bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability and Solvation of Key Intermediates of Oxygen Evolution on TiO2, RuO2, IrO2 (110) Surfaces: A Comparative DFT Study
Authors: Inico Elisabetta , Di Liberto Giovanni , Giordano Livia
Published: July 2024

Oxygen Evolution Reaction (OER) is a fundamental process, with gold standards like RuO2 and IrO2. Recently, it was suggested that OER could go through unconventional intermediates, −O−H, −OO−H. −O−H is formed by the direct interaction of an adsorbed O species to a metal surface atom and a proton bound to a surface oxygen. Similarly, in −OO−H, an adsorbed −OO adduct interacts with a proton on a surface oxygen. This work compares the nature of key intermediates of OER on TiO2, RuO2, and IrO2(110) surfaces by Density Functional Theory (DFT) calculations and Ab‐Initio Molecular Dynamics (AIMD). We rationalized the nature, the relative stability trends in vacuum and the effect of water solvation of the species. −OO−H is preferred than −OOH. −OH is preferred than −O−H except for RuO2. We investigated the nature of the catalyst/water interfaces and the interaction of intermediates with water based on AIMD. On RuO2, −OH and −O−H display a different interaction with water. −OO−H is quite rigid on RuO2, while it is dynamic on IrO2 as the proton is shared between −OO and a surface oxygen atom. This study provides insights on the role of solvation to the nature of OER intermediates, that may help future studies.
Ullmann Coupling Reactions on Gold Nanoparticles
Authors: Ukah Nathaniel , Wegner Hermann A.
Published: July 2024

There has been a plethora of experience in conducting organic reactions in solution, with little to no knowledge in organic reactions on surfaces. Broadening the horizon of organic on‐surface synthesis will enable creation of functional materials and direct integration into devices. Herein, we report an Ullmann reaction on thiol‐functionalized gold nanoparticles serving as reactant, stabilizing agent, catalyst and reducing agent in this transformation. The orientation of ligands and formation of Surface Assembled Monolayer (SAM) on the gold nanoparticles were exploited to attain selectivity of hetero‐ over homo‐Ullmann coupling, thus, expanding the toolbox of organic on‐surface synthesis to nanoparticles.
Unveiling the Twisted Aromatic Donor Effect on the Nonlinear Response of D‐π‐A Type Malononitrile‐Derived Chromophores
Authors: Zhu Xiang‐Zhao , Chen Song‐Hua , Xu Jia‐Bei , Huang Jian‐hua , Yan Jian‐Feng , Yuan Yao‐Feng
Published: July 2024

This study presents the design, synthesis, and comprehensive characterization of a novel series of D‐π‐A type malononitrile‐derived chromophores, BTC‐1–BTC‐4. Combining various spectroscopic techniques, nonlinear Z‐scan measurements, and quantum chemical calculations, we revealed the intricate relationship between nonlinear optical properties and the interplay of molecular structure, intramolecular charge transfer (ICT), and dipole moments (μ). Our experimental and computational findings corroborate that the polarization degree in the ground state, the charge separation in the excited state and twisted intramolecular charge transfer (TICT) collectively dictate the nonlinear optical properties of the compounds. Notably, BTC‐1 exhibits an exceptional nonlinear absorption coefficient β value (2×10−8 m W−1), attributed to its optimized charge transfer efficiency and pronounced degree of charge separation. Our findings provide actionable insights for the rational design of high‐performance organic Nonlinear optics (NLO) materials with potential applications in advanced photonic devices.
Design, Synthesis, and Xanthine Oxidase Inhibitory Activity of 4‐(5‐Aminosubstituted‐4‐cyanooxazol‐2‐yl)benzoic Acids
Authors: Kobzar Oleksandr , Beiko Alona , Merzhyievskyi Danylo , Shablykin Oleg , Brovarets Volodymyr , Tanchuk Vsevolod , Vovk Andriy
Published: July 2024

Xanthine oxidase is a known therapeutic target for the treatment of hyperuricemia and related diseases. Despite the availability of current drugs such as allopurinol and febuxostat, the search for new compounds to effectively inhibit this enzyme remains relevant. In our study, 75 virtual structures of 4‐(5‐aminosubstituted‐4‐cyanooxazol‐2‐yl)benzoic acids with structural similarity to febuxostat were designed for evaluation of their potency against xanthine oxidase. After molecular docking simulations, eight compounds were selected for synthesis and in vitro testing. The synthesized compounds were found to exhibit in vitro xanthine oxidase inhibitory activity in the nanomolar concentration range. The most effective inhibitors with 4‐benzylpiperidin‐1‐yl or 1,2,3,4‐tetrahydroisoquinolin‐2‐yl substituents at position 5 of the oxazole ring had IC50 values close to that of febuxostat. The kinetic data suggest a mixed‐type inhibition when the inhibitor binds preferentially to the free enzyme rather than to the enzyme‐substrate complex. Molecular docking and molecular dynamic simulations were carried out to get insight into the key interactions of the inhibitors bound to the xanthine oxidase active site.
Carbon‐Based 3D Architectures as Anodes for Lithium‐Ion Battery Systems
Authors: Aslam Junaid , Ahsan Waseem Muhammad , Zhang Yifan , Wang Yong
Published: July 2024

