bluuebunny/crossref_metadata_2025 huggingface dataset:
Obesity's Unexpected Influence: Reduced Alphavirus Transmission and Altered Immune Activation in the Vector
Authors: Rai Pallavi , Webb Emily M. , Paulson Sally L. , Kang Lin , Weger‐Lucarelli James
Published: October 2024

Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are emerging/re‐emerging alphaviruses transmitted by Aedes spp. mosquitoes and responsible for recent disease outbreaks in the Americas. The capacity of these viruses to cause epidemics is frequently associated with increased mosquito transmission, which in turn is governed by virus−host−vector interactions. Although many studies have explored virus−vector interactions, significant gaps remain in understanding how vertebrate host factors influence alphavirus transmission by mosquitoes. We previously showed that obesity, a ubiquitous vertebrate host biological factor, reduces alphavirus transmission potential in mosquitoes. We hypothesized that alphavirus‐infected obese bloodmeals altered immune genes and/or pathways in mosquitoes, thereby inhibiting virus transmission. To test this, we conducted RNA sequencing (RNA‐seq) and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) on midgut RNA from mosquitoes fed on alphavirus‐infected lean and obese mice. This approach aimed to identify potential antiviral or proviral genes and pathways altered in mosquitoes after consuming infected obese bloodmeals. We found upregulation of the Toll pathway and downregulation of several metabolic and other genes in mosquitoes fed on alphavirus‐infected obese bloodmeals. Through gene knockdown studies, we demonstrated the antiviral role of Toll pathway and proviral roles of AAEL009965 and fatty acid synthase (FASN) in the transmission of alphaviruses by mosquitoes. Therefore, this study utilized obesity to identify factors influencing alphavirus transmission by mosquitoes and this research approach may pave the way for designing broadly effective antiviral measures to combat mosquito‐borne viruses, such as releasing transgenic mosquitoes deficient in the identified genes.
Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity
Authors: Yee Elliott J. , Thielen Otto N. , Truong Ronald , Gilbert Danielle , Michel Kylie , Couts Kasey L. , Robinson William A. , McCarter Martin D.
Published: October 2024

Introduction

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking.

Methods

A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan–Meier curves with log‐rank tests were used to analyze time‐to‐event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival.

Results

Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI‐specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis.

Conclusions

GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.
Novel Clinical Practice Assessments: Informational Statements by the Musculoskeletal Tumor Society
Authors: Tedesco Nicholas S. , Wallace Matthew , Doung Yee‐Cheen , Colman Matthew , Wodajo Felasfa
Published: October 2024

Musculoskeletal oncology involves rare diseases. As a result, there is a paucity of literature to guide practitioners. Studies are often clinical experience, retrospective reviews, noncomparative studies, and involve small numbers of patients. However, technological advances consistently arise in this field. This article represents the Musculoskeletal Tumor Society efforts to improve multispecialty collaboration and research credibility. It involves brief systematic reviews of novel ideas and suggests high‐quality research needed to provide and standardize best practices within this field.
Accessible Trail Tourism: Trail Accessibility and Difficulty Rating Approach Designed for Individuals, Including With Mobility Impairments
Authors: Lukoseviciute Goda , Nelson Mark Andrew
Published: October 2024

This study introduces a novel approach to trail accessibility and difficulty rating tailored specifically for individuals, including those with mobility impairments, aiming to promote accessible trail tourism. Grounded in theoretical frameworks of inclusive outdoor recreation, equality, and complex adaptive systems, the proposed rating system incorporates criteria addressing physical access, terrain challenges, and amenities to accommodate diverse user needs. This study employed a sensor technology, called wheeled instrumentation sensor package (WISP) within the framework of the high‐efficiency trail assessment process (HETAP) to develop a new quantitatively based trail classification scheme. A case study trail and two hypothetical synthetic data trails were used to demonstrate both the trail wheelchair accessibility binary classification approach and the proposed trail difficulty classification approach. This research pioneers trail accessibility and difficulty rating and underscores the importance of integrating accessibility considerations into trail management practices to create truly inclusive outdoor recreational experiences.
Relative size matters: Spawning substrate roughness size and spacing affect egg dislodgement and retention in the benthos
Authors: Carman Jake , Zhao Yingming , Ackerman Josef D.
Published: October 2024

The consequences of hydrodynamic effects on survival of embryonic benthic organisms remain unknown. This is because the interaction of hydrodynamics and substrate roughness is complex, but it can be conceptualized in two dimensions by roughness flow regimes (isolated, wake interference, and skimming flow) or roughness types (k‐ and d‐type). We examined the effect of different roughness flow regimes/roughness types and roughness heights (k) on the dislodgement of walleye (Sander vitreus) eggs (2 mm diameter, ⌀) using a wall jet apparatus. We expected that lower wall shear stress (τw) would be required for dislodgement in more‐exposed/less‐sheltered roughness type/flow regimes (i.e., k‐type/isolated roughness flow) and when k ≤ ⌀. Surprisingly, the opposite was found, indicating that other mechanism(s) are also responsible for egg dislodgement on these rough surfaces. Hydrodynamic sheltering occurred when flow was directed over exposed eggs (k ≤ ⌀) adjacent to roughness elements effectively increasing their width, and thus requiring higher τw for rolling and then ejection. When k > ⌀, eggs dislodgement likely occurred via the lower pressure in the eddies recirculating in the groove width between roughness elements, rather than due to τw. These results indicate the relevance of heterogeneous sorting and sizing of substrate elements to provide suitable spawning habitats in benthic environments.
Tunable Liquid Crystal Twisted‐Planar Fresnel Lens for Vortex Topology Determination
Authors: Melnikova Elena , Pantsialeyeva Yekatsiaryna , Gorbach Dmitry , Tolstik Alexei , Karabchevsky Alina
Published: October 2024

