bluuebunny/crossref_metadata_2025 huggingface dataset:
Sheltering Role of Well-Decayed Conifer Logs for Forest Floor Fungi in Long-Term Polluted Boreal Forests
Authors: Mikryukov Vladimir S. , Dulya Olesya V. , Bergman Igor E. , Lihodeevskiy Georgiy A. , Loginova Anzhelika D. , Tedersoo Leho
Published: October 2021

Coarse woody debris (CWD) provides food and shelter to a large proportion of forest biota and is considered vital for biodiversity during periods of harsh weather. However, its importance in long-term stressed ecosystems remains largely unknown. In this work, we explored the contribution of CWD to fungal diversity along the gradient of boreal forest degradation caused by 77 years of heavy industrial emissions. We analyzed the diversity and composition of fungi in 270 samples of well-decayed Picea abies and Abies sibirica logs, as well as forest litter both adjacent to and distant from the logs. Compared with forest litter, the wood had higher water content and possessed substantially lower concentrations of heavy metals, which suggests its potential favorability for biota in polluted areas. The pollution-induced loss of fungal diversity in forest litter reached 34% and was stronger in the microhabitats not influenced by CWD. Meanwhile, wood fungal communities lost less than 10% of their total richness and even increased in alpha diversity. These processes led to the diversity and compositional convergence of fungal communities from different microhabitats and substrates in polluted areas. Despite this, the importance of wood and CWD-influenced microhabitats for fungal diversity maintenance was low. Apart from wood-associated fungi, the taxa whose diversity increased in the wood of polluted areas were ectomycorrhizal fungi and eurytopic soil saprotrophs (Mucoromycota, Mortierellomycota, Eurotiomycetes, and Helotiales) that easily tolerate highly toxic litter. Within the majority of pollution-sensitive soil saprotrophic groups, only terricolous Tricholomataceae benefit from CWD as microrefugia. Upon considering the ecological variability within low-rank taxa, the importance of decayed logs as safe sites can be high for certain soil-inhabiting fungal groups in polluted areas.
Vaccine Development Against Tuberculosis Over the Last 140 Years: Failure as Part of Success
Authors: Kaufmann Stefan H. E.
Published: October 2021

The year 2020 was shaped by the COVID-19 pandemic which killed more people than any other infectious disease in this particular year. At the same time, the development of highly efficacious COVID-19 vaccines within less than a year raises hope that this threat can be tamed in the near future. For the last 200 years, the agent of tuberculosis (TB) has been the worst killer amongst all pathogens. Although a vaccine has been available for 100 years, TB remains a substantial threat. The TB vaccine, Bacille Calmette-Guérin (BCG), has saved tens of millions of lives since its deployment. It was the best and only choice available amongst many attempts to develop efficacious vaccines and all competitors, be they subunit vaccines, viable vaccines or killed whole cell vaccines have failed. Yet, BCG is insufficient. The last decades have witnessed a reawakening of novel vaccine approaches based on deeper insights into immunity underlying TB and BCG immunization. In addition, technical advances in molecular genetics and the design of viral vectors and adjuvants have facilitated TB vaccine development. This treatise discusses firstly early TB vaccine developments leading to BCG as the sole preventive measure which stood the test of time, but failed to significantly contribute to TB control and secondly more recent attempts to develop novel vaccines are described that focus on the genetically modified BCG-based vaccine VPM1002, which has become the frontrunner amongst viable TB vaccine candidates. It is hoped that highly efficacious vaccines against TB will become available even though it remains unclear whether and when this ambition can be accomplished. None the less it is clear that the goal of reducing TB morbidity and mortality by 90% or 95%, respectively, by 2030 as proposed by the World Health Organization depends significantly on better vaccines.
Characterization of the Cancer-Associated Meprin Βeta Variants G45R and G89R
Authors: Gellrich Antonin , Scharfenberg Franka , Peters Florian , Sammel Martin , Helm Ole , Armbrust Fred , Schmidt Frederike , Lokau Juliane , Garbers Christoph , Sebens Susanne , Arnold Philipp , Becker-Pauly Christoph
Published: October 2021

