bluuebunny/crossref_metadata_2025 huggingface dataset:
Ninjurin1 drives lung tumor formation and progression by potentiating Wnt/β-Catenin signaling through Frizzled2-LRP6 assembly
Authors: Hyun Seung Yeob , Min Hye-Young , Lee Ho Jin , Cho Jaebeom , Boo Hye-Jin , Noh Myungkyung , Jang Hyun-Ji , Lee Hyo-Jong , Park Choon-Sik , Park Jong-Sook , Shin Young Kee , Lee Ho-Young
Published: April 2022

Background

Cancer stem-like cells (CSCs) play a pivotal role in lung tumor formation and progression. Nerve injury-induced protein 1 (Ninjurin1, Ninj1) has been implicated in lung cancer; however, the pathological role of Ninj1 in the context of lung tumorigenesis remains largely unknown.

Methods

The role of Ninj1 in the survival of non-small cell lung cancer (NSCLC) CSCs within microenvironments exhibiting hazardous conditions was assessed by utilizing patient tissues and transgenic mouse models where Ninj1 repression and oncogenicKrasG12D/+or carcinogen-induced genetic changes were induced in putative pulmonary stem cells (SCs). Additionally, NSCLC cell lines and primary cultures of patient-derived tumors, particularly Ninj1highand Ninj1lowsubpopulations and those with gain- or loss-of-Ninj1expression, and also publicly available data were all used to assess the role of Ninj1 in lung tumorigenesis.

Results

Ninj1 expression is elevated in various human NSCLC cell lines and tumors, and elevated expression of this protein can serve as a biomarker for poor prognosis in patients with NSCLC. Elevated Ninj1 expression in pulmonary SCs with oncogenic changes promotes lung tumor growth in mice. Ninj1highsubpopulations within NSCLC cell lines, patient-derived tumors, and NSCLC cells with gain-of-Ninj1expression exhibited CSC-associated phenotypes and significantly enhanced survival capacities in vitro and in vivo in the presence of various cell death inducers. Mechanistically, Ninj1 forms an assembly with lipoprotein receptor-related protein 6 (LRP6) through its extracellular N-terminal domain and recruits Frizzled2 (FZD2) and various downstream signaling mediators, ultimately resulting in transcriptional upregulation of target genes of the LRP6/β-catenin signaling pathway.

Conclusions

Ninj1 may act as a driver of lung tumor formation and progression by protecting NSCLC CSCs from hostile microenvironments through ligand-independent activation of LRP6/β-catenin signaling.
Germline BRCA1 and BRCA2 mutations and the risk of bladder or kidney cancer in Poland
Authors: Złowocka-Perłowska Elżbieta , Tołoczko-Grabarek Aleksandra , Narod Steven A. , Lubiński Jan
Published: April 2022

Introduction

The role of the BRCA1 and BRCA2 genes in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of specific founder mutations genes BRCA1 (5328 insC, C61G and 4153 delA) and BRCA2 (C5972T) mutations in bladder and kidney cancer patients from Poland.

Materials and methods

We genotyped 1028 patients with bladder cancer and 688 cases with kidney cancer and two control groups.

Results

A BRCA1 mutation (all variants combined) was detected in peripheral blood leukocytes in 5 out of 1028 (0.5%) bladder cases and in 17 of 4000 controls (0.4%) (odds ratio [OR], (OR = 1.1; 95% CI 0.42–3.11; p = 1.0). Among 688 unselected kidney cancer cases a BRCA1 mutations was reported in three patients (0.4%) (OR = 1.0; 95% CI 0.29–3.51; p = 1.0). The mutation C5972T in BRCA2 was observed in 54 bladder cancer patients (5.2%) and in 159 of 2791 healthy controls (5.7%) (OR = 0.9; 95% CI 0.66–1.26; p = 0.6). Fifty kidney cancer cases carried a BRCA2 mutation (7.3%) (OR = 1.3; 95% CI 0.93–1.80; p = 0.1).

Conclusion

In conclusion, we found no difference in the prevalence of BRCA1 and BRCA2 founder mutations between cases and healthy controls. The mutations BRCA1 and BRCA2 seem not to play a role in bladder and kidney cancer development in Polish patients.
SETMAR, a case of primate co-opted genes: towards new perspectives
Authors: Lié Oriane , Renault Sylvaine , Augé-Gouillou Corinne
Published: April 2022

Background

We carry out a review of the history and biological activities of one domesticated gene in higher primates, SETMAR, by discussing current controversies. Our purpose is to open a new outlook that will serve as a framework for future work about SETMAR, possibly in the field of cognition development.

Main body

What is newly important about SETMAR can be summarized as follows: (1) the whole protein sequence is under strong purifying pressure; (2) its role is to strengthen existing biological functions rather than to provide new ones; (3) it displays a tissue-specific pattern of expression, at least for the alternative-splicing it undergoes.

Studies reported here demonstrate that SETMAR protein(s) may be involved in essential networks regulating replication, transcription and translation. Moreover, during embryogenesis, SETMAR appears to contribute to brain development.

