bluuebunny/crossref_metadata_2025 huggingface dataset:
Microtubule polymerization induced by iridium‐fullerene photosensitizers for cancer immunotherapy via dual‐reactive oxygen species regulation strategy
Authors: Chen Xiao‐Xiao , Peng Kun , Chen Xi , Pan Zheng‐Yin , Shen Qing‐Hua , Ling Yu‐Yi , Zhao Jian‐Zhang , Tan Cai‐Ping
Published: June 2024

Microtubules (MTs) are key players in cell division, migration, and signaling, and they are regarded as important targets for cancer treatment. In this work, two fullerene (C60)‐functionalized Ir(III) complexes (Ir‐C601 and Ir‐C602) are rationally designed as dual reactive oxygen species (ROS) regulators and MT‐targeted Type I/II photosensitizers. In the dark, Ir‐C601 and Ir‐C602 serve as ROS scavengers to eliminate O2•− and •OH, consequently reducing the dark cytotoxicity and reversing dysfunctional T cells. Due to the efficiently populated C60‐localized intraligand triplet state, Ir‐C601 and Ir‐C602 can be excited by green light (525 nm) to produce O2•− and •OONO− (Type I) and 1O2 (Type II) to overcome tumor hypoxia. Moreover, Ir‐C601 is also able to photooxidize tubulin, consequently interfering with the cellular cytoskeleton structures, inducing immunogenic cell death and inhibiting cell proliferation and migration. Finally, Ir‐C601 exhibits promising photo‐immunotherapeutic effects both in vitro and in vivo. In all, we report here the first MT stabilizing photosensitizer performing through Type I/II photodynamic therapy pathways, which provides insights into the rational design of new photo‐immunotherapeutic agents targeting specific biomolecules.
Disparities in seeking care for olfactory and gustatory dysfunction: A population analysis
Authors: Gorelik Daniel , Dhanda Aatin K. , Khan Najm S. , Takashima Masayoshi , Nisar Tariq , Brissett Ella , Ramanathan Murugappan , Pinto Jayant M. , Rowan Nicholas R. , Ahmed Omar G.
Published: June 2024

Introduction

Despite effects on quality of life from olfactory and gustatory dysfunction (OD and GD), screening practices are limited, and patients’ self‐reporting of symptoms remains the only way to understand the burden of chemosensory dysfunction (CSD). Using a large population‐based database, we sought to understand factors leading to reduced likelihood of discussing CSD with a provider.

Methods

The 2013‒2014 National Health and Nutrition Examination Survey (NHANES) chemosensory protocol was queried for factors influencing discussion of OD/GD with a healthcare provider. Sociodemographic, comorbidity, and objective OD/GD testing results were assessed with a multivariate analysis.

Results

Out of 146.1 million US adults, there were an estimated 41.4 million individuals with self‐reported OD/GD in the prior 12 months (28.3%). A total of 86.8% of participants did not discuss their problem with a healthcare provider. Men were about half as likely to speak with a healthcare provider (odds ratio [OR] 0.42; 0.26–0.66; p < 0.001) and those with a college education were about nine times more likely to discuss the problem compared to those with less than a ninth‐grade educational achievement (OR 8.83; 1.86–41.98; p = 0.02). Those with objective confirmation of CSD were still unlikely to speak with a provider (OR 0.77; 0.44–1.33; p = 0.36).

Conclusion

Men and those with less education are less likely to discuss OD/GD with a healthcare provider. These populations tend to be at increased risk for CSD, and there are severe downstream health and quality of life implications related to CSD. Dedicated screening and increased public awareness are critical to ensure more equitable care.
Supporting left‐handed trainees in sinus and skull base surgery: A call for inclusive ergonomics
Authors: Spielman Daniel B.
Published: June 2024

Key points

The surgeon's hand dominance impacts ergonomics in endoscopic endonasal surgery.

Left‐handed trainees experience difficulty learning certain surgical techniques.

OR adjustments optimize ergonomics for left‐handed trainees without compromising others.
KLOTHO KL‐VS heterozygosity is associated with diminished age‐related neuroinflammation, neurodegeneration, and synaptic dysfunction in older cognitively unimpaired adults
Authors: Driscoll Ira Frahmand , Lose Sarah , Ma Yue , Bendlin Barbara B. , Gallagher Catherine , Johnson Sterling C. , Asthana Sanjay , Hermann Bruce , Sager Mark A. , Blennow Kaj , Zetterberg Henrik , Carlsson Cynthia , Kollmorgen Gwendlyn , Quijano‐Rubio Clara , Dubal Dena , Okonkwo Ozioma C.
Published: June 2024

INTRODUCTION

We examined whether the aging suppressor KLOTHO gene's functionally advantageous KL‐VS variant (KL‐VS heterozygosity [KL‐VSHET]) confers resilience against deleterious effects of aging indexed by cerebrospinal fluid (CSF) biomarkers of neuroinflammation (interleukin‐6 [IL‐6], S100 calcium‐binding protein B [S100B], triggering receptor expressed on myeloid cells [sTREM2], chitinase‐3‐like protein 1 [YKL‐40], glial fibrillary acidic protein [GFAP]), neurodegeneration (total α‐synuclein [α‐Syn], neurofilament light chain protein), and synaptic dysfunction (neurogranin [Ng]).

