bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates of Sudden Unexpected Infant Death Before and During the COVID-19 Pandemic
Authors: Guare Emma G. , Zhao Rong , Ssentongo Paddy , Batra Erich K. , Chinchilli Vernon M. , Paules Catharine I.
Published: September 2024

Importance

Infection has been postulated as a driver in the sudden infant death syndrome (SIDS) cascade. Epidemiologic patterns of infection, including respiratory syncytial virus and influenza, were altered during the COVID-19 pandemic. Comparing month-to-month variation in both sudden unexpected infant death (SUID) and SIDS rates before and during the pandemic offers an opportunity to generate and expand existing hypotheses regarding seasonal infections and SUID and SIDS.

Objective

To compare prepandemic and intrapandemic rates of SUID and SIDS, assessing for monthly variation.

Design, Setting, and Participants

This cross-sectional study assessed US mortality data provided by the Centers for Disease Control and Prevention for January 1, 2018, through December 31, 2021. Events with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for SIDS (R95), unknown (R99), and accidental suffocation and strangulation in bed (W75) causes of death were examined. The data analysis was performed between November 2, 2023, and June 2, 2024.

Exposure

COVID-19 pandemic.

Main Outcomes and Measures

The primary and secondary outcomes were the monthly rates of SUID and SIDS during the COVID-19 pandemic (March 1, 2020, to December 31, 2021) compared with the prepandemic period (March 1, 2018, to December 31, 2019) as measured using generalized linear mixed-effects models. Seasonal trends in RSV and influenza rates were also examined.

Results

There were 14 308 SUID cases from January 1, 2018, to December 31, 2021 (42% female infants). Compared with the prepandemic period, the risk of SUID increased during the intrapandemic period (intensity ratio [IR], 1.06; 95% CI, 1.05-1.07). Monthly assessments revealed an increased risk of SUID beyond the prepandemic baseline starting in July 2020, with a pronounced epidemiologic shift from June to December 2021 (ranging from 10% to 14%). Rates of SIDS were elevated throughout the intrapandemic period compared with the prepandemic baseline, with the greatest increase in July 2021 (IR, 1.18; 95% CI, 1.13-1.22) and August 2021 (IR, 1.17; 95% CI, 1.13-1.22). Seasonal shifts in RSV hospitalizations correlated with monthly changes in SUID observed during 2021.

Conclusions and Relevance

This cross-sectional study found increased rates of both SUID and SIDS during the COVID-19 pandemic, with a significant shift in epidemiology from the prepandemic period noted in June to December 2021. These findings support the hypothesis that off-season resurgences in endemic infectious pathogens may be associated with SUID rates, with RSV rates in the US closely approximating this shift. Further investigation into the role of infection in SUID and SIDS is needed.
Complete Response to Locoregional Therapy Plus Immunotherapy for Hepatocellular Carcinoma
Authors: Chiang Chi Leung , Chan Kenneth Sik Kwan , Chiu Keith Wan Hang , Lee Francis Ann Shing , Chen Wenqi , Wong Natalie Sean Man , Ho Ryan Lok Man , Lee Venus Wan Yan , Man Kwan , Kong Feng Ming (Spring) , Chan Albert Chi Yan
Published: September 2024

Importance

Previous studies showed that 42% to 50% of patients with locally advanced hepatocellular carcinoma (HCC) achieved complete remission (CR) after combined locoregional therapy (LRT) plus immunotherapy (IO). However, data on predictors of CR and long-term clinical outcomes without surgery and after discontinuation of IO are lacking.

Objective

To assess the long-term clinical outcomes among patients with unresectable HCC who achieved CR after LRT-IO and were placed on a watch-and-wait protocol.

Design, Setting, and Participants

This cohort study included patients with unresectable HCC who achieved CR after LRT-IO in 2 prospective studies between January 2018 and December 2022. The time of data cutoff was June 2023. Radiologic CR was defined per modified Response Evaluation Criteria in Solid Tumors. All patients underwent close surveillance after CR without surgical interventions, and IO was discontinued.

Exposure

All patients had received stereotactic body radiotherapy followed by anti–programmed cell death protein 1 or anti–programmed death ligand 1 therapy. Forty-nine patients had received a dose of transarterial chemoembolization before stereotactic body radiotherapy.

Main Outcomes and Measures

The primary outcome was the 3-year overall survival (OS) rate. Secondary outcomes included the 3-year time-to-progression rate, 3-year local control rate, and relapse pattern. Factors associated with CR were analyzed using multivariate analyses.

