bluuebunny/crossref_metadata_2025 huggingface dataset:
A Jacobian‐based frequency‐sweeping approach for constructing stability crossing curves of systems with two delays
Authors: Cai Tiao‐Yang , Hwang Chyi , Wang Tzu‐Chi , Lu Li‐Shin
Published: February 2025

This paper introduces a novel Jacobian‐based frequency‐sweeping approach for constructing a stability map on a delay plane for linear time‐invariant (LTI) systems with two delays. It is demonstrated that by imposing a zero Jacobian condition on the Rekasius‐transformed polynomial equations defining the stability crossing curves (SCCs), the set of stability crossing frequencies (SCFs) can be determined exactly and exhaustively. Compared to existing frameworks that use a discrimination criterion to identify the upper bound of SCFs, our proposed framework offers the following three merits: (i) it establishes a direct link between the zero Jacobian criterion and the end points of the SCF intervals; (ii) it reveals the invariance property of the curve‐wise crossing direction for each SCC; (iii) it provides a simple Jacobian calculation to determine the root crossing directions relative to the imaginary axis. These merits significantly enhance the cluster treatment of the characteristic root (CTCR) paradigm for investigating stability robustness against delay uncertainties. A computational procedure is provided for the implementation of the proposed framework. Additionally, the role of Jacobian in constructing stability crossing curves is demonstrated through two examples.
Exposure to pseudoephedrine during pregnancy and major congenital malformations: Findings from a large population‐based cohort of pregnancies
Authors: Dor Saar , Michael Tal , Levi Yael , Pariente Gali , Lunenfeld Eitan , Levy Amalia , Birenstock‐Cohen Shira , Daniel Sharon
Published: February 2025

Aims

The aim of this study was to assess the risk of major congenital malformations following first‐trimester pseudoephedrine (PSE) exposure.

Methods

A population‐based observational cohort study was conducted on pregnancies of women aged 15–49 years, insured by Clalit Health Services in southern Israel, who gave birth or had elective pregnancy terminations due to suspected fetal malformation at Soroka Medical Center (1999–2017). The study focused on Clarinase, a drug that contains a high dose of PSE (120 mg) and 5 mg of loratadine. Multivariable negative binomial regression models were used to evaluate the risk for major congenital malformations, adjusting for potential confounders.

Results

Of 251 543 pregnancies, 313 (0.12%) were exposed to high‐dose PSE in the first trimester. PSE exposure was not associated with major congenital malformations overall (adjusted relative risk [aRR] = 0.90, 95% confidence interval [CI] 0.558–1.45; P = 0.66) or by organ system (cardiovascular: aRR = 0.938, 95% CI 0.499–1.762; central nervous system: aRR = 0.618, 95% CI 0.086–4.451; musculoskeletal: aRR = 1.800, 95% CI 0.801–4.042; gastrointestinal: aRR = 1.013, 95% CI 0.142–7.241; genitourinary: aRR = 0.704, 95% CI 0.225–2.204).

Conclusions

First‐trimester PSE exposure was not an independent risk factor for major congenital malformations, either overall or by organ system.
Solanidine‐derived CYP2D6 phenotyping elucidates phenoconversion in multimedicated geriatric patients
Authors: Sarömba Jens Andreas , Müller Julian Peter , Tupiec Jolanta , Roeth Anjali , Kurt Berkan , Kahles Florian , Laurentius Thea , Bollheimer Cornelius , Stingl Julia C. , Just Katja S.
Published: February 2025

Aims

Phenoconversion, a genotype‐phenotype mismatch, challenges a successful implementation of personalized medicine. The aim of this study was to detect and determine phenoconversion using the solanidine metabolites 3,4‐seco‐solanidine‐3,4‐dioic acid (SSDA) and 4‐OH‐solanidine as diet‐derived cytochrome P450 2D6 (CYP2D6) biomarkers in a geriatric, multimorbid cohort with high levels of polypharmacy.

Methods

Blood samples and data of geriatric, multimedicated patients were collected during physician counsel (CT: NCT05247814). Solanidine and its metabolites were determined via liquid chromatography/tandem mass spectrometry and used for CYP2D6 phenotyping. CYP2D6 genotyping was performed and activity scores (AS) were assigned. Complete medication intake was assessed. A shift of the AS predicted via genotyping as measured by phenotyping was calculated.

Results

Solanidine and its metabolites were measured in 88 patients with complete documentation of drug use. Patients had a median age of 83 years (interquartile range [IQR] 77‐87) and the majority (70.5%, n = 62) were female. Patients took a median of 15 (IQR 12‐17) medications. The SSDA/solanidine metabolic ratio correlated significantly with the genotyping‐derived AS (P < .001) and clearly detected poor metabolizers. In the model adjusted for age, sex, Charlson Comorbidity Index and estimated glomerular filtration rate each additional CYP2D6 substrate/inhibitor significantly lowered the expected AS by 0.53 (95% confidence interval 0.85‐0.21) points in patients encoding functional CYP2D6 variants (R2 = 0.242).