METHODS

This Alzheimer disease risk‐enriched cohort consisted of 454 cognitively unimpaired adults (Mage = 61.5 ± 7.75). Covariate‐adjusted multivariate regression examined relationships between age (mean‐split[age ≥ 62]) and CSF biomarkers (Roche/NeuroToolKit), and whether they differed between KL‐VSHET (N = 122) and non‐carriers (KL‐VSNC; N = 332).

RESULTS

Older age was associated with a poorer biomarker profile across all analytes (Ps ≤ 0.03). In age‐stratified analyses, KL‐VSNC exhibited this same pattern (Ps ≤ 0.05) which was not significant for IL‐6, S100B, Ng, and α‐Syn (Ps ≥ 0.13) in KL‐VSHET. Although age‐related differences in GFAP, sTREM2, and YKL‐40 were evident for both groups (Ps ≤ 0.01), the effect magnitude was markedly stronger for KL‐VSNC.

DISCUSSION

Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults were attenuated in KL‐VSHET.

Highlights

Older age was associated with poorer profiles across all cerebrospinal fluid biomarkers of neuroinflammation, neurodegeneration, and synaptic dysfunction.

KLOTHO KL‐VS non‐carriers exhibit this same pattern, which is does not significantly differ between younger and older KL‐VS heterozygotes for interleukin‐6, S100 calcium‐binding protein B, neurogranin, and total α‐synuclein.

Although age‐related differences in glial fibrillary acidic protein, triggering receptor expressed on myeloid cells, and chitinase‐3‐like protein 1 are evident for both KL‐VS groups, the magnitude of the effect is markedly stronger for KL‐VS non‐carriers.

Higher levels of neuroinflammation, neurodegeneration, and synaptic dysfunction in older adults are attenuated in KL‐VS heterozygotes.
In vivo detection of Alzheimer's and Lewy body disease concurrence: Clinical implications and future perspectives
Authors: Baiardi Simone , Hansson Oskar , Levin Johannes , Parchi Piero
Published: June 2024

INTRODUCTION

The recent introduction of seed amplification assays (SAAs) detecting misfolded α‐synuclein, a pathology‐specific marker for Lewy body disease (LBD), has allowed the in vivo identification and phenotypic characterization of patients with co‐occurring Alzheimer's disease (AD) and LBD since the early clinical or even preclinical stage.

METHODS

We reviewed studies with an in vivo biomarker‐based diagnosis of AD‐LBD copathology.

RESULTS

Studies in large cohorts of cognitively impaired individuals have shown that cerebrospinal fluid (CSF) biomarkers detect the coexistence of AD and LB pathology in approximately 20%–25% of them, independently of the primary clinical diagnosis. Compared to those with pure AD, AD‐LBD patients showed worse global cognition, especially in attentive/executive and visuospatial functions, and worse motor functions. In cognitively unimpaired individuals, concurrent AD‐LBD pathologies predicted longitudinal cognitive progression with faster worsening of global cognition, memory, and attentive/executive functions.

DISCUSSION

Future research studies aiming for a better precision medicine approach should develop SAAs further to reach a quantitative evaluation or staging of each underlying pathology using a single biofluid sample.

Highlights

α‐Synuclein seed amplification assays (SAAs) provide a specific marker for Lewy body disease (LBD).

SAAs allow for the in vivo identification of co‐occurring LBD in patients with Alzheimer's disease (AD).

AD‐LBD coexist in 20‐25% of cognitively impaired elderly individuals, and ∼8% of those asymptomatic.

Compared to pure AD, AD‐LBD causes a faster worsening of cognitive functions.

AD‐LBD is associated with worse attentive/executive, memory, visuospatial and motor functions.
Zwitterionic Acridinium Amidate: A Nitrogen‐Centered Radical Catalyst for Photoinduced Direct Hydrogen Atom Transfer
Authors: Entgelmeier Lukas‐Maximilian , Mori Soichiro , Sendo Shion , Yamaguchi Rie , Suzuki Ryuhei , Yanai Takeshi , García Mancheño Olga , Ohmatsu Kohsuke , Ooi Takashi
Published: June 2024

The development of small organic molecules that can convert light energy into chemical energy to directly promote molecular transformation is of fundamental importance in chemical science. Herein, we report a zwitterionic acridinium amidate as a catalyst for the direct functionalization of aliphatic C−H bonds. This organic zwitterion absorbs visible light to generate the corresponding amidyl radical in the form of excited‐state triplet diradical with prominent reactivity for hydrogen atom transfer to facilitate C−H alkylation with a high turnover number. The experimental and theoretical investigations revealed that the noncovalent interactions between the anionic amidate nitrogen and a pertinent hydrogen‐bond donor, such as hexafluoroisopropanol, are crucial for ensuring the efficient generation of catalytically active species, thereby fully eliciting the distinct reactivity of the acridinium amidate as a photoinduced direct hydrogen atom transfer catalyst.
Confining Conversion Chemistry in Intercalation Host for Aqueous Batteries
Authors: Gui Qiuyue , Cui Wenjun , Ba Deliang , Sang Xiahan , Li Yuanyuan , Liu Jinping
Published: June 2024