The development of straightforward and effective methods to determine the topological charge of phase singular beams is crucial for broadening the applications of optical vortices. Here, a straightforward and elegant method for determining the topological charge of an optical vortex using an innovative switchable achromatic nematic liquid crystal Fresnel lens is proposed. The approach allows for the unambiguous determination of both the absolute value and the sign of the topological charge of a singular beam across a wide range of the visible spectrum, as demonstrated both experimentally and theoretically. The research outcomes are promising for applications in optical information transmission systems, cryptography, and quantum computing.
Sulfonated Covalent Organic Frameworks Anchoring Cobalt as High‐Efficient and Stable Catalysts for Peroxymonosulfate Activation
Authors: Zhang Xinke , Li Yutong , Cao Fengliang , Sun Xiaohui , Jin Zhihan , Xue Song , Wagner Manfred , Zhi Linjie
Published: October 2024

Heterogeneous cobalt‐based catalysts are highly effective in activing peroxymonosulfate (PMS) and produce free radicals to deal with recalcitrant organic pollutants in water. However, unfeasible recyclability and gradual performance degradation remain challenging due to the easy agglomeration and leaching of active cobalt species. Herein, a strategy is proposed to construct stably anchored and highly dispersed Co2+ sites on dual functional sulfonated covalent organic frameworks (COF‐Co). The sulfonic acid groups are able to realize the targeted binding with cobalt ions through a two‐step cation‐exchange method, leading to strong combination with active Co2+ sites and utmost utilization efficiencies. Moreover, the super‐hydrophility of sulfonic acid groups favors the rapid accessibility of organic molecules to the catalyst and accelerates the degradation. Remarkably, COF‐Co exhibits high activity in PMS activation, effective oxidation for tetracycline degradation (92% within 30 min at 30 mg L−1) and other coloring contaminants, and excellent recycle stability. This work can guide the rational design of efficient and environmentally friendly PMS‐activated catalyst with great potential for application in wastewater treatment.
Delta‐Like Homolog 2 Facilitates Malignancy of Hepatocellular Carcinoma via Activating EGFR/PKM2 Signaling Pathway
Authors: Liu Xiangye , Li Tingting , Wang Yuting , Gao Xiaoge , Wang Feitong , Chen Yang , Wang Kaisheng , Luo Weiming , Kong Fanyun , Kou Yanbo , You Hongjuan , Kong Delong , Zhang Qing , Tang Renxian
Published: October 2024

Delta‐like homolog 2 (DLK2) plays a crucial role in adipogenesis, chondrogenic differentiation, and the progression of certain cancers. However, the key roles of DLK2 underlying the progression of hepatocellular carcinoma (HCC) remain ambiguous. In the current study, we demonstrate that DLK2 is upregulated in HCC, significantly correlated with clinicopathological variables and serves as an independent diagnostic marker. Functional assays reveal that DLK2 facilitates malignant progression of HCC in vitro and in vivo models. Mechanistically, DLK2 binds to EGFR resulting in its auto‐phosphorylation, which activates NF‐κB pathway leading to P65‐dependent transcriptional upregulation of PKM2. Furthermore, that elevates both enzyme‐dependent and ‐independent activities of PKM2 contributing to cancer proliferation and metastasis. In summary, our findings demonstrate a novel pro‐tumoral role and mechanism of DLK2 in the regulation of HCC malignant progression, suggesting its potential as a clinical diagnostic marker and therapeutic target.
Effect of Technological Innovation, Servitisation and Human Capital Structure on Performance in Manufacturing Enterprises
Authors: Ying Miao , Yue Shi , Hao Jing
Published: October 2024

To analyse the relationships amongst technology innovation, servitisation, human capital structure and performance in manufacturing firms, a sample of 1247 manufacturing firms listed on the A‐share market in China from 2013 to 2020 were collected. The conclusions are as follows. (1) Technological innovation has positive effect on performance. (2) Service transformation can mediate the effect of technological innovation on performance. (3) Advanced human capital skills can positively moderate the effect of service transformation on performance, whereas advanced human capital education can positively moderate the effect of technological innovation on performance. (4) The effect differs by firm type and location.
Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey
Authors: Higashimoto Tomoyasu , Garber Martin E. , Hipp Lauren , Damon Jenna , Li Qing
Published: October 2024

Background

Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal‐recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN‐IV). The most commonly reported features include anhidrosis, intellectual disability, self‐mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain.

