bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA‐582‐5p targeting Creb1 modulates apoptosis in cardiomyocytes hypoxia/reperfusion‐induced injury
Authors: Niu Rui‐Ze , Wang Lu‐Qiao , Yang Wei , Sun Li‐Zhong , Tao Jie , Sun Huang , Mei Song , Wang Wen‐Jie , Feng Ke‐Xiang , Qian Dian‐Lun , Bai Xiang‐Feng
Published: October 2022

Background

Myocardial ischemia–reperfusion injury (MIRI) caused by the reperfusion therapy of myocardial ischemic diseases is a kind of major disease that threatens human health and lives severely. There are lacking of effective therapeutic measures for MIRI. MicroRNAs (miRNAs) are abundant in mammalian species and play a critical role in the initiation, promotion, and progression of MIRI. However, the biological role and molecular mechanism of miRNAs in MIRI are not entirely clear.

Methods

We used bioinformatics analysis to uncover the significantly different miRNA by analyzing transcriptome sequencing data from myocardial tissue in the mouse MIRI model. Multiple miRNA‐related databases, including miRdb, PicTar, and TargetScan were used to forecast the downstream target genes of the differentially expressed miRNA. Then, the experimental models, including male C57BL/6J mice and HL‐1 cell line, were used for subsequent experiments including quantitative real‐time polymerase chain reaction analysis, western blot analysis, hematoxylin and eosin staining, flow cytometry, luciferase assay, gene interference, and overexpression.

Results

MiR‐582‐5p was found to be differentially upregulated from the transcriptome sequencing data. The elevated levels of miR‐582‐5p were verified in MIRI mice and hypoxia/reperfusion (H/R)‐induced HL‐1 cells. Functional experiments revealed that miR‐582‐5p promoted apoptosis of H/R‐induced HL‐1 cells via downregulating cAMP‐response element‐binding protein 1 (Creb1). The inhibiting action of miR‐582‐5p inhibitor on H/R‐induced apoptosis was partially reversed after Creb1 interference.

Conclusions

Collectively, the research findings reported that upregulation of miR‐582‐5p promoted H/R‐induced cardiomyocyte apoptosis by inhibiting Creb1. The potential diagnostic and therapeutic strategies targeting miR‐582‐5p and Creb1 could be beneficial for the MIRI treatment.
Association of asthma and herpes zoster, the role of vaccination: A literature review
Authors: Shrestha Abhigan Babu , Umar Tungki Pratama , Mohammed Yasmine Adel , Aryal Manjil , Shrestha Sajina , Sapkota Unnat Hamal , Adhikari Lukash , Shrestha Shumneva
Published: October 2022

Herpes Zoster (HZ) is the reactivation of a previous infection with varicella‐zoster virus (VZV) which shares the same mode of transmission as HZ. It presents with painful erythematous vesicles in a dermatome which is characterized by a burning sensation before and after the rash. Any conditions with suppressed cellular immunity example diabetes mellitus, chronic obstructive pulmonary disease, asthma, cardiovascular diseases, chronic steroid uses, malignancy, etc. causes reactivation of the virus. Impaired immune responses in asthma patients either in any age group may increase their susceptibility to HZ infection owing to skewed Th1/Th2 immunity, resulting in predominant Th2 conditions and an unwarranted Th2 cell response against respiratory allergens. Similarly, many studies have delineated the association of asthma with HZ. However, the relation between steroid use in asthma and HZ is uncertain, its immunosuppressive effect might be responsible for increased susceptibility to the infection. As HZ increases the economic burden and morbidity, its prevention should use vaccines. There are two types of Food and Drug Administration (FDA)‐approved vaccine available against HSV one of which is given as a single dose vaccine called Zostavax, for people 50–59 years but its efficacy falls after 3rd dose and on the subsequent 4th dose and is also contraindicated in human immunodeficiency virus/acquired immunodeficiency syndrome, pregnancy and people taking immunosuppressive drugs. Shingrix is preferred by FDA which is a two doses vaccine that is given 6 months apart for people above 50 years and to immunocompromised people. Hence, proper counseling and education about the risks of herpes should be informed to the patients with timely utilization of the vaccine.
Symptomatology, prognosis, and clinical findings of Monkeypox infected patients during COVID‐19 era: A systematic‐review
Authors: Jaiswal Vikash , Nain Priyanshu , Mukherjee Dattatreya , Joshi Amey , Savaliya Mittal , Ishak Angela , Batra Nitya , Maroo Dipansha , Verma Deepak
Published: October 2022

Background

The recent outbreak of Human Monkeypox (MPXV) in nonendemic regions of the world is of great concern.

Objective

We aimed to systematically analyze the current epidemiology, clinical presentation, and outcomes of the Monkeypox virus.

Method

Systematic literature was conducted in PubMed, Embase, Google Scholar, and Scopus using predefined MESH terms by using “AND” and “OR.” The following search terms were used: Monkeypox [MeSH] OR “Monkeypox virus” [MeSH] OR “POX” OR “Monkeypox” AND “Outbreak” AND “Outcomes” from December 2019 till 14th June 2022 without restrictions of language.

Results

A total of 1074 (99.90%) patients tested positive for Monkeypox virus through RT‐PCR while 1 (0.09) patient was suspected. There was a gender difference with male predominance (54.23% vs. 45.48%) compared with female patients. Mean age (±SD) of patients was 20.66 ± 16.45 years. The major symptoms were rash (100%), fever (96%), and other important symptoms were upper respiratory symptoms (97%), headache (95%), vomiting (95%), oral ulcers (96%), conjunctivitis (96%) and lymphadenopathy (85%). The average mean duration of treatment was 5 days, while the mean hospitalization duration was 13.3 ± 6.37 days. The outcome of 20 patients was available, 19 of 20 patients recovered fully from monkeypox, however, 1 patient was not able to survive resulting in death.