Conversion‐type anode materials with high theoretical capacities play a pivotal role in developing future aqueous rechargeable batteries (ARBs). However, their sustainable applications have long been impeded by the poor cycling stability and sluggish redox kinetics. Here we show that confining conversion chemistry in intercalation host could overcome the above challenges. Using sodium titanates as a model intercalation host, an integrated layered anode material of iron oxide hydroxide‐pillared titanate (FeNTO) is demonstrated. The conversion reaction is spatially and kinetically confined within sub‐nano interlayer, enabling superlow redox polarization (ca. 4–6 times reduced), ultralong lifespan (up to 8700 cycles) and excellent rate performance. Notably, the charge compensation of interlayer via universal cation intercalation into host endows FeNTO with the capability of operating well in a broad range of aqueous electrolytes (Li+, Na+, K+, Mg2+, Ca2+, etc.). We further demonstrate the large‐scale synthesis of FeNTO thin film and powder, and rational design of quasi‐solid‐state high‐voltage ARB pouch cells powering wearable electronics against extreme mechanical abuse. This work demonstrates a powerful confinement means to access disruptive electrode materials for next‐generation energy devices.
Enhancement of octreotide antiproliferative activity by PEGylated PAMAM dendrimers delivery
Authors: Díaz Carola F. , Cifuentes Diego L. , Oyarzún Maximiliano , Guzmán José L. , Jiménez Verónica A.
Published: June 2024

PEGylated PAMAM dendrimers (PEG‐PAMAM) are well‐characterized biomaterials with still unexplored applications as carriers of drugs acting via membrane receptors, such as octreotide. This work confirmed the safety and negligible internalization capacity of fourth‐generation 50%‐PEG‐PAMAM in HEK‐293 cells, to then assessed their supramolecular binding to octreotide through tryptophan quenching experiments and Gaussian‐accelerated molecular dynamics (GaMD) simulations. Tryptophan quenching showed that PEG‐PAMAM binds octreotide with a Kbind of 6 × 106 M−1 and a complex stoichiometry of 1:1.4, unlike native PAMAM. GaMD simulations revealed that octreotide binds at the outer PEG shell of PEG‐PAMAM, potentially hindering the drug from proteolytic degradation and enabling its release at a membrane level. Viability experiments on HeLa, PC‐12, and HEK‐293 cells incubated with increasing concentrations of octreotide in free drug solutions and equimolar mixtures with PEG‐PAMAM confirmed that the PEGylated dendrimer acts as an efficient supramolecular carrier for octreotide and enhances the antiproliferative effects of the drug. Our findings highlight a novel facet for PEG‐PAMAM dendrimers as macromolecular vehicles for peptide or non‐peptide drugs acting via membrane receptor sites.
Seawater‐degradable poly(ethylene adipate‐co‐terephthalate) copolyester: Synthesis, properties, and degradation behavior
Authors: Liu Tianyuan , Wang Weihao , Yin Tian , Jiang Zhikui , Zhen Zhichao , Yan Guochun , Ji Junhui
Published: June 2024

The application and promotion of biodegradable plastics are hindered by the imbalance between their mechanical and degradation performance imbalance, as well as high costs. Herein, a series of poly(ethylene adipate‐co‐terephthalate) (PEAT) copolyesters with excellent mechanical and degradation properties are synthesized by one‐step melt polycondensation. The influence of the proportion of aliphatic groups in the molecular chain on the structure and properties, especially the degradation performance, of the copolyesters was studied. The molecular chain flexibility and degradability of PEAT increases with increasing of adipic acid content and decreasing of ET fragment length (LET). The comprehensive mechanical properties of PEAT60 can be comparable to traditional packaging material poly(butylene adipateco‐terephthalate) (PBAT). The degradation performance of PEAT can be adjusted the molecular chain structure. PEAT with LET < 3 exhibit degradation performance, and PEAT with LET < 2.2 exhibit significant degradation acceleration. The excellent mechanical and degradable properties of PEAT copolyester make it expected to be used in degradable packaging and other fields to help solve plastic pollution, while its lower cost will aid in the promotion of degradable materials.
Cranial musculature of batoids: A standardized nomenclature
Authors: Ramírez‐Díaz C. , Kolmann M. A. , Peredo C. M. , Cruz‐Escalona V. H. , Peña R.
Published: June 2024

