinical Center; in the UK: Moorfields Eye Hospital, Royal Liverpool University Hospital, Birmingham Women’s and Children’s).ExposuresBiallelic disease-causing variants in the novel candidate IRD disease gene, UBAP1L.Main Outcome and MeasuresParticipants underwent comprehensive clinical ophthalmic assessments to characterize the features of retinal dystrophy. Exome and genome sequencing revealed candidate variants in the UBAP1L gene; no other plausible disease variants in known IRD genes were identified. A minigene assay provided functional insights for a noncanonical splice variant, and a knockout mouse model was used for in vivo functional elucidation.ResultsFour homozygous UBAP1L variants were identified in the affected individuals from 6 families, including 2 frameshift variants (c.710del and c.634_644del), 1 canonical splice variant (c.121-2A&amp;gt;C), and 1 noncanonical splice variant (c.910-7G&amp;gt;A), which was shown to cause aberrant splicing and frameshift in a minigene assay. Participants presented with retinal dystrophy including maculopathy, cone dystrophy, and cone-rod dystrophy. Single-cell RNA sequencing of the retina showed that human UBAP1L is highly expressed in both cones and retinal pigment epithelium, whereas mouse Ubap1l is highly expressed in cone cells only. Mice with truncation of the C-terminal SOUBA domain did not manifest retinal degeneration up to 15 months of age.Conclusions and RelevanceStudy results reveal clinical and genetic evidence that loss of UBAP1L function was associated with inherited retinopathy in humans. These findings hold promise for improved clinical diagnostics, prognosis, and the potential development of targeted therapies for individuals affected by IRDs.
SNPs Give LACTB Oncogene‐Like Functions and Prompt Tumor Progression via Dual‐Regulating p53
Authors: Huang Guanyu , Zhang Jiajun , Xu Yu , Wu Fei , Fu Yiwei , Zhang Xuelin , Yin Hanxiao , You Yuanyuan , Zhao Peng , Liu Weihai , Shen Jingnan , Yin Junqiang 
Published: September 2024

AbstractLACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTBM5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene‐like functions to LACTB. Mechanistically, LACTBM5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53R156P protein from lysosomal degradation, which suggesting LACTBM5L+R469K is a dual‐regulator for wt‐p53 and mutant p53, and derive oncogene‐like functions. More importantly, clavulanate potassium, a bacterial β‐lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTBM5L+R469K. These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene‐like functions to LACTB. Inhibiting LACTBM5L+R469K can suppress the progression of osteosarcoma harbouring wild‐type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTBM5L+R469K‐p53 pathway for the treatment of osteosarcoma patients.
Two‐Pronged Attack: Dual Activation of Fat Reduction Using Near‐Infrared‐Responsive Nanosandwich for Targeted Anti‐Obesity Treatment
Authors: Xiao Qiaqia , Tang Lu , Chen Siying , Mei Yijun , Wang Chuying , Yang Jing , Shang Jing , Li Shengliang , Wang Wei 
Published: September 2024

AbstractExcessive fat accumulation and chronic inflammation are two typical characteristics of obesity. AMP‐activated protein kinase (AMPK), a master regulator of energy metabolism, is involved in adipogenesis, lipogenesis, and inflammation modulation in adipose tissue (AT). Thus, effective lipid reduction and anti‐inflammation through AMPK regulation play vital roles in treating obesity. Herein, an anti‐obesity nanosandwich is fabricated through attaching polymetformin (PolyMet) onto photothermal agent black phosphorus nanosheets (BP). PolyMet activates AMPK to inhibit adipogenesis, promote browning, and mitigate AT inflammation by decreasing macrophage infiltration, repolarizing macrophage phenotype, and downregulating pro‐inflammatory cytokines. Additionally, BP induces lipolysis and apoptosis of adipocytes and macrophages through a photothermal effect. By further functionalization using hyaluronic acid (HA) and MMP2 substrate‐linking P3 peptide‐modified HA (P3‐HA), an enhanced anti‐obesity effect is obtained by dual‐targeting of P3 and HA, and HA‐mediated CD44 poly‐clustering after MMP2 cleavage. Upon laser irradiation, the designed nanosandwich (P3‐HA/PM@BP) effectively inhibits obesity development in obese mice, increases M2/M1 ratio in AT, reduces the serum levels of cholesterol/triglyceride and improves insulin sensitivity, exhibiting promising research potential to facilitate the clinical development of modern anti‐obesity therapies.
The inverse association between cancer history and incident cognitive impairment: Addressing attrition bias
Authors: Shardell Michelle , Rathbun Alan M. , Gruber‐Baldini Ann , Ryan Alice S. , Guralnik Jack , Kapogiannis Dimitrios , Simonsick Eleanor M. 
Published: September 2024