Methods

We present a case of a 46‐year‐old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing.

Results

The patient (46‐year‐old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851 ‐ 33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re‐classified as likely pathogenic. The patient was started on a biologic disease‐modifying anti‐rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.
Serum Concentrations of Folate Forms Following Supplementation of Multimicronutrients with 400 µg or 800 µg Mix of (6S)‐5‐Methyltetrahydrofolate and Folic Acid (1:1) in Women of Childbearing Age
Authors: Obeid Rima , Rube Elena , Schön Christiane , Geisel Jürgen
Published: October 2024

Scope

A mixture of (6S)‐5‐methyltetrahydrofolate‐calcium salt ((6S)‐5‐MTHF‐Ca) and folic acid (FA) from multimicronutrient supplements may show a dose‐dependent effect on serum folate concentrations.

Methods and results

The study compares fasting concentrations of serum folate spices after 8 weeks of either 400 or 800 µg day−1 of 1:1 folate mixture in 172 nonpregnant women. Serum (6S)‐5‐MTHF concentrations raise from a mean (SD) of 19.1 (13.4) to 73.9 (19.6) nmol L−1 in the 800 µg group and from 17.5 (9.4) to 54.5 (21.1) nmol L−1 in the 400 µg group (p < 0.001 within‐group changes). The raise in serum (6S)‐5‐MTHF is stronger in the 800 µg compared to the 400 µg group (p < 0.001 between‐group). The prevalence of FA concentrations ≥0.20 nmol L−1 increases between baseline and week 8 in both groups, but is not different between the groups (p = 0.116). The mean percentage of (6S)‐5‐MTHF of total serum folate increases in both intervention groups, but is not different between the groups at 8 weeks (95.5 (4.1)% versus 94.4 (5.7)%, p = 0.309).

Conclusions

Supplementation of multimicronutrients with 800 µg folate mix for 8 weeks causes higher serum (6S)‐5‐MTHF concentrations, but not a higher prevalence of detectable FA compares to 400 µg folate.
A compact dual‐band omnidirectional antenna with folded microstrip lines and slotlines for 5G applications
Authors: Dou Jiangling , Chen Haokang , Gong Hao , Chen Yujie , Shen Tao , Song Jian
Published: October 2024

A compact dual‐band omnidirectional antenna with folded microstrip lines and slotlines is proposed. The antenna is composed of a substrate and a superstrate. The superstrate is employed to broaden the antenna bandwidth. The radiating patch is situated on the upper surface of the substrate and consists of folded microstrip lines. The performance of the high‐frequency band can be optimized based on the analysis of the current distribution intensity. The bottom of the substrate is composed of a ground plane with slotlines. The introduction and improvement of the low‐frequency band are achieved by modifying the ground plane structure with characteristic modal analysis. The antenna demonstrates omnidirectional radiation characteristics across both frequency bands. The dimensions of the antenna are π × 0.178 λ0 × 0.178 λ0 × 0.049 λ0 (π × 22 × 22 × 6 mm). The antenna achieves a maximum gain of 3.37 dBi at 2.5 GHz and 2.74 dBi at 5.8 GHz. The measured impedance bandwidths for the two frequency bands are 17.3% and 21.7%, respectively.
Early Cell Lineage Formation in Mammals: Complexity, Species Diversity, and Susceptibility to Disruptions Impacting Embryo Viability
Authors: Latham Keith E.
Published: October 2024

The emergence of the earliest cell lineages in mammalian embryos is a complex process that utilizes an extensive network of chromatin regulators, transcription factors, cell polarity regulators, and cellular signaling pathways. These factors and pathways operate over a protracted period of time as embryos cleave, undergo compaction, and form blastocysts. The first cell fate specification event separates the pluripotent inner cell mass from the trophectoderm lineage. The second event separates pluripotent epiblast from hypoblast. This review summarizes over 50 years of study of these early lineage forming events, addressing the complexity of the network of interacting molecules, cellular functions and pathways that drive them, interspecies differences, and aspects of these mechanisms that likely underlie their high susceptibility to disruption by numerous environmental factors that can compromise embryo viability, such as maternal health and diet, environmental toxins, and other stressors.
Rehabilitation is [still] necessary to optimize function in neuromuscular disorders
Authors: Omura Jaclyn , Stratton Anne , Fournier Christina , Howard Ileana
Published: October 2024

The landscape of care for children and adults with neuromuscular disorders (NMDs) is rapidly changing as more disease‐modifying treatments (DMTs) become available. These DMTs provide hope and opportunity for evolving phenotypes, though none (yet) are curative. Rehabilitation has been the standard of care for patients with NMDs and should remain so, even with the advent of novel DMTs. An interdisciplinary rehabilitation approach is holistic and comprehensive, addressing functional needs, musculoskeletal complications, pain, durable medical equipment, and bracing needs. This care will continue to be essential for patients who experience impairments and disability, despite receiving DMTs. Additionally, we must consider how to care for a new rapidly expanding cohort of patients aging with NMDs. Children with NMDs are expected to live longer into adulthood; a population that we may not have the workforce to support at this time. At this point, we have the perfect opportunity to reemphasize the importance of rehabilitation in the care of persons with NMDs, while we reexamine historical rehabilitation practices and innovatively deliver services to optimize the effects of these high‐cost DMTs.
Deformation Analysis of Cosserat Rods Using Piecewise Clothoid Approximation
Authors: Sivaj Sreejath , Saha Subir Kumar , Singh Satinder Paul
Published: October 2024