Short conclusion

Our review underlines for the first time that SETMAR directly interacts with genes involved in brain functions related to vocalization and vocal learning. These findings pave the way for future works regarding SETMAR and the development of cognitive abilities in higher primates.
Automatic cardiac evaluations using a deep video object segmentation network
Authors: Sirjani Nasim , Moradi Shakiba , Oghli Mostafa Ghelich , Hosseinsabet Ali , Alizadehasl Azin , Yadollahi Mona , Shiri Isaac , Shabanzadeh Ali
Published: April 2022

Background

Accurate cardiac volume and function assessment have valuable and significant diagnostic implications for patients suffering from ventricular dysfunction and cardiovascular disease. This study has focused on finding a reliable assistant to help physicians have more reliable and accurate cardiac measurements using a deep neural network. EchoRCNN is a semi-automated neural network for echocardiography sequence segmentation using a combination of mask region-based convolutional neural network image segmentation structure with reference-guided mask propagation video object segmentation network.

Results

The proposed method accurately segments the left and right ventricle regions in four-chamber view echocardiography series with a dice similarity coefficient of 94.03% and 94.97%, respectively. Further post-processing procedures on the segmented left and right ventricle regions resulted in a mean absolute error of 3.13% and 2.03% for ejection fraction and fractional area change parameters, respectively.

Conclusion

This study has achieved excellent performance on the left and right ventricle segmentation, leading to more accurate estimations of vital cardiac parameters such as ejection fraction and fractional area change parameters in the left and right ventricle functionalities, respectively. The results represent that our method can predict an assured, accurate, and reliable cardiac function diagnosis in clinical screenings.
PET-CT imaging of pulmonary inflammation using [68Ga]Ga-DOTA-TATE
Authors: Puuvuori Emmi , Liggieri Francesco , Velikyan Irina , Chiodaroli Elena , Sigfridsson Jonathan , Romelin Hampus , Ingvast Sofie , Korsgren Olle , Hulsart-Billström Gry , Perchiazzi Gaetano , Eriksson Olof
Published: April 2022

Purpose

In the characterization of severe lung diseases, early detection of specific inflammatory cells could help to monitor patients’ response to therapy and increase chances of survival. Macrophages contribute to regulating the resolution and termination of inflammation and have increasingly been of interest for targeted therapies. [68Ga]Ga-DOTA-TATE is an established clinical radiopharmaceutical targeting somatostatin receptor subtype 2 (SSTR 2). Since activated macrophages (M1) overexpress SSTR 2, the aim of this study was to investigate the applicability of [68Ga]Ga-DOTA-TATE for positron emission tomography (PET) imaging of M1 macrophages in pulmonary inflammation.

Methods

Inflammation in the pig lungs was induced by warm saline lavage followed by injurious ventilation in farm pigs (n = 7). Healthy pigs (n = 3) were used as control. A 60-min dynamic PET scan over the lungs was performed after [68Ga]Ga-DOTA-TATE injection and [18F]FDG scan was executed afterward for comparison. The uptake of both tracers was assessed as mean standardized uptake values (SUVmean) 30–60-min post-injection. The PET scans were followed by computed tomography (CT) scans, and the Hounsfield units (HU) were quantified of the coronal segments. Basal and apical segments of the lungs were harvested for histology staining. A rat lung inflammation model was also studied for tracer specificity using lipopolysaccharides (LPS) by oropharyngeal aspiration. Organ biodistribution, ex vivo autoradiography (ARG) and histology samples were conducted on LPS treated, octreotide induced blocking and control healthy rats.

Results

The accumulation of [68Ga]Ga-DOTA-TATE on pig lavage model was prominent in the more severely injured dorsal segments of the lungs (SUVmean = 0.91 ± 0.56), compared with control animals (SUVmean = 0.27 ± 0.16, p < 0.05). The tracer uptake corresponded to the damaged areas assessed by CT and histology and were in line with HU quantification. The [68Ga]Ga-DOTA-TATE uptake in LPS treated rat lungs could be blocked and was significantly higher compared with control group.

Conclusion

The feasibility of the noninvasive assessment of tissue macrophages using [68Ga]Ga-DOTA-TATE/PET was demonstrated in both porcine and rat lung inflammation models. [68Ga]Ga-DOTA-TATE has a great potential to be used to study the role and presence of macrophages in humans in fight against severe lung diseases.
Risk factors for peripheral intravascular catheter-related phlebitis in critically ill patients: analysis of 3429 catheters from 23 Japanese intensive care units
Authors: Yasuda Hideto , Rickard Claire M. , Marsh Nicole , Yamamoto Ryohei , Kotani Yuki , Kishihara Yuki , Kondo Natsuki , Sekine Kosuke , Shime Nobuaki , Morikane Keita , Abe Takayuki ,   the AMOR-NUS study group
Published: April 2022

Background

Phlebitis is an important complication occurring in patients with peripheral intravascular catheters (PIVCs). The risk factors for phlebitis in the intensive care unit (ICU) was examined.

Methods

A secondary analysis of a prospective multicenter cohort study was conducted, involving 23 ICUs in Japan—the AMOR–VENUS study. Consecutive patients aged ≥ 18 years admitted to the ICU with newly inserted PIVCs after ICU admission were enrolled. Characteristics of the ICU, patients, PIVCs, and the drugs administered via PIVCs were recorded. A marginal Cox regression model was used to identify the risk factors associated with phlebitis.