Batoids (rays and skates) are cartilaginous fishes whose jaws are not articulated directly to the neurocranium. The only point of contact between them are the hyomandibular cartilages, resulting in a unique mandibular suspension called euhyostyly. Due to this decoupling of the jaws from the skull, muscles play an essential role in modulating mandibular movements during the feeding process, especially during mandibular protrusion. The main objectives of our study were: (1) to examine the mandibular musculature of eight batoid species from different orders in the Batoidea and (2) establish a standardized musclulature terminology for future comparative myological studies in batoids. For each muscle bundle, the general characteristics of each cranial muscle were described and their origin and insertions were identified. The number of muscle bundles differed intraspecifically. On the dorsal surface, we reported the first evidence of the presence of the precranial muscle (PCM) in U. halleri, as well as the ethmoideo‐parethmoidalis muscle (ETM) in R. velezi, P. glaugostigma and Z. exasperata; in addition, the insertion of the spiracularis muscle (SP) extended to the ventral surface of the oropharyngeal tract in myliobatiforms. On the ventral surface of the head, both N. entemedor and M. californica exhibited additional muscles in the mandibular area. These muscles were renamed as part of the standardization of mandibular terminology: the depressor mandibularis minor (DMM) in N. entemedor and the adductor mandibulae profundus (AMP) in M. californica. The standardization of terminology is essential for futures studies of the mandibular apparatus in batoids, to facilitate the morphological description of muscles in species without anatomical accounts and for continuity in broader comparative analyses.
Reflections on zooarchaeology in East Polynesia: human‐animal interactions and human ecodynamics
Authors: Butler Virginia L.
Published: June 2024

The essay summarizes the key pillars of human ecodynamics (HE) research and then highlights the most trenchant ideas from each of the seven papers in the Special Issue, especially as they intersect with HE.
Eine gleichmäßige und konstante Energiequelle mit der neu entwickelten Energiesäule
Authors: Friedrich Thomas , Groh Sebastian
Published: June 2024

Um unsere Gebäude zukünftig zu klimatisieren, müssen wir erneuerbare Energien nutzen. Ein wichtiger Baustein auf dem Weg dorthin wird die Wärmepumpe sein. Diese nutzt als Energiequelle die verschiedenen Alternativen der erneuerbaren Energie. Die Leistungsfähigkeit der Wärmepumpe wird von der Temperaturdifferenz zwischen Quelle und Raumtemperatur bestimmt. Je geringer dieser Wert ausfällt, umso geringer ist der Stromverbrauch. Das vorgestellte Verfahren stellt eine Form von Zwischenspeicher zum Sammeln von Strahlungsenergie dar. Dabei wird die Temperatur in dem Speicher auf ein höheres Niveau als die Ausgangsquellen angehoben. Wird Wärmeenergie gebraucht, kann die Wärmepumpe immer auf eine Quelle mit hohem Temperaturniveau zurückgreifen. Die vorgestellte Energiesäule ist in der Lage, Energie aus Strahlung auf einem hohen Temperaturniveau einzusammeln. Die beiden zugehörigen Wärmespeicher bevorraten die erzeugte Wärmeenergie als Input für die Wärmepumpe im Heizfall. Sofern überschüssiger Strom vorhanden ist, wird das Temperaturniveau in den beiden Speichern angehoben.
Acoustic travel time tomography for simultaneous indoor air temperature and airflow measurements
Authors: Dokhanchi Najmeh Sadat , Vogel Albert , Völker Conrad
Published: June 2024

Developing the technique of Acoustic travel time TOMography (ATOM) for monitoring the indoor air temperature and airflow measurements represents a significant breakthrough for modern buildings especially those prioritizing thermal comfort. While conventional measurement methods are limited to individual measuring points, ATOM technique can measure the climatic parameters’ distribution across the entire room with high spatial resolution utilizing sound velocity measurements along various propagation sound paths. This research outlines the ongoing development of the ATOM technique for simultaneous measuring the indoor air temperature and airflow velocity at the Department of Building Physics at the Bauhaus‐University Weimar. It presents both the challenges confronted and the solutions developed in establishing a straightforward measuring system that can optimally fulfil the requirements of the indoor climate projects.
Transcriptional response of primary hippocampal neurons following exposure to 3.0 GHz radiofrequency electromagnetic fields
Authors: Cantu Jody C. , Butterworth Joseph W. , Payne Jason A. , Echchgadda Ibtissam
Published: June 2024

Exposure to radiofrequency (RF) electromagnetic fields (EMF) has been associated with the modulation of neuronal electrophysiology and synaptic plasticity. Given the potential of these changes to coincide with alterations in gene expression, this study investigated whether a transcriptional response would occur in neurons following exposure to RF‐EMF, under both thermal and nonthermal conditions. Rat primary hippocampal neurons (PHNs) underwent either a single (one‐time) or a multiple (3‐times, once a day) exposures to RF‐EMF (3.0 GHz, CW) at two different mean specific absorption rate (SAR) values of 0.57 W/kg or 5.91 W/kg, which induced a temperature change (ΔT °C) of approximately 0.3°C or 3.6°C, respectively. Alteration in transcription in the RF‐EMF‐exposed PHNs versus the sham counterparts was assessed at 0, 4, and 24 h postexposure via high‐throughput RNA sequencing using Illumina HiSeq. 2000. A total of 20 differentially expressed genes (DEGs) exhibited significant upregulation due to RF‐EMF exposure, observed only with the high SAR dose that induced a thermal rise. However, the expression of these DEGs was not significant at 24 h postexposure. Our findings confirmed a lack of nonthermal effects on gene expression under low RF‐EMF exposure conditions as evaluated. Additionally, the results indicated a slight thermal effect of exposures at the dose nearing the standards threshold of 4 W/kg; however, the effect appeared to be transient. The study suggests that RF‐EMF exposures at a level close to the standards threshold, despite inducing mild temperature elevations (i.e., 3–5°C above normal), would not trigger biologically critical cellular changes.
Cross‐cultural adaptation and validation of the Chinese version of Skills and Needs Inventories in Functional Behavior Assessments and Interventions (SNI‐FBAI‐CN)
Authors: Chen Mo , Dutt Anuradha S. , Nair Rahul
Published: June 2024

