bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting tRNA‐Derived Non‐Coding RNA Alleviates Diabetes‐Induced Visual Impairment through Protecting Retinal Neurovascular Unit
Authors: Yao Jin , Yao Wen , Zhu Jun‐Ya , Liu Yan , Liu Jin‐Hong , Ji Yu‐Ke , Ni Xi‐Shen , Mu Wan , Yan Biao
Published: November 2024

Diabetes is a major risk factor for compromised visual health, leading to retinal vasculopathy and neuropathy, both of which are hallmarks of neurovascular unit dysfunction. Despite the critical impact of diabetic retinopathy, the precise mechanism underlying neurovascular coupling and effective strategies to suppress neurovascular dysfunction remain unclear. In this study, the up‐regulation of a tRNA‐derived stress‐induced RNA, 5′tiRNA‐His‐GTG, in response to diabetic stress is revealed. 5′tiRNA‐His‐GTG directly regulates Müller glia action and indirectly alters endothelial angiogenic effects and retinal ganglion cell (RGC) survival in vitro. Downregulation of 5′tiRNA‐His‐GTG alleviates diabetes‐induced retinal neurovascular dysfunction, characterized by reduced retinal vascular dysfunction, decreased retinal neurodegeneration, and improved visually‐guided behaviors in vivo. Mechanistically, 5′tiRNA‐His‐GTG acts as a key regulator of retinal neurovascular dysfunction, primarily by modulating arachidonic acid (AA) metabolism via the CYPs pathway. The 5′tiRNA‐His‐GTG‐CYP2E1‐19(S)‐HETE signaling axis is identified as a key driver of retinal neurovascular dysfunction. Thus, targeting 5′tiRNA‐His‐GTG presents a promising therapeutic strategy for treating vasculopathy and neuropathy associated with diabetes mellitus. Modulating this novel signaling pathway can open up new avenues for intervention in diabetic retinopathy and its related complications.
Assessing the efficacy of Arthrospira maxima biofertilizers and commercial alternatives on cash crop growth
Authors: Marín‐Marín Camila Andrea , Estrada José Alberto , Delgado Naranjo Juan Martín , Zapata Ocampo Paola Andrea
Published: November 2024

Biofertilizers offer a sustainable alternative to chemical fertilizers, notorious for their harmful impact on the environment and human health. Sources of biofertilizers include cyanobacteria, such as those from the genus Arthrospira, which contain bioactive compounds that enhance plant growth directly and indirectly. To promote widespread biofertilizer adoption, experimental trials are essential to compare their efficacy against chemical fertilizers and different biofertilizer varieties. Some biofertilizers rely on ultrasonication for cell rupture, but since A. maxima undergoes sun‐drying to obtain the biomass powder, which also ruptures cells, ultrasonication may be unnecessary. We assessed the biofertilizer capabilities of Arthrospira maxima (Setchell & N.L. Gardner) Geitler biomass on three cash crops, banana (Musa acuminata Colla), cowpea (Vigna unguiculata L. Walp.), and eggplant (Solanum melongena Mill. Dunal). We compared sonicated and non‐sonicated biomass (both 20 g L−1) against a commercially available, brown algae Ascophyllum nodosum (L.) biofertilizer (4 mL L−1 OptiMar), a commercially available chemical fertilizer (1.5 mL L−1 Triple15), and a negative control of tap water. Few differences were observed among A. maxima treatments, suggesting sonication might be unnecessary. OptiMar, Triple15, and the negative control did not yield the highest biometric values of any trait in any crop. If commercially available fertilizers and biofertilizers do not outperform the negative control, it raises crucial questions regarding their effectiveness and the appropriate concentrations at which they should be applied. Non‐sonicated biomass often outperformed OptiMar, Triple15, and the negative control, demonstrating the potential Arthrospira maxima has for stimulating plant growth without ultrasonication.
Die Herausforderungen der molekularen Interpretationen von Infrarotspektren komplexer Proben
Authors: Eissa Tarek , Voronina Liudmila , Huber Marinus , Fleischmann Frank , Žigman Mihaela
Published: November 2024

Die Schwingungsspektroskopie ist eine weit verbreitete Technik zur chemischen Charakterisierung in verschiedenen analytischen Disziplinen. Ihre Anwendungen erstrecken sich zunehmend auf die Analyse komplexer Proben wie Bioflüssigkeiten und ermöglichen molekulares Profiling mit hohem Durchsatz. Trotz ihrer Leistungsfähigkeit leidet diese Technologie unter einer inhärenten Einschränkung: Der Überlapp von Absorptionsinformationen über verschiedene Spektralbereiche hinweg behindert die Fähigkeit, einzelne Substanzen zu identifizieren, welche zu den gemessenen Gesamtsignal beitragen. Obwohl man sich dieser Herausforderung bewusst ist, wird die Schwierigkeit der Analyse von Multimolekülspektren oft unterschätzt, was zu Fehlinterpretation führen kann. In dieser Arbeit diskutieren wir kritisch den weit verbreiteten übermäßigen Verlass auf einzelne Absorptionsbanden bei der Dateninterpretation und beleuchten die Fallstricke bei der Korrelation von spektral Signalen mit diskreten Substanzen oder physiologischen Zuständen ohne rigorose Validierung. Mit Fokus auf blutbasierte Infrarotspektroskopie liefern wir Beispiele, die zeigen, wie Überlappungen lokaler Absorptionsmaxima zwischen verschiedenen Substanzen, relative Konzentrationen von Substanzen und Datenvorverarbeitungsschritte zu fehlerhaften Interpretationen führen können. Wir plädieren für einen Paradigmenwechsel hin zu einem vorsichtigeren Verständnis komplexer Spektren, was dazu führen sollte, entweder deren Charakter als molekularen Fingerabdruck zu akzeptieren und maschinelles Lernen zur Analyse zu nutzen – oder zusätzliche Messmodalitäten für eine robuste molekulare Interpretationen einzubeziehen. Mit dem Ziel, analytische Praktiken in diesem Bereich zu verbessern und weiterzuentwickeln, heben wir die Grenzen molekularer Interpretationen hervor und stellen mögliche Anwendungen vor.
Energy storaging multifunctional carbon fiber composites based on Nano‐SiO2 reinforced epoxy matrix structural electrolytes
Authors: Yu Benyuan , Wang Zhongbao , Sun Jie , Li Jialiang , Lei Xin , Li Shichao , Sun Tao , Wu Zhanjun
Published: November 2024

