bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoter Methylation of RASSF1A Associates to Adult Secondary Glioblastomas and Pediatric Glioblastomas
Authors: Muñoz Jorge , Inda María del Mar , Lázcoz Paula , Zazpe Idoya , Fan Xing , Alfaro Jorge , Tuñón Teresa , Rey Juan A. , Castresana Javier S.
Published: January 2012

While allelic losses and mutations of tumor suppressor genes implicated in the etiology of astrocytoma have been widely assessed, the role of epigenetics is still a matter of study. We analyzed the frequency of promoter hypermethylation by methylation-specific PCR (MSP) in five tumor suppressor genes (PTEN, MGMT, RASSF1A, p14ARF, and p16INK4A), in astrocytoma samples and cell lines. RASSF1A was the most frequently hypermethylated gene in all grades of astrocytoma samples, in cell lines, and in adult secondary GBM. It was followed by MGMT. PTEN showed a slight methylation signal in only one GBM and one pilocytic astrocytoma, and in two cell lines; while p14ARFand p16INK4Adid not show any evidence of methylation in primary tumors or cell lines. In pediatric GBM, RASSF1A was again the most frequently altered gene, followed by MGMT; PTEN, p14 and p16 showed no alterations. Lack or reduced expression of RASSF1A in cell lines was correlated with the presence of methylation. RASSF1A promoter hypermethylation might be used as a diagnostic marker for secondary GBM and pediatric GBM. Promoter hypermethylation might not be an important inactivation mechanism in other genes like PTEN, p14ARFand p16INK4A, in which other alterations (mutations, homozygous deletions) are prevalent.
Prebiotics and Probiotics: Some Thoughts on Demonstration of Efficacy Within the Regulatory Sphere
Authors: Brooks Stephen P J , Kalmokoff Martin L
Published: January 2012

Probiotics and prebiotics present regulators with challenges because they require a demonstrated positive health outcome and proof that the prebiotic or probiotic is the agent of action once safety aspects have been satisfied. Thus, probiotic and prebiotic definitions are important because they will set the criteria by which these materials will be judged within the regulatory sphere. Use of the terms probiotic and prebiotic are, themselves, considered health claims in some jurisdictions, so that both product health claims and product content labeling may be regulated. Currently accepted definitions of prebiotic and probiotic make it easier to draw a straight line between ingestion and health outcome for probiotics but much more difficult for prebiotics, where a health outcome must be linked to changes in specific bacterial species within the gut microbial community. These challenges highlight the difficulties facing regulatory bodies and the scientific community when emerging science is turned into consumable product.
Bidirectional Associations of Depressive Symptoms and Cognitive Function Over Time
Authors: Yin Jiamin , John Amber , Cadar Dorina
Published: June 2024

Importance

Cognitive decline and depressive symptoms often co-occur among older adults, and they share several mechanisms. Despite the fact that cognitive dysfunction has been linked to increased depressive symptoms, the directionality of this association remains unclear.

Objective

To examine whether there is a bidirectional association between depressive symptoms and cognitive function in English adults aged 50 years or older throughout a 16-year follow-up period.

Design, Setting, and Participants

This cohort study included a nationally representative sample of community-dwelling English adults aged 50 years or older. The current analysis included 8268 eligible participants with relevant data. These participants were examined every other year from 2002 and 2003 until 2018 and 2019, resulting in a follow-up period of up to 16 years. Data were analyzed from July to November 2023.

Main Outcomes and Measures

The bivariate dual change score models were used to estimate the multivariable associations between depressive symptoms and cognitive function, which were interchangeably used as exposures and outcomes. Cognitive measures include memory and verbal fluency tests, while the Center for Epidemiologic Studies Depression Scale evaluated depressive symptoms.

Results

The study population of 8268 participants had a mean (SD) age of 64 (10) years at the study baseline, and 4517 participants (55%) were female. Higher depressive symptoms were cross-sectionally associated with poorer memory (β intercept, −0.018; standard error [SE], 0.004; P < .001) and verbal fluency (β intercept, −0.009; SE, 0.004; P = .02) at study baseline. A steeper linear change in depressive symptoms was associated with an accelerated memory change (β intercept, −0.253; SE, 0.079; P = .001), and a linear change in memory was associated with an acceleration in depressive symptoms over time (β intercept, 0.016; SE, 0.006; P = .005). This bidirectional change was not observed with verbal fluency.

Conclusions and Relevance

In this study, greater depressive symptoms were associated with poorer memory at the study baseline and steeper memory change over time. A gradual linear change in depressive symptoms contributed to accelerated memory loss and vice versa, suggesting that psychological mood and memory performance are intrinsically associated.
Laterally π‐Extensed Nitrogen‐Doped Molecular Nanographenes – From Anti‐Kasha Emission to Ping‐Pong Energy Transfer Events
Authors: Beneventi Giovanni M. , Schöll Kilian , Platzer Benedikt , Krug Marcel , Mai Lukas A. , Negri Fabrizia , Cadranel Alejandro , Jux Norbert , Guldi Dirk M.
Published: June 2024