Meprin β is a metalloprotease associated with neurodegeneration, inflammation, extracellular matrix homeostasis, transendothelial cell migration, and cancer. In this study, we investigated two melanoma-associated variants of meprin β, both exhibiting a single amino acid exchange, namely, meprin β G45R and G89R. Based on the structural data of meprin β and with regard to the position of the amino acid exchanges, we hypothesized an increase in proteolytic activity in the case of the G45R variant due to the induction of a potential new activation site and a decrease in proteolytic activity from the G89R variant due to structural instability. Indeed, the G89R variant showed, overall, a reduced expression level compared to wild-type meprin β, accompanied by decreased activity and lower cell surface expression but strong accumulation in the endoplasmic reticulum. This was further supported by the analysis of the shedding of the interleukin-6 receptor (IL-6R) by meprin β and its variants. In transfected HEK cells, the G89R variant was found to generate less soluble IL-6R, whereas the expression of meprin β G45R resulted in increased shedding of the IL-6R compared to wild-type meprin β and the G89R variant. A similar tendency of the induced shedding capacity of G45R was seen for the well-described meprin β substrate CD99. Furthermore, employing an assay for cell migration in a collagen IV matrix, we observed that the transfection of wild-type meprin β and the G45R variant resulted in increased migration of HeLa cells, while the G89R variant led to diminished mobility.
The Usages and Potential Uses of Alginate for Healthcare Applications
Authors: Mollah M. Z. I. , Zahid H. M. , Mahal Z. , Faruque Mohammad Rashed Iqbal , Khandaker M. U.
Published: October 2021

Due to their unique properties, alginate-based biomaterials have been extensively used to treat different diseases, and in the regeneration of diverse organs. A lot of research has been done by the different scientific community to develop biofilms for fulfilling the need for sustainable human health. The aim of this review is to hit upon a hydrogel enhancing the scope of utilization in biomedical applications. The presence of active sites in alginate hydrogels can be manipulated for managing various non-communicable diseases by encapsulating, with the bioactive component as a potential site for chemicals in developing drugs, or for delivering macromolecule nutrients. Gels are accepted for cell implantation in tissue regeneration, as they can transfer cells to the intended site. Thus, this review will accelerate advanced research avenues in tissue engineering and the potential of alginate biofilms in the healthcare sector.
Potential of Sorghum Polyphenols to Prevent and Treat Alzheimer’s Disease: A Review Article
Authors: Rezaee Nasim , Fernando W.M.A.D. Binosha , Hone Eugene , Sohrabi Hamid R. , Johnson Stuart K. , Gunzburg Stuart , Martins Ralph N.
Published: October 2021

Alzheimer’s disease (AD) is characterized by the excessive deposition of extracellular amyloid-beta peptide (Aβ) and the build-up of intracellular neurofibrillary tangles containing hyperphosphorylated tau proteins. This leads to neuronal damage, cell death and consequently results in memory and learning impairments leading to dementia. Although the exact cause of AD is not yet clear, numerous studies indicate that oxidative stress, inflammation, and mitochondrial dysfunction significantly contribute to its onset and progression. There is no effective therapeutic approach to stop the progression of AD and its associated symptoms. Thus, early intervention, preferably, pre-clinically when the brain is not significantly affected, is a better option for effective treatment. Natural polyphenols (PP) target multiple AD-related pathways such as protecting the brain from Aβ and tau neurotoxicity, ameliorating oxidative damage and mitochondrial dysfunction. Among natural products, the cereal crop sorghum has some unique features. It is one of the major global grain crops but in the developed world, it is primarily used as feed for farm animals. A broad range of PP, including phenolic acids, flavonoids, and condensed tannins are present in sorghum grain including some classes such as proanthocyanidins that are rarely found in others plants. Pigmented varieties of sorghum have the highest polyphenolic content and antioxidant activity which potentially makes their consumption beneficial for human health through different pathways such as oxidative stress reduction and thus the prevention and treatment of neurodegenerative diseases. This review summarizes the potential of sorghum PP to beneficially affect the neuropathology of AD.
Cognitive Dysfunctions in Glaucoma: An Overview of Morpho-Functional Mechanisms and the Impact on Higher-Order Visual Function
Authors: Arrigo Alessandro , Aragona Emanuela , Saladino Andrea , Arrigo Davide , Fantaguzzi Federico , Battaglia Parodi Maurizio , Bandello Francesco
Published: October 2021

Background: Glaucoma is a chronic, vision-threatening disease, and a major cause of legal blindness. The current view is no longer limited to the progressive optic nerve injury, since growing evidence strongly support the interpretation of glaucoma as a complex neurodegenerative disease. However, the precise pathogenic mechanisms leading to the onset and progression of central nervous system (CNS) impairment, and the functional consequences of this damage, are still partially understood. The main aim of this review is to provide a complete and updated overview of the current knowledge regarding the CNS involvement in glaucoma, and the possible therapeutic perspectives.