Graphite, with its exceptional cyclic performance, continues to dominate as the preferred anode material for lithium‐ion batteries. However as high‐energy application gains momentum, there is growing demand for higher capacities that alloying/de alloying and conversion type anode materials can offer. Despite their potential, these materials are plagued by challenges such as volumetric fluctuations, low conductivities, and poor cyclic stability. Carbon nanostructures, on the other hand, show tremendous promise with their low volume expansion, high ion diffusion rates, and excellent conductivity. Nevertheless, their limited areal and volumetric densities restrict their widespread utilization. To address these limitations, various strategies such as doping, composite formation, and structural modification have been proposed. This article provides a succinct overview of carbon nanomaterials and their electrochemical performance as 3D carbon‐based anodes, along with a comprehensive analysis of the strategies employed to overcome associated challenges while evaluating their potential prospects in the field.
Acoustic Shock‐Induced Low Dielectric Loss in Glycine and Oxalic Acid‐Based Single Crystals
Authors: Muniraj Deepa , Kumar Raju Suresh , Almansour Abdulrahman I. , Kim Ikhyun , Dhas S. A. Martin Britto
Published: July 2024

Glycinium oxalate (GO) and Bis(glycinium) oxalate (BGO) crystals are successfully grown using the slow evaporation solution growth technique. Following their growth, the crystals are subjected to a series of acoustic shock pulses. The effects of these shock pulses on the structural, optical, dielectric, and morphological properties of the crystals are comprehensively analyzed using various characterization techniques, including powder X‐ray diffraction (XRD), UV‐Visible spectroscopy, dielectric spectroscopy, and optical microscopy. Structural analysis through XRD reveals shifts in diffraction peak positions, indicating structural deformations. Fourier transform infrared spectroscopy analysis assesses the chemical stability of GO and BGO under shocked conditions. UV‐Visible spectroscopy shows alterations in optical transmission with successive shock pulses, attributed to structural and surface defects. Dielectric properties are investigated over a frequency range from 1 Hz to 1 MHz, revealing variations in dielectric constant and loss tangent, which provide insights into the electrical behavior of the materials under normal and shocked conditions. Optical and scanning electron microscopy examine surface morphology, visualizing defects induced by the shock pulses. This study highlights the significant impact of shock pulses on the structural properties, optical transmission, dielectric properties, and surface morphology of GO and BGO crystals, offering valuable information on their resilience under dynamic conditions and potential applications.
Immunostimulatory effects of Toll‐like receptor ligands as adjuvants in establishing a novel mouse model for pemphigus vulgaris
Authors: Gao Changxing , Liu Mei , Xin Yue , Zeng Yong , Yang Hui , Fan Xinyu , Zhao Cheng , Zhang Bo , Zhang Lingzhi , Li Jing J. , Zhao Ming , Wang Zijun , Lu Qianjin
Published: July 2024

Background

The meticulous selection of appropriate vaccine adjuvants is crucial for optimizing immune responses. Traditionally, pemphigus vulgaris (PV), an autoimmune disorder, has been modelled using complete Freund's adjuvant (CFA). In this study, we aimed to discern potential variations in immune responses elicited by Toll‐like receptor (TLR) ligands as compared to CFA.

Methods

A comprehensive investigation was conducted, comparing the effects of these adjuvants in conjunction with ovalbumin or desmoglein‐3. Flow cytometry was employed to analyse distinct cell subsets, while enzyme‐linked immunosorbent assay quantified antigen‐specific antibodies and cytokine levels. Histological examination of harvested skin tissues and transcriptome analysis of skin lesions were performed to identify differentially expressed genes.

Results

TLR ligands demonstrated efficacy in inducing PV‐like symptoms in wild‐type mice, in contrast to CFA. This underscored the substantial impact of the adjuvant on self‐antigen tolerance. Furthermore, we proposed an enhanced method for establishing a PV model through adoptive transfer, substituting CFA with TLR ligands. Our results revealed that in contrast to the perception that CFA being the most potent immunopotentiator reported, CFA promoted regulatory T cells (Treg), follicular regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10. This suggested potential implications for the recruitment and activation of Treg subsets. While B cell and CD8+ T cell responses exhibited similarity, CFA induced less activation in dendritic cell subsets. A novel mouse model of PV and systemic comparison of immunostimulatory effects of adjuvants were provided by this study.

Conclusions

The systematic comparison of CFA and TLR ligands shed light on the distinctive properties of these adjuvants, presenting innovative mouse models for the investigation of pemphigus. This study significantly contributes to adjuvant research and advances our understanding of PV pathogenesis.

Key points/highlights

Immunization with desmoglein 3 and Toll‐like receptor (TLR) ligands effectively induces pemphigus symptoms in wild‐type mice, whereas complete Freund's adjuvant (CFA) fails.

TLR ligands heightened the autoreactivity of donor cells in the adoptive transfer pemphigus model.

