bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneously screening multiple UGT1A1 inhibitors from Polygonum multiflorum root using ultrafiltration LC–MS
Authors: Jiang Yan , Zhang Cai , Zheng Xian , Zhao Zhen , Li Hui‐Jun
Published: December 2021

Liver injury induced by Polygonum multiflorum root (PMR) is an immediate issue requiring global attention. UDP‐glucuronosyltransferase 1A1 (UGT1A1) inhibitors are suspected to additively contribute to the hepatotoxicity of PMR. This study was deliberately designed to simultaneously screen UGT1A1 inhibitors from PMR, and their co‐contribution to hepatotoxicity was determined. Using ultrafiltration coupled to LC–MS method, four compounds, namely cis‐2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐glucoside, trans‐2,3,5,4′‐tetrahydroxystilbene‐2‐O‐β‐d‐glucoside, emodin‐8‐O‐β‐d‐glucoside, and emodin, were screened, exhibiting the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, and 34.02 μM, respectively. The varying activities of the screened UGT1A1 inhibitors were demonstrated by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co‐contributed to the hepatotoxicity of PMR. These findings are conducive to understand the role of UGT1A1 inhibitors in PMR‐induced hepatotoxicity.
Differential mechanisms of posterior cingulate cortex downregulation and symptom decreases in posttraumatic stress disorder and healthy individuals using real‐time fMRI neurofeedback
Authors: Nicholson Andrew A. , Rabellino Daniela , Densmore Maria , Frewen Paul A. , Steyrl David , Scharnowski Frank , Théberge Jean , Neufeld Richard W.J. , Schmahl Christian , Jetly Rakesh , Lanius Ruth A.
Published: December 2021

Background

Intrinsic connectivity networks, including the default mode network (DMN), are frequently disrupted in individuals with posttraumatic stress disorder (PTSD). The posterior cingulate cortex (PCC) is the main hub of the posterior DMN, where the therapeutic regulation of this region with real‐time fMRI neurofeedback (NFB) has yet to be explored.

Methods

We investigated PCC downregulation while processing trauma/stressful words over 3 NFB training runs and a transfer run without NFB (total n = 29, PTSD n = 14, healthy controls n = 15). We also examined the predictive accuracy of machine learning models in classifying PTSD versus healthy controls during NFB training.

Results

Both the PTSD and healthy control groups demonstrated reduced reliving symptoms in response to trauma/stressful stimuli, where the PTSD group additionally showed reduced symptoms of distress. We found that both groups were able to downregulate the PCC with similar success over NFB training and in the transfer run, although downregulation was associated with unique within‐group decreases in activation within the bilateral dmPFC, bilateral postcentral gyrus, right amygdala/hippocampus, cingulate cortex, and bilateral temporal pole/gyri. By contrast, downregulation was associated with increased activation in the right dlPFC among healthy controls as compared to PTSD. During PCC downregulation, right dlPFC activation was negatively correlated to PTSD symptom severity scores and difficulties in emotion regulation. Finally, machine learning algorithms were able to classify PTSD versus healthy participants based on brain activation during NFB training with 80% accuracy.

Conclusions

This is the first study to investigate PCC downregulation with real‐time fMRI NFB in both PTSD and healthy controls. Our results reveal acute decreases in symptoms over training and provide converging evidence for EEG‐NFB targeting brain networks linked to the PCC.
What if the future of HER2‐positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study
Authors: Pizzamiglio Sara , Cosentino Giulia , Ciniselli Chiara M. , De Cecco Loris , Cataldo Alessandra , Plantamura Ilaria , Triulzi Tiziana , El‐abed Sarra , Wang Yingbo , Bajji Mohammed , Nuciforo Paolo , Huober Jens , Ellard Susan L. , Rimm David L. , Gombos Andrea , Daidone Maria Grazia , Verderio Paolo , Tagliabue Elda , Di Cosimo Serena , Iorio Marilena V.
Published: December 2021

Background

Neoadjuvant therapy with dual HER2 blockade improved pathological complete response (pCR) rate in HER2‐positive breast cancer patients. Nevertheless, it would be desirable to identify patients exquisitely responsive to single agent trastuzumab to minimize or avoid overtreatment. Herein, we evaluated the predictive and prognostic value of basal primary tumor miRNA expression profile within the trastuzumab arm of NeoALTTO study (ClinicalTrials.gov Identifier:NCT00553358).

Methods

RNA samples from baseline biopsies were randomized into training (n= 45) and testing (n= 47) sets. After normalization, miRNAs associated with Event‐free survival (EFS) and pCR were identified by univariate analysis. Multivariate models were implemented to generate specific signatures which were first confirmed, and then analyzed together with other clinical and pathological variables.

Results

We identified a prognostic signature includinghsa‐miR‐153‐3p(HR 1.831, 95% CI: 1.34–2.50) andhsa‐miR‐219a‐5p(HR 0.629, 95% CI: 0.50–0.78). For two additional miRNAs (miR‐215‐5pandmiR‐30c‐2‐3p), we found a statistically significant interaction term with pCR (p.interaction: 0.017 and 0.038, respectively). Besides, a two‐miRNA signature was predictive of pCR (hsa‐miR‐31‐3p, OR 0.70, 95% CI: 0.53–0.92, andhsa‐miR‐382‐3p, OR: 1.39, 95% CI: 1.01–1.91). Notably, the performance of this predictive miRNA signature resembled that of the genomic classifiers PAM50 and TRAR, and did not improve when the extended models were fitted.