Results

A total of 2741 consecutive patients from 23 ICUs were reviewed for eligibility, resulting in 1359 patients and 3429 PIVCs being included in the analysis population. The median dwell time was 46.2 h (95% confidence interval [CI], 21.3–82.9). Phlebitis occurred in 9.1% (95% CI, 8.2–10.1%) of catheters (3.5 cases/100 catheter days). The multivariate analysis revealed that the only factors that increased the risk of developing phlebitis were drugs administered intravenously. This study included 26 drugs, and 4 were associated with increased phlebitis: nicardipine (HR, 1.85; 95% CI, 1.29–2.66), noradrenaline (HR, 2.42; 95% CI, 1.40–4.20), amiodarone (HR, 3.67; 95% CI, 1.75–7.71) and levetiracetam (HR, 5.65; 95% CI, 2.80–11.4). Alternatively, factors significantly associated with a reduced risk of phlebitis were: standardized drug administration measures in the ICU (HR, 0.35; 95% CI, 0.17–0.76), 30≤ BMI (HR, 0.43; 95% CI, 0.20–0.95), catheter inserted by a doctor as nurse reference (HR, 0.55; 95% CI, 0.32–0.94), and upper arm insertion site as forearm reference (HR, 0.52; 95% CI, 0.32–0.85). The nitroglycerin was associated with a reduced phlebitis risk (HR, 0.22; 95% CI, 0.05–0.92).

Conclusion

Various factors are involved in the development of phlebitis caused by PIVCs in critically ill patients, including institutional, patient, catheter, and drug-induced factors, indicating the need for appropriate device selection or models of care in the ICU.

Trial registration: UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019, July 1, 2017).
Combining precoding and equalization for interference cancellation in MU-MIMO systems with high density users
Authors: Phuong Nguyen Thu , Son Vu Van , Hiep Pham Thanh
Published: April 2022

In multiple users (MU) multiple input multiple output (MIMO) systems, the non-orthogonal multiple access (NOMA) method can provide multiple access. However, a spectrum efficiency of NOMA method is restricted because of remaining an interference signal of another user. A beamforming method can also be applied into MU-MIMO systems for implementation of multiple access without the interference with the other users; however, it is unavailable for a high density user environment in which multiple users locate close to each other. In order to further improve the spectrum efficiency, we propose a novel signal processing method which joints a precoding and an equalization. First, a precoding matrix is prepared for every user at base station, and we design an equalization which is orthogonal to the precoding matrix. Second, a set of linear weights is proposed to calculate at users for cancelling any interference signal. Therefore, signals for other users are eliminated according to the orthogonal feature and linear signal processing, and then, every user can receive its own signal without the interference signal. The proposed method is compared with the beamforming and NOMA methods in several scenarios, and the calculation result shows that our method outperforms other methods. Especially, our novel method works properly in the case of high density users.
The management of anticoagulants in patients with atrial fibrillation and history of falls or risk of falls: protocol for a systematic review and meta-analysis
Authors: Galvain Thibaut , Hill Ruaraidh , Donegan Sarah , Lisboa Paulo , Lip Gregory Y. H. , Czanner Gabriela
Published: April 2022

Background

Atrial fibrillation affects an estimated 33 million individuals worldwide and is a major cause of stroke, heart failure, and death. Anticoagulants substantially reduce the risk of stroke but are also associated with an increased risk of bleeding and especially intracranial hemorrhage which is the most concerning complication. Because of this, many patients are not offered anticoagulants, particularly patients at risk of falls or with a history of falls. It is unclear what anticoagulant treatment these patients should be offered. The Liverpool AF-Falls project aims to investigate this area, and this protocol for a systematic review and meta-analysis aims to define what is the most appropriate anticoagulant treatment option for the management of atrial fibrillation patients at risk of falls or with a history of falls.

Methods

This systematic review and meta-analysis will include randomized and non-randomized studies evaluating the safety and efficacy of different anticoagulant treatments (vitamin K antagonist and non-vitamin K antagonist oral anti-coagulant). Bibliographic databases (Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov, Embase, MEDLINE, Scopus and Web of Science) will be searched according to a pre-specified search strategy. Titles, abstracts, and full texts will be assessed by two independent reviewers and disagreements resolved with a third independent reviewer. The Cochrane Risk of Bias tool 2 (RoB 2) will be used to assess the risk of bias in randomized trials, and the Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool will be used for non-randomized studies. A pairwise meta-analysis based on the fixed and random-effects models will be conducted. Publication bias will be evaluated with a funnel plot and Egger’s test. Heterogeneity will be assessed with the I2 statistic. If conditions for indirect comparison are met and sufficient data are available, a network meta-analysis will be conducted using frequentist and Bayesian methodologies.

Discussion

This review will be the first to summarize direct and indirect evidence on the safety and efficacy of anticoagulant treatments in atrial fibrillation patients at risk of falls or with a history of falls. The findings will be important to patients, clinicians, and health policy-makers to inform best practices in the use of these treatments.