Results

A total of 63 patients were enrolled (58 male [92.1%]; median age, 69 years [range, 18-90 years]); 38 patients (60.3%) had macrovascular invasion, and the median tumor diameter was 10 cm (range, 3.8-31.1 cm). The median follow-up time was 34.7 months (95% CI, 6.5-64.6 months). Twenty-nine patients (46.0%) achieved CR. The patients achieving CR had a significantly better 3-year OS rate than patients not achieving CR (75.5% [95% CI, 58.2%-98.3%] vs 28.1% [95% CI, 7.4%-29.4%]; P < .001). Among the 29 patients with CR, the 3-year time-to-progression rate was 58.7% (95% CI, 38.7%-79.1%) and the 3-year local control rate was 90.5% (95% CI, 78.2%-100%). Ten patients (34.5%) developed recurrence; among them, 6 (60.0%) with solitary intrahepatic disease relapse underwent curative surgical treatment. The absence of tumor vascular invasion (odds ratio, 0.30; 95% CI, 0.10-0.89) and the sum of the largest lesion diameters of 8 cm or less (odds ratio, 0.26; 95% CI, 0.07-0.98) were associated with CR.

Conclusions and Relevance

This cohort study of LRT-IO with long-term follow-up data found a durable response in patients with locally advanced unresectable HCC. Long-term survival was attainable in patients with radiologic CR. Further randomized clinical trials are warranted.
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

Importance

Inherited 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.

Objective

To 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 Participants

This 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).

Exposures

Biallelic disease-causing variants in the novel candidate IRD disease gene, UBAP1L.

Main Outcome and Measures

Participants 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.

Results

Four 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>C), and 1 noncanonical splice variant (c.910-7G>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 Relevance

Study 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

LACTB 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

Excessive 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

INTRODUCTION

Cancer is inversely associated with cognitive impairment. Whether this is due to statistical handling of attrition (death and censoring) is unknown.

METHODS

We 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.

RESULTS

After 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).

DISCUSSION

Cause‐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

Immune 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

Mild 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

ZIF‐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

Heterometallic 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

An 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

Postmortem 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

Daunorubicin (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

Assessing 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

The 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

Carborazine (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.
Analytical and Diagnostic Performance of a Dual‐Target Blood Detection Test for Hepatocellular Carcinoma
Authors: Yang Qiankun , Dong Lanlan , Zhang Lianglu , Zhang Wei , Zhang Yan , Huang Yue , Jin Huifang , Yang Hao , Liu Xing , Zhao Yanteng
Published: September 2024

Background

Surveillance approaches with high sensitivity and specificity for hepatocellular carcinoma (HCC) are still urgently needed. Previous studies have shown that methylation of GNB4 and Riplet can effectively diagnose HCC.

Aims

This study plan to analyze the performance of a blood test for detecting HCC using GNB4 and Riplet methylation.

Methods and Results

This study mainly investigated the analytical performance of the dual‐target HCC blood test (DT‐HBT), including cut‐off value, limit of detection (LOD), precision, analytical specificity, and coincidence rate. In addition, the detection performance for HCC was validated in 1030 clinical plasma samples (214 HCC and 816 non‐HCC). Plasma samples from 25 HCC patients after hepatectomy were collected to assess the feasibility of the kit for postoperative recurrence monitoring. All analytical performance of the DT‐HBT met prespecified requirements. The LOD for GNB4, Riplet, and β‐actin was 1% methylation/100 copies/μL with cut‐offs of 43, 43, and 35, respectively. The DT‐HBT showed excellent precision, within 5% CV. It had a specificity of 91.5% for detecting other cancers, and 100% for breast, lung, and bladder cancer. No cross‐reactions were observed with 9 potential interfering substances. The DT‐HBT achieved a 100% coincidence rate in detecting reference and clinical samples. The clinical performance study found that the kit showed a sensitivity of 81.7% for stage I HCC, and an overall sensitivity and specificity of 87.4% and 92.3%, respectively. The detection sensitivity for postoperative recurrent patients was 95.8%, with a specificity of 100%.

Conclusion

The analytical performance of the DT‐HBT met prespecified criteria. It provided HCC patients with a reliable and high‐performing new blood test for the HCC diagnosis and surveillance.