Conclusion

The recent monkeypox virus outbreak has shown that the virus could transmit in ways that were not previously expected. Further research is needed to understand the possible outcomes and association with humans and their different organ systems.
The role of imaging in infective endocarditis
Authors: Ivanovic Branislava , Popovic Jovana , Dukic Djordje , Petkovic Ana , Petrovic Olga
Published: October 2022

Infective endocarditis (IE) poses a large diagnostic and therapeutical challenge. An early diagnosis is necessary for a positive outcome. Echocardiography is initial diagnostic method when there is a possibility of IE presence. TTE and TEE are useful in detection, accurate localisation and estimation of vegetation size, and also in detection of paravalvular spreading of infection. In certain situations, there is a need for usage of complementary methods like CCT and nuclear techniques. This article will outline advantages and limitations of certain diagnostic methods in diagnosis of IE.
Comparative study on changes in Cd accumulation and ionome between rice and spinach: Impact of zinc ion activity
Authors: Wang Meie , Ma Wankai , Chaney Rufus L. , Green Carrie E. , Chen Weiping
Published: October 2022

Excessive Cd accumulation in rice grain has caused chronic Cd diseases in humans. In most crops, 100 times more Zn than Cd strongly inhibits Cd uptake and translocation. However, this response is not found for rice (Oryza sativa L.), which was found to have an unusual Cd uptake pattern compared with other crops, such as spinach (Spinacia oleracea L.). Moreover, studies on shared transporters between Zn and Cd using normal solution experiments with traditional high concentrations of metal ions may result in irrelevant interactions. Therefore, we developed ethyleneglycoltetraacetate‐buffered nutrient solutions in this work. Rice and spinach seedlings were grown under calibrated low Cd2+ activity and low to phytotoxic Zn2+ activity levels while buffering other micronutrient cations at sufficient levels. Results showed that as rice grew with pZn2+ = 8.1–5.4, root Cd and shoot Ni decreased significantly and gradually. However, shoot Cd and Mn in rice decreased slightly with the increase of solution Zn2+ from deficiency to sufficiency and then increased at toxic Zn2+ solution (pZn2+ = 5.4). The shoot/root ratios of Cd in rice under toxic pZn2+ (5.6 and 5.4 pZn2+ activity) were significantly increased (p < .05). It could be concluded that rice absorption of Cd is not inhibited by co‐contaminating (toxic) Zn. For spinach, with Zn varying from pZn2+ = 8.1–5.7, both shoot and root Cd substantially decreased, as did shoot Ni. This work revealed that, to understand food chain Cd risks, one needs to consider the inhibitory role of Zn in limiting Cd absorption in all crops studied except rice.
Attention‐based Deep Learning for the Preoperative Differentiation of Axillary Lymph Node Metastasis in Breast Cancer on DCE‐MRI
Authors: Gao Jing , Zhong Xin , Li Wenjuan , Li Qin , Shao Huafei , Wang Zhongyi , Dai Yi , Ma Heng , Shi Yinghong , Zhang Han , Duan Shaofeng , Zhang Kun , Yang Ping , Zhao Feng , Zhang Haicheng , Xie Haizhu , Mao Ning
Published: October 2022

Background

Previous studies have explored the potential on radiomics features of primary breast cancer tumor to identify axillary lymph node (ALN) metastasis. However, the value of deep learning (DL) to identify ALN metastasis remains unclear.

Purpose

To investigate the potential of the proposed attention‐based DL model for the preoperative differentiation of ALN metastasis in breast cancer on dynamic contrast‐enhanced MRI (DCE‐MRI).

Study Type

Retrospective.

Population

A total of 941 breast cancer patients who underwent DCE‐MRI before surgery were included in the training (742 patients), internal test (83 patients), and external test (116 patients) cohorts.

Field Strength/Sequence

A 3.0 TMRscanner,DCE‐MRIsequence.

Assessment

A DL model containing a 3D deep residual network (ResNet) architecture and a convolutional block attention module, named RCNet, was proposed for ALN metastasis identification. Three RCNet models were established based on the tumor, ALN, and combined tumor‐ALN regions on the images. The performance of these models was compared with ResNet models, radiomics models, the Memorial Sloan‐Kettering Cancer Center (MSKCC) model, and three radiologists (W.L., H.S., and F. L.).

Statistical Tests

Dice similarity coefficient for breast tumor and ALN segmentation. Accuracy, sensitivity, specificity, intercorrelation and intracorrelation coefficients, area under the curve (AUC), and Delong test for ALN classification.

Results

The optimal RCNet model, that is, RCNet−tumor+ALN, achieved an AUC of 0.907, an accuracy of 0.831, a sensitivity of 0.824, and a specificity of 0.837 in the internal test cohort, as well as an AUC of 0.852, an accuracy of 0.828, a sensitivity of 0.792, and a specificity of 0.853 in the external test cohort. Additionally, with the assistance of RCNet−tumor+ALN, the radiologists' performance was improved (external test cohort,P < 0.05).

Data Conclusion

DCE‐MRI‐based RCNet model could provide a noninvasive auxiliary tool to identify ALN metastasis preoperatively in breast cancer, which may assist radiologists in conducting more accurate evaluation of ALN status.