Multifunctional carbon fiber composite materials capable of storing energy and carrying structural loads have advantages for aerospace structures. In this paper, a structural supercapacitor that consists of an epoxy‐based solid polymer electrolytes (E‐SPEs) and carbon fiber was proposed. To develop an E‐SPEs with better mechanical properties and ionic conductivity, Nano‐SiO2 was introduced into the solid polymer electrolytes. Nano‐SiO2 reinforced E‐SPEs (Nano‐SiO2/E‐SPEs) show improved mechanical properties (Young's modulus [E] = 0.85 GPa) and ionic conductivity (4.99 × 10−4 S cm−1), compared to E‐SPEs without Nano‐SiO2. Structural supercapacitors were further prepared by combining E‐SPEs with carbon fibers. The structural supercapacitor prepared with Nano‐SiO2/E‐SPEs exhibits the higher power and energy density (261.93 W kg−1 and 2.11 Wh kg−1) compared to the structural supercapacitor prepared with E‐SPEs without Nano‐SiO2 (51 W kg−1 and 0.34 Wh kg−1), indicating improved mechanical and energy storage properties for structural supercapacitors after incorporation of Nano‐SiO2. This strategy has great potential in enhancing performance of structural energy storage composite materials for application in next‐generation aerospace vehicles.
Synergistic effect of Ca/Zn main stabilizer and maltitol auxiliary stabilizer on the thermal stability, mechanical properties, and transparency of poly(vinyl chloride)
Authors: Wang Xuhui , Zhang Guojie , Dong Huanhuan , Zhang Yong
Published: November 2024

Maltitol, a natural compound, offers a potentially eco‐friendly alternative to conventional auxiliary thermal stabilizers. Its auxiliary stabilization effect was studied by discoloration tests, Congo red tests, thermogravimetric analysis, and UV–visible spectroscopy. Additionally, x‐ray photoelectron spectroscopy and discoloration tests were used to study the stabilizing mechanisms of maltitol. Compared to dipentaerythritol, commonly used in the PVC industry, maltitol as an auxiliary stabilizer exhibits better improvement in thermal stability. This improvement is related to its melting point, ability to complex with zinc chloride, and content of hydroxyl groups. Furthermore, the addition of maltitol in PVC not only maintains good transparency of PVC basically unchanged but also improves the mechanical properties. Maltitol, as a natural, eco‐friendly, and efficient auxiliary thermal stabilizer, exhibits a promising application prospect in PVC materials.
PGE2 Binding Affinity of Hemocyte Membrane Preparations of Manduca sexta and Identification of the Receptor‐Associated G Proteins in Two Lepidopteran Species
Authors: Khan Falguni , Tunaz Hasan , Haas Eric , Kim Yonggyun , Stanley David
Published: November 2024

Prostaglandin E2 (PGE2) is an eicosanoid that mediates a range of physiological actions in vertebrates and invertebrates, including reproduction and immunity. The PGE2 receptor was identified and functionally assessed in two lepidopteran insects, Manduca sexta and Spodoptera exigua. However, its binding affinity to the receptor has not been reported. The PGE2 receptor is a G‐protein coupled receptor (GPCR) although its corresponding G‐protein is not identified. PGE2 binding assays were performed with membrane preparations from hemocytes of M. sexta larvae. We recorded an optimal binding in 4 h reactions conducted at pH 7.5 with 12 nM tritium‐labeled PGE2. We found that hemocytes express a single population of PGE2 binding sites with a high affinity (Kd = 35 pmol/mg protein), which are specific and saturable. The outcomes of experiments on the influence of purine nucleotides suggested these are functional GPCRs. A bioinformatics analysis led to a proposed trimeric G‐protein in the S. exigua transcriptome, in which the Gα subunit is classified into five different types: Gα(o), Gα(q), Gα(s), Gα(12), and Gα(f). After confirming expressions of these five types in S. exigua, individual RNA interference (RNAi) treatments were applied to the larvae using gene‐specific double‐stranded RNAs. RNAi treatments specific to Gα(s) or Gα(12) gene expression significantly suppressed the cellular immune responses although the RNAi treatments specific to other three Gα components did not. While PGE2 treatments led to elevated hemocyte cAMP or Ca2+ levels, the RNAi treatments specific to Gα(s) or Gα(12) genes led to significantly reduced second messenger levels under PGE2, although the RNAi treatments specific to the other three Gα components did not. These results showed that the PGE2 receptor has high PGE2 affinity in the nanomolar range and binds G‐proteins containing a Gα(s) or Gα(12) trimeric component in S. exigua and M. sexta, and likely, all lepidopteran insects.
Chalcogen Bond‐Driven Alkylations: Selenoxide‐Pillar[5]arene as a Recyclable Catalyst for Displacement Reactions in Water
Authors: Cordeiro Pâmella , Menezes Victor , Ángel Alix Y. Bastidas , de Andrade Karine N. , Fiorot Rodolfo G. , Alberto Eduardo E. , Nascimento Vanessa
Published: November 2024