Systematic review registration

PROSPERO registry number: CRD42020201086
Generalized variational inequalities for linguistic interpretations using intuitionistic fuzzy relations and projected dynamical systems
Authors: Xie Ting , Li Dapeng
Published: April 2022

The fuzzy set theory enables us to represent our knowledge under multiple interpretations and axiomatic foundations from linguistic to computational representations. While the intuitionistic fuzzy set, as a generalization of the fuzzy set, cannot only represent the tolerance levels, but also the intolerance levels which a decision maker can tolerate and cannot tolerate in the accomplishment of a linguistic interpretation, in this paper, we introduce the generalized variational inequalities for linguistic interpretations using intuitionistic fuzzy relations. It is shown that such problems can be transformed into the classical (nonfuzzy) generalized variational inequalities by means of level sets of the intuitionistic fuzzy relation. Furthermore, the equivalence between the generalized variational inequalities with intuitionistic fuzzy relations and the fuzzy fixed point problems is established. Finally, based on the projection method, we propose an iterative algorithm and a projected neural network model for the generalized variational inequalities with intuitionistic fuzzy relations, and the stability of the proposed projected dynamical system is also investigated.
The impact of the COVID-19 pandemic on pediatric developmental services: a cross-sectional study on overall burden and mental health status
Authors: Borusiak Peter , Mazheika Yuliya , Bauer Susanne , Haberlandt Edda , Krois Ilona , Fricke Christian , Simon Liane , Beschoner Petra , Jerg-Bretzke Lucia , Geiser Franziska , Hiebel Nina , Weidner Kerstin , Albus Christian , Morawa Eva , Erim Yesim
Published: April 2022

Background

The COVID-19 outbreak has taken a heavy toll on the mental well-being of healthcare workers, even those who have not been directly involved in the care of acutely ill patients. The aims of this study were to identify the overall burden and mental health status of healthcare workers in pediatric developmental services under the influence of the COVID-19 pandemic, and to identify the risk and protective factors associated with mental health.

Methods

This cross-sectional web-based study was part of a large multicenter VOICE study conducted among employees ((neuro-)pediatricians, psychologists, speech therapists, occupational therapists, etc.) from various pediatric developmental services between June and July 2020. A total of 1291 questionnaires regarding overall burden, mental health status (depression, generalized anxiety disorder and emotional exhaustion) and risk and protective factors for mental health (working conditions, potential problems during the COVID-19 pandemic and psychological resources) were analyzed. Descriptive statistics and multiple linear regression were used for data analysis.

Results

A total of 44.5% (574/1291) participants felt a high or very high overall burden during the COVID-19 pandemic. Of all the participants, 14.6% (171/1173) reported clinically significant levels of depressive symptoms, 17.0% (199/1173) reported generalized anxiety disorder symptoms and 44.6% (532/1192) reported emotional exhaustion. Multiple linear regression analyses identified several common risk and protective factors for mental health status variables. The burden of an increase in the quantity of work, fear of work and fear of becoming infected showed the strongest negative associations, whereas psychological resources and sufficient relaxation in leisure time exhibited the strongest positive associations.

Conclusion

Employees who were not directly involved in the care of acutely ill patients were also exposed to considerable stress, some of which was not different from that experienced by professionals who were directly affected. These employees should not be lost sight of and must be offered appropriate support.
Genetic heterogeneity on sleep disorders in Parkinson’s disease: a systematic review and meta-analysis
Authors: Huang Jingxuan , Cheng Yangfan , Li Chunyu , Shang Huifang
Published: April 2022

A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson’s disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase (GBA), 25 studies on Leucine-rich repeat kinase 2 (LRRK2) and 7 on parkin (PRKN) genes, and 3 studies on alpha-synuclein gene (SNCA) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA, LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.
α-Synuclein arginylation in the human brain
Authors: Zhao Jun , Pan Buyan , Fina Marie , Huang Yun , Shimogawa Marie , Luk Kelvin C. , Rhoades Elizabeth , Petersson E. James , Dong Dawei W. , Kashina Anna
Published: April 2022

Background

Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated in the mouse brain and that lack of arginylation leads to neurodegeneration in mice.

Methods

Here, we tested α-syn arginylation in human brain pathology using newly derived antibodies in combination with Western blotting, biochemical assays, and experiments in live neurons.

Results

We found that α-syn was arginylated in the human brain on E46 and E83, two sites previously implicated in α-syn pathology and familial cases of Parkinson’s disease. The levels of arginylation in different brain samples ranged between ~ 3% and ~ 50% of the total α-syn pool, and this arginylation nearly exclusively concentrated in the subcellular α-syn fraction that sedimented at low centrifugation speeds and appeared to be simultaneously targeted by multiple posttranslational modifications. Arginylated α-syn was less susceptible to S129 phosphorylation and pathological aggregation in neurons. The arginylation level inversely correlated with the overall α-syn levels and with patient age, suggesting a possible causal relationship between arginylation decline and α-syn-dependent neuropathology.