Evidence Level

3

Technical Efficacy

Stage 2
Multiparametric Magnetic Resonance Imaging of the Kidneys: Effects of Regional, Side, and Hydration Variations on Functional Quantifications
Authors: Chen Jie , Zhang Zhen , Liu Juan , Li Chengjie , Yin Meng , Nie Lisha , Song Bin
Published: October 2022

Background

To standardize renal functional magnetic resonance imaging (MRI), it is important to understand the influence of side‐to‐side variation, regional variation within the organ, and hydration states in MRI and to search for variables that are not affected by those variations.

Purpose

To assess MRI‐based biomarkers for characterizing the kidney in healthy volunteers while considering variations in anatomic factors and hydration states.

Study Type

Prospective.

Subjects

Twenty‐five healthy volunteers (15 females and 10 males, median age 25 years).

Field Strength/Sequence

3.0 T intravoxel incoherent motion diffusion‐weighted imaging, arterial spinning labeling imaging, blood oxygenation level dependent imaging, and three‐dimensional MR elastography.

Assessment

Functional variables were measured before and after water challenge. Regions of interest were manually drawn by two investigators (JC and ZZ, with 8‐ and 5‐year experiences in abdominal radiology) in the cortex, the medulla, and the entire kidney. The medulla/cortex ratio was calculated.

Statistical Tests

Paired t‐test or Wilcoxon signed rank test; interobserver correlation coefficient; repeatability coefficients; Spearman's correlation; significance level: P < 0.05.

Results

Diffusion parameters were only subject to regional variation. R2*, RBF, and renal stiffness (RS) showed regional variation, side variation, and dependence on hydration states. For each side and hydration state, the cortex showed significantly higher standard apparent diffusion coefficient (sADC), higher true diffusion (D), lower R2*, and lower RS than the medulla. For each region at baseline, the left kidney showed significantly higher R2*, higher RS, and lower renal blood flow (RBF) than the right kidney. For each region and side, RS and RBF increased significantly while R2* decreased significantly after water intake. After introducing the intrinsic regional difference, significantly higher medulla/cortex ratio of RS remained after water intake except for RS@90 Hz in the right kidney.

Data Conclusion

Renal multiparametric MRI quantifications were affected by regional variation, side variation, and hydration states.

Level of Evidence

2

Technical Efficacy

Stage 1
Sinonasal IgG4‐related sclerosing disease: A rare entity and challenging diagnosis
Authors: Hess Andrew O. , Lobo Brian C. , Leon Marino E. , Duarte Ernesto M. , Mulligan Jennifer K. , Justice Jeb M.
Published: October 2022

Objectives

To describe the rare presentation, imaging and histological findings, and treatments in patients with IgG4‐related disease (IgG4‐RD) and diagnostic pitfalls and difficulties.

Methods

Cases of sinonasal IgG4‐RD were retrieved, and clinicopathological features were reviewed.

Results

Seven cases of sinonasal IgG4‐RD were identified over an 11‐year period, including four males and three females, with an age range of 19–66 years (median 58 years). Patients presented with symptoms related to the mass effect of the lesions or the destructive nature of the disease including fullness, swelling, obstruction, and pain. Serum IgG and IgG4 levels, IgG/IgG4 ratios, storiform fibrosis, obliterative phlebitis, and plasma cell infiltration were seen in varying proportions. Bony erosion and tissue inflammation were present in some cases.

Conclusion

Sinonasal IgG4‐RD is exceedingly rare among other IgG4‐RD and varied in its clinical presentation thus posing as a clinically difficult disease to diagnosis. Proper clinical, pathological, and immunohistopathological analysis is required for accurate diagnosis. Such disease should be considered in all cases of similar presentation to those in this study.

Level of Evidence: 4.
Ultra‐Broadband Photoluminescent Carbon Dots Synthesized by Laser‐Induced Thermal Shock
Authors: Sinelnik Artem D. , Rybin Mikhail V. , Gets Dmitry S. , Khubezhov Soslan A. , Zelenkov Lev E. , Makarov Sergey V. , Shishkin Ivan I.
Published: October 2022

Carbon dots (CDs) emerge as a novel type of fluorescent materials with a good photostability, biocompatibility, and high quantum yield. They become a promising alternative to conventional fluorescent materials such as rare‐earth phosphors and semiconductor quantum dots owing to their ease of synthesis and fabrication from ready‐available compounds. Near‐infrared (NIR) CDs are of high demand for in vivo studies owing to little photoinduced damage to surrounding tissues, deep penetration of radiation into tissue, and low autofluorescence. A laser‐assisted synthesis approach is demonstrated, which allows NIR‐emitting CDs to be obtained. By rapidly heating the precursors (4,4’‐bis(diethylamino)benzophenone in sol–gel matrix) with femtosecond pulses, NIR emitting CDs can be obtained with the emission in the ranges of 800–1000 and 1100–1600 nm of the resulting CDs.
Women directors and firm innovation: The role of women directors' representative function
Authors: Joecks Jasmin , Pull Kerstin , Scharfenkamp Katrin
Published: October 2022

We argue that the link between women directors in co‐determined supervisory boards and firm innovation depends on two contextual factors: (1) Women directors' power, as measured by their share among shareholder representatives, and (2) on whether women are represented in both representative functions, that is, shareholder and employee representatives. In our empirical analysis based on German panel data, we find the positive link between women directors and firm innovation to be driven by women shareholder representatives, and we find the joint presence of women among shareholder and employee representatives to be positively linked to firm innovation.
Tensor denoising of multidimensional MRI data
Authors: Olesen Jonas L. , Ianus Andrada , Østergaard Leif , Shemesh Noam , Jespersen Sune N.
Published: October 2022

Purpose

To develop a denoising strategy leveraging redundancy in high‐dimensional data.