A novel strategy to catalyze alkylation reactions through chalcogen bond interaction using a supramolecular structure is presented herein. Utilizing just 1.0 mol % of selenoxide‐pillar[5]arene (P[5]SeO) as the catalyst we achieved efficient catalysis in the cyanation of benzyl bromide in water. Our approach demonstrated high efficiency and effectiveness, with the results supported by designed control experiments and theoretical models, highlighting the catalytic effect of the pillar[5]arene through noncovalent interactions. Quantum‐chemical calculations (ωB97X‐D/def2‐TZVP@SMD) pointed out that the catalyzed cyanation reaction followed an SN2‐like mechanism, with energy barriers (ΔH≠) ranging from 16.7 to 18.2 kcal mol−1, exhibiting dissociative character depending on the para‐substituent. 1H NMR analysis revealed that P[5]SeO acted as a catalyst through inclusion complex formation, facilitating the transfer of the electrophilic substrate to the aqueous solution for nucleophilic displacement. Our reaction protocol proved applicable to various substrates, including aromatic and alpha‐carbonyl derivatives. The use of sodium azide as the nucleophile was also feasible. Importantly, our method allowed scalability, and the catalyst P[5]SeO could be recovered and reused effectively for multiple reaction cycles, showcasing sustainability.
Hematopoietic stem cell metabolism within the bone marrow niche – insights and opportunities
Authors: Kemna Koen , van der Burg Mirjam , Lankester Arjan , Giera Martin
Published: November 2024

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo‐SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.
Metabolic Engineering of Nonmodel Yeast Issatchenkia orientalis SD108 for 5‐Aminolevulinic Acid Production
Authors: Tan Shih‐I , Ng I‐Son , Zhao Huimin
Published: November 2024

Biological production of 5‐aminolevulinic acid (5‐ALA) has received growing attention over the years. However, there is the tradeoff between 5‐ALA biosynthesis and cell growth because the fermentation broth will become acidic due to the production of 5‐ALA. To address this limitation, we engineered an acid‐tolerant yeast, Issatchenkia orientalis SD108, for 5‐ALA production. We first discovered that the cell growth rate of I. orientalis SD108 was boosted by 5‐ALA and its endogenous ALA synthetase (ALAS) showed higher activity than those homologs from other yeasts. The titer of 5‐ALA was improved from 28 mg/L to 120‐, 150‐, and 300 mg/L, by optimizing plasmid design, overexpressing a transporter, and increasing gene copy number, respectively. After redirecting the metabolic flux using the pyruvate decarboxylase (PDC) knockout strain (SD108ΔPDC) and culturing with urea, we increased the titer of 5‐ALA to 510 mg/L, a 13‐fold enhancement, proving the importance of the newly identified IoALAS with higher activity and the strategic selection of nitrogen sources for knockout strains. This study demonstrates the acid‐tolerant I. orientalis SD108ΔPDC has a high potential for 5‐ALA production at a large scale in the future.
Implementation of Innovative Process Analytical Technologies to Characterize Critical Quality Attributes of Co‐Formulated Monoclonal Antibody Products
Authors: Godbole Apurva , Chen Lyufei , Desai Jay , Raghava Smita , Ruzanski Richard , Patel Bhumit , Appiah‐Amponsah Emmanuel , Feng Hanzhou
Published: November 2024

Characterizing co‐formulated monoclonal antibodies (mAbs) poses significant challenges in the pharmaceutical industry. Due to the high structural similarity of the mAbs, traditional analytical methods, compounded by the lengthy method development process, hinder product development and manufacturing efficiency. There is increasing critical need in the pharmaceutical industry to streamline analytical approaches, minimizing time and resources, ensuring a rapid clinical entry and cost‐effective manufacturing. This study investigates the application of process analytical technologies (PAT) to address such challenges. Our investigation introduces two complementary technologies, on‐line ultra‐performance liquid chromatography (online UPLC) and multimode fluorescence spectroscopy (MMFS), as potential PAT tools tailored for characterizing critical quality attributes (CQA) in co‐formulated mAb products. Specifically, the CQAs under evaluation include the total protein concentration of the mAbs within the co‐formulation and the ratio of mAb A to mAb B. Online UPLC enables direct and automated measurement of the CQAs through physical separation, while MMFS determines them in a non‐destructive and more swift manner based on chemometric modeling. We demonstrate these technologies' comparable performance to conventional methods, alongside substantial benefits such as reduced analytical turnaround time and decreased laboratory efforts. Ultimately, integrating them as innovative PAT tools expedites the delivery of therapeutic solutions to patients and enhances manufacturing efficiency, aligning with the imperative for swift translation of scientific discoveries into clinical benefits.
Identification of Mood Disorders in Self‐Reported Versus Health Administrative Data
Authors: Dohouin Irène , Laberge Maude , Lacasse Anaïs , Poder Thomas G. ,   TorSaDE Cohort working group
Published: November 2024

Background

Producing relevant knowledge on the prevalence of mood disorders (MDs) requires a clear identification of people living with the condition. Analyzing this multifaceted disease from the perspective of health administrative data and population‐based surveys could contribute to document inconsistencies between these data sources and highlight the strengths and limitations of each methodological approaches.