Nanographenes, which feature at least one dimension smaller than 100 nm, are drawing interdisciplinary attention. Understanding the interplay between structure and properties is, however, still in its infancy. Molecular nanographenes are much better suited to fill this knowledge gap than graphene quantum dots or nanoribbons. Their bottom‐up synthesis allows atomic precision and, thereby, assists in handling structure and connecting it with properties. Herein, the effects of nitrogen‐doping and lateral π‐extension in molecular nanographenes and in their coordination complexes with ruthenium porphyrins are investigated. The presence of just nitrogen resulted in an increase of the fluorescence quantum yield, without, however, affecting the energy levels. Lateral π‐extension of the nanographenes, instead, resulted in a modulation of the excited states energy, which leads to a thermally‐activated dual fluorescence with quantum yields as high as 61%. In the corresponding coordination complexes, lateral π‐extension resulted in a ping‐pong energy transfer cascade, that is, from the nanographene to the metalloporphyrin and back to the nanographene. The results help to directly rationalize properties observed in both graphene quantum dots and nanoribbons. Moreover, they prove that molecular nanographenes are appealing components for solar energy conversion schemes, where the modulation of inter‐component energy transfer is of utmost importance.
Low circulating tumor cell levels correlate with favorable outcomes and distinct biological features in multiple myeloma
Authors: Kostopoulos Ioannis V. , Ntanasis‐Stathopoulos Ioannis , Rousakis Pantelis , Malandrakis Panagiotis , Panteli Chrysanthi , Eleutherakis‐Papaiakovou Evangelos , Angelis Nikolaos , Spiliopoulou Vasiliki , Syrigou Rodanthi‐Eleni , Bakouros Panagiotis , Dimitrakopoulou Georgia , Fotiou Despina , Migkou Magdalini , Kanellias Nikolaos , Paschalidis Nikolaos , Gavriatopoulou Maria , Kastritis Efstathios , Dimopoulos Meletios‐Athanasios , Tsitsilonis Ourania E. , Terpos Evangelos
Published: June 2024

There is growing interest in multiple myeloma (MM) circulating tumor cells (CTCs), but their rareness in peripheral blood (PB) and inconsistency in cutoffs question their clinical utility. Herein, we applied next‐generation flow cytometry in 550 bone marrow (BM) and matched PB samples to define an optimal CTC cutoff for both transplant‐eligible and transplant‐ineligible newly diagnosed MM (NDMM) patients. Deep phenotyping was performed to investigate unique microenvironmental features associated with CTC dissemination. CTCs were detected in 90% of patients (median 0.01%; range: 0.0002%–12.6%) and increased levels associated with adverse features. Correlations were observed between high CTC percentages and a diffused MRI pattern, a distinct BM composition characterized by altered B‐cell differentiation together with an expansion of effector cells and tumor‐associated macrophages, as well as a greater phenotypic dissimilarity between BM and PB clonal cells. Progression‐free survival (PFS) and overall survival (OS) gradually worsened with each logarithmic increment of CTCs. Conversely, NDMM patients without CTCs showed unprecedented outcomes, with 5‐year PFS and OS rates of 83% and 97%, respectively. A cutoff of 0.02% CTCs was independent of the ISS, LDH, and cytogenetics in a multivariate analysis of risk factors for PFS. The 0.02% CTC cutoff synergized with the MGUS‐like phenotype and the R‐ISS for improving the risk stratification systems. MRD negativity was less frequent if CTCs were ≥0.02% at diagnosis, but whenever achieved, the poor prognosis of these patients was abrogated. This study shows the clinical utility of CTC assessment in MM and provides evidence toward a consensus cutoff for risk stratification.
Synthese und Charakterisierung eines Kupfer‐Distickstoff‐Komplexes unter Verwendung eines schwach koordinierenden Anions
Authors: Willrett Julie , Schmitt Manuel , Zhuravlev Vadim , Sellin Malte , Malinowski Przemysław J. , Krossing Ingo
Published: June 2024

Wir stellen die Synthese und vollständige Charakterisierung des Kupfer‐Distickstoff‐Komplexes [(η1‐N2)Cu{Al(ORF)4}] 2 (RF=C(CF3)3) vor, welcher durch eine Kaskaden‐Metathese‐Reaktion zwischen Ag[Al(ORF)4] und einem CuI‐Überschuss in iso‐Perfluorhexan (i‐pfh) unter N2‐Atmosphäre hergestellt wurde. Die Titelverbindung 2 weist eine außerordentlich hohe N2‐Streckschwingungsfrequenz von 2313/2314 cm−1 (IR/Raman) auf und wurde durch Einkristall‐ und Pulver‐Röntgendiffraktometrie charakterisiert. Quantenchemische Ladungsverschiebungsanalysen basierend auf natürlichen Orbitalen der chemischen Valenz (CD‐NOCV) legen nahe, dass die Kupfer‐Distickstoff‐Interaktion durch eine schwache π‐Rückbindung charakterisiert wird, welche jedoch im Vergleich zu allen literaturbekannten Übergangsmetall‐Distickstoff‐Komplexen stark abgeschwächt ist.
Dichloromethane as C1 Synthon for the Photoredox Catalytic Cyclopropanation of Aromatic Olefins
Authors: Aragón Jordi , Sun Suyun , Fernández Sergio , Lloret‐Fillol Julio
Published: June 2024