Methods: We made a careful survey of the current literature reporting all the relevant findings related to the cognitive dysfunctions occurring in glaucoma, with specific remarks dedicated on the higher-order visual function impairment and the possible employment of neuroprotective agents.

Results: The current literature strongly support the interpretation of glaucoma as a multifaceted chronic neurodegenerative disease, widely affecting the CNS. The cognitive impairment may vary in terms of higher-order functions involvement and in the severity of the degeneration. Although several neuroprotective agents are currently available, the development of new molecules represents a major topic of investigation for future clinical trials.

Conclusions: Glaucoma earned the right to be fully considered a neurodegenerative disease. Glaucomatous patients may experience a heterogeneous set of visual and cognitive symptoms, progressively deteriorating the quality of life. Neuroprotection is nowadays a necessary therapeutic goal and a future promising way to preserve visual and cognitive functions, thus improving patients’ quality of life.
Effects of Transcranial Direct Current Stimulation and High-Definition Transcranial Direct Current Stimulation Enhanced Motor Learning on Robotic Transcranial Magnetic Stimulation Motor Maps in Children
Authors: Giuffre Adrianna , Zewdie Ephrem , Wrightson James G. , Cole Lauran , Carlson Helen L. , Kuo Hsing-Ching , Babwani Ali , Kirton Adam
Published: October 2021

Introduction: Conventional transcranial direct current stimulation (tDCS) and high-definition tDCS (HD-tDCS) may improve motor learning in children. Mechanisms are not understood. Neuronavigated robotic transcranial magnetic stimulation (TMS) can produce individualised maps of primary motor cortex (M1) topography. We aimed to determine the effects of tDCS- and HD-tDCS-enhanced motor learning on motor maps.

Methods: Typically developing children aged 12–18 years were randomised to right M1 anodal tDCS, HD-tDCS, or Sham during training of their left-hand on the Purdue Pegboard Task (PPT) over 5 days. Bilateral motor mapping was performed at baseline (pre), day 5 (post), and 6-weeks retention time (RT). Primary muscle was the first dorsal interosseous (FDI) with secondary muscles of abductor pollicis brevis (APB) and adductor digiti minimi (ADM). Primary mapping outcomes were volume (mm2/mV) and area (mm2). Secondary outcomes were centre of gravity (COG, mm) and hotspot magnitude (mV). Linear mixed-effects modelling was employed to investigate effects of time and stimulation type (tDCS, HD-tDCS, Sham) on motor map characteristics.

Results: Twenty-four right-handed participants (median age 15.5 years, 52% female) completed the study with no serious adverse events or dropouts. Quality maps could not be obtained in two participants. No effect of time or group were observed on map area or volume. LFDI COG (mm) differed in the medial-lateral plane (x-axis) between tDCS and Sham (p = 0.038) from pre-to-post mapping sessions. Shifts in map COG were also observed for secondary left-hand muscles. Map metrics did not correlate with behavioural changes.

Conclusion: Robotic TMS mapping can safely assess motor cortex neurophysiology in children undergoing motor learning and neuromodulation interventions. Large effects on map area and volume were not observed while changes in COG may occur. Larger controlled studies are required to understand the role of motor maps in interventional neuroplasticity in children.
Non-parametric MRI Brain Atlas for the Polish Population
Authors: Borys Damian , Kijonka Marek , Psiuk-Maksymowicz Krzysztof , Gorczewski Kamil , Zarudzki Lukasz , Sokol Maria , Swierniak Andrzej
Published: October 2021

Introduction: The application of magnetic resonance imaging (MRI) to acquire detailed descriptions of the brain morphology in vivo is a driving force in brain mapping research. Most atlases are based on parametric statistics, however, the empirical results indicate that the population brain tissue distributions do not exhibit exactly a Gaussian shape. Our aim was to verify the population voxel-wise distribution of three main tissue classes: gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF), and to construct the brain templates for the Polish (Upper Silesian) healthy population with the associated non-parametric tissue probability maps (TPMs) taking into account the sex and age influence.

Material and Methods: The voxel-wise distributions of these tissues were analyzed using the Shapiro-Wilk test. The non-parametric atlases were generated from 96 brains of the ethnically homogeneous, neurologically healthy, and radiologically verified group examined in a 3-Tesla MRI system. The standard parametric tissue proportion maps were also calculated for the sake of comparison. The maps were compared using the Wilcoxon signed-rank test and Kolmogorov-Smirnov test. The volumetric results segmented with the parametric and non-parametric templates were also analyzed.