Conclusion

We propose that α-syn arginylation constitutes a potential neuroprotective mechanism that prevents its abnormal accumulation during neurodegeneration and aging in the human brain.
The clinical characteristics and prognosis in adult Ph negative acute lymphoblastic leukemia with TP53 aberrations
Authors: Fang Qiuyun , Gong Xiaoyuan , Liu Kaiqi , Jia Yujiao , Song Yang , Zhang Guangji , Li Yan , Hao Qishan , Ma Yueshen , Wei Shuning , Liu Bingcheng , Wang Ying , Wei Hui , Wang Jianxiang , Mi Yingchang
Published: April 2022

Very few reports elucidate the prognosis of patients with TP53 aberrations using both measurable residual disease (MRD) and the status of having undergone allogeneic hematopoietic stem cell transplantation (allo-SCT). In this study, aberrations of TP53 were analyzed using next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) in patients with Philadelphia chromosome-negative (Ph−) ALL enrolled in a prospective single-arm clinical trial at our leukemia center. We analyzed the survival of the patients grouped according to the MRD level at the third month and whether or not received allo-SCT. We found that allo-SCT could improve the OS in patients with TP53 aberrations; Patients having negative MRD at the third month still showed worse 3-year OS and 3-year DFS without undergoing allo-SCT, which is different from previous studies, moreover, the prognostic significance of TP53 deletions was as important as TP53 mutations, the importance of screening both TP53 deletions and mutations in adult Ph− ALL at diagnosis should be emphasized.
Reciprocal associations between housing instability and youth criminal legal involvement: a scoping review
Authors: Almquist Lars , Walker Sarah Cusworth
Published: April 2022

Background

Youth experiencing homelessness have disproportionate contact with the criminal legal system. This system contact represents a critical inflection point for enhancing risk or opportunities for stabilization; however, the policy and scholarly traditions examining the criminal legal system have not traditionally incorporated housing or other social determinants as a central focus of intervention.

Methods

We conducted a scoping review using PRISMA-ScR guidelines to examine how the research literature is currently addressing housing within the context of youth involvement in the legal system. Databases searched included PubMed, Web of Science, and Academic Search Complete. Google Scholar was used to identify papers not indexed in the academic databases of interest. Database searches were conducted between September and December 2019 and articles were restricted to those published in English between the year 2000 and 2019. Key study components extracted included demographic information regarding each sample, type of article, study methodology, direction of effects of interest, outcome measures and primary findings, as well as theoretical frameworks engaged by the authors.

Results

The search results returned 2154 titles for review. After screening all 2154 titles, 75 met eligibility for inclusion. Abstract reviews were conducted for all 75 papers. 36 abstracts met eligibility criteria and underwent full-text review. Ultimately, 29 articles satisfied eligibility criteria and were included in this scoping review.

Conclusions

Publications are primarily focused on the social epidemiology of risk factors and behaviors determining youth justice contact, but relatively less so on studies of interventions targeting youth delinquency, crime reduction, or recidivism that included housing support. The lack of continuity in theorizing from epidemiology to applied science in this area represents a gap in the literature that is likely reducing the effectiveness of interventions to interrupt patterns of legal system contact for youth. Integrating a public health framework that emphasizes the upstream social determinants leading to contact with the youth justice system would represent a paradigm shift for the field that would have beneficial effects on long term health outcomes for youth.
Comprehensive study of 12th century wall painting fragments from the St. George Cathedral of the Yuryev Monastery in Veliky Novgorod (Russia) using complementary physico-chemical methods
Authors: Philippova O. S. , Dmitriev A. Yu. , Tsarevskaya T. J. , Dmitrieva S. O.
Published: April 2022

A total of 7 complementary methods have been applied to investigate unique pre-Mongolian 12th century wall paintings from the St. George Cathedral of the Yuriev Monastery in Veliky Novgorod, Russia. Both archaeological samples from the main space of the Cathedral and fragments in situ in the stairs tower of the Cathedral were studied. For the first time in Russia, sensitive neutron methods were used to study the elemental composition of pigments and plasters—neutron activation analysis and prompt gamma activation analysis. This research made it possible to determine elemental and mineral composition of the pigments and plasters used during creation of wall paintings; identify the technique of paintings; make assumptions about the different time of the paintings creation in the main space of the Cathedral and in its stairs tower; as well as reconstruct the presumable original view of the painting of the St. George figure. The discovery of the expensive lazurite pigment attested to the high status of the ktetor of the Cathedral’s murals. The obtained data were compared with Byzantine and Italian paintings of the same period churches.
An exploration into the use of Hansen solubility parameters for modelling reversed-phase chromatographic separations
Authors: Ribar David , Rijavec Tjaša , Kralj Cigić Irena
Published: April 2022

The suitability of Hansen solubility parameters as descriptors for modelling analyte retention during reversed-phase chromatographic experiments was investigated. A novel theoretical model using Hansen solubility parameters as the basis for a complete mathematical derivation of the model was developed. The theoretical model also includes the cavitation volumes of the analytes, which were calculated using ab initio density functional theory methods. A set of three homologous phthalates was used for experimental data collection and subsequent model construction. The training error and the generalization error of the model were additionally evaluated using a range of chemically diverse analytes. Statistical evaluation of the results revealed that the model is suitable for analyte retention prediction but is limited to the analytes used in the model construction. Therefore, the resulting theoretical model cannot be easily generalized. A retention anomaly attributed to the column temperature and mobile phase composition was experimentally observed and mathematically investigated.
Masked emotions: Do face mask patterns and colors affect the recognition of emotions?
Authors: Blazhenkova Olesya , Dogerlioglu-Demir Kivilcim , Booth Robert W.
Published: April 2022