Dichloromethane, as a readily available and inexpensive C1 synthon is proposed as a powerful building block for cyclopropanation of alkenes under mild conditions. Herein, we report a highly efficient and versatile dual photoredox system, involving a nickel aminopyridine coordination complex and a photocatalyst, for the cyclopropanation of aromatic olefins using dichloromethane, under visible‐light irradiation. The cyclopropanation protocol has been successfully applied at gram scale. Mechanistic studies suggest a Ni(II) pyridyl radical complex as the key intermediate for the homolytic cleavage of the Csp3−Cl bond, generating a chloromethyl radical that is captured by the olefin coupling partner. Our findings also highlight the versatility of this methodology. By directing the radical/polar crossover process, we were able to selectively drive the reaction towards either the formation of cyclopropyl derivatives or the corresponding non‐cyclic alkyl chloride products. The methodology also successfully apply to geminal dichloroalkanes, including the formation of spiro[2,2] compounds. Moreover, our methodology extends to the synthesis of deuterium‐labelled cyclopropanes, demonstrating its utility in isotopic labelling and broadening its applicability in chemical synthesis and drug development.
Expedited Synthesis of Metal Phosphides Maximizes Dispersion, Air Stability, and Catalytic Performance in Selective Hydrogenation
Authors: Karam Leila , Farès Christophe , Weidenthaler Claudia , Neumann Constanze N.
Published: June 2024

Metal phosphides have been hailed as potential replacements for scarce noble metal catalysts in many aspects of the hydrogen economy from hydrogen evolution to selective hydrogenation reactions. But the need for dangerous and costly phosphorus precursors, limited support dispersion, and low stability of the metal phosphide surface toward oxidation substantially lower the appeal and performance of metal phosphides in catalysis. We show here that a 1‐step procedure that relies on safe and cheap precursors can furnish an air‐stable Ni2P/Al2O3 catalyst containing 3.2 nm nanoparticles. Ni2P/Al2O3 1‐step is kinetically competitive with the palladium‐based Lindlar catalyst in selective hydrogenation catalysis, and a loading corresponding to 4 ppm Ni was sufficient to convert 0.1 mol alkyne. The 1‐step synthetic procedure alters the surface ligand speciation of Ni2P/Al2O3, which protects the nanoparticle surface from oxidation, and ensures that 85 % of the initial catalytic activity was retained after the catalyst was stored under air for 1.5 years. Preparation of Ni2P on a variety of supports (silica, TiO2, SBA‐15, ZrO2, C and HAP) as well as Co2P/Al2O3, Co2P/TiO2 and bimetallic NiCoP/TiO2 demonstrates the generality with which supported metal phosphides can be accessed in a safe and straightforward fashion with small sizes and high dispersion.
Synthesis and Characterization of a Copper Dinitrogen Complex Supported by a Weakly Coordinating Anion
Authors: Willrett Julie , Schmitt Manuel , Zhuravlev Vadim , Sellin Malte , Malinowski Przemysław J. , Krossing Ingo
Published: June 2024

We report the synthesis and full characterization of the copper dinitrogen complex [(η1‐N2)Cu{Al(ORF)4}] 2 (RF=C(CF3)3) prepared by a cascade metathesis reaction of Ag[Al(ORF)4] with CuI‐excess in iso‐perfluorohexane (i‐pfh) under N2 atmosphere. Title compound 2 features an extraordinarily high N2 stretching frequency at 2313/2314 cm−1 (IR/Raman) and was characterized by single‐crystal and powder X‐ray diffractometry. Quantum chemical charge displacement analysis based on natural orbitals of chemical valence (CD‐NOCV) indicates that the copper‐dinitrogen interaction is still governed by weak π‐backdonation, but is significantly reduced compared to all literature‐known transition metal dinitrogen complexes.
Photoactivated Circularly Polarized Room‐Temperature Phosphorescence from Phenoselenazine Derivative and Its Application in Information Security†
Authors: Fu Shiyao , Chen Yi , Xie Yujun , Li Zhen
Published: June 2024

Comprehensive Summary

Room‐temperature phosphorescence (RTP) materials have experienced rapid development due to their potential in organic light‐ emitting diode, information security, bioimaging, etc. However, the design of chiral organic phosphors with circularly polarized RTP (CPP) property remains a formidable challenge. Here, we introduce a chiral perturbation approach using a combination of chiral binaphthol and phenoselenazine derivative to achieve CPP. The photoactivated CPP in polystyrene (PS) film demonstrates a luminescence dissymmetry factor (glum), emission efficiency, and RTP lifetime up to 9.32 × 10–3, 27.0%, and 40.0 ms, respectively. The remarkable sensitivity of PS film to oxygen and temperature enables the adjustable emission colors, ranging from green to offwhite and blue under varying conditions. The doping systems, utilizing hosts of triphenylphosphine and 9‐phenylcarbazole, demonstrate an extended CPP lifetime of 85.9 ms and exhibit a persistent mechanoluminescence property with low pressure response threshold as low as 0.15 N. The information security provided by this CPP material was attained via the using of diverse emission colors and afterglow generated by distinct UV irradiation times and host materials. Alternately, it can also be achieved by observing different emission patterns using R‐ and L‐polarizer. The research has presented a reliable approach for producing CPP materials with high emission efficiency and glum.
Clinical Translation of Inorganic Nanoparticles and Engineered Living Materials for Cancer Therapy
Authors: Gandarias Lucía , Faivre Damien
Published: June 2024