CFA promoted regulatory T cells and IL‐10‐producing neutrophils, whereas TLR ligands downregulated CCL17 and IL‐10, leading to more effective immune responses.
The clinicopathologic significance of psammoma bodies in cytology specimens: A series of 78 cases
Authors: Braun Ankica , Hassan Dina , Findley John , Cheng Lin , Yan Lei
Published: July 2024

Background

Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies.

Methods

Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed.

Results

A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies.

Conclusion

Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.
In situ loading of a pore network model for quantitative characterization and visualization of gas seepage in coal rocks
Authors: Jiao Huazhe , Chen Xi , Zhang Tiegang , Michael Quilligan , Yang Yixuan , Yang Xiaolin , Yang Tongyi
Published: July 2024

The flow characteristics of coalbed methane (CBM) are influenced by the coal rock fracture network, which serves as the primary gas transport channel. This has a significant effect on the permeability performance of coal reservoirs. In any case, the traditional techniques of coal rock fracture observation are unable to precisely define the flow of CBM. In this study, coal samples were subjected to an in situ loading scanning test in order to create a pore network model (PNM) and determine the pore and fracture dynamic evolution law of the samples in the loading path. On this basis, the structural characteristic parameters of the samples were extracted from the PNM and the impact on the permeability performance of CBM was assessed. The findings demonstrate that the coal samples' internal porosity increases by 2.039% under uniaxial loading, the average throat pore radius increases by 205.5 to 36.1 μm, and the loading has an impact on the distribution and morphology of the pores in the coal rock. The PNM was loaded into the finite element program COMSOL for seepage modeling, and the M3 stage showed isolated pore connectivity to produce microscopic fissures, which could serve as seepage channels. In order to confirm the viability of the PNM and COMSOL docking technology, the streamline distribution law of pressure and velocity fields during the coal sample loading process was examined. The absolute permeability of the coal samples was also obtained in order for comparison with the measured results. The macroscopic CBM flow mechanism in complex low‐permeability coal rocks can be revealed through three‐dimensional reconstruction of the microscopic fracture structure and seepage simulation. This study lays the groundwork for the fine description and evaluation of coal reservoirs as well as the precise prediction of gas production in CBM wells.
The Role of Self‐Organized TiO2 Nanotube Thickness on the Electrochemical Performance of Anodes for Li‐Ion Microbatteriess
Authors: Ghigo Clement , Sopha Hanna , Sepúlveda Marcela , Hromadko Ludek , Rodriguez‐Pereira Jhonatan , Vacandio Florence , Dénoue Killian , Macak Jan M. , Djenizian Thierry
Published: July 2024

Self‐organized TiO2 nanotube (TNT) layers with different thicknesses are prepared by anodization of Ti foils and then characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), and electrochemical techniques to be used as potential anodes for Li‐ion microbatteries. Electrochemical behaviors between 1 and 190 μm thick electrodes, which are the thickest ever studied layers as electrode, have been evaluated by cyclic voltammetry (CV) and chronopotentiometry at various kinetics. The highest areal capacity is obtained for TNT layers of 190 μm providing an initial discharge capacity of ≈5.3 mAh cm−2 at C/10. At faster kinetics, the ≈80 μm thick TNT layer reveals the best electrochemical behavior by offering 256 μAh cm−2 at 5 C and a good stability for 200 cycles at C/5. The influence of the increasing thickness on the electrochemical performance at fast rates can be attributed to the uncomplete reaction of TNT layers with Li ions and the enhancement of the formation of a solid electrolyte interphase. It is also shown that a very thick electrode is not able to sustain long and very fast cycles due to the mechanical deformations occurring during the successive insertion/extraction of Li ions.
Effects of polyphenols extracted from Keemun black tea on CYP450s activity and molecular mechanisms
Authors: Zuo Dan , Lv Le , Ren Hong , Sun Haiyan
Published: July 2024

Keemun black tea (KBT) is a luxurious traditional tea in China that has been commonly consumed because of its superior aroma and special taste. However, the risks remain unknown when KBT is used concomitantly with other drugs or food products. Therefore, we aimed to explore the effect of the tea polyphenols from KBT on the protein and mRNA levels of CYP450 and related mechanisms. The extraction of tea polyphenols from KBT and the content and component analysis of polyphenols were performed. A total of 24 female C57BL/6J mice were given tea polyphenols (0, 75, 150, 300 mg/kg) for 7 days, respectively. Liver tissues were collected 2 h after the last administration. The expression of Cyp3a11, Cyp1a2, Cyp2e1, Cyp2c37, and PXR mRNA was detected by real‐time PCR, and the expression of Cyp3a11, Cyp1a2, Cyp2e1, Cyp2c37, and PXR protein was detected by Western blotting. A transient co‐transfection reporter gene assay on HepG2 cells was also used to verify the role of PXR in regulating CYP3A4 expression. Our results showed that tea polyphenols from KBT significantly induced the expression of CYP 3A11 and PXR in general, inhibited the expression of Cyp1a2 and Cyp2e1 in general, and significantly inhibited the mRNA expression of Cyp2c37 but induced its protein expression. The reporter gene‐transfected cells demonstrated that tea polyphenols could enhance the PXR‐mediated transactivation of the CYP3A4 promoter via rifampicin‐induction. Meanwhile, tea polyphenols could significantly accelerate CYP3A11/3A4 expression by activating the PXR‐CYP3A4 pathway. In conclusion, KBT polyphenols could significantly affect the expression of various subtypes of the Cyp450 enzyme in mice livers via the PXR‐CYP450 pathway, suggesting that metabolism‐based interactions can occur when they are used in combination with medicines.
Optimizing Genetic Algorithm With Momentum Strategy for Technical Trading Rules: Evidence From Futures Markets
Authors: Li Shihan , Li Shuyao , Liu Qingfu , Tse Yiuman
Published: July 2024