AbstractINTRODUCTIONCancer is inversely associated with cognitive impairment. Whether this is due to statistical handling of attrition (death and censoring) is unknown.METHODSWe quantified associations between cancer history and incident cognitive impairment among Health, Aging, and Body Composition Study participants without baseline cognitive impairment or stroke (n = 2604) using multiple competing‐risks models and their corresponding estimands: cause‐specific, subdistribution, and marginal hazards, plus composite‐outcome (cognitive impairment or all‐cause mortality) hazards. All‐cause mortality was also modeled.RESULTSAfter covariate adjustment (demographics, apolipoprotein E ε4, lifestyle, health conditions), cause‐specific and marginal hazard ratios (HRs) were similar to each other (≈ 0.84; P values < 0.05). The subdistribution HR was 0.764 (95% confidence interval [CI] = 0.645–0.906), and composite‐outcome Cox model HR was 1.149 (95% CI = 1.016–1.299). Cancer history was positively associated with all‐cause mortality (HR = 1.813; 95% CI = 1.525–2.156).DISCUSSIONCause‐specific, subdistribution, and marginal hazards models produced inverse associations between cancer and cognitive impairment. Competing risk models answer slightly different questions, and estimand choice influenced findings here.Highlights
Cancer history is inversely associated with incident cognitive impairment.
Findings were robust to handling of competing risks of death.
All models also addressed possible informative censoring bias.
Cancer history was associated with 16% lower hazard of cognitive impairment.
Cancer history was associated with 81% higher all‐cause mortality hazard.
Specifically Editing Cancer Sialoglycans for Enhanced In Vivo Immunotherapy through Aptamer‐Enzyme Chimeras
Authors: Liu Qin , Xing Hang , Xiong Mengyi , Zhang Xiao‐Bing 
Published: September 2024

AbstractImmune checkpoint blockade (ICB) therapies have demonstrated remarkable clinical success in treating cancer. However, their objective response rate remains suboptimal because current therapies rely on limited immune checkpoints that fail to cover the multiple immune evasion pathways of cancer. To explore potential ICB strategies, we propose a glycoimmune checkpoint elimination (glycoICE) therapy based on targeted editing of sialoglycans on the tumor cell surface using an aptamer‐enzyme chimera (ApEC). The ApEC can be readily generated via a one‐step bioorthogonal procedure, allowing for large‐scale and uniform production. It specifically targets and desialylates cancer cells, disrupting the sialoglycan‐Siglec axis to activate immune cells and enhance immunotherapy efficacy, while its high tumor selectivity minimizes side effects from indiscriminate desialylation of normal tissues. Furthermore, the ApEC has the potential to be a versatile platform for specific editing of sialoglycans in different tumor models by adjusting the aptamer sequences to target specific protein markers. This research not only introduces a novel molecular tool for the effective editing of sialoglycans in complex environments, but also provides valuable insights for advancing DNA‐based drugs towards in vivo and clinical applications.
Facile Synthesis of Fe‐Based Metal‐Quinone Networks for Mutually Enhanced Mild Photothermal Therapy and Ferroptosis
Authors: Liu Zhendong , Liu Sainan , Liu Bin , Meng Qi , Yuan Meng , Ma Xinyu , Wang Jiwei , Wang Meifang , Li Kai , Ma Ping'an , Lin Jun 
Published: September 2024