This paper presents an alternative to isogeometric analysis (IGA) for static analysis of planar curved slender beams. Geometrically exact Cosserat rod model is employed to establish the governing equations. In contrast to conventional IGA, which uses NURBS as the basis function, our method incorporates clothoid curves to represent the curved geometry. We use piecewise clothoid curves to approximate the initial curvature of the undeformed beam, facilitating a seamless integration into the Cosserat rod model. A straightforward solution of the governing equations is implemented using shooting method, verifying applicability across a range of problems. Interestingly, the parameters that define the clothoid segments also appear in the governing equations of the beam. This bridges the gap between the geometric design of the beams and their static simulations. In this way, we present the proposed formulation as an alternative to conventional IGA. The notable features of the method are easy implementation, good accuracy, and convergence. Moreover, the method predicts bending stress in the beam, capturing the nonlinearity of the deformation.
Anti‐VEGFR2 neutralising antibody slows the progression of multistep oral carcinogenesis
Authors: Shirogane Yoichiro , Usami Yu , Okumura Masashi , Hirose Katsutoshi , Naniwa Kohei , Ikebe Kazunori , Toyosawa Satoru
Published: October 2024

Angiogenesis plays an important role in cancer growth and metastasis, and it is considered a therapeutic target to control tumour growth following anti‐angiogenic therapy. However, it is still unclear when tissues initiate angiogenesis during malignant transformation from premalignant condition and whether this premalignant condition could be a therapeutic target of anti‐angiogenic therapy. In this study, we aimed to analyse the onset of angiogenesis by evaluating morphological and functional alterations of microvessels during oral multistep carcinogenesis using a 4‐nitroquinoline 1‐oxide (4NQO)‐induced oral carcinogenesis mouse model. In the study, we initially confirmed that with the use of 4NQO, oral lesions develop in a stepwise manner from normal mucosa through oral epithelial dysplasia (OED) to oral squamous cell carcinoma (OSCC). Evaluation of CD31‐immunostained specimens revealed that microvessel density (MVD) increases in a stepwise manner from OEDs. Histological and functional analyses revealed the structural abnormalities and leakage of blood vessels had already taken place in OED. Then we evaluated the expression profiles of Hif1a and Vegfa along with hypoxic status and found that OED exhibited increased Vegfa expression under hypoxic conditions. Finally, we tested the possibility of OEDs as a target of anti‐angiogenic therapy and found that anti‐VEGFR2 neutralising antibody in OED slowed the disease progression from OED to OSCC. These data indicate that an angiogenic switch occurs at the premalignant stage and morphological, and functional alterations of microvessels already exist in OED. These findings also elucidate the tumour microenvironment, which gradually develops along with carcinogenic processes, and highlight usefulness of the 4NQO‐induced carcinogenesis model in the study of epithelial and stromal components, which will support epithelial carcinogenesis. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Focused Ion Beam Milling as a Method for Machining Explosive Crystals**
Authors: Stirrup Kerry‐Ann M. , Gilpin Christopher J. , Chen Weinong W.
Published: October 2024

Experimental pore collapse studies have traditionally relied on machining methods that are mechanically active and result in rough surfaces, added stresses, and premature material fractures which are a source of experimental error. This work focuses on the method development and the results of adapting the focused ion beam to mill micro and nano‐scale pores with increased geometrical freedom into explosive crystals. Results include developing a simplified mathematical relationship between the electron beam energy and mill rate, assessments of pore quality, and material and machine‐specific optimal milling parameters.
Association of race with incidence, characteristics, and mortality from incidental prostate cancer: Analysis of two North American contemporary cohorts
Authors: Finati Marco , Morrison Chase , Stephens Alex , Chiarelli Giuseppe , Cirulli Giuseppe Ottone , Tinsley Shane , Davis Matthew , Sood Akshay , Buffi Nicolò , Lughezzani Giovanni , Salonia Andrea , Briganti Alberto , Montorsi Francesco , Busetto Gian Maria , Bettocchi Carlo , Rogers Craig , Carrieri Giuseppe , Abdollah Firas
Published: October 2024

Background

Non‐Hispanic Black (NHB) men are at higher risk both for incidence and mortality from prostate cancer (PCa) compared to Non‐Hispanic White (NHW) men, but these findings arise from biopsy‐detected PCa reports. We aimed to compare the incidence, subsequent management and cancer‐specific mortality (CSM) of incidental PCa among NHB and NHW men, using two different North American cohorts.

Methods

The Surveillance, Epidemiology and End‐Result (SEER: 2004‐2017) and our institutional Henry Ford Health (HFH: 1995‐2022) databases were queried to identify men diagnosed with incidental PCa. Cumulative incidence estimates were used to calculate CSM differences between NHB and NHW men. Competing‐risk multivariable regression analysis tested the impact of race on CSM, after accounting for all available covariates.