This paper introduces an innovative genetically optimized dynamic composite strategy for achieving profitability in futures markets. Utilizing daily data from 35 actively traded futures contracts (1984–2022), we highlight the potential advantages of integrating the momentum effect into dynamic moving average strategies. This enhancement can boost the strategy's capability to capture and capitalize on market trends, ensuring consistent and stable returns. The developed dynamically composite technical trading strategy aspires to be a valuable reference for investors and the finance academic community, contributing to advancements in the field.
Non‐classical measurement error in instrumental variables estimation: An application to the medical care costs of obesity
Authors: Biener Adam I. , Meyerhoefer Chad , Cawley John
Published: July 2024

Estimates of the impact of body mass index and obesity on health and labor market outcomes often use instrumental variables estimation (IV) to mitigate bias due to endogeneity. When these studies rely on survey data that include self‐ or proxy‐reported height and weight, there is non‐classical measurement error due to the tendency of individuals to under‐report their own weight. Mean reverting errors in weight do not cause IV to be asymptotically biased per se, but may result in bias if instruments are correlated with additive error in weight. We demonstrate the conditions under which IV is biased when there is non‐classical measurement error and derive bounds for this bias conditional on instrument strength and the severity of mean‐reverting error. We show that improvements in instrument relevance alone cannot eliminate IV bias, but reducing the correlation between weight and reporting error mitigates the bias. A solution we consider is regression calibration (RC) of endogenous variables with external validation data. In simulations, we find IV estimation paired with RC can produce consistent estimates when correctly specified. Even when RC fails to match the covariance structure of reporting error, there is still a reduction in asymptotic bias.
Effectiveness of adalimumab in severe ulcerative colitis: A systematic review and a meta‐analysis
Authors: Azadbakht Saleh , Seighali Masomeh , Azadbakht Salehe , Azadbakht Morteza
Published: July 2024

Background and Aim

Ulcerative colitis (UC) causes chronic inflammation in the digestive tract, leading to abdominal pain and diarrhea. Adalimumab, a monoclonal antibody, is used to treat moderate to severe cases. This review and meta‐analysis evaluated adalimumab's effectiveness for severe UC, considering patient age, disease duration, and gender.

Methods

This study was designed as a systematic review and a meta‐analysis. Articles were searched in PubMed, Scopus, and Web of Science databases based on the keywords of adalimumab and UC. The titles, the abstracts, and, if necessary, the full texts of the articles were read. Then for further review, the full texts of the related articles were carefully examined, and the final articles were selected. Seventy‐eight articles were searched based on the keywords, and after reading the articles, 50 articles were related to the topic of the dissertation. The 50 articles were evaluated critically based on a checklist prepared by a statistical consultant and four articles with a score above 70% were selected. In the four articles, the main indicators of the effectiveness of adalimumab, including mucosal healing, clinical remission, and clinical response, were evaluated.

Results

The effectiveness of adalimumab on the mucosal healing index was 75.40%, the clinical remission index was 70.79%, and the clinical response index was 83.02%, based on different doses and treatment durations in the study. In the four meta‐analysis studies on adalimumab's effectiveness, 1613 UC patients were treated with varying doses over 8 and 52 weeks. Based on a meta‐analysis over 8 and 52 weeks for treating moderate to severe UC, adalimumab's effectiveness was 70%−83%. The highest effectiveness, based on three main indices, was with a 40 mg dose over 52 weeks.

Conclusion

According to the meta‐analysis, the effectiveness of adalimumab for treating moderate to severe UC over 8 and 52 weeks was 70%−83%. The highest effectiveness, based on three main indices, was with a 40 mg dose over 52 weeks.
Early neutrophil gelatinase‐associated lipocalin (NGAL) measurement could rule out future acute kidney injury in patients with acute coronary syndrome—Prospective observational study
Authors: Magnusson Nils Erik , Frydman Shir , Freund Ophir , Zornizki Lior , Banai Shmuel , Shacham Yacov
Published: July 2024

Background and Aims

The diagnosis of acute kidney injury (AKI) is of importance among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI). It is often delayed given the need in serial measurements of creatinine or other serum markers. Neutrophil gelatinase‐associated lipocalin (NGAL) is a proven marker for AKI, although its role as an early predictor in this setting was scarcely addressed before and was the aim of our study.

Methods

Prospective observational study including 133 patients with STEMI treated with PCI. Plasma NGAL was drawn immediately before PCI (NGAL‐0) and 24 h after (NGAL‐24). Similar analysis of C‐reactive protein (CRP) was performed for additional comparison.