Cross‐cultural adaptation and validation of measures are necessary to provide evidence‐based educational intervention services among children with autism spectrum disorder (ASD) across countries. Language plays an integral role in the cross‐cultural adaptation and validation process of measures. Currently, there are limited validated tools in Chinese available to assess special education teachers' skills in functional behavior assessments and interventions in Mainland China to effectively support students with ASD. This study aimed to validate a Chinese version of the Skills and Needs Inventories in Functional Behavior Assessments and Interventions (SNI‐FBAI‐CN) in mainland China. The SNI‐FBAI, originally developed and validated in Singapore, in the English language, was translated, culturally adapted, and then administered to 239 special education teachers in two schools for children with ASD in China. Results show that the SNI‐FBAI‐CN has a three‐factor structure (i.e., skills in behavioral assessment, skills in behavioral interventions, and needs for training) that fits the data well, with good reliability for the overall scale, as well as the three subscales. Partial measurement invariance was established between the Chinese and the original Singapore samples, providing additional construct validity evidence for this tool. Limitations of this study and directions for future research are discussed.
Development of a model for the ethanol concentration limit as a function of temperature and initial substrate concentration using the yeast Saccharomyces cerevisiae
Authors: SILVA Ruan Dionízio , da Silva Flávio Luiz Honorato , de Melo Santos Sharline Florentino , Neto Alberto Brandão Torres , Lopes Julice Dutra , de Assis Cavalcante Josilene
Published: June 2024

In this study, a model was developed to simulate the effect of temperature () and initial substrate concentration () on the ethanol concentration limit () using the yeast Saccharomyces cerevisiae. To achieve this, regressions were performed using data provided by other authors for to establish a model dependent on and capable of predicting results with statistical significance. After constructing the model, a response surface was generated to determine the conditions where reaches higher values: temperatures between 28°C and 32°C and an initial substrate concentration around 200 g/L. Thus, the proposed model is consistent with the observations that increasing temperatures decrease the ethanol concentration obtained, and substrate concentrations above 200 g/L lead to a reduction in ethanol concentration even at low temperatures such as 28°C.
Metabolomic characterization of monoclonal antibody‐producing Chinese hamster lung (CHL)‐YN cells in glucose‐controlled serum‐free fed‐batch operation
Authors: Sukwattananipaat Puriwat , Kuroda Hirotaka , Yamano‐Adachi Noriko , Omasa Takeshi
Published: June 2024

The fast‐growing Chinese hamster lung (CHL)‐YN cell line was recently developed for monoclonal antibody production. In this study, we applied a serum‐free fed‐batch cultivation process to immunoglobulin (Ig)G1‐producing CHL‐YN cells, which were then used to design a dynamic glucose supply system to stabilize the extracellular glucose concentration based on glucose consumption. Glucose consumption of the cultures rapidly oscillated following three phases of glutamine metabolism: consumption, production, and re‐consumption. Use of the dynamic glucose supply prolonged the viability of the CHL‐YN‐IgG1 cell cultures and increased IgG1 production. Liquid chromatography with tandem mass spectrometry‐based target metabolomics analysis of the extracellular metabolites during the first glutamine shift was conducted to search for depleted compounds. The results suggest that the levels of four amino acids, namely arginine, aspartate, methionine, and serine, were sharply decreased in CHL‐YN cells during glutamine production. Supporting evidence from metabolic and gene expression analyses also suggest that CHL‐YN cells acquired ornithine‐ and cystathionine‐production abilities that differed from those in Chinese hamster ovary‐K1 cells, potentially leading to proline and cysteine biosynthesis.
Survival by first‐line therapy and prognostic group among men with metastatic castration‐resistant prostate cancer
Authors: Caram Megan E. V. , Kumbier Kyle , Tsao Phoebe A. , Burns Jennifer , Sparks Jordan B. , Stensland Kristian D. , Reichert Zachery R. , Alumkal Joshi J. , Hollenbeck Brent K. , Shahinian Vahakn , Tsodikov Alexander , Skolarus Ted A.
Published: June 2024

Introduction

Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration‐resistant diagnosis. Optimal first‐line therapy for those with different prognoses is unknown.