Results

A total of 418 and 6,124 incidental PCa cases were recorded in HFH and SEER database respectively. No pathological differences were observed between NHB and NHW men in both the cohorts, except for prostate‐specific antigen (PSA) value at diagnosis, which was higher in NHB men. At 10‐years, the CSM rates were 5.5% vs 7.2% in our cohort and 8.6% vs 10.3% in the SEER cohort for NHW and NHB men, respectively (all Gray's test p‐value > 0.05). At multivariable, race was not an independent predictor of CSM in our HFH cohort (HR: 1.46, 95% CI: 0.57‐3.71, p = 0.6). In the SEER cohort, NHB men were 34% less likely to die from PCa from 1 year to the next (95% CI: 0.49‐0.90, p = 0.008), when compared with NHW men.

Conclusions

In the comparison of incidental PCa findings between NHB and NHW men, both groups had similar pathological characteristic and survival outcomes. These findings are different from the ‘conventional’ screening‐detected PCa and suggest that racial differences have minimal to no adverse effects on PCa‐specific mortality after incidental diagnosis.
Assessing the predictive value of intraductal carcinoma of the prostate (IDC‐P) in determining abiraterone efficacy for metastatic hormone‐sensitive prostate cancer (mHSPC) patients
Authors: Wei Xinyuan , Zhao Jinge , Nie Ling , Shi Yifu , Zhao Fengnian , Shen Yu , Chen Junru , Sun Guangxi , Zhang Xingming , Liang Jiayu , Hu Xu , Shen Pengfei , Chen Ni , Zeng Hao , Liu Zhenhua
Published: October 2024

Background

This study explored the value of intraductal carcinoma of the prostate (IDC‐P) in predicting the efficacy of abiraterone treatment in metastatic hormone‐sensitive prostate cancer (mHSPC) patients.

Methods

A retrospective study of 925 patients who underwent prostate biopsies to detect IDC‐P was conducted, with participants divided into two cohorts. The first cohort of 165 mHSPC patients receiving abiraterone treatment was analyzed to compare therapeutic effectiveness between IDC‐P positive and negative cases. Utilizing propensity score matching (PSM) to reduce bias, outcomes such as PSA response, progression‐free survival (PSA‐PFS), radiographic progression‐free survival (rPFS), and overall survival were assessed. Additionally, the second cohort of 760 mHSPC patients compared the efficacy of abiraterone with conventional hormone therapy, focusing on differences between IDC‐P positive and negative individuals.

Results

After PSM, our first cohort included 108 patients with similar baseline characteristics. Among them, 50% (54/108) were diagnosed with IDC‐P, with 22.2% (12/54) having IDC‐P pattern 1 and 77.8% (42/54) with IDC‐P pattern 2. While no notable difference was seen in PSA responses between IDC‐P positive and negative patients, IDC‐P presence linked to worse clinical outcomes (PSA‐PFS: 18.6 months vs. not reached [NR], p = 0.009; rPFS: 23.6 months vs. NR, p = 0.020). Further analysis showed comparable outcomes for IDC‐P pattern 1 but significantly worse prognosis for IDC‐P pattern 2 (PSA‐PFS: 18.6 months vs. NR, p = 0.002; rPFS: 22.4 months vs. NR, p = 0.010). Subgroup analysis revealed IDC‐P pattern 2 consistently predicted poorer outcomes across patient subgroups. Remarkably, both IDC‐P positive and negative patients gained more from androgen deprivation therapy with abiraterone than conventional treatment, with IDC‐P negative patients showing a more significant survival advantage, supported by better hazard ratios (0.47 and 0.66).

Conclusion

This study found that IDC‐P, especially pattern 2, predicts poor prognosis in mHSPC patients on abiraterone therapy. Also, abiraterone's advantage over hormone therapy is reduced in cases with IDC‐P compared to those without.
Unraveling the molecular mechanism of FgGcn5 inhibition by phenazine‐1‐carboxamide: combined in silico and in vitro studies
Authors: Li Lei , Luo Qing , Yang Shuai , Wang Hancheng , Mu Yuguang , Guo Jingjing , Zhang Feng
Published: October 2024

BACKGROUND

Fusarium head blight (FHB), mainly caused by Fusarium graminearum (F. graminearum), remains a devastating disease worldwide. The histone acetyltransferase Gcn5 plays a crucial role in epigenetic regulation. Aberrant Gcn5 acetylation activity can result in serious impacts such as impaired growth and development in organisms. The secondary metabolite phenazine‐1‐carboxamide (PCN) inhibits F. graminearum by blocking the acetylation process of Gcn5 (FgGcn5), and is currently used to control FHB. However, the molecular basis of acetylation inhibition by PCN remains to be further explored.

RESULTS

Our molecular dynamics simulations revealed that PCN binds to the cleft in FgGcn5 where histone H3 is bound, with key amino acid residues including Leu96 (L96), Arg121 (R121), Phe133 (F133), Tyr169 (Y169), and Tyr201 (Y201), preventing FgGcn5 from binding to histone H3 and affecting histone H3 from being acetylated. Experimental validation of key amino acid mutations further confirmed the impact of these mutations on the interaction of FgGcn5 with PCN and histone H3 peptide.