A wide range of particle‐based nano‐ to microsystems is currently under investigation for potential use in personalized nanomedicine. However, only a small fraction of these innovations is likely to make it to clinical use. In this concept article, we start by discussing the potential applications of inorganic nanoparticles in cancer treatment and diagnosis, and shed light on the challenges they must overcome to become clinically available. In the second part, we focus on engineered living materials, which have begun to revolutionize the way medical interventions could be performed. Finally, we share our insights and opinions to explain why, despite significant advancements in research on these technologies, their translation to clinical practice remains limited.
Design Strategy for the Synthesis of Self‐Doped n‐Type Molecules
Authors: Wang Cheng , Guo Kai , Deng Yunfeng , Geng Yanhou
Published: June 2024

n‐Type organic conductive molecules play a significant role in organic electronics. Self‐doping can increase the carrier concentration within the materials to improve the conductivity without the need for additional intentional dopants. This review focuses on the various strategies employed in the synthesis of self‐doped n‐type molecules, and provides an overview of the doping mechanisms. By elucidating these mechanisms, the review aims to establish the relationship between molecular structure and electronic properties. Furthermore, the review outlines the current applications of self‐doped n‐type molecules in the field of organic electronics, highlighting their performance and potential in various devices. It also offers insights into the future development of self‐doped materials.
Photoelectrocatalytic Reduction of Nitrobenzene to Azobenzene by Using Ag Nanoparticles‐Decorated Si Nanocone Arrays Photocathodes
Authors: Zhang Kai , Yu Jiacheng , Ru Changzhou , Mu Lixuan , Li Junjie , Shi Wensheng , She Guangwei
Published: June 2024

Photoelectrocatalytic (PEC) reduction of nitrobenzene (NB) is an extremely promising technology for renewable energy utilization and conversion. PEC reduction of NB to produce higher‐value azobenzene (AZB) instead of aniline (AN), which is now commonly reported, is not currently achievable. In this work, we fabricated Ag nanoparticles (AgNPs)‐decorated silicon nanocone (SiNC) array photocathodes with which the PEC reduction of NB to azobenzene (AZB) was realized for the first time. The SiNC array structure constructed by cryogenic dry etching greatly improved the light absorption ability of the photoelectrode. Ag was chosen as the cocatalyst because of its larger potential difference for the NB reduction reaction and the competing side reaction hydrogen evolution reaction. The Schottky junction formed by AgNPs with Si facilitates the rapid extraction of photogenerated electrons to participate in the PEC reaction. Under the optimized conditions, the PEC reduction of NB was achieved with a conversion of more than 90 %, with the reduction products being mainly AZB (9 : 1 ratio of AZB to AN) as well as excellent stability. The present work provides a photoelectrode that highly selectively PEC reduction of NB to AZB, and also provides insights into the design and preparation of high‐performance silicon‐based photoelectrodes.
Advanced electrocatalysts for fuel cells: Evolution of active sites and synergistic properties of catalysts and carrier materials
Authors: Kong Zhijie , Wu Jingcheng , Liu Zhijuan , Yan Dafeng , Wu Zhi‐Peng , Zhong Chuan‐Jian
Published: June 2024

Proton exchange‐membrane fuel cell (PEMFC) is a clean and efficient type of energy storage device. However, the sluggish reaction rate of the cathode oxygen reduction reaction (ORR) has been a significant problem in its development. This review reports the recent progress of advanced electrocatalysts focusing on the interface/surface electronic structure and exploring the synergistic relationship of precious‐based and non‐precious metal‐based catalysts and support materials. The support materials contain non‐metal (C/N/Si, etc.) and metal‐based structures, which have demonstrated a crucial role in the synergistic enhancement of electrocatalytic properties, especially for high‐temperature fuel cell systems. To improve the strong interaction, some exciting synergistic strategies by doping and coating heterogeneous elements or connecting polymeric ligands containing carbon and nitrogen were also shown herein. Besides the typical role of the crystal surface, phase structure, lattice strain, etc., the evolution of structure‐performance relations was also highlighted in real‐time tests. The advanced in situ characterization techniques were also reviewed to emphasize the accurate structure‐performance relations. Finally, the challenge and prospect for developing the ORR electrocatalysts were concluded for commercial applications in low‐ and high‐temperature fuel cell systems.
The impact of ChatGPT on teaching and learning in higher education: Exploring the dual perspectives of participants who were students and teachers
Authors: Fuller Michele , Barnes Neil
Published: June 2024

This study explored the perceived impact of integrating Generative Artificial Intelligence Systems (GenAI) such as ChatGPT into a postgraduate Master of Education program, drawing on the dual perspectives of participants who were students and educators teaching students at different levels of education in England. Using the Situated Expectancy‐Value Theory and Activity‐Centered Analysis and Design theoretical frameworks, the findings revealed opportunities, benefits, and challenges. Benefits included personalized learning and efficiencies in course design while the challenges consisted of ethical concerns, holistic skill development and problem solving. The surprising outcome of this study was the strong emotive anxiety around using AI and GenAI in participants’ academic and personal lives. A balanced, critically reflective approach can help realize ChatGPT's educational potential while navigating implementation barriers and associated challenges. Participants insights can add to the dialogue negotiating ways of effectively integrating GenAI into the higher education curriculum.

Practical Takeaways

Foster collaboration: Educators and students should work together to develop critical evaluation skills, ethical frameworks, and adaptive strategies for responsible GenAI use.