Objectives

The aim of this study was to estimate the prevalence of MD disease, assess concordance of MD patterns in population‐based surveys versus health administrative data, and investigate statistical differences in characteristics between individuals presenting the disease in each data sources.

Methods

This study used the Care Trajectories—Enriched Data (TorSaDE) cohort. The TorSaDE cohort is built by merging five waves of the Canadian Community Health Survey (CCHS) with health administrative data of the province of Quebec, Canada. The sample includes individuals who participated in at least one round of CCHS and for whom evidence of use of health services in the year of CCHS completion and the year before were present in health administrative data. The cohort was split into four groups based on the presence and absence of MD in self‐reported versus health administrative data. Groups' characteristics were compared using chi‐square tests and ANOVA.

Results

The study cohort was composed of 96,079 individuals, of which 10,418 (10.8%) had MD, regardless of the data sources. Self‐reported prevalence of MD was 6.03%, while the prevalence from health administrative data was about 7.79%. Estimates showed a low level of concordance between the two measures, as only 27.4% of people presenting this medical condition were identified in both data sources. Furthermore, individuals identified with MD only in survey data had poorer socioeconomic outcomes but better health outcomes than those from the concordant group (i.e., identified in both data sources). In addition, people presenting MD in health administrative data only had better socioeconomic and health outcomes than those who reported MD diagnosis only in survey data.

Conclusion

Findings suggest that each measure capture different specific subpopulations. Estimates obtained from each source should thus be contextualized and interpreted with caution.
Racial and Ethnic Differences in Liver Transplantation and Post–Liver Transplant Survival Among Patients With Hepatocellular Carcinoma
Authors: Grewal Udhayvir S. , Chandar Apoorva K. , Gaddam Shiva J. , Al Armashi Abdul Rahman , Alkreshi Akram , Garikipati Subhash C.
Published: November 2024

Background

Racial and ethnic disparities in diagnosis and overall outcomes for HCC are well known. We present updated real‐world data on racial or ethnic differences in LT and post‐LT survival among patients with HCC in a large population‐based database.

Methods

We used the TriNetX database to retrospectively identify patients who had HCC (ICD‐10 C22.0, C22.8) and underwent LT (CPT codes 47,135, 47,140, 47,140, 47,141, 47,142) from 2012 to 2022 and compared outcomes across racial and ethnic subgroups.

Results

Majority of the patients were Caucasians (2403/2901, 84.8%), followed by African Americans (267/2901, 9.2%) Hispanic/Asian (231/2901, 7.9%). At follow up of 5 years, we noted no significant difference in mortality between AA and Caucasian patients [HR = 1.087 (95% CI 0.76, 1.56, p = 0.59)] as well as Hispanic/Asian and Caucasian patients [HR = 1.14 (95% CI 0.73, 1.78, p = 0.10)].

Conclusions

These results indicate that stringent implementation of policies aimed at ensuring equitable access to LT may contribute to bridging disparities in overall outcomes in HCC.
Data Augmentation and Fault Diagnosis for Imbalanced Industrial Process Data Based on Residual Wasserstein Generative Adversarial Network With Gradient Penalty
Authors: Tian Ying , Shen Jian , Wang Ao , Li Zeqiu , Huang Xiuhui
Published: November 2024

In practical industrial applications, equipment usually operates normally and failures are relatively rare, resulting in serious imbalances in the collected data. This imbalance leads to issues such as overfitting, instability, and poor robustness, significantly reducing the accuracy and stability of fault diagnosis system. To address these challenges, this research proposes a method for imbalanced data augmentation and industrial process fault diagnosis based on improved Generative Adversarial Network (GAN). The method adopts Wasserstein distance with gradient penalty and integrates residual connections into the architecture of the generator. This innovation not only helps improve gradient transfer in the generator, but also significantly enhances the data generation capabilities of the generative model through improving the stability of training. Limited industrial process data is used by a generative model to produce synthetic samples with high similarity and diversity. These high‐quality samples improve fault diagnosis by enriching the imbalanced dataset. Experimental results on two industrial datasets confirm the method's effectiveness in enhancing fault diagnosis performance with limited data.
Seeing Double: The Persistent Dimer‐of‐Dimers Structure of Drug Resistant Influenza A M2
Authors: Stampolaki Marianna , Cherian Varkey Abel , Nimerovsky Evgeny , Leonov Andrei , Becker Stefan , Andreas Loren B.
Published: November 2024