CONCLUSION

In summary, our study sheds light on the mechanism by which PCN inhibits the acetylation function of FgGcn5, providing a foundation for the development of drugs or fungicides targeting histone acetyltransferases. © 2024 Society of Chemical Industry.
First‐Principles Calculation of SnSe2 Material as Anode Material of Zinc Ion Battery
Authors: Zhong Ensong , Liu Wenbo
Published: October 2024

The development of high‐performance ion battery anode materials is conducive to the rapid development of urban rail transit. Based on first‐principles calculations, this paper studies the potential performance of the recently discovered two‐dimensional material SnSe2 as a negative electrode for zinc ion batteries. By calculating the adsorption energy, the most stable adsorption configuration of Zn was determined. The band gap of intrinsic SnSe2 decreases after strain, which promotes the transition of carriers. The band gap opens after the strain occurs in the Zn adsorbed SnSe2 system (Zn‐SnSe2), which confirms the regulation of strain on the band gap. The lowest diffusion barrier of Zn is 0.083 eV. The theoretical zinc storage capacity is calculated to be 387.550 mAh/g. The calculation results provide theoretical parameters for the application of SnSe2 in ion batteries.
A Brief Introduction on Latent Variable Based Ordinal Regression Models With an Application to Survey Data
Authors: Wieditz Johannes , Miller Clemens , Scholand Jan , Nemeth Marcus
Published: October 2024

The analysis of survey data is a frequently arising issue in clinical trials, particularly when capturing quantities which are difficult to measure. Typical examples are questionnaires about patient's well‐being, pain, or consent to an intervention. In these, data is captured on a discrete scale containing only a limited number of possible answers, from which the respondent has to pick the answer which fits best his/her personal opinion. This data is generally located on an ordinal scale as answers can usually be arranged in an ascending order, for example, “bad”, “neutral”, “good” for well‐being. Since responses are usually stored numerically for data processing purposes, analysis of survey data using ordinary linear regression models are commonly applied. However, assumptions of these models are often not met as linear regression requires a constant variability of the response variable and can yield predictions out of the range of response categories. By using linear models, one only gains insights about the mean response which may affect representativeness. In contrast, ordinal regression models can provide probability estimates for all response categories and yield information about the full response scale beyond the mean. In this work, we provide a concise overview of the fundamentals of latent variable based ordinal models, applications to a real data set, and outline the use of state‐of‐the‐art‐software for this purpose. Moreover, we discuss strengths, limitations and typical pitfalls. This is a companion work to a current vignette‐based structured interview study in pediatric anesthesia.
Statistical Design and Analysis for Enhanced Production of Tetracycline‐Conjugated Copper Oxide Nanoparticles with Improved Antimicrobial Properties
Authors: Sharma Sakshi , Srivastava Saurabh , Chaudhary Abhishek
Published: October 2024

Purpose: Since decades, numerous antibiotics have been used to treat different bacterial illnesses; among these, tetracycline is one of the commonly used antibiotics, which has led to development of bacterial resistance. To tackle this critical issue, we have developed a novel, biocompatible nanodrug that improves the antibacterial activity of tetracycline by conjugating it with copper oxide nanoparticles, thereby addressing the problem of multidrug resistance in bacteria. Methods: In this study, using unipot approach, tetracycline conjugated copper oxide nanoparticles were synthesized where tetracycline act as reducing as well as stabilizing agent. These nanoparticles were characterized by different analytical and microscopic technique. For statistical analysis, FFD and CCD model were employed to assess the effect of various parameters (concentration, pH, temperature and time). Results: The synthesis of nanoparticles was confirmed through different techniques. Synthesized nanoparticles exhibited the highest antibacterial activity against various microbes including multi‐drug resistant microbes compared to its individual constituents. DPPH and ABTS assays revealed high antioxidant activity of nanoparticles whereas, biocompatibility was assessed via MTT assay. The drug release profile confirms the sustained release of tetracycline molecules. Conclusions: We have successfully developed tetracycline conjugated copper oxide nanoparticles exhibiting potent antibacterial, antioxidant and biocompatible activity.
Dimethyl Sulfoxide Promoted Quinazolinone Synthesis
Authors: Kisan Devadkar Ajitrao , Paul Ishita , Sau Abhijit , Panda Tarun K.
Published: October 2024

An efficient and one‐step synthesis of quinazolinones using 2‐aminobenzamide and benzylamine in DMSO under external catalyst‐ and base‐free conditions is reported. A broad substrate scope and environment‐benign mild reaction conditions are the major attributes of this straightforward synthesis. Moreover, the synthesized quinazolinone derivatives were used to produce pharmaceutically active rutaecarpine analogues using a two‐step reaction: N‐alkylation followed by intramolecular cyclization.
Green Biosynthesis and Catalytic Application in Environmental Pollutants of Functionalized Pd‐Ag Bimetallic Nanoparticle by Deinococcus Radiodurans Extracts
Authors: Wang Yuxian , Bai Pengfei , Sheng Xian , Qing Molan , Yi Yuanyang , Zhang Zhidong , Jiang Ling , Zhu Liying
Published: October 2024