Prioritize ethical considerations: Promote ongoing reflection on the personal and academic implications of GenAI, including potential biases and impacts on equity.

Balance innovation with traditional skills: Emphasize that GenAI augments, rather than replaces, core academic skills like critical thinking, source verification, and effective communication.

Align with student values: To sustain engagement, connect GenAI's use with students' immediate goals, future aspirations, and the potential to improve their learning experiences and outcomes.
Artificial intelligence and advanced data analytics: Implications for higher education
Authors: Webber Karen L. , Zheng Henry Y.
Published: June 2024

Recently, the rise of generative AI tools such as ChatGPT have prompted deep and wide considerations about teaching and learning, student success, research and development, and the use of data for informed institutional decision making. In this volume, authors discuss specific concepts, considerations for use, and some specific tools and applications of advanced data analytics and artificial intelligence that are gaining prominence in higher education. Although these tools and our perceptions about the tools will continue to evolve, we believe that aspects of advanced data analytics and artificial intelligence will remain in our midst in the future. We believe that members of our community will become better educators and higher education managers as we engage deeply with these tools, stay vigilant about the risks and limitations, and establish policies that ensure student and institution success.

Practical Takeaways

The soaring interest in aspects of artificial intelligence (AI) prompts consideration of its potential applications, impact, and implications for the higher education community.

AI‐supported tools hold the promise to help students learn more efficiently and effectively as well as assist faculty and staff with more mundane tasks, yet getting to the place where GenAI helps will take some effort. Since we must consider data privacy, ethical use, security, and accountability, the path may not be straight and narrow.

Analytics through AI tools have a particular promise to support underrepresented and disabled students through focused websites, learning support, and customized tutoring. AI has the potential to narrow the gap in student success, but without focused attention, it could serve to widen the gap across some student groups.

We acknowledge that perceptions about and implications due to artificial intelligence in higher education will change as we move forward; the articles in this volume seek to contribute to the current discussion and may prompt considerations for future conversations.
T‐cell responses in COVID‐19 survivors 6−8 months after infection: A longitudinal cohort study in Pune
Authors: Suryawanshi Poonam , Patil‐Takbhate Bhagyashri , Athavale Prachi , Mirza Shahzad , Tripathy Anuradha , Kanitkar Shubhangi , Shivnitwar Sachin , Barthwal Madhusudan S. , Dole Sachin , Chavan Hanumant , Jali Priyanka , Pawale Sujata , Kakad Dhanashree , Kakrani Arjun Lal , Bhawalkar Jitendra , Gandhi Madhura , Chaturvedi Sarika , Karandikar Mahesh , Tripathy Srikanth
Published: June 2024

Background

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) immune response is crucial for disease management, although diminishing immunity raises the possibility of reinfection.

Methods

We examined the immunological response to SARS‐CoV‐2 in a cohort of convalescent COVID‐19 patients in matched samples collected at 1 and 6−8 months after infection. The peripheral blood mononuclear cells were isolated from enrolled study participants and flow cytometry analysis was done to assess the lymphocyte subsets of naive, effector, central memory, and effector memory CD4+ or CD8+ T cells in COVID‐19 patients at 1 and 6−8 months after infection. Immunophenotypic characterization of immune cell subsets was performed on individuals who were followed longitudinally for 1 month (n = 44) and 6−8 months (n = 25) after recovery from COVID infection.

Results

We observed that CD4 +T cells in hospitalized SARS‐CoV‐2 patients tended to decrease, whereas CD8+ T cells steadily recovered after 1 month, while there was a sustained increase in the population of effector T cells and effector memory T cells. Furthermore, COVID‐19 patients showed persistently low B cells and a small increase in the NK cell population.

Conclusion

Our findings show that T cell responses were maintained at 6−8 months after infection. This opens new pathways for further research into the long‐term effects in COVID‐19 immunopathogenesis.
Exploring the prognostic significance of immunogenic cell death‐related genes as risk biomarkers in cervical cancer
Authors: Jin Shuangmei , Chen Jingdong
Published: June 2024

Background

Immunogenic cell death (ICD) is a process in which dying cells stimulate an immune response. It is a regulated form of cell death that can remodel the tumor microenvironment (TME) and activate the immune system, making immunotherapy more effective. This work was designed to identify prognostic gene features associated with ICD in cervical cancer (CC).

Methods

Based on CC datasets and a set of ICD‐related genes obtained from public databases, we first filtered out ICD‐related genes unrelated to CC survival using univariate analysis. Subsequently, LASSO regression and multivariate Cox regression analysis were employed to develop prognostic feature genes based on ICD. For the construction and validation of the model, eight genes (CXCL1, IL1B, TNF, YKT6, PDIA3, ROCK1, CXCR3, and CLEC9A) were chosen. A nomogram was created to forecast the prognosis of CC individuals, and Kaplan–Meier curves were utilized to explore the survival disparities among different risk groups of CC individuals.

Results

ssGSEA analysis was employed to investigate immune differences between two risk groups, revealing that the low‐risk group exhibited elevated levels of immune cell infiltration, enhanced activation of immune function, and a higher immunophenoscore compared with the other group, which highlighted the relevance of ICD to TME.