AbstractMild photothermal therapy (MPTT) has emerged as a promising therapeutic modality for attenuating thermal damage to the normal tissues surrounding tumors, while the heat‐induced upregulation of heat shock proteins (HSPs) greatly compromises the curative efficacy of MPTT by increasing cellular thermo‐tolerance. Ferroptosis has been identified to suppress the overexpression of HSPs by the accumulation of lipid peroxides and reactive oxygen species (ROS), but is greatly restricted by overexpressed glutathione (GSH) in tumor microenvironment and undesirable ROS generation efficiency. Herein, a synergistic strategy based on the mutual enhancement of MPTT and ferroptosis is proposed for cleaving HSPs to recover tumor cell sensitivity. A facile method for fabricating a series of Fe‐based metal‐quinone networks (MQNs) by coordinated assembly is proposed and the representative FTP MQNs possess high photothermal conversion efficiency (69.3 %). Upon 808 nm laser irradiation, FTP MQNs not only trigger effective MPTT to induce apoptosis but more significantly, potentiate Fenton reaction and marked GSH consumption to boost ferroptosis, and the reinforced ferroptosis effect in turn can alleviate the thermal resistance by declining the HSP70 defense and reducing ATP levels. This study provides a valuable rationale for constructing a large library of MQNs for achieving mutual enhancement of MPTT and ferroptosis.
Restricting Linker Rotation in Nanocages of ZIF‐8 Membranes using Crown Ether “Molecular Locks” for Enhanced Propylene/Propane Separation
Authors: Zhang Zinan , Zhu Han , Jin Hua , Cao Yi , Fang Wei , Zhang Zhenxin , Ma Qiang , Choi Jungkyu , Li Yanshuo 
Published: September 2024

AbstractZIF‐8 membranes have long been prized for their exceptional C3H6/C3H8 separation performance. On the other hand, ZIF‐8 has structural flexibility, where the external pressure triggers channel expansion, potentially deteriorating the molecular sieving ability. Here, we demonstrate a reliable strategy to fine‐tune the flexible pore structure of ZIF‐8 by embedding crown ether within a ZIF‐8 membrane. Benzo‐15‐crown‐5 (15C5) was selected as the cavity occupant and perfectly confined in the sodalite (SOD) cage of ZIF‐8. The 15C5 molecules, which have a size comparable to the nanocage, impose a spatial constraint on linker rotation, enabling the phase transition to a rigid structure in the flexible ZIF‐8. The corresponding 15C5@ZIF‐8 membranes achieve an ultrahigh C3H6/C3H8 selectivity of 220, outperforming that of most membranes. Unlike their flexible counterparts, the resulting membranes manifest a positive increase in the C3H6/C3H8 separation factor with elevated pressure, securing a record‐high C3H6/C3H8 separation factor of 331 under 7 bar. More importantly, extraordinary separation stability was demonstrated with continuous measurement, which is highly desirable for practical applications.
Ultra‐High Metal‐Ion Selectivity Induced by Intramolecular Cation‐π Interactions for the One‐Pot Synthesis of Precise Heterometallic Architectures
Authors: Shi Junjuan , Li Kehuan , Yu Hao , Han Ningxu , Yang Tianyi , Jiang Xin , Hao Xin‐Qi , Chen Zhi , Wu Guanglu , Zhang Houyu , Li Bingling , Wang Ming 
Published: September 2024

AbstractHeterometallic supramolecules, known for their unique synergistic effects, have shown broad applications in photochemistry, host‐guest chemistry, and catalysis. However, there are great challenges to precisely construct heterometallic supramolecules rather than a statistical mixture, due to the limited metal‐ion selectivity of coordination units. In particular, heterometallic architectures precisely encoded with different metal ions usually fail to form in a one‐pot method when only one type of coordinated motif exists due to its poor metal‐ion selectivity. Herein, we propose an effective intramolecular cation‐π (ICπ) strategy and successfully constructed the heterometallic supramolecule Zn2Cu4L34 by the one‐pot self‐assembly of tritopic terpyridyl ligand L3 with Zn(II) and Cu(II), following a clear self‐assembly mechanism in which only thermodynamic dimers ZnL12 and Cu2L22 were constructed with model ligands L1, L2, Zn(II) and Cu(II) with perfect self‐sorting and an ultra‐high metal‐selectivity feature. The successful construction of the heterometallic supramolecule Zn2Cu4L34, in which the definite sequence of metal ions Zn(II) and Cu(II) is encoded in the one‐pot method, will offer a novel approach to precisely construct heterometallic architectures.
A Nematode Isolate, Oscheius tipulae, Exhibiting a Wide Entomopathogenic Spectrum and its Application to Control Dipteran Insect Pests
Authors: Abdisa Eticha , Esmaeily Mojtaba , Kwon Jiyoon , Jin Gahyeon , Kim Yonggyun 
Published: September 2024