The currently circulating S31N variant of the M2 proton channel of influenza A is resistant to antiviral drugs. Recently, there has been a growing concern regarding the impact of the lipid environment on the structural features of the S31N variant. The native symmetry of the M2 tetramer remains controversial. Here we show that S31N M2 persists in a dimer‐of‐dimers structure in different lipid preparations independent of the amount of solvating lipids up to at least 180 lipids per tetramer. NMR spectra clearly detect the characteristic resonances of the dimer‐of‐dimers of M2 (residues 18–60 or 18–62) reconstituted in lipids. NMR‐based distance measurements indicate that two isoleucine residues with upfield shifted alpha carbon resonances, typical of extended conformations, are compatible with a particular side‐chain rotameric state and helical backbone geometry. These chemical shifts are therefore compatible with the expected native transmembrane helical fold. Symmetry breaking at the pH sensing H37 residues, detected via peak doubling, is a stable feature of S31N M2 based on the reference strain Udorn/1972(H3N2). By contrast, the spectrum is dramatically altered for Columbia/2014/(H3N2) M2, which differs in sequence in the amphipathic helices. This highlights an allosteric coupling between the amphipathic helices and the pH sensing residues.
Monitoring Transient Sorption of Hexane Isomer Mixtures in a Large ZSM‐5 Single Crystal via Infrared Microimaging
Authors: Seidel Patricia , Hwang Seungtaik , Kasera Aastha , Goepel Michael , Chmelik Christian , Snurr Randall Q. , Kärger Jörg , Gläser Roger
Published: November 2024

Infrared (IR) microimaging is employed for selectively recording two‐dimensional plots of the individual distributions of the components n‐hexane (nC6) and 3‐methylpentane (3MP) over a single crystal of zeolite ZSM‐5 during mixture adsorption. At a pressure change from 0 to 0.02 mbar, the scenario of “overshooting” is observed, with the concentration of nC6 temporarily exceeding its equilibrium value. After the next pressure step from 0.02 to 2 mbar, 3MP is progressively driven out of the pores, in parallel with an increase in nC6 concentration. The IR microimaging results are corroborated by grand canonical Monte Carlo simulations, which help explain the peculiarities of mass transfer by providing visual representations of the distribution and packing densities of the guest molecules in the pores.
Analysis of Wilms Tumour Epidemiology, Clinicopathological Features and Treatment Outcomes in 84 Moroccan Patients
Authors: Benlhachemi Sara , Khattab Mohammed , Hattoufi Kenza , Abouqal Redouane , Boutayeb Saber , El Fahime Elmostafa
Published: November 2024

Background

Wilms tumour (WT), the second most reported childhood cancer in Morocco, is a malignant kidney tumour that affects children under 15 years old. Prognosis has improved with the adoption of multimodal treatment. However, data on WT in Morocco remain limited.

Aims

This study aims to comprehensively describe and analyse the epidemiological, clinicopathological features and treatment outcomes of WT in Moroccan patients, including treatment response and recurrence rates.

Methods and Results

A retrospective study involved 84 children under 15 years with WT, treated according to the SIOP protocol and followed at the Paediatric Haematology and Oncology Centre at Children's hospital of Rabat, between January 2014 and February 2018. The median age of participants was 36 months, with a male/female sex ratio of 0.79. Abdominal mass was the primary concern in 55 cases (66%). Five patients (6%) had bilateral WT. Metastatic WT occurred in 21 cases (25%). Stage III was predominant in 33 cases (43%). Twenty cases (26%) had high‐risk WT, and IVC tumour thrombus was observed in 12 cases (14%). WT histotype correlated significantly with both sex and tumour localisation (p values of 0.040 and 0.013, respectively). Age correlated significantly with WT extension, overall stage and SIOP histology risk grades (p values of 0.003, 0.003 and 0.045, respectively). Overall stage was statistically related to the occurrence of IVC tumour thrombus (p = 0.002). Over a 5‐year span post‐nephrectomy, complete remission was achieved in 63 patients (75%), partial remission in one patient (1%), while 19 patients (23%) died and one patient (1%) relapsed.

Conclusion

These findings are encouraging for a developing country. However, the elevated rates of Stages III and IVC thrombus in this series are still high, primarily attributed to delays in diagnosis and treatment and the limited number of paediatric haematology and oncology units at the time of the study. Nevertheless, further multicentric research is warranted to enrich Moroccan data and establish a national register for WT cases.
Auto‐Tuning Mixed‐Precision Computation by Specifying Multiple Regions
Authors: Ren Xuanzhengbo , Kawai Masatoshi , Hoshino Tetsuya , Katagiri Takahiro , Nagai Toru
Published: November 2024

Mixed‐precision computation is a promising method for substantially improving high‐performance computing applications. However, using mixed‐precision data is a double‐edged sword. While it can improve computational performance, the reduction in precision introduces more uncertainties and errors. As a result, precision tuning is necessary to determine the optimal mixed‐precision configurations. Much effort is therefore spent on selecting appropriate variables while balancing execution time and numerical accuracy. Auto‐tuning (AT) is one of the technologies that can assist in alleviating this intensive task. In recent years, ppOpen‐AT, an AT language, introduced a directive for mixed‐precision tuning called “Blocks.” In this study, we investigated an AT strategy for the “Blocks” directive for multi‐region tuning of a program. The non‐hydrostatic icosahedral atmospheric model (NICAM), a global cloud‐resolving model, was used as a benchmark program to evaluate the effectiveness of the AT strategy. Experimental results indicated that when a single region of the program performed well in mixed‐precision computation, combining these regions resulted in better performance. When tested on the supercomputer “Flow” Type I (Fujitsu PRIMEHPC FX1000) and Type II (Fujitsu PRIMEHPC CX1000) subsystems, the mixed‐precision NICAM benchmark program tuned by the AT strategy achieved a speedup of nearly 1.31× on the Type I subsystem compared to the original double‐precision program, and a 1.12× speedup on the Type II subsystem.
A Comparative Study of Nonsuicidal Self‐Injury, Hopelessness and Meaning in Life Before and After COVID‐19 in Adolescents
Authors: Sanz‐Sendra X. , Mora‐Ascó J. , Gallego‐Hernández de Tejada B. , Marco J. H. , Pérez Rodríguez S.
Published: November 2024