Conclusion

We constructed a prognostic model based on genetic biomarkers of ICD for prognostic prediction of CC patients. Our model demonstrated excellent discriminative and calibration capabilities, providing a valuable tool for prognostic prediction and assessing the potential efficacy of immunotherapy in CC.
Histopathological phenotyping of cancers in PTEN Hamartoma Tumor Syndrome for improved recognition: A single‐center study
Authors: Schei‐Andersen Ane J. , Hendricks Linda A. J. , van der Post Rachel S. , Mensenkamp Arjen R. , Schieving Jolanda ,   PTEN Study Group, Schuurs‐Hoeijmakers Janneke H. M. , Hoogerbrugge Nicoline , Vos Janet R.
Published: June 2024

PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition. Genetic testing results and pathology reports were collected for patients tested for germline PTEN variants between 1997 and 2020 from the diagnostic laboratory and the Dutch nationwide pathology databank (Palga). The cancer spectrum and age of onset were assessed in patients with (PTENpos) and without (PTENneg) a germline PTEN variant. Histopathological cancer characteristics were assessed in a nested cohort. 341 PTENpos patients (56% females) and 2882 PTENneg patients (66% females) were included. PTENpos patients presented mostly with female breast (BC, 30%), endometrial (EC, 6%), thyroid (TC, 4%) or colorectal cancer (4%). PTENpos were significantly younger at cancer onset (43 vs. 47 years) and had more often (46% vs. 18%) a second BC than PTENneg. PTEN detection rates were highest for BC <40 years (9%), TC <20 years (15%) and EC <50 years (28%), and dropped to 6%, 4%, and 15% by age 60. Histopathological characteristics were similar between groups. No histopathological cancer characteristics were distinctive for PHTS. However, PTENpos were significantly younger at cancer onset. Therefore early‐onset BC, EC, or TC warrants consideration of PHTS diagnostics either through a pre‐screen for other PHTS features or direct germline testing.
Effects of a novel regimen of repetitive transcranial magnetic stimulation (rTMS) on neural remodeling and motor function in adult male mice with ischemic stroke
Authors: Peipei Wang , Yu Deng , Xiaoyan Lin , Yunxia Liu , Liuming Liang , Tongbin Cheng , Shaoping Lv
Published: June 2024

Neuroinflammation caused by excessive microglial activation plays a key role in the pathogenesis of ischemic stroke. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuromodulatory technique that has recently been reported to regulate microglial functions and exert anti‐inflammatory effects. The intermittent burst stimulation (iTBS) regimen in rTMS improves neuronal excitability. However, whether iTBS exerts its anti‐inflammatory effects by stimulating neurons and thereby modulating microglial polarization remains unclear. Motor function was assessed after 1 week of rTMS (iTBS regimen) treatment in adult male mice with occlusion/reperfusion of the middle cerebral artery (MCAO/r) injury. We also investigated the molecular biological alterations associated with microglial polarization using a cell proliferation assay, multiplex cytokine bioassays, and immunofluorescence staining. iTBS regimen can improve balance and motor coordination function, increase spontaneous movement, and improve walking function in mice with early cerebral ischemia injury. Expression levels of IL‐1β, TNF‐α, and IL‐10 increased significantly in mice with MCAO injury. Especially, rTMS significantly increased the number of proliferating cells in the infarcted cortex. The fluorescence intensity of MAP2 in the peri‐infarct area of MCAO injured mice was low, but the signal was broader. Compared with MCAO group, the fluorescence intensity of MAP2 in rTMS group was significantly increased. rTMS inhibited pro‐inflammatory M1 activation (Iba1+/CD86+) and improved anti‐inflammatory M2 activation (Iba1+/CD206+) in the peri‐infarct zone, thus significantly changing the phenotypic ratio M1/M2. rTMS improves motor dysfunction and neuroinflammation after cerebral I/R injury in mice by regulating microglial polarization.
Progresses in the establishment, evaluation, and application of in vitro blood–brain barrier models
Authors: Yin Panfeng , Wang Xianchun
Published: June 2024

The blood–brain barrier (BBB) is a barrier between the circulatory system and the central nervous system (CNS), contributing to CNS protection and maintaining the brain homeostasis. Establishment of in vitro BBB models that are closer to the microenvironment of the human brain is helpful for evaluating the potential and efficiency of a drug penetrating BBB and thus the clinical application value of the drug. The in vitro BBB models not only provide great convenience for screening new drugs that can access to CNS but also help people to have a deeper study on the mechanism of substances entering and leaving the brain, which makes people have greater opportunities in the treatment of CNS diseases. Up to now, although much effort has been paid to the researches on the in vitro BBB models and many progresses have been achieved, no unified method has been described for establishing a BBB model and there is much work to do and many challenges to be faced with in the future. This review summarizes the research progresses in the establishment, evaluation, and application of in vitro BBB models.
Effects of chopping temperature on the gel quality of silver carp (Hypophthalmichthys molitrix) surimi: insight from gel‐based proteomics
Authors: Bao Yulong , Yan Dan , Xu Guoliang , Hong Hui , Gao Ruichang
Published: June 2024

BACKGROUND

Morden advanced analytical tools offer valuable information into the understanding of molecular mechanism of traditional food processing. Chopping temperature is well‐known to affect the surimi gel quality of silver carp, but the detailed molecular mechanism is not very clear. In this study, a gel‐based proteomics was performed on the extracted surimi proteins under different chopping temperatures (0, 5, 10, and 25 °C) along with other physicochemical characterization of surimi proteins and gels.