Theory and Methods

The SNR fundamentally limits the information accessible by MRI. This limitation has been addressed by a host of denoising techniques, recently including the so‐called MPPCA: principal component analysis of the signal followed by automated rank estimation, exploiting the Marchenko‐Pastur distribution of noise singular values. Operating on matrices comprised of data patches, this popular approach objectively identifies noise components and, ideally, allows noise to be removed without introducing artifacts such as image blurring, or nonlocal averaging. The MPPCA rank estimation, however, relies on a large number of noise singular values relative to the number of signal components to avoid such ill effects. This condition is unlikely to be met when data patches and therefore matrices are small, for example due to spatially varying noise. Here, we introduce tensor MPPCA (tMPPCA) for the purpose of denoising multidimensional data, such as from multicontrast acquisitions. Rather than combining dimensions in matrices, tMPPCA uses each dimension of the multidimensional data's inherent tensor‐structure to better characterize noise, and to recursively estimate signal components.

Results

Relative to matrix‐based MPPCA, tMPPCA requires no additional assumptions, and comparing the two in a numerical phantom and a multi‐TE diffusion MRI data set, tMPPCA dramatically improves denoising performance. This is particularly true for small data patches, suggesting that tMPPCA can be especially beneficial in such cases.

Conclusions

The MPPCA denoising technique can be extended to high‐dimensional data with improved performance for smaller patch sizes.
Core concepts in pharmacoepidemiology: Key biases arising in pharmacoepidemiologic studies
Authors: Acton Emily K. , Willis Allison W. , Hennessy Sean
Published: October 2022

Pharmacoepidemiology has an increasingly important role in informing and improving clinical practice, drug regulation, and health policy. Therefore, unrecognized biases in pharmacoepidemiologic studies can have major implications when study findings are translated to the real world. We propose a simple taxonomy for researchers to use as a starting point when thinking through some of the most pervasive biases in pharmacoepidemiology. We organize this discussion according to biases best assessed with respect to the study population (including confounding by indication, channeling bias, healthy user bias, and protopathic bias), the study design (including prevalent user bias and immortal time bias), and the data source (including misclassification bias and missing data/loss to follow up). This tutorial defines, provides a curated list of recommended references, and illustrates through relevant case examples these key biases to consider when planning, conducting, or evaluating pharmacoepidemiologic studies.
Weather patterns in Southeast Asia: Enhancing high‐impact weather subseasonal forecast skill
Authors: Gonzalez Paula L. M. , Howard Emma , Ferrett Samantha , Frame Thomas H. A. , Martínez‐Alvarado Oscar , Methven John , Woolnough Steven J.
Published: October 2022

While skilful forecasts of heavy rainfall are highly desirable for weather warnings and mitigating impacts, forecasting such events is notoriously difficult, even with the most advanced numerical weather prediction models, due to the strong dependence on convective‐scale processes. The large‐scale circulation, on the other hand, is typically more predictable. Weather patterns (WPs) are a set of circulation types obtained statistically that can be used to characterize regional weather and harness the predictability of the large‐scale circulation. In this work we produce pattern‐conditioned probabilistic rainfall forecasts by projecting the horizontal winds from the Met Office GloSea5 prediction system on to WPs and then using the observed relationship between each WP and rainfall estimated by satellite. The WPs are derived following a novel two‐tier clustering technique: the WPs in the first tier represent planetary‐scale variability, such as El Niño–Southern Oscillation (ENSO), while the WPs in the second tier capture synoptic‐scale variability. We investigate WP predictability as well as the improvement in skill of subseasonal rainfall forecasts gained by this technique. GloSea5 predicts the WP occurrence with skill extending beyond lead day 10. The pattern‐conditioned rainfall forecasts were evaluated against climatological forecasts and model‐simulated rainfall hindcasts. We show that the pattern‐conditioned forecasts are skilful and outperform the model‐simulated rainfall hindcasts for lead times extending to days 10–20, depending on the specific exceedance criteria and region. Spatial aggregation leads to increased levels of skill, but not to a significant extension of the skilful prediction horizon. These results constitute a fundamental step for the development of subseasonal prediction systems for Southeast Asia.
A two‐fluid single‐column model of turbulent shallow convection. Part III: Results and parameter sensitivity
Authors: McIntyre William A. , Efstathiou Georgios A. , Thuburn John
Published: October 2022

Two‐fluid modelling has recently emerged as a promising approach to representing cumulus convection in weather and climate models. This study applies the two‐fluid model described in Part II to a shallow cumulus convection case study over land (ARM). Large‐eddy simulation data are used to tune the majority of the closures that determine the properties of entrained and detrained air. The two‐fluid model is generally able to reproduce the profiles of the mean and turbulent quantities over all stages of the diurnal cycle. As such, the initiation of shallow convection and the evolution of the cloud layer are well captured. The robustness of the two‐fluid model is verified further using a steady‐state test case (BOMEX), in which the cloud properties are also well modelled.
Fe3O4 ‐PTh‐SO3H: A Retrievable Solid‐acid Nanocatalyst for the Green Synthesis of Imidazole and Tetrazole Derivatives
Authors: Karegar Mohsen , Khodaei Mohammad Mehdi
Published: October 2022