Previous research has shown that face masks impair the ability to perceive social information and the readability of emotions. These studies mostly explored the effect of standard medical, often white, masks on emotion recognition. However, in reality, many individuals prefer masks with different styles. We investigated whether the appearance of the mask (pattern: angular vs. curvy and color: black vs. white) affected the recognition of emotional states. Participants were asked to identify the emotions on faces covered by masks with different designs. The presence of masks resulted in decreasing accuracy and confidence and increasing reaction times, indicating that masks impair emotion recognition. There were no significant effects of angularity versus curvature or color on emotion recognition, which suggests that mask design may not impair the recognition beyond the effect of mere mask wearing. Besides, we found relationships between individual difference variables such as mask wearing attitudes, mask design preferences, individual traits and emotion recognition. The majority of participants demonstrated positive attitudes toward mask wearing and preferred non-patterned black and white masks. Preferences for white masks were associated with better emotion recognition of masked faces. In contrast, those with negative attitudes toward masks showed marginally poorer performance in emotion recognition for masked faces, and preferred patterned more than plain masks, perhaps viewing masks as a fashion item rather than a necessity. Moreover, preferences to wear patterned masks were negatively related to actual wearing of masks indoors and perceived risks of COVID.
More than skin deep: about the influence of self-relevant avatars on inhibitory control
Authors: Friehs Maximilian A. , Dechant Martin , Schäfer Sarah , Mandryk Regan L.
Published: April 2022

One important aspect of cognitive control is the ability to stop a response in progress and motivational aspects, such as self-relevance, which may be able to influence this ability. We test the influence of self-relevance on stopping specifically if increased self-relevance enhances reactive response inhibition. We measured stopping capabilities using a gamified version of the stop-signal paradigm. Self-relevance was manipulated by allowing participants to customize their game avatar (Experiment 1) or by introducing a premade, self-referential avatar (Experiment 2). Both methods create a motivational pull that has been shown to increase motivation and identification. Each participant completed one block of trials with enhanced self-relevance and one block without enhanced self-relevance, with block order counterbalanced. In both experiments, the manipulation of self-relevance was effective in a majority of participants as indicated by self-report on the Player-Identification-Scale, and the effect was strongest in participants that completed the self-relevance block first. In those participants, the degree of subjectively experienced that self-relevance was associated with improvement in stopping performance over the course of the experiment. These results indicate that increasing the degree to which people identify with a cognitive task may induce them to exert greater, reactive inhibitory control. Consequently, self-relevant avatars may be used when an increase in commitment is desirable such as in therapeutic or training settings.
Antifungal activity of chitinase produced by Streptomyces species isolated from grassland soils in Futa Area, Akure
Authors: Ekundayo Fatuyi Olanipekun , Folorunsho Abisola Eniola , Ibisanmi Tope Abraham , Olabanji Olayinka Bukola
Published: April 2022

Background

This study was carried out to investigate the antifungal activity of chitinase produced by Streptomyces species isolated from grassland soils against selected pathogenic fungi, namely: Magnaporthe oryzae, Fusarium graminearum, Rhizoctonia solani, Puccinia species and Botyrtis cinerea. Chitinase produced by Streptomyces albus was purified consecutively with dialysis, gel filtration and ion- exchange chromatography, the test isolate can be exploited for large scale production of chitinase.

Results

Seven Streptomyces species (Streptomyces rimosus, S. albus, S. riseoflavus, S. fumosus, S. spiralis, S. aureofaciens and S. flavogriseus) isolated from three different grassland soils were screened based on the morphology and their ability to produce chitinase. S. rimosus, S. fumosus, S. albus and S. flavogriseus were able to produce chitinase, although the enzyme chitinase was found to be higher in Streptomyces albus. The effect of environmental factors were determined on Streptomyces albus being the best chitinolytic producing isolate. Temperature of 30οC was favourable for Streptomyces albus and pH 6.0 was a growth factor for maximum chitinase production. The activity of the enzyme was stimulated by the addition of metal ions like Mn2+, K+, Na+, Mg+, Fe2+, Ca2+ but Zn2+ inhibited chitinase activity. Chitinase activity was favoured by maltose as carbon source and NH4 (SO4)2 as nitrogen source. Culture filtrate of Streptomyces albus was able to inhibit the growth of all the selected pathogenic fungi namely Magnaporthe oryzae, Fusarium graminearum, Rhizoctonia solani, Puccinia species and Botyrtis cinerea whereas Streptomyces rimosus has the least inhibitory activity.