Results: The results confirmed that in each brain structure (regardless of the studied sub-population) the data distribution is skewed and apparently not Gaussian. The determined non-parametric and parametric templates were statistically compared, and significant differences were found between the maps obtained using both measures (the maps of GM, WM, and CSF). The impacts of applying the parametric and non-parametric TPMs on the segmentation process were also compared. The GM volumes are significantly greater when using the non-parametric atlas in the segmentation procedure, while the CSF volumes are smaller.

Discussion and Conclusion: To determine the population atlases the parametric measures are uncritically and widely used. However, our findings suggest that the mean and parametric measures of such skewed distribution may not be the most appropriate summary statistic to find the best spatial representations of the structures in a standard space. The non-parametric methodology is more relevant and universal than the parametric approach in constructing the MRI brain atlases.
Brain-Derived Neurotrophic Factor Secreting Human Mesenchymal Stem Cells Improve Outcomes in Rett Syndrome Mouse Models
Authors: Kim Hyo Jeong , Bayarsaikhan Delger , Lee Jaesuk , Bayarsaikhan Govigerel , Lee Bonghee
Published: October 2021

Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene; MeCP2 regulates the expression of brain-derived neurotrophic factor (BDNF) and increasing BDNF levels ameliorates RTT symptoms. However, the clinical application of BDNF is limited, because of its short half-life and low penetrance across the blood-brain barrier. In this study, we generated BDNF-secreting mesenchymal stem cells (MSCs) from the human umbilical cord cells, using CRISPR-Cas9. We studied the effects of BDNF-MSCs in MECP2 knockout and MECP2-deficient mice. BDNF-MSCs upregulated the expression of BDNF, pAKT, and pERK1/2 and downregulated that of pp38, both in vitro and in vivo. In our in vivo experiments, BDNF-MSCs increased the body and brain weights in mice. BDNF-MSCs increased the neuronal cell numbers in the hippocampus, cortex, and striatum; in addition, they increased the number of synapses. BDNF-MSCs upregulated BDNF and the activity of BDNF downstream effectors, such as pAKT and pERK 1/2; this upregulation was persistent. In conclusion, BDNF-MSCs generated using CRISPR-Cas9 could be a therapeutic strategy for treating RTT.
Patients Prefer a Virtual Reality Approach Over a Similarly Performing Screen-Based Approach for Continuous Oculomotor-Based Screening of Glaucomatous and Neuro-Ophthalmological Visual Field Defects
Authors: Soans Rijul Saurabh , Renken Remco J. , John James , Bhongade Amit , Raj Dharam , Saxena Rohit , Tandon Radhika , Gandhi Tapan Kumar , Cornelissen Frans W.
Published: October 2021

Standard automated perimetry (SAP) is the gold standard for evaluating the presence of visual field defects (VFDs). Nevertheless, it has requirements such as prolonged attention, stable fixation, and a need for a motor response that limit application in various patient groups. Therefore, a novel approach using eye movements (EMs) – as a complementary technique to SAP – was developed and tested in clinical settings by our group. However, the original method uses a screen-based eye-tracker which still requires participants to keep their chin and head stable. Virtual reality (VR) has shown much promise in ophthalmic diagnostics – especially in terms of freedom of head movement and precise control over experimental settings, besides being portable. In this study, we set out to see if patients can be screened for VFDs based on their EM in a VR-based framework and if they are comparable to the screen-based eyetracker. Moreover, we wanted to know if this framework can provide an effective and enjoyable user experience (UX) compared to our previous approach and the conventional SAP. Therefore, we first modified our method and implemented it on a VR head-mounted device with built-in eye tracking. Subsequently, 15 controls naïve to SAP, 15 patients with a neuro-ophthalmological disorder, and 15 glaucoma patients performed three tasks in a counterbalanced manner: (1) a visual tracking task on the VR headset while their EM was recorded, (2) the preceding tracking task but on a conventional screen-based eye tracker, and (3) SAP. We then quantified the spatio-temporal properties (STP) of the EM of each group using a cross-correlogram analysis. Finally, we evaluated the human–computer interaction (HCI) aspects of the participants in the three methods using a user-experience questionnaire. We find that: (1) the VR framework can distinguish the participants according to their oculomotor characteristics; (2) the STP of the VR framework are similar to those from the screen-based eye tracker; and (3) participants from all the groups found the VR-screening test to be the most attractive. Thus, we conclude that the EM-based approach implemented in VR can be a user-friendly and portable companion to complement existing perimetric techniques in ophthalmic clinics.
Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice
Authors: Pan Wenlu , Pan Jing , Zhao Yan , Zhang Hongzheng , Tang Jie
Published: October 2021

Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.
Vestibular Influence on Vertebrate Skeletal Symmetry and Body Shape
Authors: Gordy Clayton , Straka Hans
Published: October 2021

Vestibular endorgans in the vertebrate inner ear form the principal sensors for head orientation and motion in space. Following the evolutionary appearance of these organs in pre-vertebrate ancestors, specific sensory epithelial patches, such as the utricle, which is sensitive to linear acceleration and orientation of the head with respect to earth’s gravity, have become particularly important for constant postural stabilization. This influence operates through descending neuronal populations with evolutionarily conserved hindbrain origins that directly and indirectly control spinal motoneurons of axial and limb muscles. During embryogenesis and early post-embryonic periods, bilateral otolith signals contribute to the formation of symmetric skeletal elements through a balanced activation of axial muscles. This role has been validated by removal of otolith signals on one side during a specific developmental period in Xenopus laevis tadpoles. This intervention causes severe scoliotic deformations that remain permanent and extend into adulthood. Accordingly, the functional influence of weight-bearing otoconia, likely on utricular hair cells and resultant afferent discharge, represents a mechanism to ensure a symmetric muscle tonus essential for establishing a normal body shape. Such an impact is presumably occurring within a critical period that is curtailed by the functional completion of central vestibulo-motor circuits and by the modifiability of skeletal elements before ossification of the bones. Thus, bilateral otolith organs and their associated sensitivity to head orientation and linear accelerations are not only indispensable for real time postural stabilization during motion in space but also serve as a guidance for the ontogenetic establishment of a symmetric body.
Prognostic Signatures of Alternative Splicing Events in Esophageal Carcinoma Based on TCGA Splice-Seq Data
Authors: Ye Ping , Yang Yan , Zhang Liqiang , Zheng Guixi
Published: October 2021

An alternative splicing (AS) event is a highly complex process that plays an essential role in post-transcriptional gene expression. Several studies have suggested that abnormal AS events were the primary element in the pathological process of cancer. However, few works are dedicated to the study of AS events in esophageal carcinoma (EC). In the present study, clinical information and RNA-seq data of EC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The percent spliced in (PSI) values of AS events were acquired from the TCGA Splice-seq. A total of 183 EC patients were enrolled in this study, and 2,212 AS events were found significantly associated with the overall survival of these patients by univariate Cox regression analysis. The prognostic signatures based on AS events were built by multivariate Cox analysis. Receiver operating characteristic (ROC) curves displayed that the area under the curve (AUC) of the following prognostic signatures, including exon skip (ES), alternate terminator (AT), alternate acceptor site (AA), alternate promoter (AP), alternate donor site (AD), retained intron (RI), and total events, was greater than 0.8, suggesting that these seven signatures had valuable prognosis prediction capacity. Finally, the risk score of prognostic signatures was indicated as an independent risk factor of survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to explore the function of splicing factors (SFs) that were associated with AS events. Also, the interactive network between AS events and SFs identified several hub genes and AS events which need further study. This was a comprehensive study that explored prognosis-related AS events and established valuable prognosis signatures in EC patients. The network of interactions between AS events and SFs might offer novel insights into the fundamental mechanisms of tumorigenesis and progression of EC.
p53-Independent Effects of Set7/9 Lysine Methyltransferase on Metabolism of Non-Small Cell Lung Cancer Cells
Authors: Daks Alexandra , Shuvalov Oleg , Fedorova Olga , Petukhov Alexey , Lezina Larissa , Zharova Arsenia , Baidyuk Ekaterina , Khudiakov Alexander , Barlev Nickolai A.
Published: October 2021