Methods

We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first‐line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow‐up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan–Meier methods to examine prostate specific antigen (PSA) progression‐free and overall survival (OS) according to prognostic group and first‐line therapy, and multivariable cox regression to determine variables associated with survival outcomes.

Results

Among 4135 patients, median PSA progression‐free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6–7.3), and median OS 18.8 months (95% CI 18.0–19.6), ranging from 5.7 months (95% CI 4.8–7.0) in the poor prognosis group to 31.3 months (95% CI 29.7–32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2–3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34–2.31; intermediate HR 1.78, 95% CI 1.41–2.25; poor HR 8.01, 95% CI 2.93–21.9).

Conclusion

Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First‐line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.
Investigating the determinants of fear of cancer recurrence in patients with early‐stage non‐small cell lung cancer: Insights from a restricted cubic spline model
Authors: Liu Man , Liu Lu , Lv Zhuoheng , Mao Yousheng , Liu Yan
Published: June 2024

Objective

This study aims to investigate the determinants and the dose–response relationship of fear of cancer recurrence among patients with early‐stage non‐small cell lung cancer (NSCLC), aiming to inform prevention and intervention strategies.

Methods

Employing a cross‐sectional design, we analyzed data from 677 postoperative NSCLC patients who received treatment at National Cancer Center between January 2022 and August 2023. Data collection involved a general demographic survey, the Fear of Progression Questionnaire‐Short Form, Hope Herth Index, and Social Support Rating Scale. We employed logistic regression and restricted cubic spline models to identify factors influencing fear of recurrence (FCR).

Results

Univariate regression analysis identified female gender and having minor children as significant risk factors, while being older than 60, a higher income, and elevated levels of hope and social support emerged as protective factors. Multivariate logistic regression revealed age (OR = 0.392, 95% CI 0.205–0.750), monthly income (OR = 0.016, 95% CI 0.315–0.886), hope level (OR = 0.305, 95% CI 0.187–0.496), and social support (OR = 0.584, 95% CI 0.375–0.908) as independent influencers of recurrence fear. The restricted cubic spline model indicated a nonlinear impact of hope and social support on this fear.

Conclusion

Analysis using the restricted cubic spline model underscores the influence of age, income, hope, and social support on FCR, with a nonlinear dose–response relationship evident between hope, social support, and fear. Prioritizing the enhancement of social support before increasing hope levels can rapidly and effectively alleviate FCR.
Overall and non‐lung cancer incidence and mortality in the National Lung Screening Trial: Opportunities for multi‐cancer early detection
Authors: Patel Alpa V. , Chang Ellen T. , Hackshaw Allan , Janes Sam M. , Buist Diana S. M. , Hubbell Earl , Clarke Christina A. , Colditz Graham A.
Published: June 2024

Background

Currently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers.

Methods

The National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009.

Results

Among 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths.

Conclusions

In the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality.
Feasibility of atezolizumab and bevacizumab combination regimens in patients with hepatocellular carcinoma and lung cancer taking direct oral anticoagulants
Authors: Nakabori Tasuku , Kunimasa Kei , Kawabata Masaki , Higashi Sena , Mukai Kaori , Kawamura Takahisa , Inoue Takako , Tamiya Motohiro , Nishino Kazumi , Ohkawa Kazuyoshi
Published: June 2024

Aim

Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs.

Methods

This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed.

Results

The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105–0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157–10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin–bilirubin score (HR: 9.083, 95% CI: 1.118–73.76) was associated with bleeding events (p = 0.039).

Conclusions

DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs.
Development of a prediction model for suicidal ideation in patients with advanced cancer: A multicenter, real‐world, pan‐cancer study in China
Authors: He Yi , Pang Ying , Yang Wenlei , Su Zhongge , Wang Yu , Lu Yongkui , Jiang Yu , Zhou Yuhe , Han Xinkun , Song Lihua , Wang Liping , Li Zimeng , Lv Xiaojun , Wang Yan , Yao Juntao , Liu Xiaohong , Zhou Xiaoyi , He Shuangzhi , Zhang Yening , Song Lili , Li Jinjiang , Wang Bingmei , Ke Yang , He Zhonghu , Tang Lili
Published: June 2024

Background

Patients diagnosed with advanced stage cancer face an elevated risk of suicide. We aimed to develop a suicidal ideation (SI) risk prediction model in patients with advanced cancer for early warning of their SI and facilitate suicide prevention in this population.

Patients and Methods

We consecutively enrolled patients with multiple types of advanced cancers from 10 cancer institutes in China from August 2019 to December 2020. Demographic characteristics, clinicopathological data, and clinical treatment history were extracted from medical records. Symptom burden, psychological status, and SI were assessed using the MD Anderson Symptom Inventory (MDASI), Hospital Anxiety and Depression Scale (HADS), and Patient Health Questionnaire‐9 (PHQ‐9), respectively. A multivariable logistic regression model was employed to establish the model structure.