In the present study, the immobilization of sulfonic acid on polythiophene (PTh)‐layered magnetite was carried out through the reaction of ClSO3H with Fe3O4‐PTh. The obtained catalyst, Fe3O4‐PTh‐SO3H, as the reusable and novel magnetic heterogeneous nanocatalyst, was used for green synthesis of 2,4,5‐trisubstituted‐1H‐imidazoles, and 2‐(1H‐tetrazole‐5‐yl) acrylonitriles. The catalyst structure was characterized by various techniques, including FT‐IR, XRD, SEM, EDX, TEM, VSM, ICP‐OES, and CHNS techniques. These analyses proved the sulfonic group's successful attachment on the outer surface of the nanocatalyst. A high number of the acidic groups on the surface of the PTh layer are conducted to the more active catalyst, and as a result, the yield of the target product increases. The sustainability of the methodology was examined by evaluating the stability and reusability of the catalyst using an external magnet. The results showed that the Fe3O4‐PTh‐SO3H catalyst could be reused for five successive runs without a significant loss in catalytic efficiency. The reactions were carried out under relatively mild conditions in ethanol to achieve imidazole and tetrazole derivatives in high to excellent yields.
Molecular Basis for the Difference in Singlet Oxygen Quantum Yield Between the First Genetically Encoded Photosensitizer, KillerRed, and its Monomeric Counterpart, SuperNova
Authors: Lee Wook
Published: October 2022

The application of protein‐based photosensitizers in diverse fields has been proposed due to their characteristic to generate reactive oxygen species (ROS) upon light irradiation. However, the first of its kind, KillerRed, has a limitation in its use because of its dimeric nature, so its monomeric counterpart, SuperNova, was developed subsequently to overcome this limitation. What is very intriguing is that, although KillerRed and SuperNova share highly similar structural and optical properties, the singlet oxygen quantum yield of SuperNova is shown to be almost three times larger than that of KillerRed, but the mechanistic details for this difference have not been addressed yet. In the present work, a hybrid quantum mechanics / molecular mechanics (QM/MM) approach with time dependent density functional theory (TDDFT) is employed to examine this issue. Excited state energy surfaces leading to intersystem crossing (ISC) for both KillerRed and SuperNova are explored, and the comparison of those results and additional electrostatic potential (ESP) calculations reveal that the lower singlet oxygen quantum yield of KillerRed is attributed to a high energy 3nπ* minimum due to a hydrogen bond between the chromophore and neighboring Asn145.
A Convenient Iodine‐Promoted Synthesis of α‐Ketothioesters
Authors: Zhao Zhengzheng , Gao Pan , Meng Lei , Wu Qingyi , Yuan Yu
Published: October 2022

An effective and practical synthesis of α‐ketothioesters has been reported for direct oxidative thioesterification of substitutional acetophenones with dimethyl sulfoxide and iodine in the presence of boric acid and acetic anhydride in high yields. According to the control experiments and literatures, the reaction mechanism was proposed to undergo via Pummerer rearrangement.
Synthesis of Unsymmetrical 1,1’‐Bibenzimidazoles via an N‐Amination Reaction Forming the Key N‐N Bond
Authors: Toman Daniel , Cankař Petr
Published: October 2022

The novel synthesis of unsymmetrical 1,1’‐bibenzimidazoles is described. The key N−N bond was introduced on 1H‐benzimidazole or 1H‐benzimidazole‐2‐sulfonic acid by N‐amination with hydroxylamine‐O‐sulfonic acid (HASA). The precursors, 1‐[(2‐nitrophenyl)amino]‐1H‐benzimidazoles, were prepared by nucleophilic aromatic substitution of 1‐fluoro‐2‐nitrobenzene with 1H‐benzimidazole‐1‐amines. The synthesis was demonstrated on 11 novel 1,1’‐bibenzimidazoles, which were prepared in the final step by one‐pot reduction/cyclization with DMF or DMA acetals under mild acidic conditions in good overall yields.
The Mechanism for Anticancer and Apoptosis‐Inducing Properties of Cu(II) Complex with Quercetin and 1,10‐Phenanthroline
Authors: Done Gulseven , Ari Ferda , Akgun Oguzhan , Akgun Halime , Cevatemre Buse , Gençkal Hasene Mutlu
Published: October 2022

This article covers the anticancer activities and mechanisms of action of Cu(II) complexes of flavonoid‐derived quercetin and 1,10‐phenanthroline ligands. The antiproliferative activity of the complex and its ligands was evaluated by MTT, ATP, and SRB viability assays in human lung cancer cells (A549, H1299). Findings for apoptosis were determined by fluorescent staining, flow cytometry analysis, and the M30 antigen method. In addition, the mechanism of action of the complex was investigated by Annexin V staining, caspase 3/7 activity, ROS formation, and cell cycle analysis. The involvement of caspases, thus, apoptosis was confirmed by rescuing cell death by using a pan‐caspase inhibitor (Z‐VAD‐FMK). Again, increased ROS levels in the cell showed that death may occur by apoptosis. For this reason, the accuracy of ROS‐induced apoptosis in cells has been proven as a result of the application of N‐acetylcysteine (NAC), which is a ROS inhibitor. The efficacy of the complex was compared with Cisplatin and ligands. The results showed that the Cu(II) flavonoid complex is cytotoxic on lung cancer cells and may have the potential to act as an effective metal‐based anticancer drug with a lower IC50 over Cisplatin.
One‐Pot Synthesis of 3‐Amino‐1,2,4‐triazoles Using Choline Chloride‐Urea and Their Antibacterial Activities
Authors: Arab Mostafa , Beyzaei Hamid , Aryan Reza
Published: October 2022