RESULTS

With increased chopping temperature, protein extractability (in 3% sodium chloride) generally decreased, while the extracted protein generally exhibited larger surface hydrophobicity, reduced intrinsic fluorescence intensity, lower sulfhydryl content. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) profile of extracted protein showed a clear difference at 25 °C when compared with the other three temperatures, and more protein fragmentation occurred. Proteomic analysis of selected bands indicated that major myofibrillar proteins react differently with chopping temperatures, especially at 25 °C. The selected bands contained a variety of other proteins or their fragments, including adenosine triphosphate (ATP) synthase, glyceraldehyde‐3‐phosphate dehydrogenase, glucose‐6‐phosphate isomerase, heat shock protein, parvalbumin, collagen, and so forth. For the surimi gel, water‐holding capacity and gel strength generally decreased with increased chopping temperature.

CONCLUSION

Our results suggested that chopping at 0–10 °C is acceptable for the production of silver carp surimi in terms of gel strength and water‐holding capacity. However, a chopping temperature near 0 °C led to less protein oxidation and denaturation. The inferior gel quality at 25 °C is linked to a decreased concentration of extracted protein and degradation of major myofibrillar protein, the latter is likely crosslinked with sarcoplasmic proteins. © 2024 Society of Chemical Industry.
Is a Vitrimer with a High Glass Transition Temperature Available? A Case Study on Rigid Polyimides Cross‐Linked with Dynamic Ester Bonds
Authors: Wang Yueh‐Hsin , Hung Du‐Yuan , Liu Ying‐Ling
Published: June 2024

Vitrimers, possessing associative covalent adaptable networks, are cross‐linked polymers exhibiting malleable (glass‐like) feature and recyclable and reprocessable (thermoplastics‐like) properties. The dynamic behaviors of vitrimer are dependent on both chain/molecular mobility (glass transition temperature, Tg) and dynamic bond‐exchanging reaction rate (topology freezing transition temperature, Tv). This work aims on probing the effect of high Tg on the stress relaxation and physical recyclability of vitrimers, employing a polyimide cross‐linked with dynamic ester bonds (Tg: 310 °C) as the example. Due to its high Tg and chain rigidity, the cross‐linked polyimide does not exhibit a high extent of stress relaxation behavior at 320 °C (10 °C above its Tg), even though the temperature is much higher than the hypothetical Tv. While raising the processing temperature to 345 °C, the cross‐linked polyimide exhibits a stress relaxation time of about 3300 s and physical malleability. Nevertheless, side reactions may occur in the recycling and reprocessing process under the harsh condition (high temperature and high pressure) to alter the thermal properties of the recycled sample. The diffusion control plays a critical role on the topography transition of a vitrimer having a high Tg. The Tg ceiling is noticeable for developments of vitrimers.
Do environmental courts drive corporate green innovation? A study based on double machine learning
Authors: Liang Yanru , Xu Jianzhong , Liu Yiqing
Published: June 2024

To investigate whether environmental court (EC) can drive corporate green innovation (GI) and the specific driving mechanisms, this study utilizes panel data from A‐share listed companies from 2003 to 2019. Employing a dual‐machine learning model, it explores the specific impact of EC on GI, the influencing pathways, and their heterogeneous effects on GI with different motivations, modes, and targets. The findings revealed that (1) EC significantly promote GI, a conclusion that remains valid after a series of robustness tests. (2) EC primarily drive GI through two pathways: deterrence and alert mechanisms. (3) Heterogeneity analysis reveals that EC exert differentiated impacts based on the varying motivations, modes, and targets of GI. In terms of motivation, compared to strategic GI, EC have a more significant promotional effect on substantive GI. As for the mode, EC can clearly enhance the level of utilization GI, but their promotional effect on exploration GI is not yet apparent. Regarding targeting, EC contribute more marginnally to GI in source control than in end‐of‐pipe. These empirical findings deepen our understanding of how EC promote GI. Furthermore, this study reveals the potential role of dual‐machine learning in solving environmental governance issues.
Loss‐of‐function polymorphisms in NQO1 are not associated with the development of subacute myelo‐optico‐neuropathy
Authors: Matsumoto Hideki , Sasai Hideo , Kawamoto Norio , Katsuyama Masato , Minamiyama Makoto , Kuru Satoshi , Fukao Toshiyuki , Ohnishi Hidenori ,   the SMON Research Group Members
Published: June 2024

Background

Subacute myelo‐optico‐neuropathy (SMON) is a neurological disorder associated with the administration of clioquinol, particularly at very high doses. Although clioquinol has been used worldwide, there was an outbreak of SMON in the 1950s–1970s in which the majority of cases were in Japan, prompting speculation that the unique genetic background of the Japanese population may have contributed to the development of SMON. Recently, a possible association between loss‐of‐function polymorphisms in NQO1 and the development of SMON has been reported. In this study, we analyzed the relationship between NQO1 polymorphisms and SMON in Japan.

Methods

We analyzed 125 Japanese patients with SMON. NQO1 loss‐of‐function polymorphisms (rs1800566, rs10517, rs689452, and rs689456) were evaluated. The allele frequency distribution of each polymorphism was compared between the patients and the healthy Japanese individuals (Human Genomic Variation Database and Integrative Japanese Genome Variation Database), as well as our in‐house healthy controls.

Results

The frequencies of the loss‐of‐function NQO1 alleles in patients with SMON and the normal control group did not differ significantly.