Conclusions

Phenotyping of CYP2D6 activity by measurement of diet‐derived biomarkers elucidates phenoconversion in geriatric patients. These results might serve as a prerequisite for the validation and establishment of a bedside method to measure CYP2D6 activity in multimorbid patients for successful application of personalized drug prescribing.
Effect of Surface Properties of Chitosan‐Based Nanoparticles in the Skin‐Diffusion Rate
Authors: Ramírez Luciana , Corral David , Betanzo Itandehui , Rodarte Deyanira , Chauhan Kanchan , Vazquez‐Duhalt Rafael
Published: February 2025

Skin diseases may cause rash, inflammation, itchiness, and other important skin changes, including dysplasia. Some skin conditions may be due to genetic and lifestyle factors and immune‐mediated factors. The current skin disease treatment can include oral medication, topical cream, or ointments. Nanotechnology is revolutionizing the drug delivery systems, increasing the time life of active therapeutic compounds and improving the treatment efficiency. This work hypothesizes that varying the surface properties of chitosan nanoparticles (Ch‐NPs) can modulate their diffusion through dermal tissue. Thus, Ch‐NPs were synthesized, and their surface was modified with polyethylene glycol, oxalic acid, and linoleic acid for transdermal therapy. The different Ch‐NPs were labeled with a fluorophore, and the dermal diffusion was measured on human skin by histological preparations and fluorescent microscopy. The surface properties of nanoparticles were shown to play an essential role in skin diffusion rate. Surface modification with a lipophilic moiety such as linoleic fatty acid showed a diffusion rate of 7.23 mm2/h in human full‐thickness abdominal flap, which is 2.7 times faster nanoparticle diffusion through dermal tissue when compared with the unmodified Ch‐NPs (2.92 mm2/h). The positive (zeta potential +27.5 mV) or negative (zeta potential −2.2 mV) surface charge does not affect the chitosan nanoparticle diffusion. Polyethylene glycol surface modification slightly improved the nanoparticle diffusion rate (3.63 mm2/h). Thus, modulating the nanoparticle surface properties can control the skin diffusion rate. The implications of this finding on dermic drug delivery are discussed.
Derivation of an Upscaled Model for Xylitol Production With Immobilized Microorganisms
Authors: Zenteno‐Catemaxca Rolando , Hernandez‐Rodriguez Roel , Morales‐Zárate Epifanio , Hernandez‐Martinez Eliseo
Published: February 2025

Xylitol, a polyalcohol with anticariogenic properties, finds broad applications in different sectors. Research into new production methods has highlighted the biochemical route using immobilized microorganisms. However, challenges remain in optimizing operating conditions and understanding mass transport and biochemical reactions. Different macroscopic models have been proposed to address these challenges. Nevertheless, those models do not consider porous particles' microstructure and biofilms' formation within them, which can determine the macroscopic performance of the process due to its hierarchical nature. In this work, we derive two macroscopic models for the mass transport and reaction of the xylitol production process with immobilized microorganisms in porous particles. Such models are derived from microscopic ones using the volume averaging method, resulting in both two‐equation and one‐equation models, written in terms of effective medium coefficients. These latter are predicted by solving ancillary problems in representative 2D unit cells of the immobilization particles, incorporating their microstructural information. Besides, kinetic parameters are estimated through kinetic fitting using experimental data from the literature. Models' accuracy is assessed by comparing them with pore‐scale simulations and experimental observations of xylitol production from sugarcane bagasse at the laboratory scale, finding good agreement. Finally, our results are compared with a macroscopic model reported in the literature, and similar predictions are found. However, unlike the reported model, the one derived here improves the modeling of the process since the effective coefficients do not need to be calculated using empirical correlations or estimators.
Complex Role of Circulating Triglycerides in Breast Cancer Onset and Survival: Insights From Two‐Sample Mendelian Randomization Study
Authors: Zhang Wu , Li Zhiru , Huang Yuquan , Zhao Jing , Guo Shaowei , Wang Qian , Guo Sihan , Li Qingxia
Published: February 2025

Background

Reducing the incidence of breast cancer and improving its prognosis have become significant challenges for the global public health sector. We aimed to investigate the role of circulating triglycerides in the occurrence and survival of patients with breast cancer, while focusing on the possible differential effects by molecular subtypes of breast cancer.

Methods

We used a Mendelian randomization approach to analyze publicly accessible genome‐wide association study data, including triglyceride levels, breast cancer risk, and survival prognosis. We performed a two‐sample causality inference analysis using the inverse‐variance weighted method. We used both Mendelian randomization–Egger regression and weighted median methods for model verification. Heterogeneity was evaluated using Cochran's Q test, and sensitivity analyses were performed using the leave‐one‐out method, Mendelian randomization–Egger intercept test, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier test.

Results

The results revealed a negative causal relationship between triglyceride levels and overall breast cancer risk (odds ratio [OR] = 0.94, confidence interval [CI] = 0.89–0.99, p = 0.011), luminal A breast cancer risk (OR = 0.93, CI = 0.87–0.99, p = 0.014), and human epidermal growth factor receptor 2 (HER2)‐enriched breast cancer risk (OR = 0.84, CI = 0.73–0.96, p = 0.010). However, no statistically significant correlations were observed for the luminal B, luminal B HER2‐negative, and triple‐negative subtypes. Furthermore, triglyceride levels showed a positive causal relationship with the risk of survival prognosis in patients with estrogen receptor‐negative breast cancer (OR = 1.33, CI = 1.00–1.76, p = 0.047). However, no statistically significant impact was observed on the survival of patients with overall breast cancer or patients with estrogen receptor‐positive, HER2‐positive, and HER2‐negative breast cancer.