Results

Mean age was 62 ± 13 years, 78% were men, and 20 (15%) developed AKI after admission. Patients with AKI after admission demonstrated higher levels of NGAL‐0 (164 vs. 95 ng/mL; p < 0.001) and NGAL‐24 (142 vs. 93 ng/mL; p < 0.001). Levels of NGAL‐0 and NGAL‐24 were similar within the AKI and non‐AKI groups. Using ROC curve analysis, NGAL‐0 had best predictive ability for AKI development (AUC 0.841, 95% CI 0.80–0.96), compared with NGAL‐24 (0.783, 95% CI 0.74–0.85), CRP‐0 (0.701, 95% CI 0.58–0.83), and CRP‐24 (0.781, 95% CI 0.66–0.90). The optimal NGAL‐0 cutoff for AKI prediction was 125 ng/mL, with 70% sensitivity, 84% specificity, and 94% negative predictive value.

Conclusions

Among STEMI patients, NGAL measurement upon admission are associated with AKI and may serve as a reliable marker for early AKI detection. Future studies may direct risk stratification using this single test can direct personalized evaluations during the admission, and focused interventions to prevent AKI.
Assessing the true prevalence of endometriosis: A narrative review of literature data
Authors: Harder Carolin , Velho Renata Voltolini , Brandes Iris , Sehouli Jalid , Mechsner Sylvia
Published: July 2024

Endometriosis is a gynecologic condition often described as the “chameleon of gynecology” because of its elusive symptoms. The World Health Organization acknowledges its severe impact on quality of life due to pain, fatigue, depression, and infertility. There is limited literature on the prevalence of endometriosis, knowledge of which is essential for effective prevention, treatment strategies, and funding. We aim to structure and present the published data on endometriosis prevalence, synthesizing the discrepancy between health insurance and clinical data. PubMed, Cochrane CENTRAL, and LIVIVO were researched for peer‐reviewed articles published between January 2000 and July 2023 on women of reproductive age. Health insurance companies argue that few women (~1%) are affected by endometriosis. Interestingly, the prevalence of clinical data studies (6.8%), population‐based surveys/self‐reported studies (6.6%), and symptomatic patient data (21%) revealed a different picture. Based on the data gathered, a multi‐layered prevalence model has been proposed to illustrate the large discrepancy in the prevalence numbers, leading to the disease being underestimated and underfunded. This variability may be influenced by the heterogeneity in designs and the analyzed data, and clinical complexity. In summary, this narrative review reveals that the prevalence of endometriosis is higher than health insurance and other stakeholders might have previously assumed.
The effect of opting‐in versus opting‐out forming on the rate of reported variants of questionable significance in prenatal microarray
Authors: Haddad‐Halloun Jumana , Wexler Ava , Echar Moran , Harari‐Shaham Amalia , Polager‐Modan Shirley , Zaatry Rawan , Maayouf Rasha , Assadi Maisa , Krivoruk Olga , Peleg Amir , Sagi‐Dain Lena
Published: July 2024

Objective

To examine the effect of patient‐selected opt‐in versus opt‐out option on the rate of reported variants of uncertain clinical significance (VOUS) and high‐frequency low‐penetrant (HFLP) findings in prenatal microarray testing.

Methods

A standard microarray consent form in Israel includes a requirement to note patient choice to be or not to be informed about the presence of VOUS and HFLP variants. The original form was designed as an opting‐out method, in which the women had to actively mark if they did not want to be informed about questionable findings. In the authors' Genetic Institute, the form was changed for an opting‐in option in October 2019. In this study we have compared the rates of reported VOUS and HFLP variants between the opt‐in and opt‐out periods.

Results

Of the 1014 prenatal CMA tests, 590 (58.2%) were performed in the opt‐out period. A significant decrease in the rate of women requesting to be informed of VOUS findings was noted (66.8% in opt‐out period vs 34.0% in opt‐in period), yielding a relative risk (RR) of 0.46 (95% confidence interval [CI] 0.39–0.53). Rate of women preferring to be informed of HFLP variants decreased from 75.3% to 48.1% (RR 0.52, 95% CI 0.45–0.60).

Discussion

We present a simple and effective method to decrease the rate of reported findings of questionable significance in the prenatal setting. These results are important not only for microarray results, but also for next‐generation sequencing techniques, such as whole exome or genome sequencing.
Approach to managing chronic vomiting in dogs
Authors: Rogers‐Smith Emma
Published: July 2024

Background: Chronic vomiting is a common and, at times, frustrating clinical presentation in our canine patients. Vomiting is considered ‘chronic’ in cases that have gone on for over three to four weeks and the clinical presentation in these cases can vary widely. Given that the list of potential differentials is extensive, a careful and methodical approach to these cases is paramount to successful management.