Introduction

Recent research shows that there has been a decrease in meaning in life and an increase in hopelessness and nonsuicidal self‐injury in adolescents after the pandemic. The present study aims to address three objectives: (1) to compare the frequency, types and functions of nonsuicidal self‐injury before and after the pandemic, (2) to explore the relationship between meaning in life, hopelessness and nonsuicidal self‐injury and (3) to study differences in nonsuicidal self‐injury, meaning in life and hopelessness levels before and following the pandemic.

Methods

This research was conducted in a community sample of N = 3800 Spanish participants, including n = 1733 from the pre‐pandemic period and n = 2067 from the post‐pandemic period. Ages ranged between 11 and 19, and the average age was 14.87 (SD = 1.58). The sample had an equal distribution by gender, with 50.5% females (n = 1919) and 49.5% males (n = 1881). Standardized tests such as ISAS‐II, BHS and PIL‐10 were used, as well as descriptive statistics, Spearman correlations and non‐parametric ANCOVAs of Quade controlling for age and gender to compare pre‐ and post‐pandemic variables.

Results

The results revealed a significant increase in the number of functions of nonsuicidal self‐injury, in the methods employed and in the levels of hopelessness, along with a notable decrease in meaning in life after the pandemic. However, the estimated prevalence of pre‐ and post‐pandemic nonsuicidal self‐injury remained similar. The estimated lifetime prevalence of NSSI was 24.9% (n = 432) before the pandemic and 19.4% (n = 401) after the pandemic. A positive correlation between nonsuicidal self‐injury and hopelessness and a negative correlation with meaning in life were observed.

Conclusions

These findings indicate that the pandemic influenced the mental health of young Spaniards and suggest it may be useful to incorporate meaning‐centred interventions in protocols to address nonsuicidal self‐injury and hopelessness in adolescent populations.
Concordance Between Pharmaceuticals and Medical Devices Agency Review and Ministry of Health, Labour and Welfare Decision Among New Drug Applications in Japan
Authors: Miyazawa Makoto , Tanaka Mototsugu , Tanaka Yusuke , Terashima Ryohei , Ezura Mio , Miyazawa Haruna , Ikuma Mutsuhiro , Tomita Yoshihiko
Published: November 2024

New drug applications (NDAs) in Japan are reviewed by the Pharmaceuticals and Medical Devices Agency (PMDA). Those that pass the review are subsequently subject to deliberation by the Ministry of Health, Labour and Welfare Pharmaceutical Affairs and Food Sanitation Councils (MHLW‐PAFSC), and the MHLW legislatively grants approval based on its positive opinions. However, little is known regarding the relationship between the PMDA review and the MHLW decision. We retrospectively assessed the MHLW decision of NDAs that passed the PMDA review at the initial MHLW‐PAFSC deliberation from 2002 to 2022. The reasoning behind a non‐supportive opinion from the MHLW‐PAFSC and the sponsor's actions to overcome unresolved issues were also documented. A total of 2,117 of 2,153 (98.3%) NDAs that passed the PMDA review were approved at the initial MHLW‐PAFSC deliberation with a positive opinion. The remaining 36 applications were not approved at the initial deliberation and subjected to continued deliberation because of a non‐supportive opinion from the councils, although 29 were finally approved through revision of the application document (24 applications), re‐analysis of the data (1 application), or additional clinical trials (4 applications). Seven applications have not been approved, of which one was refused, four were withdrawn, and two were unknown. The MHLW approves NDAs that passed the PMDA review at the initial deliberation at a high rate, suggesting that NDAs only suitable for approval passed the review and reached the MHLW‐PAFSC deliberation. Only a few NDAs were not approved at the initial deliberation; however, most of them were finally approved.
Combining Bismuth Telluride and Palladium for High Efficiency Glycerol Electrooxidation
Authors: Ren Fangfang , Pan Hongjun , Wang Cheng , Du Yukou
Published: November 2024

Designing high‐performance anodic catalysts to drive glycerol oxidation reaction (GOR) is essential for advancing direct alcohol fuel cells. Coupling Pd with oxophilic materials is an effective strategy to enhance its intrinsic catalytic activity. In this study, we successfully synthesized Pd/Bi2Te3 catalysts with tunable compositions, using Bi2Te3 as a novel promoter, and applied them to the GOR for the first time. Electrocatalytic tests revealed that the activity of the Pd/Bi2Te3 catalysts was closely linked to their compositions. Among these catalysts, the optimized Pd/Bi2Te3‐20 % showed potential to replace the commercial Pd/C catalyst, exhibiting a peak current density 5.2 times higher than that of the benchmark Pd/C catalyst. Furthermore, improved catalytic stability and faster catalytic kinetics were observed for Pd/Bi2Te3‐20 %. The synergistic effect between Pd and Bi2Te3 is responsible for the high performance of the Pd/Bi2Te3‐20 % catalyst.
Examining the clinical role and educational preparation of heart failure nurses across Europe. A survey of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) and the Association of Cardiovascular Nursing and Allied Professions (ACNAP) of the ESC
Authors: Hill Loreena , Girerd Nicolas , Castiello Teresa , Jaarsma Tiny , Metra Marco , Rosano Guiseppe , Savage Patrick , Schuuring Mark J. , Simpson Maggie , Uchmanowicz Izabella , Volterrani Maurizio , Williams Rhys , Lambrinou Ekaterini , Hage Camilla
Published: November 2024

Aims

To describe the clinical practice and educational preparation of heart failure (HF) nurses across Europe and determine the key differences between countries.