Conclusions

The potentially complex role of circulating triglycerides in the incidence and survival of patients with breast cancer provides a new perspective on the heterogeneity of the effects of triglycerides on breast cancer, thereby promoting the development of precise medical strategies. Moreover, our findings contribute to an increased understanding of overall health among patients and clinicians alike.
Synthesis and Anticancer Activity of Metformin‐Phenolic Acid Conjugates
Authors: Banerjee Biswajit , Sharma Tripti , Banerjee Sabyasachi , Banerjee Subhasis , Mondal Arijit
Published: February 2025

The leading cause of death worldwide is cancer. Several studies suggest phenolic acids and metformin as potential cancer treatment options because of their biological and therapeutic properties. So, we synthesized some novel metformin‐phenolic acid conjugates. We used an acid‐base neutralization method to extract the metformin‐free base. N,N'‐dicyclohexylcarbodiimide‐4‐dimethylaminopyridine coupling of phenolic/aromatic acids (benzoic acid, cinnamic acid, caffeic acid, ferulic acid, gallic acid, para‐hydroxybenzoic acid, para coumaric acid, protocatechuic acid, salicylic acid, and vanillic acid) with metformin was performed to produce metformin phenolic acid conjugates (M1–M10). We evaluated the structures using proton nuclear magnetic resonance, carbon‐13 nuclear magnetic resonance, Fourier‐transform infrared, and mass spectroscopy. All newly synthesized metformin phenolic acid conjugates were evaluated for their in vitro anticancer activity. Metformin phenolic acid conjugates were synthesized and showed a range of inhibitory effects. The metformin‐caffeic acid conjugate [(E)‐3‐(3,4‐dihydroxyphenyl)‐N‐(N,N‐dimethylcarbamimidoyl)carbamimidoyl)acrylamide] (M3) (IC50: 5.47 ± 2.72 and 4.42 ± 2.15 µg/mL) showed the best anticancer activity against MDA‐MB‐468 and A549 cancer cell lines.
Decarboxylative Cross‐Dehydrogenative Coupling of Tetrahydroisoquinoline and Alkynoic Acids Using Recyclable Carbon Nanotube‐Supported Copper/Nickel Oxide Catalysts
Authors: Lee Sunwoo , Rajan Robin Prakash Sirvin , Kim Ji Dang , Choi Hyun Chul
Published: February 2025

We present a decarboxylative cross‐dehydrogenative coupling (CDC) reaction between tetrahydroisoquinoline (THIQ) derivatives and alkynoic acids using a carbon nanotube‐supported copper/nickel oxide (CNT‐CuO/Ni) catalyst. This catalyst leverages the catalytic properties of copper and magnetic recoverability of nickel to facilitate efficient carbon‐carbon bond formation under mild conditions while allowing for easy separation and reuse. Under optimized conditions, the reaction produced various 1‐alkynyl‐2‐aryl‐1,2,3,4‐tetrahydroisoquinoline derivatives in good yields. The CNT‐CuO/Ni catalyst exhibited significant reusability, retaining high catalytic performance through 12 reaction cycles. Competition experiments revealed that the electronic properties of substituents on the phenyl propiolic acid and THIQ aryl groups had minimal effect on the reaction outcome. This study underscores the potential of CNT‐CuO/Ni as a recyclable catalyst for sustainable organic synthesis in decarboxylative CDC reactions.
Single Co Atom Catalyst Derived from Terpolymer Pyrolysis for Hydrogenation of Nitroarenes
Authors: Zhou Yanan , Guo Anni , Shen Huawei , Wang Yue , Zhang Fuxing , Rong Xuejiao , Li Yang , Yan Xilong , Chen Ligong , Wang Bowei
Published: February 2025

Recently, single atom catalysts (SACs) with isolated metal atom as the active site have received extensive attention for their excellent catalytic performance. However, limited by the strong aggregation tendency of monometallic atoms, the construction of SACs remains a formidable challenge. Herein, we developed a facile ternary copolymerization‐pyrolysis approach to synthesize a single cobalt atom catalyst (Co1@NC) by employing amino‐functionalized cobalt phthalocyanine (CoPc(NH2)4) as the metal precursor. Specially, CoPc(NH2)4 was copolymerized with melamine and 1, 4‐phthalaldehyde to yield a terpolymer, thereby allowing CoPc to be more uniformly and stably distributed in the polymer network. Subsequently, the obtained terpolymer was pyrolyzed to afford Co1@NC. Aberration‐corrected high‐angle annular dark‐field scanning transmission electron microscopy (AC HAADF‐STEM) and X‐ray absorption spectroscopy (XAS) directly confirmed that the catalyst Co1@NC was a single cobalt atom catalyst. Furthermore, the large specific surface area (SBET=418.8 m2/g) and high cobalt content (2.71 wt%) of Co1@NC provided more cobalt active sites, and therefore displayed excellent catalytic activity in the hydrogenation of nitrobenzene. In addition, the catalyst showed remarkable cyclic stability in five cycles and still remained as the single atom catalyst.
Recent progress in the electrocatalytic synthesis of H2O2 from graphite‐based materials
Authors: Pan Chengsi , Shang Hengjun , Zhang Yaning , Dong Yuming , Zhu Yongfa
Published: February 2025

Graphite‐based catalysts, with their abundant availability, low cost, excellent electrical conductivity, and chemical stability, serve as an ideal candidate for eletrocatalytical synthesis of H2O2. This review explores the fundamental principles of hydrogen peroxide (H₂O₂) production via the electrochemical oxygen reduction reaction (ORR) and the theoretical basis for evaluating catalyst selectivity. It summarizes the structural characteristics, classifications, and developmental history of graphite‐based catalysts, with a focus on recent advancements. The discussion highlights strategies such as heteroatom doping, defect engineering, and surface oxygen functionalization, analyzing their effectiveness in designing novel high‐performance catalysts. By rationally designing catalyst components and fine‐tuning the microenvironment of active sites, it is possible to develop efficient and highly stable catalysts, narrowing the gap between experimental outcomes and theoretical predictions. This work aims to advance the scalable application of graphite‐based materials in green chemistry and energy fields.
Electrocatalytic Syngas Production using Metalloporphyrins with Controllable H2/CO Ratios
Authors: Wang Zhimeng , Mei Benxing , Xu Yuhan , Liu Yuze , Li Xialiang , Cao Rui
Published: February 2025