Aim of the article: This article considers an approach to achieving a diagnosis in the chronically vomiting patient, providing readers with the necessary diagnostic toolkit. It also discusses appropriate management strategies to consider in these cases.
CircCOL5A1 is involved in proliferation, invasion, and inhibition of ferroptosis of colorectal cancer cells via miR‐1287‐5p/SLC7A11
Authors: Wang Junwei , Zhang Zili , Zhuang Jianbin , Kang Di , Song Weiliang
Published: July 2024

Colorectal cancer (CRC) is the leading cause of cancer‐related death globally. Circular RNA circCOL5A1 plays an oncogene function in a variety of tumors. However, the function of circCOL5A1 in CRC is still unknown. Here, we aimed to elucidate the function and mechanism of circCOL5A1 in CRC. The correlation between circCOL5A1 and CRC clinicopathological was assessed through chi‐square. The relevance between circCOL5A1 and CRC patient survival time was evaluated by Kaplan–Meier analysis. The expressions of circCOL5A1 in CRC were determined via quantitative real‐time PCR. The function of circCOL5A1 in CRC was analyzed with Cell Counting Kit‐8, EdU assay, Transwell, detection of reactive oxygen species and Fe2+ levels, and Western blot analysis. Moreover, the mechanism of circCOL5A1 was determined by dual‐luciferase reporter assay, RNA immunoprecipitation, and RNA pull‐down. Finally, the role of circCOL5A1 in vivo was elucidated through a mouse xenograft model, hematoxylin–eosin staining, and immunohistochemistry. CircCOL5A1 expression was increased in CRC, and increased circCOL5A1 levels were related to TNM stage, lymph node metastasis, distant metastasis, and tumor differentiation in CRC patients, and CRC patients with high circCOL5A1 levels had a low overall survival rate. For the circCOL5A1 function in CRC, we found that circCOL5A1 knockdown weakened CRC cell proliferation and invasion, and enhanced cell ferroptosis. For the circCOL5A1 mechanism in CRC, we further confirmed that circCOL5A1 bound to miR‐1287‐5p, miR‐1287‐5p bound to SLC7A11. SLC7A11 was negatively interrelated to miR‐1287‐5p and was positively interrelated to circCOL5A1 in CRC tissues. Furthermore, interfering circCOL5A1 decreased SLC7A11 expression, and this trend was abolished through miR‐1287‐5p cotransfection. Rescue assays further demonstrated that circCOL5A1 knockdown alleviated CRC cell malignant phenotype via miR‐1287‐5p/SLC7A11. Moreover, interference with circCOL5A1 reduced CRC growth in vivo. CircCOL5A1 functioned as an oncogene in CRC via miR‐1287‐5p/SLC7A11.
Renal and multisystem effectiveness of 3.9 years of migalastat in a global real‐world cohort: Results from the followME Fabry Pathfinders registry
Authors: Hughes Derralynn A. , Sunder‐Plassmann Gere , Jovanovic Ana , Brand Eva , West Michael L. , Bichet Daniel G. , Pisani Antonio , Nowak Albina , Torra Roser , Khan Aneal , Azevedo Olga , Lehman Anna , Linhart Aleš , Rutecki Jasmine , Giuliano Joseph D. , Krusinska Eva , Nordbeck Peter
Published: July 2024

Fabry disease is a progressive, X‐linked lysosomal disorder caused by reduced or absent α‐galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat‐amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient‐focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry‐associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real‐world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was −0.9 (−10.8, 9.9) mL/min/1.73 m2/year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient‐years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real‐world Fabry population.
Investigating social communication in mice: A two‐intruders test approach
Authors: Morozova Maryana V. , Boldyreva Lidiya V. , Borisova Maria A. , Kozhevnikova Elena N.
Published: July 2024

Understanding the complex dynamics of social communication behaviors, such as exploration, communication, courtship, mating, and aggression in animal models, is crucial to reveal key neural and hormonal mechanisms underlying these behaviors. The two‐intruders test is designed to investigate residents' behavior toward both male and female intruders within the home cage of the test male. During this test imitating natural conditions, several aspects of social interaction were investigated: Exploration, courtship, mating, and aggressive behavior. As mating and aggression involve overlapping neural circuits, the behavioral setup testing both behaviors is best at reflecting their competitive nature. Our findings demonstrate that resident male mice exhibit strong preference to communicate with a female intruder, which correlates with baseline testosterone levels of test males. Relevant female preference in the two‐intruders test was also found in BALB/c males. Behavioral breakdown revealed the anogenital sniffing as a key behavioral feature that discriminates resident male behavior toward intruders of different sex. Furthermore, resident male interaction with female intruder was accompanied by neuronal activation in the ventromedial hypothalamus. We demonstrate that odor recognition underlies preference toward females in male residents, as experimental anosmia reduced communication with a female intruder. We conclude the two‐intruders test setup to be a useful tool to study the neurological basis of social communication in animal models, which provides detailed analysis of various aspects of the laboratory animals’ social behavior in the most natural conditions.
Factors Influencing the Visualization of Fallopian Tubes in Hysterosalpingo‐Contrast Sonography (HyCoSy)—The Value of Multimodal HyCoSy in Visualizing the Fallopian Tubes
Authors: Li Yan , Chen Xiaoyi , Wang Qin , Wang Jingping
Published: July 2024

Background

Four‐dimensional hysterosalpingo‐contrast sonography (4D‐HyCoSy) can non‐invasively evaluate the patency of the fallopian tubes and is increasingly used in clinical practice. However, some factors may lead to false‐positive diagnoses. This study aims to analyze the factors affecting clear imaging of the fallopian tubes in 4D‐HyCoSy and explore methods to improve the quality of fallopian tube imaging.