Methods and results

A survey tool was developed, in English, by the Heart Failure Association Patient Care committee of the European Society of Cardiology (ESC). It was translated into eight languages, before electronically disseminated by nurse ambassadors, presidents of HF national societies and through social media. A total of 837 nurses involved in the daily care of patients with HF from 15 countries completed the survey. Most nurses, 78% (n = 395) worked within a hospital outpatient setting, and 51% (n = 431) had access to a specialized HF multidisciplinary team. Nurses performed a range of activities including patient education to promote self‐care, virtual and in‐person symptom monitoring. A third had more than 5‐year experience in cardiac care and 22% (n = 182) prescribed HF medications. There was a significant correlation between HF nurses that prescribed HF medications and access to a specialist multidisciplinary team (p = 0.04). A small number of nurses, mainly from Belgium, supported invasive monitoring (n = 68, 8%) with 14% (n = 120) of mostly Danish nurses supporting exercise programmes. The majority of nurses surveyed were committed to further academic professional development, with 41% (n = 343) having completed a HF course.

Conclusion

The role of the HF nurse varies across Europe, however involvement in patient education, symptom monitoring and follow‐up remain core to their practice. In specific activities including the prescribing of HF medications and involvement in invasive monitoring, practice has advanced with collaboration in the multidisciplinary team. Consequently, harmonization of education, training and career pathways are required to standardize HF care aligned with expert guidelines across Europe.
Structural Modifications on Dopamine Molecules toward Polydopamine Applications
Authors: Heo Yoonji , Ji Minseo , Ryu Chae Young , Kim Haein , Choi Isaac , Kang Sung Min , Kim Min
Published: November 2024

Polydopamine (PDA) is a synthetic material synthesized through the oxidative self‐polymerization of dopamine under alkaline conditions. This material emulates the adhesive properties of mussel foot proteins, allowing the formation of robust and stable organic coatings on various surfaces. Researchers have attempted to identify and improve the surface‐coating properties of PDA by incorporating additional organic functional groups. This review explores the structural modifications of dopamine molecules at the organic chemistry level, with a focus on changes in the catechol moiety and aliphatic amines, and examines their impact on the applications of PDA. The flexibility of these modifications underscores their importance for optimizing PDA coatings for a wide range of applications.
Relative Stability and Basicity of Enamines from Aminocatalysts
Authors: Bosch Lluís , Costa Anna M. , Vilarrasa Jaume
Published: November 2024

The relative thermodynamic stability of two series of enamines has been examined using DFT (mainly M06‐2X), MP2, and CCSD(T) calculations, supplemented by 1H NMR spectroscopy in some cases. The basicity of enamines derived from pyrrolidine and various carbonyl compounds has been computationally compared in the gas phase and in water; the results indicate which enamines or iminium ions may predominate in nonpolar and polar acidic media when pyrrolidine and two or more carbonyl groups or carbonyl compounds are present in the reaction flask. The relative basicity of a second series of enamines, from propanal and chiral pyrrolidines or imidazolidin‐4‐ones, has also been investigated; this sheds light on the main intermediates that should be expected when two or more secondary amines are present in acid‐catalyzed aldehyde reactions. Non‐covalent interactions explain the stability of folded side‐chain conformers of O‐silylated prolinol enamines, according to the predictions of M06–2X, ωB97X−D, and B3LYP−D3 (but not B3LYP). The significant stability of iminium ions containing appropriate electron‐donating atoms or groups accounts for the basicity of the corresponding enamines. These findings pave the way for the future development of dual aminocatalytic processes.
Data‐driven methods for quantitative imaging
Authors: Dong Guozhi , Flaschel Moritz , Hintermüller Michael , Papafitsoros Kostas , Sirotenko Clemens , Tabelow Karsten
Published: November 2024

In the field of quantitative imaging, the image information at a pixel or voxel in an underlying domain entails crucial information about the imaged matter. This is particularly important in medical imaging applications, such as quantitative magnetic resonance imaging (qMRI), where quantitative maps of biophysical parameters can characterize the imaged tissue and thus lead to more accurate diagnoses. Such quantitative values can also be useful in subsequent, automatized classification tasks in order to discriminate normal from abnormal tissue, for instance. The accurate reconstruction of these quantitative maps is typically achieved by solving two coupled inverse problems which involve a (forward) measurement operator, typically ill‐posed, and a physical process that links the wanted quantitative parameters to the reconstructed qualitative image, given some underlying measurement data. In this review, by considering qMRI as a prototypical application, we provide a mathematically‐oriented overview on how data‐driven approaches can be employed in these inverse problems eventually improving the reconstruction of the associated quantitative maps.
Sporadic Breast Angiosarcoma With MYC Amplification on Extrachromosomal Circular DNA Detected Using Nanopore Sequencing in an Adolescent Female
Authors: Makise Naohiro , Lin Jason , Kageyama Hajime , Oikawa Mariko , Sugiyama Takahiro , Kawana Hidetada , Araki Akinobu , Hayama Shouko , Nakamura Rikiya , Kinoshita Hideyuki , Kamoda Hiroto , Hagiwara Yoko , Yonemoto Tsukasa , Kawazu Masahito , Itami Makiko
Published: November 2024