Electrochemical methods to produce syngas present a promising strategy for energy conservation and environmental protection. The H₂/CO ratio of syngas is crucial for its applications. However, few catalysts can achieve catalytic generation of syngas that can be directly used because the H₂/CO ratio is difficult to be controlled. To address this issue, bicomponent electrocatalysts are utilized to produce syngas with controllable H₂/CO ratios. These two catalysts in the bicomponent electrocatalysts can efficiently and selectively catalyze CO2 reduction reaction (CO2RR) to generate CO and hydrogen evolution reaction (HER) to generate H2, respectively. Metalloporphyrins are promising electrocatalysts for both CO2RR and HER. A series of metalloporphyrins 1‐M (M = Fe, Co, Ni, Cu) were synthesized as electrocatalysts to produce syngas with different H2/CO ratios. Among these metalloporphyrins, 1‐Co and 1‐Cu can selectively produce CO and H2, respectively, through CO2RR and HER in KHCO3 aqueous solutions. The ratio of 1‐Co and 1‐Cu in bicomponent electrocatalysts 1‐Co/1‐Cu is adjusted to achieve the regulation of H2/CO ratio (0.1‐6.4) at high catalytic currents. This work provides a new approach for designing more efficient syngas catalysts with tunable H2/CO ratios.
Enzymatic Synthesis of Saturated Bioisosteres of Ortho‐Substituted Benzenes by Artificial Photoenzyme
Authors: Bai Yuting , Sheng Yuhui , Fu Yi , Zhou Zhi , Wu Jing
Published: February 2025

Saturated bioisosteres of ortho‐substituted benzenes are of significant interest due to their enhanced pharmacokinetic properties, such as improved metabolic stability and reduced toxicity, making them valuable in drug design and development. However, efficient synthesis of them remains a challenge in organic chemistry. Herein, we report the biocatalytic synthesis of saturated bioisosteres of ortho‐substituted benzenes using engineered artificial photoenzymes. The artificial photoenzyme, incorporating genetically encoded unnatural amino acids with benzophenone photosensitizer residue, facilitate the formation of chiral saturated bioisosteres with moderate enantiomeric excess via the energy transfer process. Our results demonstrate the versatility of artificial photoenzymes in mediating new‐to‐nature reactions that are difficult to achieve with conventional chemical or enzymatic methods.
Stereoselective Synthesis of 1,2‐Cis O‐Linked Glycosyl Amino Acids via Additive‐Modulation for Glycopeptide Synthesis
Authors: Zhang Miaomiao , Gan Jinjuan , Peng Peng , Li Tianlu
Published: February 2025

A highly stereoselective strategy to facilitate the synthesis of 1,2‐cis‐O‐linked glycosyl amino acids was established via a additive‐modulated trichloroacetimidate glycosylation approach. This mild and practical protocol demonstrates broad applicability with diverse glycosyl donors, including D‐gluco‐, D‐galacto‐, 2‐deoxy‐2‐azido‐D‐gluco‐, 2‐deoxy‐2‐azido‐D‐galacto‐, D‐xylo‐, L‐fuco‐pyranosyl and L‐arabinofuranosyl trichloroacetimidates, and orthogonally protected amino acids such as Ser, Thr, Tyr, and 4‐hydroxyproline (Hyp) as acceptors. These 1,2‐cis linked glycosyl amino acids serve as valuable building blocks for glycopeptide synthesis via solid‐phase peptide synthesis (SPPS), offering significant potential for advancing glycoprotein research.
Fines deposition during hydrotreating: Effects of catalyst size and bed arrangement
Authors: Kwao Simon , Vedachalam Sundaramurthy , Dalai Ajay K. , Adjaye John
Published: February 2025

Fines deposition presents a significant problem during the hydrotreating of bitumen‐derived gas oils. The accumulation of fines leads to reactor clogging and consequently, pressure drop buildup. At critical levels, the hydrotreating reactor must be prematurely shutdown, resulting in substantial economic losses for refineries. Hence, research into finding measures to address fines deposition is crucial and of interest to stakeholders in the refining industry. This research explored the effects of catalyst size and bed arrangement on fines deposition, with the goal of identifying strategies to obtain longer hydrotreating run times. Cold and hot flow fines deposition tests were conducted in three‐zone reactors using NiMo/γ‐Al2O3 catalysts, with sizes ranging from 1.3 to 2.5 mm. Under cold flow conditions, maximum fines deposition was reached in 12, 14, and 25 days for 1.3, 1.6, and 2.5 mm catalyst sizes, respectively. For the hot flow tests, maximum fines deposition occurred in 15, 17, and 28 days for 1.3, 1.6, and 2.5 mm catalyst sizes, respectively. Thus, both flow tests suggested that reducing catalyst size accelerated fines deposition, primarily due to straining. However, when the catalyst bed was arranged with decreasing size from top to bottom of the reactor, the time to reach maximum fines deposition increased to 28 days (cold flow) and 34 days (hot flow). Therefore, configuring the catalyst bed to have a downward gradient of decreasing catalyst size is proposed as a potential strategy to extend hydrotreating run times.
Mechanisms of GPM6A in Malignant Tumors
Authors: Huang Bei , Li Xihong
Published: February 2025

Background

Glycoprotein M6A (GPM6A) encodes a transmembrane protein, expressing in large quantities on the cell surface of central nervous system (CNS) neurons. GPM6A acts importantly in neurodevelopment by modulating neuronal differentiation, migration, axon growth, synaptogenesis, and spine formation, but its role in malignancy remains controversial and requires further research. This article reviewed the mechanisms of GPM6A in colorectal cancer, liver cancer, lung cancer, glioblastoma, and other malignant tumors, and made a “one‐stop” summary of the relevant mechanisms.