Methods

A total of 118 patients were enrolled in this retrospective study. After injecting the SonoVue into the uterine cavity, three modes of HyCoSy were completed in sequence: 4D‐HyCoSy, 2D‐HyCoSy, and second harmonic imaging (SHI). Participants were divided into two groups: the easy visualization group (fallopian tubes could be visualized using only 4D‐HyCoSy) and the difficult visualization group (a multimodal combination was required for visualization). The position of the uterus, the relationship between the ovaries and the uterus, endometrial thickness, time of catheterization in the uterine cavity, presence or absence of lesions in the uterine cavity, whether intestinal gas covers the fallopian tubes and the imaging effect of different modes on the fallopian tubes was analyzed, to determine the key factors affecting the clear imaging of the fallopian tubes.

Results

The positional relationship between the ovary and the uterus (OR = 4.711, 95% CI: 1.322–19.77, P = 0.023), the positioning of the uterus (OR = 3.843, 95% CI: 1.129–15.26, P = 0.04), endometrial thickness (OR = 3.985, 95% CI: 1.168–15.99, P = 0.036), and the duration of intrauterine catheter placement (OR = 3.547, 95% CI: 1.042–13.52, P = 0.05) were independent factors that affecting difficulty in visualizing the fallopian tubes.

Conclusion

Uterine position, the positional relationship between the ovary and the uterus, endometrial thickness, and the time of catheter insertion are factors that affect visualizing the fallopian tubes during 4D‐HyCoSy. The combination of multimodal imaging, especially the combination of 4D‐HyCoSy with SHI mode, can help improve the quality of fallopian tube visualization.
Sjögren syndrome from a dermatological perspective: A retrospective study of 185 SSA‐Ro positive patients
Authors: André Fiona , Bujak Martha , Frischhut Nina , Kronbichler Andreas , Sepp Norbert , Ratzinger Gudrun , Böckle Barbara
Published: July 2024

Background

Sjögren syndrome (SS) is a systemic autoimmune disease characterised by oral and ocular mucosal dryness.

Objectives

Our study focused on skin manifestations of SS. The differences between primary SS (pSS) and secondary SS (sSS) were investigated. Furthermore, we elucidated factors predicting internal organ involvement.

Methods

This was a single centre retrospective cohort study. We analysed clinical and laboratory data from 185 Ro‐SSA positive SS patients between January 2000 and December 2016.

Results

Skin manifestations were present in 74.9% (n = 137) of SS patients. Dermatitis and Lupus erythematosus (LE)‐specific skin manifestations were present in 34.1% (n = 63) and 21.6% (n = 40) of SS patients respectively. 65.9% (n = 122) of SS patients had internal organ involvement, with 53% (n = 98) presenting neuropsychiatric manifestations. Several risk factors for internal organ involvement were identified: presence of myalgia/arthralgia (odds ratio [OR] = 3.05, confidence interval [CI] 1.29−7.22), fatigue (OR = 2.53, CI 1.11−5.73) and age older than 50 years (OR = 2.23, CI 1.01−4.93).

Conclusions

Internal organ involvement is frequent in SS, however there is no significant difference between pSS and sSS concerning its occurrence.
Two pemphigoid cases with mucous membrane involvement successfully treated with baricitinib
Authors: Malkovics Tamás , Horváth Orsolya N. , Sárdy Miklós
Published: July 2024

Both bullous pemphigoid and mucous membrane pemphigoid are autoimmune bullous diseases that can be challenging to treat in individual cases. Janus kinase inhibitors have shown efficacy in several autoimmune and inflammatory diseases, although these drugs are not yet widely used in autoimmune bullous diseases. We report two recalcitrant cases of pemphigoid with mucous membrane involvement which were successfully treated with the JAK 1/2 inhibitor baricitinib after all other feasible therapeutic options had been exhausted.
Seafloor bioturbation intensity on the deep sea: More complex than organic matter
Authors: Miguez‐Salas Olmo , Saeedi Hanieh , Brandt Angelika , Riehl Torben
Published: July 2024

Deep‐sea benthic communities are strongly controlled by the quantity and quality of organic matter sinking from the ocean surface. The interaction between benthic fauna and seafloor sediments mainly occurs through bioturbation that modifies substrate properties (e.g., geochemical profiles). The intensity of the bioturbation has long been linked with organic matter and measured as a diffusive process by considering the vertical particle reworking (endobenthic bioturbation), disregarding the seafloor horizontal mixing (epibenthic bioturbation). Here, a novel approach to quantify horizontal mixing is presented: Seafloor Bioturbation Intensity (SBI). SBI calculations were based on seafloor image datasets from eight stations that reflected different environmental conditions in the north‐western Pacific (e.g., chlorophyll a, silicate). To calculate SBI, we characterized the area occupied by all different types of traces (i.e., lebensspuren) related to epibenthic bioturbation, trace makers, and their ingested sediment thickness. Our results showed a weak negative correlation between organic matter and SBI. This relationship contrast with the traditionally held view on vertical bioturbation intensity, where a dominant positive correlation is expected. It is demonstrated that lebensspuren morphotypes contributed differently to SBI. Not all morphotypes—and, by extension, their corresponding trace makers—are equally controlled by the same environmental factors. This investigation does not dismiss the importance of organic matter content, but emphasizes the importance of other environmental variables that need to be considered when determining the long‐term relation between epibenthic fauna and bioturbation intensity. Finally, we emphasize the importance of characterizing horizontal bioturbation for approaching global biogeochemical cycles and conservational strategies.
Observation of Polymerization‐Induced Phase Separation During Polymerization of Methyl Methacrylate in the Presence of Poly(Ethylene Glycol)
Authors: Onozato Shodai , Kojima Chie , Matsumoto Akikazu , Suzuki Yasuhito
Published: July 2024