Conclusion

Analyses of primary tumor tissue miRNAs hold the potential of a parsimonious tool to identify patients with differential clinical outcomes after trastuzumab based neoadjuvant therapy.
Assimilating problematic life script themes in clinical supervision: The case of Sarah
Authors: van Rijn Biljana , Agar Jamie , Sills Charlotte , Stiles William B.
Published: December 2021

Objectives

Life script is a transactional analysis concept describing a pattern of human experience, interaction and meaning making developed in childhood that can be activated in adulthood, sometimes creating problems. Problematic life script themes can impact a therapist's experience and interaction during clinical work and interfere with therapeutic effectiveness. This study used the comparative script system theory to assess how one therapist's problematic life script themes were manifested in supervision, how they were addressed, and whether addressing them advanced assimilation of the problematic material.

Method

Seven consecutive monthly supervision sessions with a 50‐year‐old, highly experienced female therapist in private practice (pseudonym ‘Sarah’) were analysed by a team of five investigators using a qualitative theory‐building approach. The assimilation of problematic experiences sequence (APES) was used to track changes in Sarah's life script themes.

Results

Problematic life script themes were evident in each supervision session. Progress though the APES varied across themes and six different clients discussed during the sessions.

Conclusions

The supervisee's life script themes emerged prominently in supervision session content, and most were successfully navigated. The observations supported the theoretical suggestion that assimilation of supervisee unprocessed life script material may be a prominent component of routine professional supervision.
Advances on biological functions of exosomal non‐coding RNAs in osteoarthritis
Authors: Chen Jialei , Yu Xi , Zhang Xiang
Published: December 2021

Exosomes can be secreted by various cells and function as intercellular communication vehicles by delivering specific cargoes from the donor cells to the recipient cells through their paracrine activity. Recently, an increasing number of studies have shown that non‐coding RNAs (ncRNAs) could be entrapped in and transferred between cartilage‐related cells as exosomal cargoes to modulate the expression of various target genes by regulation at post‐transcriptional and post‐translational levels. They are mainly comprised of microRNAs, long non‐coding RNAs, and circular RNAs. Articular cartilage degeneration is one of the main pathological features of osteoarthritis. Exosomal ncRNAs are involved in pathological processes of osteoarthritis, such as proliferation, migration, chondrogenesis, chondrocyte differentiation induction, extracellular matrix formation, apoptosis, and inflammation. In this review, we summarize the biological functions of exosomal ncRNAs in cartilage homeostasis and osteoarthritis progression and discuss the perspectives and challenges of exosomal ncRNAs application for osteoarthritis patients in the future. Exosomal ncRNA has an important regulatory role in the pathogenesis of osteoarthritis, but more evidence is needed for clinical application.
Spirolindemers A and B, Lindenane Sesquiterpenoid Oligomers Equipped with Oxaspiro[4.5]decane from Chloranthus henryi
Authors: Li Jixin , Chi Jun , Tang Pengfei , Sun Yunpeng , Lu Weijia , Xu Wenjun , Wang Yongyue , Luo Jun , Kong Lingyi
Published: December 2021

Comprehensive Summary

Spirolindemers A and B, unprecedented lindenane sesquiterpenoid dimer (1) and trimer (2) equipped with oxaspiro[4.5]decane unit, were discovered from the medicinal plant Chloranthus henryi. Their structures including absolute configurations were achieved by HRMS, NMR, ECD, X‐ray diffraction analyses, and quantum chemical calculations. Biogenetically, hetero‐ and homo‐Diels‐Alder additions may dominate the formation of oxaspiro[4.5]decane and spiro[4.5]decane skeletons, respectively. Compound 1 showed anti‐inflammatory activity by inhibiting the expression of iNOS and COX‐2.
Chronic urticaria patients are interested in apps to monitor their disease activity and control: A UCARE CURICT analysis
Authors: Cherrez‐Ojeda Ivan , Vanegas Emanuel , Cherrez Annia , Felix Miguel , Weller Karsten , Magerl Markus , Maurer Rasmus Robin , Mata Valeria L. , Kasperska‐Zajac Alicja , Sikora Agnieszka , Fomina Daria , Kovalkova Elena , Godse Kiran , Rao Nimmagadda Dheeraj , Khoshkhui Maryam , Rastgoo Sahar , Criado Roberta F. J. , Abuzakouk Mohamed , Grandon Deepa , Van Doorn Martijn B. A. , Rodrigues Valle Solange Oliveira , De Souza Lima Eduardo Magalhães , Thomsen Simon Francis , Ramón German D. , Matos Benavides Edgar E. , Bauer Andrea , Giménez‐Arnau Ana M. , Kocatürk Emek , Guillet Carole , Larco Jose Ignacio , Zhao Zuo‐Tao , Makris Michael , Ritchie Carla , Xepapadaki Paraskevi , Ensina Luis Felipe , Cherrez Sofia , Maurer Marcus
Published: December 2021

Background

Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self‐evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study.