Results

In total, 2814 participants were included in the final analysis. Nine predictors including age, sex, number of household members, history of previous chemotherapy, history of previous surgery, MDASI score, HADS‐A score, HADS‐D score, and life satisfaction were retained in the final SI prediction model. The model achieved an area under the curve (AUC) of 0.85 (95% confidential interval: 0.82–0.87), with AUCs ranging from 0.75 to 0.95 across 10 hospitals and higher than 0.83 for all cancer types.

Conclusion

This study built an easy‐to‐use, good‐performance predictive model for SI. Implementation of this model could facilitate the incorporation of psychosocial support for suicide prevention into the standard care of patients with advanced cancer.
Sydenham's chorea in a 16‐year‐old female from Bhutan: A case report
Authors: Penjor Tshering , Dorji Thinley , Wangchuk Sangay
Published: June 2024

Key Clinical Message

Rheumatic heart disease is a preventable disease. Patients may not present with a typical history of sore throat and polyarthritis but may present with Sydenham's chorea. We should not rely completely on clinical findings to rule out carditis. Echocardiography should be done to rule out subclinical carditis.

Sydenham's chorea is a major manifestation of rheumatic fever. It occurs primarily in children and is seen rarely after the age of 20 years. We describe a 16‐year‐old girl who presented with purposeless involuntary movements of her upper and lower limbs. Laboratory blood reports showed raised erythrocyte sedimentation rate and anti‐streptolysin O. 2D Doppler Echocardiography confirmed subclinical carditis, thickened mitral and aortic valve with mild mitral regurgitation. She was managed as Acute Rheumatic Fever with oral Phenoxymethyl penicillin and Carbamazepine. At the latest follow‐up interviewing the caregiver, the patient had no sequelae. Early diagnosis is key to preventing late consequences of acute rheumatic fever and rheumatic heart disease. Sydenham's chorea is a rare presentation of acute rheumatic fever. The absence of clinical carditis does not rule out carditis.
Total talar replacement for metastatic pulmonary adenocarcinoma of the talus: A case report
Authors: Sakai Tatsuya , Fujii Masanori , Mawatari Masaaki
Published: June 2024

Key Clinical Message

Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48‐year‐old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient's activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight‐bearing ambulation 2 weeks post‐operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.
Hypoxia drives CBR4 down‐regulation promotes gastroenteropancreatic neuroendocrine tumors via activation mammalian target of rapamycin mediated by fatty acid synthase
Authors: Ye Mujie , Xu Lin , Lu Feiyu , Chen Lingyi , Hu Chunhua , Chen Jinhao , Xue Bingyan , Gu Danyang , Xu Ruitong , Xu Yanling , Yu Ping , Wang Yan , Tian Ye , Zhu Guoqin , Tang Qiyun
Published: June 2024

Hypoxia has been highly proven a hallmark of tumor micro‐environment, promoting the malignant phenotypes, playing a crucial role from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Increasing evidence also showed that hypoxia mediated the abnormal lipid metabolism in cancer by regulating various oncogenic signal pathways. However, it is still unclear but attractive how hypoxia specifically functioned and changed the condition of the tumor micro‐environment. In present study, we find that hypoxia promoted the methylation degree of CBR4 promoter region thus downgraded the expression of CBR4, which promoted GEP‐NETs progression and increased the sensitivity of GEP‐NETs cells to everolimus. Further, CBR4 interacted with fatty acid synthase (FASN), displaying a down‐regulation of FASN by activating the ubiquitin proteasome pathway and suppressed mTOR signaling. Overall, our results uncovers the CBR4/FASN/mTOR axis as a mechanism for tumor development and inspires us a new molecular guide for the therapeutic strategies for GEP‐NETs treatment.
Symmetry‐Breaking and Symmetry‐Retaining Morphological Evolution of the Single Crystals of Cyclodextrin Metal‐Organic Frameworks
Authors: Zhang Jiayin , Chen Yifu , Zhang Ying‐Ming , Gong Junbo
Published: June 2024

The morphological symmetry‐retaining and symmetry‐breaking of single crystals of the γ‐cyclodextrin metal‐organic framework have been achieved via introducing lower symmetric β‐cyclodextrins and α‐cyclodextrins, respectively. β‐cyclodextrins led to a morphological evolution with retained symmetry from cubic to rhombic dodecahedra, while α‐cyclodextrins resulted in the original cubic crystal missing a vertex angle presenting symmetry‐breaking behavior. The crystal structures of rhombic dodecahedra and angle‐deficient crystals were confirmed through X‐ray crystallography, and the mechanisms underlying the morphological transformation evolution were further analyzed. Our work not only provides a rare case realizing two different paths of morphological evolution in one system, but also encourages future efforts towards the evolution of artificial crystal systems in a natural way.
Clathrate Hydrates as a Kind of Promising Ice Nanoreactors
Authors: Chang Ruisi , Cheng Shibo , Bu Yuxiang
Published: June 2024