In this study, a new one‐pot method was proposed for the synthesis of novel and known 3‐amino‐1,2,4‐triazole derivatives in choline chloride/urea (1 : 2) as a biodegradable, nontoxic, biorenewable and inexpensive solvent and reagent. It efficiently catalyzed the reaction between alkyl/aryl hydrazides with urea. Some of the advantages of the proposed method are: eco‐friendly and low‐cost procedure, easy work‐up and purification, good to excellent product yields and acceptable reaction times. This method can be a model for Pellizzari‐type reactions. Antimicrobial activity of the synthesized 1,2,4‐triazoles were evaluated against five Gram‐positive and three Gram‐negative pathogenic bacteriaviaKirby‐Bauer disk diffusion method. Triazoles containing 3‐bromophenyl and 4‐(tert‐butyl)phenyl substituents were the most effective antibacterial agents against all tested bacterial strains.
Enhanced Crystallinity of Covalent Organic Frameworks Formed Under Physical Confinement by Exfoliated Graphene
Authors: Roys Joshua S. , O'Brien Jennifer M. , Stucchi Nicholas D. , Raj Gaurav , Hill Adam D. , Ye Jingyun , Brown Ryan D.
Published: October 2022

The polymerization of 1,4‐benzenediboronic acid (BDBA) on mica to form a covalent organic framework (COF‐1) reveals a dramatic increase in crystallinity when physically confined by exfoliated graphene. COF‐1 domains formed under graphene confinement are highly geometric in shape and on the order of square micrometers in size, while outside of the exfoliated flakes, the COF‐1 does not exhibit long‐range mesoscale structural order, according to atomic force microscopy imaging. Micro‐Fourier transform infrared spectroscopy confirms the presence of COF‐1 both outside and underneath the exfoliated graphene flakes, and density functional theory calculations predict that higher mobility and self‐assembly are not causes of this higher degree of crystallinity for the confined COF‐1 domains. The most likely origin of the confined COF‐1's substantial increase in crystallinity is from enhanced dynamic covalent crystallization due to the water confined beneath the graphene flake.
Surveilling the Surveillants: From Relational Surveillance to WikiLeaks
Authors: Borghini Andrea , Scalia Vincenzo , Tafani Daniela
Published: October 2022

This chapter deals with the analysis of Julian Assange as a public figure through the use of three perspective angles. In the first part, Assange’ history is briefly outlined, tracing it back to the systems of thought of authors such as Norbert Elias and Pierre Bourdieu, with the aim of highlighting how the Australian journalist’s biography helps to illuminate his (and our) historical time and, vice versa, how historical time helps to depict his biography and his courageous journalistic campaigns more precisely. The second part shows how the apparently subversive aspects of Assange’s activity in fact need to be analysed within the web of social control and the subsequent fight between rulers and outsiders. The criminalisation of Julian Assange is, by this token, a consequence of the reaction enacted by power against militant practice aimed at claiming an alternative use of the web. The third paragraph examines three basic principles of Enlightenment which are apparent in the WikiLeaks approach and explicitly recalled by Assange: the connection between the duty to improve knowledge and the right to communicate, publicity as a test to reveal injustice and the understanding of freedom of the press as an antitotalitarian device.
Traces of Social Binding: Interpretive Tracing as a Bridging Concept
Authors: Grenz Tilo , Robinson Keith
Published: October 2022

This chapter continues the recent debate on the epistemological dimension of traces and tracing. Following our own preliminary work and in confrontation with an explicitly non-Western epistemology—namely, the case of “First Australians”—the chapter proposes the perspective of interpretive tracing. It calls for the systematic reflection of practices and underlying epistemologies of traces as objects of interpretation in a cross-cultural, i.e., cosmopolitan, perspective. It is a perspective that is sensitive to the tacit assumptions of objectivity and linear inferencing that underlie many Western approaches. Further, it is an open perspective that is sensitive to various embedded notions of time and temporality (not just time as a linear approach to the world) in particular. Furthermore, this perspective we advocate can eventually show that trace and tracing entail different social, cultural, and societal notions of social binding.
What Do Museum Visitors Leave Behind? The New Experience and the New Visitor in the Twenty-First Century
Authors: Rosso Aluminé A.
Published: October 2022

Visits to museums in the twenty-first century do not merely involve coming in contact with art but also living an interactive and relational experience that has changed the organization of museums, not only the exhibition rooms but also other museum spaces: boutiques, cafés, restaurants, and public areas. This new type of visit implies the role of an original agent: the frontalier visitor who, by inhabiting spaces adjacent to exhibition rooms, expands and reinforces the museum’s boundaries and the museum experience itself. This work is focused on visitors’ footprints as material and virtual marks and aims at showing the results of a field analysis carried out from 2017 to 2019 addressing the architecture of modern art museums. Fourteen museums have been analyzed, and four of them have been selected as the main objects of analysis: Malba, Moma, Tate Modern, and Centre Pompidou. We have studied their façades, esplanades, and entrance halls as spaces advancing what the public will experience inside the buildings. This analysis considers these adjacent spaces essential for the pass-through from the material experience to the virtual experience and from material footprints to virtual ones.
Geschichte und Zustand der sozialwissenschaftlichen Polizeiforschung
Authors: Weißmann Martin
Published: October 2022