ABSTRACTAn entomopathogenic nematode, Oscheius tipulae, was isolated from a soil sample. The identification of this species was supported by morphological and molecular markers. The nematode isolate exhibited pathogenicity against different target insects including lepidopteran, coleopteran, and dipteran insects. The virulence of this nematode was similar to that of a well‐known entomopathogenic nematode, Steinernema carpocapsae, against the same insect targets. A comparative metagenomics analysis of these two nematode species predicted the existence of a combined total of 272 bacterial species in their intestines, of which 51 bacterial species were shared between the two nematode species. In particular, the common gut bacteria included several entomopathogenic bacteria including Xenorhabdus nematophila, which is known as a symbiotic bacterium to S. carpocapsae. The nematode virulence of O. tipulae to insects was enhanced by an addition of dexamethasone but suppressed by an addition of arachidonic acid, suggesting that the immune defenses of the target insects against the nematode infection is mediated by eicosanoids, which would be manipulated by the symbiotic bacteria of the nematode. Unlike S. carpocapsae, O. tipulae showed high virulence against dipteran insects including fruit flies, onion flies, and mosquitoes. O. tipulae showed particularly high control efficacies against the onion maggot, Delia platura, infesting the Welsh onion in the rhizosphere in both pot and field assays.
Autism is associated with in vivo changes in gray matter neurite architecture
Authors: Christensen Zachary P. , Freedman Edward G. , Foxe John J. 
Published: September 2024

AbstractPostmortem investigations in autism have identified anomalies in neural cytoarchitecture across limbic, cerebellar, and neocortical networks. These anomalies include narrow cell mini‐columns and variable neuron density. However, difficulty obtaining sufficient post‐mortem samples has often prevented investigations from converging on reproducible measures. Recent advances in processing magnetic resonance diffusion weighted images (DWI) make in vivo characterization of neuronal cytoarchitecture a potential alternative to post‐mortem studies. Using extensive DWI data from the Adolescent Brain Cognitive Developmentsm (ABCD®) study 142 individuals with an autism diagnosis were compared with 8971 controls using a restriction spectrum imaging (RSI) framework that characterized total neurite density (TND), its component restricted normalized directional diffusion (RND), and restricted normalized isotropic diffusion (RNI). A significant decrease in TND was observed in autism in the right cerebellar cortex (β = −0.005, SE =0.0015, p = 0.0267), with significant decreases in RNI and significant increases in RND found diffusely throughout posterior and anterior aspects of the brain, respectively. Furthermore, these regions remained significant in post‐hoc analysis when the autism sample was compared against a subset of 1404 individuals with other psychiatric conditions (pulled from the original 8971). These findings highlight the importance of characterizing neuron cytoarchitecture in autism and the significance of their incorporation as physiological covariates in future studies.
Design of casein‐based nanocarriers for targeted delivery of daunorubicin to leukemia cells
Authors: Beigrezaei Ali , Rafipour Ronak 
Published: September 2024