Recent Findings

Researches have indicated that GPM6A is related to malignant tumors. It affects epithelial‐mesenchymal transition and induces the formation of filopodia, participating in the adhesion, migration, and metastasis of cancer cells. Its role in malignant tumors remains controversial, however. On the one hand, GPM6A may have carcinogenic properties and is related to poor prognosis of malignant tumors. It is highly expressed in lymphoblastic leukemia and is a potential oncogene. It also shows carcinogenic properties in colorectal cancer, glioblastoma, gonadotroph adenomas and so on. On the other hand, the expression of GPM6A decreases in lung adenocarcinoma, liver cancer, thyroid cancer, and so forth as the tumor progresses, and it can inhibit the progression of malignant tumors by inhibiting some signaling pathways, suggesting that it may be a tumor suppressor gene.

Conclusion

Carcinogenic or tumor suppressive? Although the biological function of GPM6A in the development of malignant tumors is still unclear, according to the current research progress, it is still expected to become an effective molecular marker for predicting tumor occurrence, metastasis and prognosis, as well as a new target for diagnosis and treatment.
Distribution, Risk Factors and Epidemiological Trends of Pancreatic Cancer Across Countries’ Income Levels: A Comprehensive Analysis
Authors: Wik Sofia Laila , Tian Wenxin , Zhong Claire Chenwen , Sawhney Apurva , Gao Mingjun , Yu Qinyao , Xue Fanyu , Chan Sze Chai , Chow Shui Hang , Adebisi Yusuff Adebayo , Yuan Jinqiu , Lucero‐Prisno Don Eliseo , Wong Martin C. S. , Huang Junjie ,   Global Health Focus Epidemiology Group (GHFEG)
Published: February 2025

Background

Globally, pancreatic cancer poses a significant concern for public health.

Aims

The objective of this study was to assess the burden of pancreatic cancer on varying income levels.

Methods and Results

Data from the Global Burden of Disease Study (GBD) 2021 and Gross Domestic Product Per Capita data were utilised in this study. All countries were categorised into four groups based on their income levels. Age‐standardised incidence, mortality and disability‐adjusted life years (DALYs) rates were the primary parameters to analyse the burden of pancreatic cancer. The associations between pancreatic cancer burden and countries' economic levels were analysed with linear regression models. High‐income‐level countries generally had a higher burden compared to other income levels in 2021. Greenland had the highest rate of age‐standardised DALYs at 374.93 per 100 000, followed by Uruguay (297.06) and Monaco (290.87). A higher gross domestic product (GDP) per capita was linked to a higher age‐standardised incidence (β = 0.77, 95% CI = 0.63, 0.90, p < 0.001), mortality (β = 0.72, 95% CI = 0.59, 0.86, p < 0.001) and DALYs (β = 14.59, 95% CI = 11.38, 17.80, p < 0.001). From 1990 to 2021, the pancreatic cancer burden increased across all income levels, with the most pronounced rise seen in lower‐middle‐income countries. Smoking‐related age‐standardised DALYs have decreased since 1990. However, there was a notable increase in males in upper‐middle‐income countries during the same period.

Conclusion

In conclusion, the pancreatic cancer burden has been increasing globally. The burden of pancreatic cancer varies significantly among countries with different income levels. Effective preventions are needed to control the burden of pancreatic cancer.
The DeepLabV3+ Algorithm Combined With the ResNeXt Network for Medical Image Segmentation
Authors: Wu Yanyan , Xie Yajun , Hong Yintao
Published: February 2025

This paper presents a semantic segmentation algorithm for medical images, leveraging the DeepLabV3+ architecture in conjunction with the ResNeXt network. The proposed algorithm takes into account the correlation between each structure of lung images and the unique characteristics of image features. Firstly, the cavity convolution algorithm is employed to enhance the receptive field of the network's feature map without augmenting the number of network parameters. Then, the extraction of dense pixel features and the expansion of the receptive field for lung images are conducted using a Densely Connected Atrous Spatial Pyramid Pooling (DenseASPP) module integrated with the ResNeXt network, which is based on multi‐scale feature fusion. This ultimately leads to improved refinement of the edges in segmented lung images. The algorithm has shown excellent performance in clinical applications, providing medical professionals with more precise and accurate data to inform diagnostic and treatment strategies. Our algorithm achieved Mean Pixel Accuracy (MPA) of 0.9866, Intersection Over Union (IOU) of 0.9886 and Mean Intersection over Union (MIoU) of 0.9761, which demonstrates superiority over other state‐of‐the‐art algorithms.
Stabilization of Verdigris Pigment on Paper: Evaluation of Antioxidants Under Mild Accelerated Degradation Conditions
Authors: Malešič Jasna , Retko Klara , Finšgar Matjaž , Kralj Cigić Irena
Published: February 2025