Methods

The methodology for CURICT has been reported. Briefly, a 23‐item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria‐related purposes.

Results

As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03–1.79]) and females versus males (OR [95% CI], 1.47 [1.17–1.85]) were more likely to be very to extremely interested in an app to assess disease control.

Conclusions

Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well‐designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.
Silicate as a Versatile Matrix for the Aqueous Synthesis of Metal Sulfide Nanoparticles
Authors: Estrada‐Mendoza Tatiana A. , Burgess Thomas F. , Edirisinghe Dimuthu S. , Gonzalez Aleida G. , Khalaf Jawad N. , Brentley Fravel J. , McMillen Colin D. , Chumanov George
Published: December 2021

The addition of metals to the oligomeric sodium metasilicate in water results in insoluble metal silicate complexes that form nanoparticles, in which further chemical reactions can be carried out. Copper sulfide, copper tin sulfide, tin sulfide, bismuth sulfide and zinc sulfide doped with manganese nanoparticles were synthesized using this method. The silicate matrix resulted in a narrow particle size distribution and imparted long‐term stability to the nanoparticle suspensions. The reactions were monitored via UV‐Vis‐NIR spectroscopy, and the nanoparticles were characterized by AFM, powder X‐ray diffraction, and Raman spectroscopy. The described method is expected to become a general and versatile approach for aqueous synthesis of multimetallic, doped chalcogenide and other complex nanoparticles without the need of complicated chemical precursors, stabilizing agents, and multiple steps.
A Sharp Inequality on the Exponentiation of Functions on the Sphere
Authors: Chang Sun‐Yung Alice , Gui Changfeng
Published: December 2021

In this paper we show a new inequality that generalizes to the unit sphere the Lebedev‐Milin inequality of the exponentiation of functions on the unit circle. It may also be regarded as the counterpart on the sphere of the second inequality in the Szegö limit theorem on the Toeplitz determinants on the circle. On the other hand, this inequality is also a variant of several classical inequalities of Moser‐Trudinger type on the sphere. The inequality incorporates the deviation of the center of mass from the origin into the optimal inequality of Aubin for functions with mass centered at the origin, and improves Onofri's inequality with the contribution of the shifting of the mass center explicitly expressed. © 2021 Wiley Periodicals LLC.
Evaluating the effect of nitrogen fertilizer rate and source on the performance of open‐pollinated rye (Secale cereale L.) cultivars in contrasting European environments
Authors: Tupits Ilme , Tamm Ilmar , Magistrali Amelia , Rempelos Leonidas , Cakmak Ismail , Leifert Carlo , Grausgruber Heinrich , Wilkinson Andrew , Butler Gillian , Bilsborrow Paul
Published: December 2021

Rye (Secale cereale L.) is a minor cereal with potential to support sustainable farming practices. This study evaluated the performance of four old and modern European open‐pollinated winter rye cultivars grown with different nitrogen (N) sources (cattle slurry, farmyard manure, biogas digestate, mineral N) at two rates of N 50 and 100 kg ha−1 in the United Kingdom and Estonia, in the 2014–2015 and 2015–2016 growing seasons. Grain yield in Estonia was higher than the United Kingdom (6.2 vs. 4.8 t ha−1), which was attributed to a higher ear density (409.4 vs. 249.7 ears m−2) and grain number per ear (50.2 vs. 43.2), although 1,000‐grain weight was higher in the United Kingdom. There were clear differences between sites in the response to N source with significant N source × year interactions. Biogas digestate and mineral N produced higher grain yield than farmyard manure and cattle slurry in the United Kingdom, whereas in Estonia cattle slurry had a lower grain yield than the other N sources. Foliar diseases were absent in Estonia and in the United Kingdom, and N source only affected powdery mildew and leaf blotch on Leaf 2. The response of grain quality to N source and variety was consistent across both sites. The modern variety Elias had the highest Hagberg falling number and specific weight but the lowest protein content, whereas the variety Schlägler had the highest protein content but lowest specific weight. The benefits of selecting cultivars for specific environments are shown by the interactions between genotype and environment.
Nonaqueous capillary electrophoresis and quantum chemical calculations applied to investigation of acid–base and electromigration properties of azahelicenes
Authors: Šolínová Veronika , Štěpánová Sille , Jančařík Andrej , Klívar Jiří , Šámal Michal , Stará Irena G. , Chocholoušová Jana Vacek , Vacek Jaroslav , Starý Ivo , Kašička Václav
Published: December 2021