AbstractDaunorubicin (DAU) is a chemotherapy drug approved for the treatment of some cancers. However, the clinical compatibility of DAU is limited due to its lack of specificity and its highly toxic effects, which interfere with normal cells. This toxicity can be reduced with nanocarriers and targeted drug delivery systems. In this study, to develop the drug delivery of DAU, the surface of synthesized nanoparticles was modified by folic acid to target cancer cells optimally. Encapsulation of DAU in protein sodium caseinate (NaCAS) was done by adding calcium ions to bring the casein (CAS) in the solution to a micellar structure to synthesize dense nanoparticles. Fourier‐transform infrared spectroscopy transmission, fluorescence spectroscopy, UV–Vis spectroscopy, field emission scanning electron microscopy, and zeta potential studies designed and distinguished the synthesized nanocomplexes. The results showed that CAS nanoparticles successfully encapsulated DAU, and the protein surface was targeted by folic acid. Light scattering analysis determined that the particles with a scattering index number of 306.0 and an average size of 8.117 nm were synthesized. The zeta potential of CAS micelles is more harmful than CAS nanoparticles. This is because calcium ions are added during the formation of CAS nanoparticles during the drug‐loading stages. These studies prove that the synthesized “NaCAS‐DAU” and “NaCAS‐DAU‐folic acid” complexes can be favorable carriers in the targeted drug delivery of cancer drugs.
Virtual reality for training on measuring human exposure to electromagnetic fields around cellular base stations
Authors: Cuiñas Iñigo , González‐Alonso Iago , Expósito Isabel , García‐Sánchez Manuel , Torío Pablo 
Published: September 2024

AbstractAssessing of human exposure to electromagnetic field is one of the tasks of a telecommunication engineer. This activity has significant social interest, as the measured levels must comply with health safety limits. It is also an appealing area for students as it integrates concepts related to radiofrequency, antennas, and propagation, both theoretically and practically. We offer our students practical activities for measuring field levels, using test and measurement equipment. Additionally, we have developed a virtual reality tool to enhance our students' skills in this area, which is presented in this paper. We compare the learning outcomes of two separate groups of students to validate the performance of this new tool. The first group attended a lesson with theoretical content and then performed outdoor measurements. The second group had the added virtual reality experience before using the test equipment. Quantitative results show an improvement in the assimilation of the concepts, and qualitative feedback from the users confirms the effectiveness of this approach.
Essential Oils of Neotropical Myrtaceae Species From 2011 Until 2023: An Update
Authors: de Amorim Magali S. , Verdan Maria H. , Oliveira Cristhian S. , Santos Alan D. C. 
Published: September 2024

AbstractThe Myrtaceae family is renowned for its rich diversity of bioactive metabolites with broad applications across various industries. This review comprehensively explores the chemical composition and biological activities of Neotropical species within the Myrtaceae family from 2011 to 2023. A total of 170 papers were analyzed, covering 148 species from 28 genera, with notable emphasis on Eugenia, Eucalyptus, Myrcia, and Psidium. Compounds with relative abundance exceeding 10 % were tabulated to highlight the most significant volatiles for each genus. Our findings were cross‐referenced with previous reviews whenever feasible. Antioxidant, antibacterial, and antimicrobial activities emerged as the primary focus, collectively representing 41 % of the studies, predominantly conducted in vitro. Additionally, we discuss less conventional approaches to essential oil studies in Myrtaceae species, underscoring avenues for future exploration. The investigation of essential oils from Myrtaceae holds promise for significant advancements in biotechnology, with potential benefits for the economy, environment, and human health. This review serves as a valuable resource for guiding future research strategies in this field.
Aromaticity in Isoelectronic Analogues of Benzene, Carborazine and Borazine, from Electronic Structure and Magnetic Property
Authors: Wu Yang , Yan Xiufen , Liu Zeyu , Lu Tian , Zhao Mengdi , Xu Jingbo , Wang Jiaojiao 
Published: September 2024

AbstractCarborazine (B2C2N2H6) and borazine (B3N3H6) are isoelectronic analogues of benzene (C6H6). The aromatic character of borazine have basically reached a consensus after a long period of controversy, but the related properties of carborazine are even rarely reported. In this work, we systematically investigated the geometric structure, charge distribution, frontier molecular orbital characteristics, bonding, electronic delocalization, magnetic shielding effect, and induced ring current of carborazine and borazine, and compared the studied characteristics with those of benzene to determine the aromatic character of the two analogues. The combination of multiple properties shows that although they are isoelectronic, carborazine is evidently aromatic, while borazine only exhibits rather weak aromaticity. The C atom acting as a connecting bridge between B and N atoms in carborazine reduces the electronegativity difference on the molecular backbone and enhances the electronic delocalization over the conjugated path, which is the essence of the distinct disparity of aromaticity between carborazine and borazine.