Die doppelgleisige öffentliche Beobachtung von Polizeiarbeit in Hinblick auf ihre Rechtmäßigkeit einerseits, ihre Effektivität andererseits sowie die daraus folgende polizeiinterne Spannung zwischen Regeltreue und Erfolg sind ein zentrales Thema der Soziologie der Polizei, zu der dieses Buch beitragen will. In dieser Einleitung werden zunächst die zentralen Episoden der deutschsprachigen Polizeiforschung rekonstruiert (1.1), daran anschließend wird an die in dieser Forschung kaum rezipierten Einsichten und Perspektiven der englischsprachigen Polizeisoziologie der 1960er und 1970er Jahre erinnert (1.2). Abschließend wird die Diagnose einer institutionellen Isolation und disziplinären Heimatlosigkeit der zeitgenössischen Polizeiforschung begründet (1.3) und die Absicht der Arbeit formuliert, einen Brückenschlag zwischen der ansonsten oft empiristischen Polizeiforschung und den stärker theorieorientierten Bereichen soziologischer Forschung zu leisten.
Charged dark matter in supersymmetric twin Higgs models
Authors: Badziak Marcin , Grilli di Cortona Giovanni , Harigaya Keisuke , Łukawski Michał
Published: October 2022

Abstract

Supersymmetric Twin Higgs models ameliorate the fine-tuning of the electroweak scale originating from the heavy scalar top partners required by the non-discovery of them at the Large Hadron Collider. If the Lightest Supersymmetric Particle resides in the twin sector, it may play the role of dark matter even if it is charged under twin gauge interactions. We show that the twin stau is a viable candidate for charged dark matter, even if the twin electromagnetic gauge symmetry is unbroken, with thermal relic abundance that naturally matches the observed dark matter abundance. A wide parameter space satisfies all the experimental constraints including those on dark matter self-interactions. Twin stau dark matter can be observed in future direct detection experiments such as LUX-ZEPLIN. The stau has a mass in the range of 300–500 GeV, and in the minimal scenario, has a decay length long enough to be observed as a disappearing track or a long-lived particle at the Large Hadron Collider.
Towards the construction of multi-centered black holes in AdS
Authors: Cai Yide , Liu James T.
Published: October 2022

Abstract

We find a class of approximate perturbative solutions describing multi-centered BPS black holes in asymptotically AdS4. These black holes are moving coplanarly in a circular orbit with common radius but fixed phase differences, where the radius is characterized by a common boost velocity v. While the solutions are not complete, as they are only accurate up to $$ \mathcal{O} $$
O
(M2v2), we are able to locally investigate their supersymmetric properties in four-dimensional $$ \mathcal{N} $$
N
= 2 supergravity. The result indicates that, while a single BPS black hole preserves half of the supersymmetries, a configuration with two or more black holes is only 1/4 BPS. These perturbative solutions reduce in the asymptotically Minkowski limit to the multi-black hole solution of Majumdar and Papapetrou.
Multi-instantons in minimal string theory and in matrix integrals
Authors: Eniceicu Dan Stefan , Mahajan Raghu , Murdia Chitraang , Sen Ashoke
Published: October 2022

Abstract

We compute the normalization of the general multi-instanton contribution to the partition function of (p′, p) minimal string theory and also to the dual two-matrix integral. We find perfect agreement between the two results.
Integrin alpha9 emerges as a key therapeutic target to reduce metastasis in rhabdomyosarcoma and neuroblastoma
Authors: Navarro Natalia , Molist Carla , Sansa-Girona Júlia , Zarzosa Patricia , Gallo-Oller Gabriel , Pons Guillem , Magdaleno Ainara , Guillén Gabriela , Hladun Raquel , Garrido Marta , Segura Miguel F. , Hontecillas-Prieto Lourdes , de Álava Enrique , Ponsati Berta , Fernández-Carneado Jimena , Almazán-Moga Ana , Vallès-Miret Mariona , Farrera-Sinfreu Josep , de Toledo Josep Sánchez , Moreno Lucas , Gallego Soledad , Roma Josep
Published: October 2022

The majority of current cancer therapies are aimed at reducing tumour growth, but there is lack of viable pharmacological options to reduce the formation of metastasis. This is a paradox, since more than 90% of cancer deaths are attributable to metastatic progression. Integrin alpha9 (ITGA9) has been previously described as playing an essential role in metastasis; however, little is known about the mechanism that links this protein to this process, being one of the less studied integrins. We have now deciphered the importance of ITGA9 in metastasis and provide evidence demonstrating its essentiality for metastatic dissemination in rhabdomyosarcoma and neuroblastoma. However, the most translational advance of this study is to reveal, for the first time, the possibility of reducing metastasis by pharmacological inhibition of ITGA9 with a synthetic peptide simulating a key interaction domain of ADAM proteins, in experimental metastasis models, not only in childhood cancers but also in a breast cancer model.
The left–right side-specific endocrine signaling in the effects of brain lesions: questioning of the neurological dogma
Authors: Bakalkin Georgy
Published: October 2022

Each cerebral hemisphere is functionally connected to the contralateral side of the body through the decussating neural tracts. The crossed neural pathways set a basis for contralateral effects of brain injury such hemiparesis and hemiplegia as it has been already noted by Hippocrates. Recent studies demonstrated that, in addition to neural mechanisms, the contralateral effects of brain lesions are mediated through the humoral pathway by neurohormones that produce either the left or right side-specific effects. The side-specific humoral signaling defines whether the left or right limbs are affected after a unilateral brain injury. The hormonal signals are released by the pituitary gland and may operate through their receptors that are lateralized in the spinal cord and involved in the side-specific control of symmetric neurocircuits innervating the left and right limbs. Identification of features and a proportion of neurological deficits transmitted by neurohormonal signals vs. those mediated by neural pathways is essential for better understanding of mechanisms of brain trauma and stroke and development of new therapies. In a biological context, the left–right side-specific neuroendocrine signaling may be fundamental for the control of the left- and right-sided processes in bilaterally symmetric animals.
The contribution of functional HNF1A variants and polygenic susceptibility to risk of type 2 diabetes in ancestrally diverse populations
Authors: Stalbow Lauren A. , Preuss Michael H. , Smit Roelof A. J. , Chami Nathalie , Bjørkhaug Lise , Aukrust Ingvild , Gloyn Anna L. , Loos Ruth J. F.
Published: October 2022

Aims/hypothesis

We examined the contribution of rare HNF1A variants to type 2 diabetes risk and age of diagnosis, and the extent to which their impact is affected by overall genetic susceptibility, across three ancestry groups.