Catalytic reduction of organic pollutants using metal nanoparticles (MNPs) as nanocatalyst is a promising approach. The widespread application of MNPs have led to an increase demand for their production. The green biosynthesis of MNPs using microbes is becoming increasingly important as they are benign and environmentally friendly. In this work, Deinococcus wulumuqiensis (D. wulumuqiensis) with high resistance to stresses was applied for the green preparation of different MNPs, including palladium nanoparticles (Pd NPs), silver nanoparticles (Ag NPs), and Pd−Ag bimetallic nanoparticles (Pd−Ag BNPs). The resultant MNPs exhibited a face‐centered cubic structure, with average size of 6.70 (Pd NPs), 6.24 (Ag NPs), and 6.13 nm (Pd−Ag BNPs), respectively. FT‐IR spectra indicated that the proteins and polysaccharides expressed by D. wulumuqiensis could potentially contributed to the formation of MNPs. The application of as‐prepared biocatalyst in catalytic degradation of pollutant dyes demonstrated that Pd−Ag BNPs had greater degradation ability of 4‐nitrophenol (95.1 %) and Rhodamine B (85.1 %) than monometallic nanoparticles. The pseudo‐first‐order kinetics results further indicated the superior catalytic ability of Pd−Ag BNPs, with rate constant of 0.450±0.009 (4‐nitrophenol) and 1.54×10−2 min−1 (Rhodamine B), respectively. Thus, the present study confirms that D. wulumuqiensis represents a promising candidate for the biosynthesis of Pd‐based nanoparticles with small size, which exhibited potential applications as bionanocatalyst in the degradation of water pollutants.
Structure‐Based Computational Approach in Search of the Potent Molecules Targeting Phosphoglycerate Dehydrogenase (PHGDH) Enzyme for Cancer Treatment
Authors: Solanki Priyanka , Manhas Anu , Patel Dhaval , Jha Prakash
Published: October 2024

This work aims to target phosphoglycerate dehydrogenase (PHGDH), a promising druggable target, that is overexpressed in various types of cancer. A structure‐based approach was employed to identify novel inhibitors against the enzyme. A common five‐feature pharmacophore model (RRHDA) was constructed using the active site co‐crystalized ligands. These chemical features were responsible for showing inhibition. The generated models were subsequently subjected to the validation method using a test set, receiver‐operator characteristic analysis, enrichment factor, and Güner–Henry studies. The validated models were subjected to the screening of a dataset of natural compounds. The screened unique natural compounds (1795) were further selected for the interaction analysis and study of ligand binding affinity considering the effect of the hydrogen bonding and desolvation and hydrophobic interactions contribution to the binding. The natural compounds which exhibited good ligand binding efficiency were selected and further subjected to pharmacokinetics and pharmacodynamic study. The natural compounds which exhibited good ligand binding efficiency were selected and further subjected to pharmacokinetics and pharmacodynamic study. The finalized complexes were selected for the simulation studies and MM/PBSA‐based binding free energy calculations. This study expands the possibilities for the development of shortlisted molecules as novel anti‐cancer compounds.
Synthesis and Electrochemical Performances of Fluffy Carbonized Hexagonal KCoPO4 as Pseudocapacitive Electrode for High performing Hybrid Supercapacitor Applications
Authors: Gopal Nigam Krishna , Kumar Singh Abhijeet , Mukherjee Soham , Singh Preetam
Published: October 2024

Electrochemical energy storage is one of the effective ways that can address the mentioned issues as alternative energy/power produced through solar or windmills can effectively be stored for continuous usage. Hybrid/Asymmetric supercapacitors can deliver a significant amount of power density as well as increased energy density with better rate capability and longer lifespan. The fluffy carbonized hexagonal KCoPO4 synthesized via a simple sol‐gel method accompanied by calcination has delivered high capacitance and longer cyclibility as a positive electrode in aqueous asymmetric supercapacitors. The fluffy carbonized hexagonal KCoPO4 exhibited a specific capacitance equal to 725 F/g at 0.5 A/g current density with excellent cyclic stability. The predominant intercalative pseudocapacitive charge storage behavior seems to be the reason behind the high capacitance of the electrode due to the active involvement of Co2+/3+ redox couple mediate charge storage as intercalative (inner) and capacitive, (outer) surface charges storage on the electrode were close to 37 % and 63 % respectively. Aqueous Asymmetric supercapacitor mode with KCoPO4 being a positive electrode and activated carbon being a negative electrode (KCoPO4//AC) was designed to address its performance in 2 M KOH aqueous electrolyte. The fabricated device in AASc mode (AC//KCoPO4) achieved the highest energy density close to 121.1 Wh/kg with a high power density of 6945 W/kg in the potential window of 1.5 V in 2 M KOH electrolyte.
Exploring Charge Transfer Mechanisms in Schiff Base‐Modified N‐Doped GQDs: Insights from DFT and Pump‐Probe Spectroscopy for Bioimaging Applications
Authors: Hançe Saadet , Erdener Diğdem , Öztürk Berfin Ilayda , Akhuseyin Yildiz Elif , Karatay Ahmet , Boyacioglu Bahadir , Ünver Hüseyin , Yilmazer Açelya , Yıldız Mustafa , Elmali Ayhan
Published: October 2024