Nonaqueous capillary electrophoresis (NACE) using methanol (MeOH) as a solvent of the BGEs and quantum mechanical density functional theory (DFT) have been applied to determine the thermodynamic acidity (ionization) constants (pKa) of mono‐ and diaza[5]helicenes, mono‐ and diaza[6]helicenes, and their dibenzo derivatives in MeOH and water. First, the mixed acidity constants, , of ionogenic pyridinium groups of azahelicenes and their derivatives in MeOH were obtained by nonlinear regression analysis of pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by NACE in a large series of methanolic BGEs within a wide conventional pH range (pHMeOH 1.6–12.0) and at ambient temperature (21–26°C) in a home‐made CE device. Prior to mixed acidity constant calculation, the effective mobilities were corrected to reference temperature (25°C) and constant ionic strength (25 mM). Then, the mixed acidity constants were recalculated to the thermodynamic acidity constants pKa,MeOH by the Debye–Hückel theory of nonideality of electrolyte solutions. Finally, from the methanolic thermodynamic pKa,MeOH values, the aqueous thermodynamic constants were estimated using the empirical relations between methanolic and aqueous acidity constants derived for structurally related pyridine derivatives. Depending on the number and position of the nitrogen atoms in their molecules, the analyzed azahelicenes were found to be weak to moderate bases with methanolic pKa,MeOH in the range 2.01–8.75 and with aqueous in the range 1.67–8.28. The thermodynamic pKa,MeOH obtained by the DFT calculations were in a good agreement with those determined experimentally by NACE.
Community support for policy interventions targeting unhealthy food environments in public institutions
Authors: Cranney Leonie , Thomas Margaret , Cobcroft Megan , Drayton Bradley , Rissel Chris , Bauman Adrian , Phongsavan Philayrath
Published: December 2021

Issue addressed

Understanding community support for obesity prevention policy is important for developing effective preventive health action. This study assessed support for a range of obesity prevention interventions, including food environment policies designed to improve healthy food and drink availability and promotion within public institutions.

Methods

An online cross‐sectional survey was completed by 2006 NSW adults. Questions explored attitudes and beliefs about obesity, the importance of government‐led prevention and support for eight obesity prevention interventions. Regression analyses examined associations between intervention support and sociodemographic, attitudinal and behavioural characteristics.

Results

Most respondents (80%) believed obesity was a large problem and that poor individual choices (86%) and the widespread availability of unhealthy food and drink (78%) contributed to the issue. There was moderate to high support for most (n = 7) initiatives. Support for food environment policies was highest for schools (76%‐82%) and hospitals (67%‐79%). Supporters and opponents rationalised opinions based on perceived effectiveness, the government's role and cost benefits. Opponents were a minority, but principles of autonomy were predominant. Attributing obesity to environment‐related factors, and personal lower SSB consumption strongly predicted support.

Conclusion

There is a significant recognition of the obesity issue and strong support for policies designed to improve the availability and promotion of healthy food and drink in public institutions, particularly in schools and hospitals.

So what?

Substantial community support for healthy food environment policies in schools and hospitals warrants continued implementation in NSW. This may foster further acceptance for wider implementation. Our findings could inform the framing of policy advocacy messages.
Complexity against current cancer research: Are we on the wrong track?
Authors: Kasikci Yasenya , Gronemeyer Hinrich
Published: December 2021

Cancer genetics has led to major discoveries, including protooncogene and tumor‐suppressor concepts, and cancer genomics generated concepts like driver and passenger genes, revealed tumor heterogeneity and clonal evolution. Reconstructing trajectories of tumorigenesis using spatial and single‐cell genomics is possible. Patient stratification and prognostic parameters have been improved. Yet, despite these advances, successful translation into targeted therapies has been scarce and mostly limited to kinase inhibitors. Here, we argue that current cancer research may be on the wrong track, by considering cancer more as a “monogenic” disease, trying to extract common information from thousands of patients, while not properly considering complexity and individual diversity. We suggest to empower a systems cancer approach which reconstructs the information network that has been altered by the tumorigenic events, to analyze hierarchies and predict (druggable) key nodes that could interfere with/block the aberrant information transfer. We also argue that the interindividual variability between patients of similar cohorts is too high to extract common polygenic network information from large numbers of patients and argue in favor of an individualized approach. The analysis we propose would require a structured multinational and multidisciplinary effort, in which clinicians, and cancer, developmental, cell and computational biologists together with mathematicians and informaticians develop dynamic regulatory networks which integrate the entire information transfer in and between cells and organs in (patho)physiological conditions, revealing hierarchies and available drugs to interfere with key regulators. Based on this blueprint, the altered information transfer in individual cancers could be modeled and possible targeted (combo)therapies proposed.
Oncologic outcomes of conservative treatment of atypical polypoid adenomyoma of the uterus: A two‐center experience
Authors: Casadio Paolo , Raffone Antonio , Travaglino Antonio , Raimondo Diego , Zizolfi Brunella , Armano Giulia , Buonaiuto Roberto , Insabato Luigi , Mollo Antonio , Seracchioli Renato , Di Spiezio Sardo Attilio
Published: December 2021

Objective

Atypical polypoid adenomyoma (APA) is a rare uterine premalignant lesion mainly occurring in premenopausal and nulliparous women. Although hysteroscopic resection (HR) has showed promising results, the conservative management of APA in young women is not standardized, and few data are available in the literature. We aimed to assess oncologic outcomes of the conservative treatment of APA.

Methods

A multicenter observational retrospective cohort study was performed including all patients with APA who underwent conservative treatment from January 2006 to June 2020. Rates of each oncologic outcome (i.e. initial complete response, persistence, progression to cancer, recurrence, long‐term treatment success, and treatment failure) were calculated for all conservative treatment together and separately.

Results

Twenty‐five patients were included. Conservative treatments consisted of HR alone (n = 14) and HR + progestin (n = 11). Overall, 24 (96%) patients showed initial complete response, of which 21 (84%) showed long‐term treatment success; four (16%) patients had progression to cancer, of which two (8%) first recurred as APA. Long‐term treatment success was achieved in 13 of 14 (92.9%) patients with HR alone and 8 of 11 (72.3%) with HR + progestin.