Conclusion

We conclude that known NQO1 polymorphisms are not associated with the development of SMON.
Reliable segmentation of multiple lesions from medical images
Authors: Wang Meng , Yu Kai , Tan Zhiwei , Zou Ke , Goh Rick Siow Mong , Fu Huazhu
Published: June 2024

Background

Focusing on the complicated pathological features, such as blurred boundaries, severe scale differences between symptoms, and background noise interference, we aim to enhance the reliability of multiple lesions joint segmentation from medical images.

Purpose

Propose a novel reliable multi‐scale wavelet‐enhanced transformer network, which can provide accurate segmentation results with reliability assessment.

Methods

Focusing on enhancing the model's capability to capture intricate pathological features in medical images, this work introduces a novel segmentation backbone. The backbone integrates a wavelet‐enhanced feature extractor network and incorporates a multi‐scale transformer module developed within the scope of this work. Simultaneously, to enhance the reliability of segmentation outcomes, a novel uncertainty segmentation head is proposed. This segmentation head is rooted in the SL, contributing to the generation of final segmentation results along with an associated overall uncertainty evaluation score map.

Results

Comprehensive experiments are conducted on the public database of AI‐Challenge 2018 for retinal edema lesions segmentation and the segmentation of Thoracic Organs at Risk in CT images. The experimental results highlight the superior segmentation accuracy and heightened reliability achieved by the proposed method in comparison to other state‐of‐the‐art segmentation approaches.

Conclusions

Unlike previous segmentation methods, the proposed approach can produce reliable segmentation results with an estimated uncertainty and higher accuracy, enhancing the overall reliability of the model. The code will be release on https://github.com/LooKing9218/ReMultiSeg.
Self‐nucleation in poly(butylene adipate‐co‐terephthalate) of initially different crystal forms
Authors: Zhou Cheng , Ye Shihang , Liu Zhishen , Jing Mengfan , Liu Chuntai , Shen Changyu , Wang Yaming
Published: June 2024

Poly(butylene adipate‐co‐terephthalate) (PBAT) is an important biodegradable copolymer, but its crystallization rate is slow. Herein, the effect of self‐nucleation on the crystallization behavior of PBAT with initially different crystalline modifications (melt‐crystallized specimens and as‐received pellets) was investigated. The melt‐crystallized and as‐received PBAT specimens are confirmed as the α‐ and β‐form, respectively. It is found that the self‐nucleation domains of β‐form PBAT are almost the same as those of α‐form one. After self‐nucleation, the maximum shift of the crystallization peak toward higher temperature is around 60 °C upon the followed cooling process, suggesting that self‐nucleation remarkably promotes PBAT crystallization. The self‐nucleation temperature span of self‐nucleation domain is about 10 °C, which provides substantial benefits to industrial processing. Moreover, for both the initial α‐ and β‐form PBAT, the final crystal is α‐form after self‐nucleation treatment. This work demonstrates that self‐nucleation is highly effective in enhancing PBAT crystallization.
Love and Learning in the Age of Algorithms: How Intimate Relationships with Artificial Intelligence May Shape Epistemology, Sociality, and Linguistic Justice
Authors: Nash Brady L.
Published: June 2024

Generative artificial intelligence (GAI) programs such as ChatGPT and other large language models are designed to engage in complex, responsive dialogues that feel like human interactions. The dialogic and responsive nature of GAI signals the potential for users to form relationships with GAI platforms or digital personalities created on these platforms. Given the degree to which language use and broader conceptual understandings are deeply embedded in social relationships, the relational nature of GAI has powerful implications for the future of literacy and learning. This speculative essay draws upon sociocultural, affective, and posthuman perspectives on literacy to explore key concerns regarding the nature of intimate relationships with GAI. The author highlights three central concerns for literacy researchers and educators: epistemological issues stemming from intimate relationships with GAI, the potential for students to (re)conceptualize human relationships through GAI, and the role of relational GAI in linguistic justice.
Flexible Aqueous Supercapacitors for Long Cycle‐Life Using Electrode with Multiple Active C═S Sites
Authors: Xing Xinxin , Farhadi Bita , Wang Le , Wang Kai , Zhu Yan , Wang Hui , Di Lanbo , Zhang Haoxiang , Liu Shengzhong (Frank)
Published: June 2024

Even though a few organic materials have attracted considerable attention for energy storage applications, their dissolution in the electrolyte during the charging‐discharging processes presents a formidable challenge to their long‐term performance. In this work, according to the principle of like dissolves like, non‐polar trithiocyanuric acid (TCA) can effectively inhibit dissolution in an aqueous electrolyte, hence prolonging the cycle life. Moreover, theoretical calculations suggest that TCA lowers lowest unoccupied molecular orbital (LUMO) energy level, thereby promoting reaction kinetics. The CV curves of TCA maintain a rectangular structure even at a high scan rate of 1000 mV s‒1 and exhibit a remarkable capacitance retention rate of 93.1% after 50,000 cycles. Asymmetric flexible supercapacitors utilizing the TCA exhibit an impressive energy density. Moreover, they maintain 94.2% of their capacitance after undergoing 80,000 cycles. Their integration with perovskite solar cells to facilitate the rapid storage of photogenerated charges enables efficient solar energy utilization, providing a practical solution for capturing and storing renewable energy.