Copper‐based pigments, such as verdigris, have caused severe damage to many important historical documents, and their preservation remains a significant concern for paper conservators and researchers. This study re‐evaluates the efficacy of two promising antioxidants, tetrabutylammonium bromide (TBABr) and benzotriazole (BTA), as stabilization agents for paper documents containing verdigris pigment. To assess the stability of the mock‐up papers, various parameters were measured during accelerated degradation, including colour, molecular weight (Mw), and pH value. Size exclusion chromatography measurements of Mw confirmed that TBABr provided superior stabilization compared to BTA. Additionally, the total colour change was slightly more pronounced in the samples treated with BTA compared to those treated with TBABr. However, during degradation, some paper samples containing thicker application of pigment exhibited significant black and brown spots, regardless of treatment (untreated, treated with BTA, or TBABr). X‐ray photoelectron spectroscopy confirmed the presence of both Cu(I) and Cu(II) oxidation states in all samples, with a higher Cu(II) content on the surface of TBABr treated samples compared to those treated with BTA. This may indicate differences in the mechanisms of degradation. Raman spectroscopy identified the spots on both untreated and TBABr‐treated samples as copper(II) oxide.
Synthesis and Photophysical Study of 3‐(Isoxazol‐5‐yl)coumarins
Authors: Ríos María-C. , Bravo Néstor-F. , Macías Mario , Iglesias Bernardo A. , Portilla Jaime
Published: February 2025

Herein, efficient synthesis and photophysical study of three novel dyes based on 3‐(isoxazol‐5‐yl)coumarins were developed, and their structures were confirmed by X‐ray crystallography. The access to these fluorophores implied two condensation reaction steps under microwave conditions, starting from 3‐acetylcoumarins and ending with the cyclization of the respective β‐enaminone intermediate with hydroxylamine hydrochloride. By investigating solvatofluorochromism, acidochromism, and properties in the solid state, it was possible to establish that the optical properties of these dyes are coumarin ring‐dependent, which was supported by TD‐DFT calculations. In addition, fluorescence quantum yields (ΦF) up to 36% with short lifetimes decay (1.40–4.60 ns) were accompanied by a redshift behavior with electro‐donating coumarins. Remarkably, solid‐state studies showed a higher emission of the unsubstituted coumarin (ΦF = 64%) due to significant supramolecular interactions; in addition, acidochromism experiments using TFA were performed, finding detection limits of up to 1.03 µM.
A crop wild relative inventory for Brazil
Authors: Moulin Monique Moreira , Santos Talles de Oliveira , Ramos Semiramis Rabelo Ramalho , Maxted Nigel , Brehm Joana Magos
Published: February 2025

Crop wild relatives (CWRs) are defined as wild plant taxa that are closely related to agricultural crops. In the face of global pressures of climates change and biodiversity loss, CWR requires urgent conservation attention. As a first step toward a national strategy for the conservation of CWRs, we present an inventory of taxa occurring in Brazil, with suggested prioritization of species based on potential value in crop improvement. The CWR checklist comprised 3652 taxa among 112 genera, and after applying the prioritization criteria, 289 CWRs were prioritized. The prioritized CWRs are related to crops of regional, national, and global importance such as cassava (Manihot esculenta Crantz), sugarcane (Saccharum officinarum L.), coffee (Coffea arabica L. and Coffea canephora Pierre ex A. Froehner), cotton (Gossypium hirsutum L.), rice (Oryza sativa L.), orange (Citrus spp.), beans (Phaseolus vulgaris L.), tomato (Solanum lycopersicum L.), potato (Solanum tuberosum L.), and cocoa (Theobroma cacao L.). More than half of the prioritized CWRs (50.86%) are endemic, and 28.03% are nationally endangered. A subsequent prioritization was also carried out using the criteria of socioeconomic value of the related crop and endemism, with 95 taxa being prioritized. The production of the first CWR inventory for Brazil is an important tool for planning conservation actions as part of a national strategy to maintain food security.
5‐hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target
Authors: Xu Nuo , Gao Zhaoya , Wu Deyan , Chen Hangyu , Zhang Zijian , Zhang Lei , Wang Yuchen , Lu Xuyang , Yao Xu , Liu Xuelan , Huang Yi‐You , Qiu Meiying , Wang Sen , Liang Jinqiang , Mao Can , Zhang Feng , Xu Huimin , Wang Yujiao , Li Xian , Chen Zhexin , Huang Dandan , Shi Jingyi , Huang Wensheng , Lei Fuming , Yang Zeruo , Chen Long , He Chuan , Zhu Haichuan , Luo Hai‐Bin , Gu Jin , Lin Jian
Published: February 2025

Metachronous liver metastases (MLM) are characterised by high incidence and high mortality in clinical colorectal cancer treatment. Currently traditional clinical methods cannot effectively predict and prevent the occurrence of metachronous liver metastasis in colorectal cancer. Based on 5hmC‐Seal analysis of blood and tissue samples, this study found that portal venous blood was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using the 10 5hmC epigenetic alterations, to accurately distinguish MLM patients from patients without metastases. Among these epigenetic alterations, phosphodiesterase 4 (PDE4D) was highly increased in MLM patients and correlated with poor survival. Moreover, our studies demonstrated that PDE4D was a key metastasis‐driven target for drug development. Interfering with the function of PDE4D significantly repressed liver metastases. Similarly, roflumilast, a PDE4 inhibitor for chronic obstructive pulmonary disease (COPD) therapy, also inhibits liver metastases. Further studies indicate that blocking the function of PDE4D can affect CRC invasion through the HIF‐1α‐CCN2 pathway. To develop a more efficient PDE4 inhibitor and reduce the occurrence of adverse events, we also designed several new compounds based on 2‐arylbenzofurans and discovered lead L11 with potent affinity for PDE4D and significant suppression of liver metastases. In this work, our study provides a promising strategy for predicting metachronous liver metastasis and discovers L11 as a potential repurposed drug for inhibiting liver metastasis, which have the potential to benefit patients with CRC in the future.