Angiosarcoma (AS) is a malignant vascular neoplasm comprising neoplastic endothelial cells accounting for 1%–4% of soft tissue sarcomas. While lymphedema‐associated and post‐irradiation ASs are almost always driven by a high‐level amplification of MYC (8q24), sporadic ASs, including those of breast parenchymal origin, typically lack MYC amplification. Here, we report a case of sporadic breast MYC‐amplified AS in a 19‐year‐old female with no history of lymphedema or irradiation, who was referred to our hospital for an enlarging right breast mass. After needle biopsy, the patient underwent right mastectomy and axillary lymphadenectomy. Microscopically, atypical endothelial cells proliferated and formed well‐defined or slit‐like vascular channels that invaded and dissected the breast parenchymal fat, ducts, and lobules. In a limited area, the tumor cells showed solid sheet‐like proliferation with increased mitotic figures of 40 per 2 mm2 with a small area of necrosis. Immunohistochemical analysis revealed strong positivity for c‐Myc. Fluorescence in situ hybridization (FISH) with MYC break‐apart probes showed a high‐level 5′ single signal amplification. The patient was disease‐free 16 months post‐surgery. Nanopore sequencing successfully detected not only a high‐level amplification of the 8q24 region, including MYC, but also multiple structural variants of the 8q24 region. In‐depth analysis revealed extrachromosomal circular DNA amplification including the MYC protein‐coding region and upstream region but not the downstream region. We also performed methylation classification using nanopore‐based methylation data to successfully categorize the tumor as AS. This case report highlights the potential utility of nanopore sequencing in the diagnosis of sarcomas.
Sex‐ and site‐specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort
Authors: Reichmann Robin , Nimptsch Katharina , Pischon Tobias , Gunter Marc J. , Jenab Mazda , Eriksen Anne Kirstine , Tjonneland Anne , Janke Jürgen , Katzke Verena , Kaaks Rudolf , Schulze Matthias B. , Eichelmann Fabian , Masala Giovanna , Sieri Sabina , Pasanisi Fabrizio , Tumino Rosario , Giraudo Maria Teresa , Rothwell Joseph , Severi Gianluca , Jakszyn Paula , Sanchez‐Perez Maria Jose , Amiano Pilar , Colorado‐Yohar Sandra M. , Guevara Marcela , van Guelpen Bethany , Aglago Elom K. , Heath Alicia K. , Smith‐Byrne Karl , Weiderpass Elisabete , Aleksandrova Krasimira
Published: November 2024

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre‐diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case–control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable‐adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98–1.37] for CRC overall, 1.26 [1.00–1.59] for colon cancer, and 1.08 [0.85–1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20–2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15–3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52–1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76–0.98], P interaction<0.01). Overall, these data suggest that pre‐diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.
Assessing pharmacy students' HIV pre‐exposure prophylaxis (PrEP) prescribing knowledge, PrEP attitudes, and HIV‐related stigma
Authors: Bustria Celeste Noelle , Yohannes Finan , Cocohoba Jennifer , Nguyen Lee , Patel Nimish , Saberi Parya
Published: November 2024

Introduction

Human immunodeficiency virus (HIV) pre‐exposure prophylaxis (PrEP) significantly reduces the risk of acquiring HIV. To increase PrEP prescribing, it is crucial to evaluate the preparedness of future pharmacists who will play a pivotal role in providing PrEP education, counseling, and prescribing.

Objective

We assessed PrEP‐prescribing knowledge, attitudes, and HIV‐related stigma of pharmacy students.

Methods

We conducted a cross‐sectional web‐based survey of student pharmacists in their final two years of education and training at the three University of California pharmacy schools. Survey questions assessed students' awareness of PrEP, familiarity with prescribing guidelines and Senate Bill 159 (SB159), PrEP knowledge, HIV‐related stigma, and attitudes about PrEP. The sample was characterized using descriptive statistics, and non‐parametric tests were used to examine associations between dependent variables and independent variables. A p‐value <0.05 was deemed statistically significant.

Results

A total of 110 students participated in the survey. The greatest familiarity with guidelines was observed in male (77.4%) (p = 0.047) and gay‐identifying (100%) (p = 0.039) students compared with other genders and sexual identities, respectively. Non‐advanced pharmacy practice experience (APPE) students (70.3%) displayed significantly more familiarity with SB159 than APPE students (65.2%) (p = 0.006). Non‐APPE students displayed higher HIV‐related stigma compared with APPE students (13.8 vs. 9.4, p = 0.0015). Significant differences in PrEP knowledge (p = 0.0105), HIV‐related stigma (p = 0.0003), and PrEP attitudes (p = 0.0098) were observed between the schools. African American students had a significantly higher mean PrEP attitudes score (mean = 51.0, standard deviation [SD] = 3.6) compared with other racial categories (p = 0.0329).

Conclusion

Elevated HIV‐related stigma, in the presence of high levels of PrEP knowledge, highlights the need to focus on destigmatizing HIV prevention services and increasing anti‐stigma training, which is imperative in preparing student pharmacists to prescribe PrEP.