Conclusions

Streptomyces albus has the highest ability to produce chitinase which can act as antifungal for degradation of the cell wall of many phytopathogenic fungi.
Autophagy-related protein UvAtg14 contributes to mycelial growth, asexual reproduction, virulence and cell stress response in rice false smut fungus Ustilaginoidea virens
Authors: He Xiang , Yu Junjie , Pan Xiayan , Cao Huijuan , Yu Mina , Song Tianqiao , Qi Zhongqiang , Du Yan , Zhang Rongsheng , Liang Dong , Liu Yongfeng
Published: April 2022

Autophagy is an evolutionarily conserved degradation process that degrades damaged proteins to maintain homeostasis and to protect cells against stress. In this study, we identified and characterized a critical autophagy-related protein, UvAtg14, in Ustilaginoidea virens, which is the ortholog of MoAtg14 in rice blast fungus Magnaporthe oryzea. UvAtg14 is co-localized with UvAtg8 (an autophagy marker protein) and is highly expressed at 1–3 days post-inoculation. Deletion of the UvATG14 gene blocked GFP-UvAtg8 trafficking and autophagic digestion and significantly reduced mycelial growth, asexual reproduction, and virulence of U. virens. UvATG14 deletion mutants also exhibited increased sensitivity to various abiotic stresses. Our findings indicate that UvAtg14 is a key autophagic protein and contributes to mycelial growth, conidia production, and pathogenicity in U. virens.
Influence of postural changes on haemodynamics in internal carotid artery bifurcation aneurysm using numerical methods
Authors: Ballambat Raghuvir Pai , Zuber Mohammad , Khader Shah Mohammed Abdul , Ayachit Anurag , Ahmad Kamarul Arifin bin , Vedula Rajanikanth Rao , Kamath Sevagur Ganesh , Shuaib Ibrahim Lutfi
Published: April 2022

Cerebral intracranial aneurysms are serious problems that can lead to stroke, coma, and even death. The effect of blood flow on cerebral aneurysms and their relationship with rupture are unknown. In addition, postural changes and their relevance to haemodynamics of blood flow are difficult to measure in vivo using clinical imaging alone. Computational simulations investigating the detailed haemodynamics in cerebral aneurysms have been developed in recent times not only to understand the progression and rupture but also for clinical evaluation and treatment. In the present study, the haemodynamics of a patient-specific case of a large aneurysm on the left side internal carotid bifurcation (LICA) and no aneurysm on the right side internal carotid bifurcation (RICA) was investigated. The simulation of these patient-specific models using fluid–structure interaction provides a valuable comparison of flow behavior between normal and aneurysm models. The influences of postural changes were investigated during standing, sleeping, and head-down (HD) position. Significant changes in flow were observed during the HD position and quit high arterial blood pressure in the internal carotid artery (ICA) aneurysm model was established when compared to the normal ICA model. The velocity increased abruptly during the HD position by more than four times (LICA and RICA) and wall shear stress by four times (LICA) to ten times (RICA). The complex spiral flow and higher pressures prevailing within the dome increase the risk of aneurysm rupture.
A regulatory GhBPE-GhPRGL module maintains ray petal length in Gerbera hybrida
Authors: Jiang Rui , Yuan Weichao , Yao Wei , Jin Xuefeng , Wang Xiaojing , Wang Yaqin
Published: April 2022

The molecular mechanism regulating petal length in flowers is not well understood. Here we used transient transformation assays to confirm that GhPRGL (proline-rich and GASA-like)—a GASA (gibberellic acid [GA] stimulated in Arabidopsis) family gene—promotes the elongation of ray petals in gerbera (Gerbera hybrida). Yeast one-hybrid screening assay identified a bHLH transcription factor of the jasmonic acid (JA) signaling pathway, here named GhBPE (BIGPETAL), which binds to the GhPRGL promoter and represses its expression, resulting in a phenotype of shortened ray petal length when GhBPE is overexpressed. Further, the joint response to JA and GA of GhBPE and GhPRGL, together with their complementary expression profiles in the early stage of petal growth, suggests a novel GhBPE-GhPRGL module that controls the size of ray petals. GhPRGL promotes ray petal elongation in its early stage especially, while GhBPE inhibits ray petal elongation particularly in the late stage by inhibiting the expression of GhPRGL. JA and GA operate in concert to regulate the expression of GhBPE and GhPRGL genes, providing a regulatory mechanism by which ray petals could grow to a fixed length in gerbera species.
Clinical Biology of the Pituitary Adenoma
Authors: Melmed Shlomo , Kaiser Ursula B , Lopes M Beatriz , Bertherat Jerome , Syro Luis V , Raverot Gerald , Reincke Martin , Johannsson Gudmundur , Beckers Albert , Fleseriu Maria , Giustina Andrea , Wass John A H , Ho Ken K Y
Published: April 2022

All endocrine glands are susceptible to neoplastic growth, yet the health consequences of these neoplasms differ between endocrine tissues. Pituitary neoplasms are highly prevalent and overwhelmingly benign, exhibiting a spectrum of diverse behaviors and impact on health. To understand the clinical biology of these common yet often innocuous neoplasms, we review pituitary physiology and adenoma epidemiology, pathophysiology, behavior, and clinical consequences. The anterior pituitary develops in response to a range of complex brain signals integrating with intrinsic ectodermal cell transcriptional events that together determine gland growth, cell type differentiation, and hormonal production, in turn maintaining optimal endocrine health. Pituitary adenomas occur in 10% of the population; however, the overwhelming majority remain harmless during life. Triggered by somatic or germline mutations, disease-causing adenomas manifest pathogenic mechanisms that disrupt intrapituitary signaling to promote benign cell proliferation associated with chromosomal instability. Cellular senescence acts as a mechanistic buffer protecting against malignant transformation, an extremely rare event. It is estimated that fewer than one-thousandth of all pituitary adenomas cause clinically significant disease. Adenomas variably and adversely affect morbidity and mortality depending on cell type, hormone secretory activity, and growth behavior. For most clinically apparent adenomas, multimodal therapy controlling hormone secretion and adenoma growth lead to improved quality of life and normalized mortality. The clinical biology of pituitary adenomas, and particularly their benign nature, stands in marked contrast to other tumors of the endocrine system, such as thyroid and neuroendocrine tumors.
A Novel Homozygous MC2R Variant Leading to Type-1 Familial Glucocorticoid Deficiency
Authors: Mohammed Idris , Haris Basma , Hussain Khalid
Published: April 2022