Conclusion

Conservative treatment appears to be a safe option in women with APA. The four‐steps HR might be considered as the first‐line conservative approach, while the addition of progestin does not seem to improve oncologic outcomes. However, the risk of progression to cancer highlights the need for a close and long‐term follow up with ultrasonography and hysteroscopic biopsies, and for hysterectomy in patients not desiring pregnancy.
Next‐generation machine vision systems incorporating two‐dimensional materials: Progress and perspectives
Authors: Wu Peisong , He Ting , Zhu He , Wang Yang , Li Qing , Wang Zhen , Fu Xiao , Wang Fang , Wang Peng , Shan Chongxin , Fan Zhiyong , Liao Lei , Zhou Peng , Hu Weida
Published: December 2021

Machine vision systems (MVSs) are an important component of intelligent systems, such as autonomous vehicles and robots. However, with the continuous increase in data and new application scenarios, new requirements are put forward for the next generation of MVS. There is an urgent need to find new material systems to complement the existing semiconductor technology based on thin‐film materials, and new architectures must be explored to improve efficiency. Because of their unique physical properties, two‐dimensional (2D) materials have received extensive attention for use in MVSs, especially in biomimetic ones: the human visual system, which can process complex visual information with low power consumption, provides a model for next‐generation MVSs. This review paper summarizes the progress and challenges of applying 2D material photodetectors in sense‐memory‐computational integration and biomimetic image sensors for machine vision.

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The multifaceted antineoplastic role of pyrimethamine against human malignancies
Authors: Ramchandani Shanaya , Mohan Chakrabhavi Dhananjaya , Mistry Jenaifer Rustom , Su Qi , Naz Irum , Rangappa Kanchugarakoppal S. , Ahn Kwang Seok
Published: December 2021

Cancer accounted for nearly 10 million deaths in 2020 and is the second leading cause of death worldwide. The chemotherapeutic agents that are in clinical practice possess a broad range of severe adverse effects towards vital organs which emphasizes the importance of the discovery of new therapeutic agents or repurposing of existing drugs for the treatment of human cancers. Pyrimethamine is an antiparasitic drug used for the treatment of malaria and toxoplasmosis with a well‐documented excellent safety profile. In the last 5 years, numerous efforts have been made to explore the anticancer potential of pyrimethamine in in vitro and in vivo preclinical models and to repurpose it as an anticancer agent. The studies have demonstrated that pyrimethamine inhibits oncogenic proteins such as STAT3, NF‐κB, DX2, MAPK, DHFR, thymidine phosphorylase, telomerase, and many more in a different types of cancer models. Moreover, pyrimethamine has been reported to work in synergy with other anticancer agents, such as temozolomide, to induce apoptosis of tumor cells. Recently, the results of phase‐1/2 clinical trials demonstrated that pyrimethamine administration reduces the expression of STAT3 signature genes in tumor tissues of chronic lymphocytic leukemia patients with a good therapeutic response. In the present article, we have reviewed most of the published articles related to the antitumor effects of pyrimethamine in malignancies of breast, liver, lung, skin, ovary, prostate, pituitary, and leukemia in in vitro and in vivo settings. We have also discussed the pharmacokinetic profile and results of clinical trials obtained after pyrimethamine treatment. From these studies, we believe that pyrimethamine has the potential to be repurposed as an anticancer drug.
Long non‐coding RNA ANRIL interacts with microRNA‐34a and microRNA‐125a, and they all correlate with disease risk and severity of Parkinson's disease
Authors: Yang Peng , Lin Guiqing , Wang Minli , Chen Xuewei , Huang Jian
Published: December 2021

Background

This study aimed to investigate the correlation of long non‐coding RNA antisense non‐coding RNA in the INK4 locus (lncRNA ANRIL) and its target microRNAs (microRNA‐34a (miR‐34a) and microRNA‐125a (miR‐125a)) with disease risk and severity of Parkinson’s disease (PD).

Methods

Seventy‐eight PD patients and 78 age‐/gender‐matched controls were consecutively enrolled. Their peripheral blood mononuclear cell samples were collected and proposed for the reverse‐transcription quantitative polymerase chain reaction to complete lncRNA ANRIL, miR‐34a, and miR‐125a measurements.

Results

LncRNA ANRIL was upregulated, while miR‐34a and miR‐125a were downregulated in PD patients compared to controls (all p < 0.001). Further, they all showed certain values for PD risk identification by ROC curve analyses, among which lncRNA ANRIL showed the highest AUC (AUC: 0.879, 95% CI: 0.824‐0.934). Furthermore, lncRNA ANRIL negatively correlated with miR‐34a (p = 0.016) and miR‐125a (p = 0.005) in PD patients, but not in controls. In addition, lncRNA ANRIL was observed to positively associate with UPDRS‐I score (p = 0.029), UPDRS‐III score (p = 0.006), and UPDRS‐IV score (p = 0.033), while negatively correlated with MMSE score (p = 0.003). These associations were less distinct as to miR‐34a and miR‐125a.