Methods

Using exome sequencing data of 160,615 individuals of the UK Biobank and 18,797 individuals of the BioMe Biobank, we identified 746 carriers of rare functional HNF1A variants (minor allele frequency ≤1%), of which 507 carry variants in the functional domains. We calculated polygenic risk scores (PRSs) based on genome-wide association study summary statistics for type 2 diabetes, and examined the association of HNF1A variants and PRS with risk of type 2 diabetes and age of diagnosis. We also tested whether the PRS affects the association between HNF1A variants and type 2 diabetes risk by including an interaction term.

Results

Rare HNF1A variants that are predicted to impair protein function are associated with increased risk of type 2 diabetes in individuals of European ancestry (OR 1.46, p=0.049), particularly when the variants are located in the functional domains (OR 1.89, p=0.002). No association was observed for individuals of African ancestry (OR 1.10, p=0.60) or Hispanic-Latino ancestry (OR 1.00, p=1.00). Rare functional HNF1A variants were associated with an earlier age at diagnosis in the Hispanic-Latino population (β=−5.0 years, p=0.03), and this association was marginally more pronounced for variants in the functional domains (β=−5.59 years, p=0.03). No associations were observed for other ancestries (African ancestry β=−2.7 years, p=0.13; European ancestry β=−3.5 years, p=0.20). A higher PRS was associated with increased odds of type 2 diabetes in all ancestries (OR 1.61–2.11, p<10−5) and an earlier age at diagnosis in individuals of African ancestry (β=−1.4 years, p=3.7 × 10−6) and Hispanic-Latino ancestry (β=−2.4 years, p<2 × 10−16). Furthermore, a higher PRS exacerbated the effect of the functional HNF1A variants on type 2 diabetes in the European ancestry population (pinteraction=0.037).

Conclusions/interpretation

We show that rare functional HNF1A variants, in particular those located in the functional domains, increase the risk of type 2 diabetes, at least among individuals of European ancestry. Their effect is even more pronounced in individuals with a high polygenic susceptibility. Our analyses highlight the importance of the location of functional variants within a gene and an individual’s overall polygenic susceptibility, and emphasise the need for more genetic data in non-European populations.

Graphical abstract
Outcomes of Local Excision Compared to Radical Excision of Rectal Gastrointestinal Stromal Tumors: A Propensity‐Score Matched Analysis of the NCDB
Authors: Emile Sameh Hany , Horesh Nir , Freund Michael R. , Garoufalia Zoe , Gefen Rachel , Silva‐Alvarenga Emanuela , Wexner Steven D.
Published: October 2022

Background

Gastrointestinal stromal tumors (GISTs) account for <1% of gastrointestinal cancers. The present study aimed to assess the outcomes of local and radical excision of non‐metastatic rectal GISTs.

Methods

This study was a retrospective cohort analysis of patients with non‐metastatic rectal GISTs in the NCDB. Patients were divided according to the surgical approach into local and radical excision and were compared in regard to the baseline characteristics and outcomes. A propensity‐score matched analysis was performed to match the two groups for baseline confounders. The main outcomes were 5‐year overall survival (OS), surgical margins, hospital stay, short‐term mortality, and readmission.

Results

228 patients (54.8% male) with rectal GISTs were included. Before matching, 127 (55.7%) patients underwent local excision and 101 (44.3%) had radical excision. Patients who underwent local excision had more cT1‐T2 and low‐grade GISTs whereas patients who had radical excision received more neoadjuvant systemic treatment. After matching for clinical T stage, tumor grade, and neoadjuvant systemic therapy, 52 patients were included in each group. Local excision had a significantly higher rate of positive resection margins (42.2% vs. 19.1%, p = 0.02) and a shorter hospital stay (0 vs. 3 days, p < 0.001) than radical excision. The two groups had similar mean OS (139.8 vs. 133.1 months, p = 0.52).

Conclusions

Local excision was associated with a significantly higher incidence of positive resection margins and shorter hospital stay, yet similar overall survival to radical excision.
In situ high-temperature behaviour and breakdown conditions of uvite at room pressure
Authors: Ballirano Paolo , Celata Beatrice , Bosi Ferdinando
Published: October 2022

The thermal behaviour of an uvite from San Piero in Campo (Elba Island, Italy) was investigated at room pressure through in situ high-temperature powder X-ray diffraction (PXRD), until the breakdown conditions were reached. The variation of uvite structural parameters (unit-cell parameters and mean bond distances) was monitored together with site occupancies and we observed the thermally induced Fe oxidation process counterbalanced by (OH)−deprotonation, which starts at 450 °C and is completed at 650 °C. The uvite breakdown reaction occurs between 800 and 900 °C. The breakdown products were identified at room temperature by PXRD and the breakdown reaction can be described as follows: tourmaline → indialite + yuanfuliite + plagioclase + “boron-mullite” phase + hematite.