Trial Registration

ClinicalTrials.govidentifier: NCT05685524
Complex epilepsy phenotype associated with chromosome 2q24.2‐q24.3 deletion involving sodium channel gene cluster
Authors: Madan Rima , Guido Fiorella S. , Brescia Nicole
Published: September 2024

Objective

The 2q24.2‐24.3 chromosome region encodes sodium channel genes important in severe childhood epilepsy, notably SCN1A linked to Dravet syndrome (DS). However, the roles of other genes, either within the SCN cluster or in the segments proximal to it, have not been clearly delineated. The combination of ketogenic diet and fenfluramine is known to provide substantial benefits to patients with DS, but there is a paucity of literature regarding its role in other developmental and epileptic encephalopathies (DEE). This report aims to further explore clinical findings and treatment outcomes in a patient with a complex epilepsy phenotype.

Methods

Our patient's extensive diagnostic evaluation revealed 14 deleted genes within the 2q24.2‐24.3 chromosome region.

Results

The patient initially presented with clusters of focal motor seizures with apnea and cyanosis requiring intubation as well as prolonged hospitalizations for status epilepticus. He has baseline hypotonia, dysphagia, and developmental delay. He had a >50% reduction in his seizures following a combination of ketogenic diet and fenfluramine. His seizures are now responsive to rescue midazolam, and he no longer has status epilepticus.

Interpretation

Our patient's remarkable clinical improvement suggests that this dual therapy may be beneficial in patients with DEE exhibiting pathogenic variations in this region of chromosome 2, beyond just DS.
A Sonochemical and Mechanochemical One‐Pot Multicomponent/Click Coupling Strategy for the Sustainable Synthesis of Bis‐Heterocyclic Drug Scaffolds
Authors: Rentería‐Gómez Manuel A. , Calderón‐Rangel David , Corona‐Díaz Alejandro , Gámez‐Montaño Rocío
Published: September 2024

Bis‐heterocycles were synthesized via a consecutive one‐pot process by a Groebke‐Blackburn‐Bienaymé reaction (GBB‐3CR) followed by Copper‐catalyzed Alkyne‐Azide Cycloaddition (CuAAC) assisted by alternative sustainable energies (ASE) such as ultrasonic and mechanical. These efficient and convergent strategies allowed the in situ generation of complex azides functionalized with imidazo[1,2‐a]pyridines (IMPs), which was used as a synthetic platform. The target molecules contain two privileged scaffolds in medicinal chemistry: IMPs and the heterocyclic bioisostere of trans‐amide bond, the 1,4‐disubstituted 1H‐1,2,3‐triazoles (1,4‐DS‐1,2,3‐Ts).
Deciphering the Degradation Mechanism Induced by the Air‐Exposure in Li2NiO2 and the Recovery Strategy
Authors: Li Shirui , Xiao Kuikui , Liu Xi , Sun Jiangdong , Cai Dong , Yang Shuo , Zhang Yinhang , Nie Huagui , Yang Zhi
Published: September 2024

Cathode prelithium agent is regarded as the most applicable approach to compensate the initial capacity loss in lithium ion batteries (LIBs). Li2NiO2 (LNO) has attracted numerous attention due to its superior environmental stability and reliable synthesis approach. To promote the commercial application of LNO, the understanding of the degradation mechanism induced by air‐exposure and finding reliable strategies to improve the air stability are necessary. Herein, by preserving the LNO in different environments (relative humidity of 70 % and 40 %), the surface chemistry evolution of LNO is subtly investigated, which shows Li2CO3 and LiOH cover the surface of the LNO, which decline the Li+ diffusion kinetics as well as the charge capacity. What′s more, the slurry turns gel when the LNO exposed to the environment of 70 % relative humidity for 2 days and 40 % relative humidity for 5 days. Facile approaches, including washing the deteriorative LNO with ethanol, reacting the alkali components with H3BO3, and coating the LNO with Al2O3 are conducted to recover the disabled LNO, which retains 84.2 % of initial capacity. In addition, a coating approach is proposed for the fresh LNO to effectively improve the air stability. This work provides guideline to the commercial application of the LNO.
Terahertz Wave Absorption of a Rubidium Manganese‐Iron Prussian Blue Phase Transition Material
Authors: Mineo Yuuki , Nakabayashi Koji , Tokoro Hiroko , Imoto Kenta , Namai Asuka , Yoshikiyo Marie , Ohkoshi Shin‐ichi
Published: September 2024