Conclusion

LncRNA ANRIL interacts with miR‐34a and miR‐125a in PD patients, and they all correlate with disease risk and severity of PD.
The clinical value of long noncoding RNA GAS5 in acute ischemic stroke: Correlation with disease risk, inflammation, severity, and risk of recurrence
Authors: Fang Pingping , Wu Yiping , Zhang Zhongbo , Cui Cui , Dong Xiaoxue , Hu Ke , Jia Jundong , Duan Xinfei , Zhang Ying , Huo Haoran
Published: December 2021

Background

Long noncoding RNA growth arrest‐specific 5 (lnc‐GAS5) is involved in the pathophysiology of acute ischemic stroke (AIS) by regulating vascular stenosis, inflammation, and neurocyte apoptosis. This study aimed to explore the clinical value of lnc‐GAS5 in patients with AIS.

Methods

Plasma samples were collected from 120 patients with AIS at admission and 60 controls after enrollment, and lnc‐GAS5 expression in the plasma of all participants was assessed by reverse transcription quantitative polymerase chain reaction. In patients with AIS, disease severity was evaluated using National Institute of Health Stroke Scale (NIHSS) score, and plasma inflammatory cytokine levels were measured by enzyme‐linked immunosorbent assay. Recurrence‐free survival (RFS) was calculated during a 36‐month follow‐up period.

Results

Lnc‐GAS5 expression levels were higher in patients with AIS than in the controls (p < 0.001), and it had the potential to discriminate the controls from patients with AIS (area under the curve: 0.893, 95% confidence interval: 0.849–0.938). In patients with AIS, elevated lnc‐GAS5 levels were positively correlated with NIHSS score (r = 0.397, p < 0.001), diabetes mellitus (p = 0.046), and higher levels of tumor necrosis factor alpha (TNF‐α; r = 0.374, p < 0.001), interleukin‐6 (IL‐6; r = 0.223, p < 0.001), and interleukin‐17A (IL‐17A; r = 0.222, p = 0.015). The expression levels of lnc‐GAS5 were also negatively correlated with the levels of interleukin‐10 (IL‐10; r = −0.350, p < 0.001) and RFS (p = 0.036).

Conclusion

Lnc‐GAS5 is correlated with higher susceptibility to AIS, inflammation, and severity, and can predict an increased risk of AIS recurrence, indicating that monitoring of lnc‐GAS5 might improve the management of AIS.
The impact of COVID‐19 on the safety, housing stability, and mental health of unstably housed domestic violence survivors
Authors: Chiaramonte Danielle , Simmons Cortney , Hamdan Noora , Ayeni Oyesola Oluwafunmilayo , López‐Zerón Gabriela , Farero Adam , Sprecher Mackenzie , Sullivan Cris M.
Published: December 2021

Using data from an ongoing longitudinal study, we examined the impact of the COVID‐19 stay‐at‐home orders on a racially diverse population of unstably housed domestic violence (DV) survivors over time. Specifically, we examined survivors' safety, housing stability, and mental health before, during, and after the onset of COVID‐19, and how demographic, social, and familial factors attenuated or exacerbated the effect of the stay‐at‐home orders. Approximately 300 participants were initially interviewed after they sought services from a DV agency, and then again, every 6 months over 2 years. COVID‐19 stay‐at‐home orders occurred midway through the completion of this multi‐year study. Longitudinal mixed effects models were estimated to examine the impact of COVID‐19 on the safety, housing stability, and mental health of survivors over time. We also examined models with several time‐varying (e.g., employment, income, social support, and number of children) and time‐invariant (baseline outcome scores, racial/ethnic identity, education, and disability status) control variables. Results revealed that safety, housing stability and mental health were improving for study participants before the onset of the COVID‐19 pandemic but plateaued after the stay‐at‐home orders were issued. Experiences of abuse, housing instability, and mental health symptomatology did not worsen as a result of the COVID‐19 stay‐at‐home orders. Notably, social support and housing services emerged as important predictors of outcomes, such that participants who received housing‐related services and greater social support reported less abuse, less housing instability, and lower mental health distress. COVID‐19 temporarily disrupted the positive trajectory unstably housed DV survivors were experiencing in regard to safety, housing stability and mental health. These findings provide critical insight into the importance of service access during and after global catastrophes. Additional resources and support may be helpful in assisting survivors to return to their pre‐pandemic recovery and growth trajectories.
Neurological Immune‐Related Adverse Events After COVID‐19 Vaccination: A Systematic Review
Authors: Shafiq Ameena , Salameh Mohammad A. , Laswi Ibrahim , Mohammed Ibrahim , Mhaimeed Omar , Mhaimeed Nada , Mhaimeed Narjis , Paul Pradipta , Mushannen Malik , Elshafeey Abdallah , Fares Ahmed , Holroyd Sean , Zakaria Dalia
Published: December 2021