Context

Type 1 familial glucocorticoid deficiency (FGD) (OMIM #607397) is a rare autosomal recessive disorder due to mutations in melanocortin-2-receptor (MC2R) gene encoding the G protein-coupled adrenocorticotropic (ACTH) transmembrane receptor.

Objective

The aim of the study is to describe 2 siblings born to a healthy consanguineous family presenting with clinical and biochemical features of FGD, harboring a novel homozygous MC2R variant.

Methods

Both patients are siblings born at term via normal delivery with normal birth weights. The first sibling presented with symptoms of hypoglycemia, repeated episodes of infections starting from 2 days of age. At 18 months of age, low serum cortisol was found, and he was started on hydrocortisone replacement therapy. The second sibling developed hypoglycemia on day 1 after birth, investigations revealed low serum sodium and cortisol levels and was also commenced on hydrocortisone treatment. Whole exome sequencing (WES) and in vitro functional studies on cell line transfected with wild-type and mutant plasmid clones were undertaken.

Results

WES revealed a novel homozygous missense mutation c.326T>A, p.Leu109Gln in the MC2R gene. In-silico prediction tools predicted the effect of this mutation to be deleterious. In vitro study using HEK293 cells transfected with MC2R wild-type and mutant clones showed a defect in protein expression and cAMP generation when stimulated with ACTH.

Conclusion

Homozygous semiconserved p.Leu109Gln mutation disrupts cAMP production and MC2R protein expression leading to ACTH resistance. This study provides additional evidence that this novel pathogenic variant in MC2R results in FGD phenotypes.
Approach to the Medical Treatment of Epilepsy
Authors: Brigo Francesco , Marson Anthony
Published: April 2022

PURPOSE OF REVIEW

This article discusses the use of antiseizure medications in the treatment of focal and generalized epilepsies using an evidence-based approach.

RECENT FINDINGS

In recent years, several new antiseizure medications with differing mechanisms of action have been introduced in clinical practice, and their efficacy and safety has been evaluated in randomized controlled clinical trials. Currently, all antiseizure medications can prevent seizure occurrence, but they have no proven disease-modifying or antiepileptogenic effects in humans. The choice of therapy should integrate the best available evidence of efficacy, tolerability, and effectiveness derived from clinical trials with other pharmacologic considerations, the clinical expertise of the treating physicians, and patient values and preferences. After the failure of a first antiseizure medication, inadequate evidence is available to inform policy. An alternative monotherapy (especially if the failure is because of adverse effects) or a dual therapy (especially if failure is because of inadequate seizure control) can be used.

Currently, several antiseizure medications are available for the treatment of focal or generalized epilepsies. They differ in mechanisms of action, frequency of administration, and pharmacologic properties, with a consequent risk of pharmacokinetic interactions. Major unmet needs remain in epilepsy treatment. A substantial proportion of patients with epilepsy continue to experience seizures despite two or more antiseizure medications, with a negative impact on quality of life. Therefore, more antiseizure medications that could provide higher seizure control with good tolerability and that could positively affect the underlying disease are needed.
Surgical Treatments for Epilepsy
Authors: Culler George W. , Jobst Barbara C.
Published: April 2022

PURPOSE OF REVIEW

More than 20 new antiseizure medications have been approved by the US Food and Drug Administration (FDA) in the past 3 decades; however, outcomes in newly diagnosed epilepsy have not improved, and epilepsy remains drug resistant in up to 40% of patients. Evidence supports improved seizure outcomes and quality of life in those who have undergone epilepsy surgery, but epilepsy surgery remains underutilized. This article outlines indications for epilepsy surgery, describes the presurgical workup, and summarizes current available surgical approaches.

RECENT FINDINGS

Class I evidence has demonstrated the superiority of resective surgery compared to medical therapy for seizure control and quality of life in patients with drug-resistant epilepsy. The use of minimally invasive options, such as laser interstitial thermal therapy and stereotactic radiosurgery, are alternatives to resective surgery in well-selected patients. Neuromodulation techniques, such as responsive neurostimulation, deep brain stimulation, and vagus nerve stimulation, offer a suitable alternative, especially in those where resective surgery is contraindicated or where patients prefer nonresective surgery. Although neuromodulation approaches reduce seizure frequency, they are less likely to be associated with seizure freedom than resective surgery.

Appropriate patients with drug-resistant epilepsy benefit from epilepsy surgery. If two well-chosen and tolerated medication trials do not achieve seizure control, referral to a comprehensive epilepsy center for a thorough presurgical workup and discussion of surgical options is appropriate. Mounting Class I evidence supports a significantly higher chance of stopping disabling seizures with surgery than with further medication trials.