Key points

5hmC epigenetic markers derived from portal venous blood could accurately predict metachronous metastasis of colorectal cancer.

PDE4D was a key metastasis‐driven target that promoted metachronous metastasis via the HIF‐1α‐CCN2 pathway.

The newly synthesised compound L11 could specifically inhibit PDE4D and abolish metachronous metastasis of colorectal cancer without obvious toxic side effects.
Muscle‐specific gene editing improves molecular and phenotypic defects in a mouse model of myotonic dystrophy type 1
Authors: Izzo Mariapaola , Battistini Jonathan , Golini Elisabetta , Voellenkle Christine , Provenzano Claudia , Orsini Tiziana , Strimpakos Georgios , Scavizzi Ferdinando , Raspa Marcello , Baci Denisa , Frolova Svetlana , Tastsoglou Spyros , Zaccagnini Germana , Garcia‐Manteiga Jose Manuel , Gourdon Genevieve , Mandillo Silvia , Cardinali Beatrice , Martelli Fabio , Falcone Germana
Published: February 2025

Background

Myotonic dystrophy type 1 (DM1) is a genetic multisystemic disease, characterised by pleiotropic symptoms that exhibit notable variability in severity, nature and age of onset. The genetic cause of DM1 is the expansion of unstable CTG‐repeats in the 3′ untranslated region (UTR) of the DMPK gene, resulting in the accumulation of toxic CUG‐transcripts that sequester RNA‐binding proteins and form nuclear foci in DM1 affected tissues and, consequently, alter various cellular processes. Therapeutic gene editing for treatment of monogenic diseases is a powerful technology that could in principle remove definitively the disease‐causing genetic defect. The precision and efficiency of the molecular mechanisms are still under investigation in view of a possible use in clinical practice.

Methods

Here, we describe the application of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) strategy to remove the CTG‐expansion in the DMPK gene in a mouse model carrying the human transgene from a DM1 patient. To optimise the editing efficiency in vivo, we identified new tools that allowed to improve the expression levels and the activity of the CRISPR/Cas9 machinery. Newly designed guide RNA pairs were tested in DM1‐patient derived cells before in vivo application. Edited cells were analysed to assess the occurrence of off‐target and the accuracy of on‐target genomic events. Gene editing‐dependent and ‐independent mechanisms leading to decreased accumulation of the mutated DMPK transcripts were also evaluated.

Results and Conclusion

Systemic delivery of CRISPR/Cas9 components in DM1 mice, through myotropic adeno‐associated viral vectors, led to significant improvement of molecular alterations in the heart and skeletal muscle. Importantly, a persistent increase of body weight, improvement of muscle strength and body composition parameters were observed in treated animals. Accurate evaluation of CRISPR/Cas9‐mediated‐phenotypic recovery in vivo is a crucial preclinical step for the development of a gene therapy for DM1 patients.

Key points

In vivo application of a therapeutic gene editing strategy for permanent deletion of the pathogenetic CTG‐repeat amplification in the DMPK gene that causes myotonic dystrophy type 1.

Following treatment, diseased mice show a significant improvement of both molecular and phenotypic defects.
Joint Design of Fronthaul and Access Links in Massive MIMO Based CRANs
Authors: Rashid Umar , Awan Faheem G.
Published: February 2025

In this paper, we address the challenge of limited channel capacity of wireless fronthaul links in cloud radio access networks (CRANs). A novel architecture is proposed in which the base band unit (BBU) is equipped with a massive multiple‐input multiple‐output (MIMO) antenna array to communicate with a set of remote radio heads (RRHs) that serve multiple user equipments (UEs). Moreover, an optimal signal quantization strategy is also designed at the BBU to accommodate for the limited fronthaul capacity. To this end, a joint optimization of power allocation at the BBU, quantization noise covariance, and RRH beamforming vectors is formulated via maximizing the achievable sum‐rate subject to power constraints at the BBU and RRHs. The resulting highly nonconvex problem is reformulated as a semidefinite relaxation (SDR) problem by using the difference of convex (DC) programming approach. It is also deduced analytically that the solution yielded by this SDR problem is always of rank one. Numerical results confirm the potential of the proposed system in improving the capacity of the CRAN systems with wireless fronthauling. In particular, the proposed design outperforms two proposed benchmark schemes.
Unraveling the Mechanisms That Regulate Osteoclast Differentiation: A Review of Current Advances
Authors: Zhang Sai , Gao Meng , Song Shuzhe , Zhao Tongdan , Zhou Bianhua , Wang Hongwei , Tian Weishun , Zhao Wenpeng , Zhao Jing
Published: February 2025

Osteoporosis is a metabolic bone disease primarily caused by a decreased bone formation and increased bone resorption. Osteoclasts are a special class of terminally differentiated cells that play an important role in normal bone remodeling and bone loss in osteoporosis as well as in a variety of osteolytic diseases. Osteoclasts can be differentiated from monocyte–macrophage cells of the hematopoietic system; they are the key cells in bone resorption. Osteoclast formation and differentiation are regulated by various cytokines and transcription factors. In this review, we summarize recent advances in research on the regulation of osteoclast differentiation and function by factors such as M‐CSF, RANKL, AP‐1, NFATC1, MITF, and PU.1. Understanding these cytokines and transcription factors can not only help identify targets for osteoclast differentiation but also aid in intervening in the treatment of osteoclast‐related diseases.
Do Whale Sharks Select for Specific Environments to Give Birth?
Authors: Womersley Freya C. , Waller Matt J. , Sims David W.
Published: February 2025