The coronavirus disease 2019 (COVID‐19) pandemic has affected millions of individuals worldwide. The global scientific effort to design an effective vaccine against this virus has led to the development of several vaccine candidates. The expedited rollout of these vaccines has created some public distrust regarding the safety of these new vaccines. This review compiles clinical data from reports of diagnosed immune‐related neurological events that have occurred after COVID‐19 vaccine administration with the exception of those secondary to hematological abnormalities. A systematic literature search was performed, using several databases, to identify reports of postvaccination adverse neurological events. The search resulted in 18 studies that met our criteria. These studies included 61 patients who had received COVID‐19 vaccines and experienced at least 1 neurological adverse effect. The most common neurological event was facial nerve palsy (50% of all events). Other less frequently reported events included the reactivation of herpes zoster, Guillain‐Barre syndrome, other demyelinating diseases, and neuropathy. The underlying mechanism was hypothesized to be related to vaccine‐induced type 1 interferon production leading to decreased tolerance of the myelin sheath antigens. Other hypotheses include vaccine‐induced transient lymphopenia and immune dysregulation. Most of the reported events were time limited and resolved spontaneously. Given the rarity of reported neurological events compared to the total number of vaccines administered, and the similarity in the incidence of events between COVID‐19 vaccines and other more common vaccines, there is little evidence to support a causal relationship between COVID‐19 vaccines and adverse neurological events.
Synthesis, molecular docking, in silico ADME, and EGFR kinase inhibitor activity studies of some new benzimidazole derivatives bearing thiosemicarbazide, triazole, and thiadiazole
Authors: Celik Ismail , Ayhan‐Kılcıgil Gülgün , Karayel Arzu , Guven Berna , Onay‐Besikci Arzu
Published: December 2021

Epidermal growth factor receptor (EGFR), one of the important targets in the development of the anticancer compound, is a member of the ErbB receptor tyrosine kinase receptor family and is highly expressed in solid tumors. Inhibition of EGFR is important for cancer treatment to inhibit the progression and growth of EGFR‐expressing tumor cells. Agents targeting EGFR are successful drugs involved in the treatment of various cancers, particularly colorectal, head, neck, lung, and breast cancers. In this study, the design of some novel benzimidazole compounds that can interact with EGFR kinase enzyme, synthesis and analysis of these compounds, and evaluation of their biological activities in vitro was aimed. To reach the target compounds, by reacting acid hydrazides with alkyl isothiocyanates, thiosemicarbazides were formed, then cyclization of these compounds with concentrated sulfuric acid or sodium hydroxide, thiadiazole, or triazole derivatives were obtained. As a result of the study, a total of 38 new benzimidazole derivatives was obtained, and the structures of these compounds were clarified by elemental analysis, mass, 1H, and 13C NMR spectroscopy. Also, the structure of compound 4c was proven by X‐ray crystallography. Molecular docking studies of the synthesized compounds have also been carried out, some molecules with high docking scores have been selected and EGFR kinase inhibitor properties have been tested. Among the compounds tested, it was determined that the most active compound was 12a, which inhibited 68% EGFR at a concentration of 10 μM.
Gender and Covid‐19: Are women bearing the brunt? A case study for Bolivia
Authors: Escalante Luis Enrique , Maisonnave Helene
Published: December 2021

The coronavirus pandemic (COVID‐19) is threatening the well‐being of citizens in most countries of the world; however, women and men could be affected in different ways. This study uses a gender‐sensitive computable general equilibrium model linked to a micro model to assess the impacts of COVID‐19 in Bolivia. The results reveal negative effects for all economic agents. Female‐headed households in general and those headed by unskilled women in particular are the most affected, as they experience significant reductions in employment and the largest increases in household burdens. This increases poverty and inequality for more women than men.
Altered Resting‐State Intranetwork and Internetwork Functional Connectivity in Patients With Chronic Unilateral Vestibulopathy
Authors: Si Lihong , Cui Bin , Li Zheyuan , Li Xiang , Li Kangzhi , Ling Xia , Shen Bo , Yang Xu
Published: December 2021

Background

Chronic unilateral vestibulopathy (CUVP) is often accompanied by dizziness and postural instability, which restrict patients' daily activities. It is important to understand central compensation mechanisms underlying these symptoms in patients with CUVP by evaluating their brain functional status.

Purpose

To analyze the changes in resting‐state intranetwork and internetwork functional connectivity (FC) and explore the state of central vestibular compensation in patients with CUVP.

Study type

Retrospective.

Population

Eighteen patients with right‐sided CUVP and 18 age‐ and sex‐matched healthy controls.

Field strength/sequence

A 3.0 T, three‐dimensional magnetization‐prepared rapid gradient‐echo (MP‐RAGE) and resting‐state echo‐planar imaging (EPI) functional MRI sequences.

Assessment

FC alterations were explored using independent component analysis (ICA). Twelve independent components were identified via ICA. Dizziness Handicap Inventory (DHI) score for all patients was determined.

Statistical tests

Two‐sample t test, family‐wise error (FWE) correction, Pearson correlation coefficient (r). A P value <0.05 was considered statistically significant.

Results

Compared with healthy controls, patients with CUVP showed significantly decreased FC in the right middle occipital gyrus within the lateral visual network, and significantly increased FC in the right supplementary motor area within the sensorimotor network. The FC was decreased between the medial visual and auditory networks, the right frontoparietal and posterior default networks, as well as the sensorimotor and auditory networks. There was a significant negative correlation between the FC changes in the visual, auditory networks and the DHI score in patients with CUVP (r = −0.583).