In recent developments, graphene quantum dots (GQDs) have emerged as valuable tools for imaging and biosensing. Various modifications on the GQDs with any desired functionality and attachment of organic molecules and/or nanostructures allow tuning their photophysical properties as well as charge transfer dynamics for bioimaging applications. This study focuses on synthesizing and characterizing of polyethyleneimine‐functionalized nitrogen‐doped GQDs (NC1), Schiff base‐ functionalized nitrogen‐doped GQDs (NC2), and silver nanocomposites of these Schiff base‐functionalized nitrogen‐doped GQDs (NC3). We explore their absorption and emission properties to understand their interactions in the ground state. Furthermore, ultrafast transient absorption spectroscopy measurements reveal that the presence of NC3 shortens the excited state lifetime of NC1 due to charge transfer, resulting in reduced fluorescence intensity. Both experimental and DFT results suggest the potential of NC3 for bioimaging and sensing applications, making them promising candidates for phototheranostic purposes.
Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds
Authors: Dahiya Aditi , Chaudhari Vishal Sharad , Bose Susmita
Published: October 2024

Carvacrol is a potent antimicrobial and anti‐inflammatory agent, while curcumin possesses antioxidant, anti‐inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D‐printed calcium phosphate (CaP) scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin‐loaded nanoparticles (CC‐NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127 nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC‐NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH‐sensitive release mechanism. In vitro studies demonstrate a 1.4‐fold increase in osteoblast cell viability with CC‐NP treatment. CC‐NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9‐fold. The antibacterial efficacy of CC‐NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.
Enhanced Structural VS4 Grown onto Hollow Carbon Mesoporous Spheres via Surficial Bonding for High Cycling Stability in Sodium‐Ion Batteries
Authors: Tang Mingxuan , Yin Xinxin , Cao Yali , Ma Huan , Zhang Xuntao , Jia Dianzeng
Published: October 2024

Transition metal sulfides are recognized as an excellent alternative to sodium ion anodes ascribed to the outstanding theoretical capacity. The unique crystal arrangement of VS4 gives it exceptional theoretical capacity, despite challenges like insufficient electrical conductivity and undesirable volume expansion. Herein, a novel stabilized anode featuring a distinctive 3D hollow spherical structure is proposed, providing a simple strategy to synthesize such anodes for VS4‐HCMSs bonded via C‐O‐S and V‐O‐C interfaces. The kinetic investigations and density functional theory reveal that the unique structure connected by interfacial bonds enhances Na+ transport rate and charge transfer efficiency, while carbon greatly mitigates the volume expansion. Unsurprisingly, the VS4‐HCMSs exhibit an impressive first‐cycle Coulombic efficiency of 91.31% and an ultrahigh reversible capacity of 612 mAh g−1 after 300 cycles at 0.5 A g−1, even exhibit the reversible capacity of 498.8 mAh g−1 after 1000 cycles at 5 A g−1. Additionally, the NaFePO4//VS4‐HCMSs full cell is cycled for 200 cycles at 0.2 C and powered the light‐emitting diodes for up to 30 minutes afterward. Overall, this work enhances the conductivity and stability of the material by combining VS4 with hollow carbon mesoporous spheres through interfacial bonding, offering an efficient strategy to anode materials in sodium‐ion batteries.
Exploring the Interaction of Lipid Bilayers with Curcumin–Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications
Authors: Pawar Nisha , Peña‐Figueroa Miriam , Verde‐Sesto Ester , Maestro Armando , Alvarez‐Fernandez Alberto
Published: October 2024

Curcumin, the active compound in turmeric, is renowned for its anti‐inflammatory, antioxidant, and antimicrobial properties, making it beneficial for treating conditions like arthritis, neurodegenerative diseases, and various cancers. Despite its promising therapeutic potential, curcumin's poor bioavailability—due to its rapid metabolism and low solubility—limits its clinical efficacy. To address this, recent research has focused on enhancing curcumin delivery using nanoparticles, liposomes, and novel nanomaterials. Among these, laponite, a synthetic nanoclay, has shown promise in improving curcumin delivery due to its unique properties, including large surface area, dual charge, and stability in solution. This study explores the use of curcumin–laponite nanoparticles as carrier vehicles for controlled delivery to in vitro model membranes. Utilizing advanced techniques such as neutron reflectometry, atomic force microscopy, quartz crystal microbalance with dissipation, and infrared spectroscopy, the interaction between curcumin–laponite nanoparticles and solid‐supported lipid bilayers is monitored, revealing enhanced stability and controlled release of curcumin across the membrane. These findings pave the way for the development of curcumin‐based therapies targeting cardiovascular, neurological, and oncological diseases, leveraging the synergistic effects of curcumin's biological activity and laponite's delivery capabilities.