Rubidium manganese hexacyanidoferrate, Rb0.97Mn[Fe(CN)6]0.99 ⋅ 0.5H2O, which has a three‐dimensional cyanido‐bridged Mn−Fe framework encapsulating Rb+ ions, shows a terahertz (THz) wave absorption property. This compound undergoes a charge‐transfer phase transition between FeIII‐CN‐MnII [high temperature (HT) phase] and FeII‐CN‐MnIII [low temperature (LT) phase] near room temperature. The HT phase exhibits a THz wave absorption at 1.06 THz due to the slow vibration of the heavy Rb+ ions encapsulated in the three‐dimensional framework. By contrast, the LT phase displays a higher resonance frequency at 1.13 THz. This shift to a higher frequency is attributed to the framework shrinkage, which decreases the space available for the trapped Rb+ ion. Indeed, the void volume accompanying the phase transition decreases by 16.4 % from 41.4 Å3 (HT phase) to 34.6 Å3 (LT phase). Tuning the THz wave absorption frequency is necessary for THz devices such as absorbers, switches, filters, and modulators, especially for THz technology with THz waves in the sub‐THz region or near 1 THz.
Deionized Water Pretreated Polyimide Nanofiber Membranes as Framework for Polymer Electrolytes Applied to Solid‐State Lithium Metal Batteries
Authors: Liu Yongqi , Chen Zijian , Li Haoyu , Hu Junyu , Xu Zhengbing , Zhu Jinliang
Published: September 2024

Incorporating a water‐immersed polyimide membrane (WPI) as a framework into a polymer electrolyte PEO/SN/LiTFSI (PSL) can address the challenges faced by solid‐state polymer electrolytes in practical applications for all‐solid‐state lithium‐ion batteries (ASSLIBs) used in flexible and wearable electronics. The inferior mechanical performance and inadequate ionic conductivity of polymer electrolytes have hampered their widespread use. By utilizing a matrix of polyethylene oxide (PEO) along with succinonitrile (SN) and lithium bis(trifluoromethane)sulfonimide (LiTFSI) as additives, the WPI enhances the stability of the PSL electrolyte structure through reinforced internal hydrogen bonds of poly(amic acid), its precursor, post‐thermal imidization in the presence of deionized water. This structural enhancement leads to improved mechanical properties, evidenced by a tensile strength of 12.2 MPa at a high porosity of 85.6%. The WPI‐PSL electrolyte exhibits favorable ionic conductivity, thermal stability, and electrochemical compatibility with lithium metal. As a result, the WPI‐PSL configuration demonstrates exceptional performance in a LiFePO4/Li ASSLIBs system, showcasing outstanding cycling performance at both 30 and 60 °C, with capacity retention ratios reaching 94.6% and 96% after 100 cycles at 0.3 C, respectively. This research significantly advances the development of polymer solid‐state electrolytes, propelling their use in flexible power sources for ASSLIBs.
The impact of digital inequities on salivary gland cancer disparities in the United States
Authors: Bruss David M. , Fei‐Zhang David J. , Kim Helena , Chelius Daniel C. , Sheyn Anthony M. , Maddalozzo John P. , Rastatter Jeffrey C. , D'Souza Jill N.
Published: September 2024

Introduction

Technology and internet access have become increasingly integrated into healthcare as the primary platform for health‐related information and provider‐patient communication. Disparities in access to digital resources exist in the United States and have been shown to impact health outcomes in various head and neck malignancies. Our objective is to evaluate the associations of digital inequity on health outcomes in patients with salivary gland cancer (SGC).

Methods

The Digital Inequity Index (DII) was developed using 17 census‐tract level variables obtained from the American Community Survey and Federal Communications Commission. Variables were categorized as digital infrastructure or sociodemographic (e.g., non‐digital) and scored based on relative rankings across all US counties. Scores were assigned to patients from the Surveillance‐Epidemiology‐End Results (SEER) database diagnosed with SGC between 2013 and 2017 based on county‐of‐residence. Regressions were performed between DII score and outcomes of surveillance time, survival time, tumor stage at time of diagnosis, and treatment modality.

Results

Among 9306 SGC‐patients, increased digital inequity was associated with advanced‐staging at presentation (OR: 1.04, 95% CI: 1.01–1.07, p = 0.033), increased odds of chemotherapy receipt (OR: 1.05, CI: 1.01–1.10, p = 0.010), and decreased odds of surgical intervention (OR: 0.94, 95% CI: 0.91–0.98, p = 0.003) after accounting for traditional sociodemographic factors. Increased digital inequity was also associated with decreased surveillance time and survival periods.