Data conclusion

Compared to healthy controls, the FC was significantly decreased in the right visual cortex and significantly enhanced in the right sensorimotor network in patients with CUVP. Patients with CUVP showed decreased FC between multiple whole‐brain networks, suggesting that abnormal integration of multisensory information may be involved in the occurrence of chronic dizziness and instability in patients with CUVP.

Level of evidence

4

Technical Efficacy

Stage 2.
Historical trend of probable maximum precipitation in Utah and associated weather types
Authors: Gu Hongping , Wang S.‐Y. Simon , Lin Yen‐Heng , Meyer Jonathan , Gillies Robert , Taylor Everett , Pokharel Binod
Published: December 2021

This study assesses the impact global climate change has had on the theoretical upper limit of precipitation for Utah's watersheds by examining historical trends in probable maximum precipitation (PMP), a metric widely used for dam construction and management. Trends in the factors of PMP driven by both frontal and monsoonal storm scenarios were studied using two networks of surface weather stations and modern gridded datasets spanning 1981–2018. It was found that the historical trend in both 3‐hr and 24‐hr PMP estimations exhibited a statistically significant increasing trend, despite that the magnitude of the trend was sensitive to which dataset was examined and the data's spatial resolution. Over the 24‐hr time scale, an interesting deviation in PMP trends was found where frontal storm events demonstrated increasing PMP trends compared to decreasing PMP trends for monsoonal storm events. However, both storm types demonstrated increasing trends over shorter 3‐hr durations, suggesting a universal increase in convective storm intensity. PMP estimates also demonstrated a dependency on the type and resolution of meteorological data used, where higher‐resolution data generally produced greater PMP values and weaker trends. A discussion on the potential causes of these dependencies is provided. This study implies the need to take the historical PMP trend into account for future PMP estimates, especially when coarse‐resolution data are used for conventional PMP studies.
Facilitating open science practices for research syntheses: PreregRS guides preregistration
Authors: Schneider Jürgen , Backfisch Iris , Lachner Andreas
Published: December 2021

Researchers increasingly engage in adopting open science practices in the field of research syntheses, such as preregistration. Preregistration is a central open science practice in empirical research to enhance transparency in the research process and it gains steady adoption in the context of conducting research synthesis. From an interdisciplinary perspective, frameworks and particularly templates are lacking which support researchers preparing a preregistration. To this end, we introduce preregRS, a template to guide researchers across disciplines through the process of preregistering research syntheses. We utilized an R Markdown template file to provide a framework that structures the process of preparing a preregistration. Researchers can write up the preregistration using the template file similar to filling out a form, with the template providing additional hints and further information for the decisions along the framework. We integrated the R Markdown template in an R package for easy installation and use, but also provide a browser‐based option for users granting low‐barrier access. PreregRS constitutes a first step to facilitate and support preregistration with research syntheses for all disciplines. It further adds to establishing open science practices in conducting research syntheses.
Optically Reconfigurable Spherical Ge‐Sb‐Te Nanoparticles with Reversible Switching
Authors: Rybin Mikhail V. , Sinelnik Artem D. , Tajik Mohammad , Milichko Valentin A. , Ubyivovk Evgenii V. , Yakovlev Sergey A. , Pevtsov Alexander B. , Yavsin Denis A. , Zuev Dmitry A. , Makarov Sergey V.
Published: December 2021

Tunable and ultracompact optical elements are highly important for the development of advanced nanophotonics. Such elements significantly expand the capabilities of photonic circuits and devices. Phase changing materials based on Ge‐Sb‐Te composition are very promising for tunable nanophotonic elements. This family of materials is excellent for the creation of tunable optical elements, since it has a non‐volatile reversible phase transition and exhibits a strong modulation of the dielectric permittivity in broad spectral range. In this work, fabrication of Ge‐Sb‐Te nanoparticles by laser ablation as well as strong and repeatable changing of their optical properties by fs‐laser irradiation are demonstrated. Beside the control of linear optical response, switchable second harmonic generation from Ge‐Sb‐Te nanoparticles over two orders of magnitude after the phase change is also demonstrated.
Photonic and Plasmonic Metasensors
Authors: Ahmadivand Arash , Gerislioglu Burak
Published: December 2021

Biosensors have been designed and developed for detecting biomarkers, biomolecules, proteins, enzymes, organisms, and various types of bacterial and viral diseases since the turn of the century. Initially marred by poor sensitivity, specificity, and selectivity, the advent of the notion of photonic biosensors has successfully addressed such drawbacks. One of the hallmarks of modern pharmaceutical industries is the miniaturization of photonic platforms via continuous scaling down of their sizes, which was accomplished by leveraging the concept of artificial media. Numerous forms of photonic and plasmonic devices have been configured for next‐generation technologies since the emergence of metamaterials. Among diverse applications, the development of cost‐effective, label‐free, selective, precise, and on‐chip immunobiosensors with rapid sample‐to‐result feature has received copious interest, recently. This focused Review brings clarity to the rapidly growing body of available and in‐development metamaterials‐enabled diagnostic instruments based on inventive and promising approaches. Through centering on the operating principles of plasmonic, photonic, and hybrid metasensors, we mechanistically characterize and describe the properties of such tools and summarize the most recent achievements in devising metasensors and bioimaging tools with high precision. This insightful understanding serves as a comprehensive source for scientists, physicians, and students to construct ultradense and high‐throughput clinical screening metadevices.