Since their discovery, clathrate hydrates (CHs) have received great attention both from theoretical and experimental aspects due to their great potential for gas storage and prospective applications as icy crystal materials. However, there has been limited research on the decomposition, reduction or other reactions of gases enclosed in CHs. Thanks to their unique hydrogen bonding network and cavity structures, CHs can serve as the promising nanoreactors to achieve chemical conversions, e. g. reducing greenhouse gases. In this review‐type article, we characterize the potential performance of such CHs nanoreactors by discussing their multiple functions including important roles of hydrogen bonds in CHs, e. g. the confinement effect and proton source, and then discuss the enhanced electron‐binding ability of guest molecules and the structures and properties of trapped electrons in the stacked nanocages, which contribute to our understanding of chemical reactions occurring in CHs. Finally, we provide detailed analyses of representative reaction mechanisms underwent in CH nanoreactors and effective calculational and molecular dynamics simulation methods. This review‐type article aims to provide a detailed summary about the functional characteristics of CHs and reactivity in CHs, which make CHs a kind of promising icy nanoreactors.
Effects of segmentation in composite phase change material on melting/solidification performance of triplex‐tube thermal energy storage systems
Authors: Alam Md Tabrez , Kumar Rajesh , Gupta Anoop K.
Published: June 2024

In this work, a numerical evaluation of the melting/solidification performance of phase change material (PCM) filled inside a triplex‐tube latent heat storage unit has been carried out. To enhance the melting/solidification performance, the porous Cu metal foam (MF) was embedded inside PCM (termed as composite PCM). Alternative segments of pure PCM and composite PCM have been allocated in such a way that both the pure PCM and composite PCM occupy the equal annular area (i.e., equal volumes). Influence of increasing number of segments was delineated on the melting/solidification rate, complete melting time, and thermal energy storage/recovery enhancement. The comparisons were drawn with reference to the model having two segments of PCM and composite PCM. The results show that the model containing 64 segments with alternate allocations of PCM and composite PCM has a faster melting/solidification rate than other models. With 32 alternate segments of MF, the full melting/solidification time reduced by 23%/77% with respect to the case with one segment of MF only. The melting/solidification performance gets saturated beyond 32 segments (M‐5) and negligible variation (only ~1%) in the thermal performance was noticed upon further segmentation. Finally, the model M‐5 proved as the best model considering the aspects of augmented melting/solidification rate and associated complexities. Moreover, the heterogeneity of MF applied in 32‐segment model confirmed that the anisotropic MF results in an increased melting rate and leads over other random isotropic distributions of MF.
Orange‐Fleshed Sweet Potato Truly an Emerging Superfood in Ethiopia
Authors: Sever Megan
Published: June 2024

Substituting this colorful root vegetable for flour in bread or white‐fleshed sweet potatoes in daily cooking can tackle the prevalent vitamin A deficiency in the African country and throughout sub‐Saharan Africa.
The role of blockchain platform in enabling circular economy practices
Authors: Souza Elieber Bragatti , Carlos Ricardo Luiz , de Mattos Claudia A. , Scur Gabriela
Published: June 2024

The circular economy concept is gaining increasing prominence in academic, corporate, and government circles; however, its dissemination is still limited. There is a lack of studies that address strategies, practices, and enabling technologies guided by the principles of developing processes and products for a more rational use of natural resources, reducing consumption, or promoting their recovery. Technological resources can be a crucial issue in enabling the implementation of circular practices. Companies need to plan IT infrastructure and collaborative platforms that can connect them with different stakeholders and leverage digital technologies such as blockchain. This study aims to analyze platforms based on blockchain technology and their contribution to the implementation of circular economy practices, identifying the design, platform functionalities, and how the platforms are being integrated into companies' circular economy programs. The research approach was qualitative, using multiple case studies. The results indicate that blockchain technology helps achieve circular economy practices by bringing transparency to the system and improving market position. The study also contributes to the emerging platform literature by exploring blockchain platforms with functionalities linked to executing circular practices such as Tokens and NFTs in the context of sustainability.
Board network and ESG performance: Evidence from China
Authors: Shu Pei‐Gi , Chiang Sue‐Jane , Wu Tian‐Yu
Published: June 2024

As ESG (Environmental, Social, and Governance) principles increasingly shape the trajectory of global economic and societal sustainability, our study delves into how a firm's network dynamics influence its ESG performance within the Chinese landscape spanning from 2011 to 2020. Drawing insights from agency theory, resource dependence theory, and social network theory, we uncover a notable correlation between board interlocking and ESG performance. This correlation suggests that well‐connected directors can potentially enhance a firm's ESG performance by facilitating information gathering, monitoring, advising, and leveraging influence to address stakeholders' concerns. Moreover, our analysis reveals that the characteristics of ownership structure, as gauged by indicators such as institutional ownership, control‐cash flow wedge, and state‐owned ownership, serve as positive moderators in this relationship. Conversely, board structure, as evaluated by board independence, does not exhibit a significant moderating effect. Additionally, we uncover noteworthy mediating effects of firm size and institutional shareholding on the relationship between board interlocking and ESG performance. Importantly, our findings hold robust across various sensitivity analyses, including alternative model specifications, variable definitions, and strategies to mitigate potential endogeneity concerns.