Neonate whale sharks < 1.5 m in length are rarely encountered, with approximately 35 sightings recorded globally between 1970 and 2020. Although potentially pregnant females seem to frequent certain sites, parturition areas are unknown, and most neonates have been sighted opportunistically in offshore environments, suggesting nursery habitat may occur in remote parts of the ocean. Here, documented accounts of neonate whale sharks with corresponding locations were mapped in relation to oceanography to identify whether there are commonalities in where they occur. Results show that locations of neonate sightings coincide with permanent oxygen minimum zones (OMZs)—with associated high surface chlorophyll‐a (Chl‐a) and low oxygen at depth—more often than would be expected by random chance. Two main hypotheses are proposed to explain this apparent association: (i) adult female whale sharks selectively pup in waters adjacent to low oxygen regions offering a proximate refuge from oceanic predators as well as enhanced foraging opportunities, or that (ii) pupping occurs randomly in the open ocean but that OMZs restrict neonates to shallower surface waters where they are more frequently encountered by humans than elsewhere. Testing both hypotheses requires more data on the relationship between whale shark movement ecology and dissolved oxygen concentrations. As a first step, a model predicts the highest likelihood of neonates occurring in waters above OMZs, focussed around intermediate Chl‐a regions at the boundaries of highly productive upwelling systems. These areas could be the focus of future, more targeted studies. Here, biologging devices measuring in situ oxygen concentrations will be useful for exploring how different life stages interact with OMZs, which are expanding due to climate‐driven deoxygenation. What this might mean for neonate whale shark conservation in future warmer oceans remains an open question.
An accurate and efficient semiautomated approach to counting birds: Estimating Northern Gannet colony size in Canada
Authors: Walker Jacob , Avery Trevor S. , St‐Pierre Francis , Rail Jean‐François , Quinn Danielle E. A. , English Matthew , Avery‐Gomm Stephanie
Published: February 2025

Improving the efficiency of population monitoring and conservation programs is beneficial, so long as the accuracy of the information collected is not diminished. The need to expeditiously estimate the population size of seabird colonies is especially acute during mass mortality events when aerial surveys can provide information quickly on the extent of effects and total mortality. In 2022, the highly pathogenic avian influenza virus caused outbreaks at most Northern Gannet Morus bassanus colonies worldwide, killing tens of thousands of gannets in eastern Canada. In this study, we evaluated the accuracy and efficiency of a semiautomated method using the free software CountEm for counting Northern Gannet nests by reanalyzing 13 years of aerial photographs from past population surveys (2009–2020 and 2022). The CountEm program uses a geometric sampling method which overlays a grid of quadrats onto photographs in which the user counts objects of interest. We developed a protocol that generated population estimates that are accurate enough to support population management objectives (i.e., within 2%–5% of manual counts) and outline additional ways to improve CountEm accuracy. Additionally, using CountEm was 1100% more efficient than manually counting based on counting time. Since CountEm relies on human identification of objects to be counted, our methods, results, and conclusions are transferable to any taxa that form large aggregations and can be identified and counted in photographs.
High‐Performance Stretchable Gallium Battery for Wearable Electronics, Through Synthesis of Foam Electrodes
Authors: Parvini Elahe , Hajalilou Abdollah , Carneiro Manuel Reis , Lopes Pedro Alhais , Tavakoli Mahmoud
Published: February 2025

The demand for sustainable and stretchable thin‐film printed batteries for bioelectronics, wearables, and e‐textiles is rapidly increasing. Recently, we developed a fully 3D‐printed soft‐matter thin‐film Ga‐Ag2O battery with 3R characteristics: resilient to mechanical strain, repairable after damage, and recyclable. This battery achieved a record‐breaking areal capacity of 26.37 mAh cm−2, increasing to 30.32 mAh cm−2 after 10 cycles under 100% strain. This performance stems from the synergistic effects of gallium's liquid metal properties and the styrene‐isoprene‐styrene polymer in the anode. Gallium's high specific capacity (1153.2 mAh g−1), deformability, and self‐healing abilities, supported by its supercooled liquid phase, significantly enhance the battery's resilience and efficiency. However, the cathode's lower theoretical capacity, due to Ag2O (231.31 mAh g−1), remains a limitation. Traditional Ag2O‐carbon black‐styrene‐isoprene‐styrene cathodes experience rapid capacity decay as only the surface area of the active materials interacts with the electrolyte. To overcome this, we designed a carbon‐filled Ag2O foam electrode using a sacrificial sugar template, increasing the effective surface area. This optimization enhanced ion‐exchange efficiency, specific capacity, and cyclability, achieving a specific capacity of 221.16 mAh g−1. Consequently, the Ga‐Ag2O stretchable battery attained a record areal capacity of 40.91 mAh cm−2—double that of nonfoam electrodes—and exhibited fivefold improved charge–discharge cycles. Using ultrastretchable Ag‐EGaIn‐styrene‐isoprene‐styrene and carbon black‐styrene‐isoprene‐styrene current collectors, the battery's specific capacity increased by 33% under 50% strain. Integrated into a soft‐matter smart wristband for temperature monitoring, the battery demonstrated its promise for wearable electronics.