Conclusions

Digital inequity significantly and independently associates with negative health and treatment outcomes in SGC patients, highlighting the importance of directed efforts to address these seldom‐investigated drivers of health disparities.
Head and neck sarcomas: Thirty years of experience in a tertiary referral center in Brazil
Authors: Cattan Marcelo Elias Schempf , Kimura Talita de Carvalho , Lavareze Luccas , Egal Erika Said Abu , Altemani Albina , Mariano Fernanda Viviane
Published: September 2024

Purpose

This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil.

Materials and methods

HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow‐up information. The Pearson chi‐square test, Kaplan–Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors.

Results

A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow‐up period of 71.9 months, from diagnosis to the last follow‐up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow‐up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence.

Conclusion

In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.
Septins: Structural Insights, Functional Dynamics, and Implications in Health and Disease
Authors: Das Aurosikha , Kunwar Ambarish
Published: September 2024

Septins are a class of proteins with diverse and vital roles in cell biology. Structurally, they form hetero‐oligomeric complexes and assemble into filaments, contributing to the organization of cells. These filaments act as scaffolds, aiding in processes like membrane remodeling, cytokinesis, and cell motility. Functionally, septins are essential to cell division, playing essential roles in cytokinetic furrow formation and maintaining the structural integrity of the contractile ring. They also regulate membrane trafficking and help organize intracellular organelles. In terms of physiology, septins facilitate cell migration, phagocytosis, and immune responses by maintaining membrane integrity and influencing cytoskeletal dynamics. Septin dysfunction is associated with pathophysiological conditions. Mutations in septin genes have been linked to neurodegenerative diseases, such as hereditary spastic paraplegias, underscoring their significance in neuronal function. Septins also play a role in cancer and infectious diseases, making them potential targets for therapeutic interventions. Septins serve as pivotal components of intracellular signaling networks, engaging with diverse proteins like kinases and phosphatases. By modulating the activity of these molecules, septins regulate vital cellular pathways. This integral role in signaling makes septins central to orchestrating cellular responses to environmental stimuli. This review mainly focuses on the human septins, their structural composition, regulatory functions, and implication in pathophysiological conditions underscores their importance in fundamental cellular biology. Moreover, their potential as therapeutic targets across various diseases further emphasizes their significance.
Diagnostic Performance of CLEIA Versus FEIA for KL‐6 Peripheral and Alveolar Concentrations in Fibrotic Interstitial Lung Diseases: A Multicentre Study
Authors: d'Alessandro Miriana , Gangi Sara , Paggi Irene , Soccio Piera , Bergantini Laura , Pianigiani Tommaso , Montuori Giusy , Moriondo Giorgia , Natalello Giulio , Marrucci Sofia , Brogna Alfonso , Scioscia Giulia , Lacedonia Donato , Cameli Paolo , Bargagli Elena
Published: September 2024

Background

Interstitial lung diseases (ILD) is a group of lung disorders characterized by interstitial lung thickening due to inflammatory and fibrotic processes. Krebs von den Lungen‐6 (KL‐6) is a molecule secreted by damaged type II alveolar pneumocytes in the alveolar space. The goal of the present study was to compare two detection methods of KL‐6 in both bronchoalveolar lavage (BAL) and serum from ILD patients at the moment of diagnosis.

Methods

Patients with suspicious of ILD and followed at two Italian referral centres for rare lung diseases were included in the study. BAL fluid and serum were collected and analysed by chemiluminescent enzyme immunoassay (CLEIA) and fluorescent enzyme immunoassay (FEIA) methods provided by Tosoh Biosciences.

Results

A total of 158 (mean age ± standard deviation, 61.5 ± 13.7, 65 females) patients were enrolled. A total of, 36 had diagnosis of idiopathic pulmonary fibrosis (IPF), 74 sarcoidosis, 15 connective tissue disease‐ILD (CTD‐ILD) and 33 other ILD. Diagnostic agreement between two methods was demonstrated for both BAL (r = 0.707, p < 0.0001) and serum (r = 0.816, p < 0.0001). BAL KL‐6 values were lower than serum (p < 0.0001). IPF patients had higher serum KL‐6 concentration than other ILDs (p = 0.0294), while BAL KL‐6 values were lower in IPF than in non‐IPF (p = 0.0023).

Conclusion

This study explored KL‐6 concentrations through the CLEIA method in serum and BAL of patients with various ILDs, showing significant differences of biomarkers concentrations between IPF and other non‐IPF ILDs. Our findings are promising as they provided further knowledge concerning KL‐6 expression across different ILDs and may suggest its utility in differential diagnosis.