Polymerization‐induced phase separation takes place when a miscible component of the monomer becomes immiscible as the polymer is formed. One example is the polymerization of methyl methacrylate (MMA) in the presence of poly(ethylene glycol) (PEG). Depending on the initial conditions, microscopic structures, including porous structures, co‐continuous monolith structures, and particle aggregation structures, are obtained. In this study, the phase separation process is analyzed using an optical microscope and fluorescence microscope. The nucleation or spinodal decomposition in the initial stage, subsequent growth in the microscopic domains, and eventual fixation of the structure are observed. The observed images are analyzed using image analysis software. The particle number and the particle size as a function of reaction time are evaluated. Conversion and molecular weight distribution as a function of reaction time are also analyzed.
Triiodothyronine (T3) suppresses hepatic tumorigenesis and development by inhibiting the phosphorylation of ERK
Authors: Dong Lili , Zhang Nan , Chen Jun , Dong Penghui , Mao Nan , Li Huiling , Wang Aiguo
Published: July 2024

The effect of triiodothyronine (T3) on the phosphorylation of ERK and the occurrence and development of hepatocellular carcinoma (HCC) is controversial and remains to be clarified. In the present study, both in vitro (hepatoma cell lines) and in vivo (wild‐type mice [WT] and mouse models of HCC [HrasG12Vand KrasG12Dtransgenic mice (Hras‐Tg and Kras‐Tg)]) systems were used to investigate the effect of T3 on p‐ERK and hepatocarcinogenesis. The results showed that, in vitro, T3 treatment elevated the levels of p‐ERK in hepatoma cells within 30 min. However, p‐ERK levels returned to normal after 1 h with no significant effects on cellular proliferation or apoptosis. Interestingly, in vivo, T3 induced early rapid and transient activation of ERK and later persistent downregulation of p‐ERK in liver tissues of WT. In Hras‐Tg, liver weight, liver/body weight ratio, hepatic tumor numbers and sizes were significantly reduced withT3treatment compared with the untreated group. Furthermore, the levels of albumin, HrasG12V, and p‐ERK in hepatic precancerous and tumor tissues were all significantly downregulated with T3 treatment; however, the levels of endogenous Hras were not affected. In WT, T3 also induced downregulation of Albumin in liver tissues, but without influence on the expression of endogenous Hras and p‐MEK. Especially, the inhibitory effect of T3 on p‐ERK and hepatic tumorigenesis and development without influence on the levels of KrasG12D and p‐MEK was further confirmed in Kras‐Tg. In conclusion, T3 suppresses hepatic tumorigenesis and development by independently and substantially inhibiting the phosphorylation of ERK in vivo.
Development of a genome atlas for discriminating benign, preinvasive, and invasive lung nodules
Authors: Liang Peng , Peng Minhua , Tao Jinsheng , Wang Bo , Wei Jinwang , Lin Lixuan , Cheng Bo , Xiong Shan , Li Jianfu , Li Caichen , Yu Ziwen , Li Chunyan , Wang Jun , Li Hui , Chen Zhiwei , Fan Jian‐Bing , Liang Wenhua , He Jianxing
Published: July 2024

To tackle misdiagnosis in lung cancer screening with low‐dose computed tomography (LDCT), we aimed to compile a genome atlas for differentiating benign, preinvasive, and invasive lung nodules and characterize their molecular pathogenesis. We collected 432 lung nodule tissue samples from Chinese patients, spanning benign, atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IA). We performed comprehensive sequencing, examining somatic variants, gene expressions, and methylation levels. Our findings uncovered EGFR and TP53 mutations as key drivers in ‐ early lung cancer development, with EGFR mutation frequency increasing with disease progression. Both EGFR mutations and EGF/EGFR hypo‐methylation activated the EGFR pathway, fueling cancer growth. Transcriptome analysis identified four lung nodule subtypes (G1‐4) with distinct molecular features and immune cell infiltrations: EGFR‐driven G1, EGFR/TP53 co‐mutation G2, inflamed G3, stem‐like G4. Estrogen/androgen response was associated with the EGFR pathway, proposing a new therapy combining tyrosine kinase inhibitors with antiestrogens. Preinvasive nodules exhibited stem cell pathway enrichment, potentially hindering invasion. Epigenetic regulation of various genes was essential for lung cancer initiation and development. This study provides insights into the molecular mechanism of neoplastic progression and identifies potential diagnostic biomarkers and therapeutic targets for lung cancer.