Set7/9 is a lysine-specific methyltransferase, which regulates the functioning of both the histone and non-histone substrates, thereby significantly affecting the global gene expression landscape. Using microarray expression profiling, we have identified several key master regulators of metabolic networks, including c-Myc, that were affected by Set7/9 status. Consistent with this observation, c-Myc transcriptional targets—genes encoding the glycolytic enzymes hexokinase (HK2), aldolase (ALDOB), and lactate dehydrogenase (LDHA)—were upregulated upon Set7/9 knockdown (Set7/9KD). Importantly, we showed the short hairpin RNA (shRNA)-mediated attenuation of Set7/9 augmented c-Myc, GLUT1, HK2, ALDOA, and LDHA expression in non-small cell lung cancer (NSCLC) cell lines, not only at the transcriptional but also at the protein level. In line with this observation, Set7/9KD significantly augmented the membrane mitochondrial potential (MMP), glycolysis, respiration, and the proliferation rate of NSCLC cells. Importantly, all these effects of Set7/9 on cell metabolism were p53-independent. Bioinformatic analysis has shown a synergistic impact of Set7/9 together with either GLUT1, HIF1A, HK2, or LDHA on the survival of lung cancer patients. Based on these evidence, we hypothesize that Set7/9 can be an important regulator of energy metabolism in NSCLC.
Comprehensive Bioinformatics Analysis to Identify the Gene HMMR Associated With Lung Adenocarcinoma Prognosis and Its Mechanism of Action in Multiple Cancers
Authors: Shi Jianguang , Chen Yingqi , Wang Zishan , Guo Jin , Tong Changyong , Tong Jingjie , Hu Wentao , Li Chenwei , Li Xinjian
Published: October 2021

Background

Lung cancer is the third most frequently diagnosed cancer in the world, with lung adenocarcinoma (LUAD) as the most common pathological type. But studies on the predictive effect of a single gene on LUAD are limited. We aimed to discover new predictive markers for LUAD.

Methods

Differentially high-expressed genes at each stage were obtained from the TCGA and GTEx databases. The functions of these genes were investigated through GO enrichment and KEGG pathway analyses. Then, the key genes were selected by applying whole gene overall survival time. The expression of the key gene was studied in LUAD, and survival analysis was performed using Kaplan-Meier mapper, followed by univariate and multifactorial COX analysis. Finally, the gene expression and its prognostic significance in the pan-cancer were examined.

Results

A total of 10,106 DEGs were obtained from the two datasets. The top 266 differentially upregulated genes intersected with the top 1,497 overall survival-related genes, and 87 key genes were identified. High-expressed HMMR was associated with a poor prognosis of LUAD. Univariate and multifactorial Cox analysis showed that HMMR was an independent prognostic factor for LUAD patients. A high HMMR expression was strongly associated with the overall survival (OS) and disease-specific survival (DSS) in 11 cancer types and with poorer OS, DSS, and PFI in 10 cancer types.

Conclusion

HMMR may be an independent prognostic indicator and an important biomarker in diagnosing and predicting the survival of LUAD patients. Also, HMMR may be a key predictor of a variety of cancers.
A Scoring System for Assessing the Risk of Malignant Partially Cystic Thyroid Nodules Based on Ultrasound Features
Authors: Xin Yuwei , Liu Feifei , Shi Yan , Yan Xiaohui , Liu Liping , Zhu Jiaan
Published: October 2021

Objective

To assess the ultrasound (US) features of partially cystic thyroid nodules (PCTNs) and to establish a scoring system to further improve the diagnostic accuracy.

Methods

A total of 262 consecutive nodules from September 2017 to March 2020 were included in a primary cohort to construct a scoring system. Moreover, 83 consecutive nodules were enrolled as an validation cohort from May 2018 to August 2020. All nodules were determined to be benign or malignant according to the pathological results after surgery or ultrasound-guided fine-needle aspiration (US-FNA). The US images and demographic characteristics of the patients were analyzed. The ultrasound features of PCTNs were extracted from primary cohort by two experienced radiologists. The features extracted were used to develop a scoring system using logistic regression analysis. Receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic efficacy of the scoring system in both the primary cohort and validation cohort. In addition, the radiologists evaluated the benign and malignant PCTNs of the validation cohort according to the ACR TI-RADS guidelines and clinical experience, and the accuracy of their diagnosis were compared with that of the scoring system.

Results

Based on the eight features of PCTNs, the scoring system showed good differentiation and reproducibility in both cohorts. The scoring system was based on eight features of PCTNs and showed good performance. The area under the curve (AUC) was 0.876 (95% CI, 0.830 - 0.913) in the primary cohort and 0.829(95% CI, 0.730 - 0.903) in the validation cohort. The optimal cutoff value of the scoring system for the diagnosis of malignant PCTNs was 4 points, with a good sensitivity of 71.05% and specificity of 87.63%. The scoring system (AUC=0.829) was superior to radiologists (AUC= 0.736) in diagnosing PCTNs and is a promising method for clinical application.

Conclusions

The scoring system described herein is a convenient and clinically valuable method that can diagnose PCTNs with relatively high accuracy. The use of this method to diagnose PCTNs, which have been previously underestimated, will allow PCTNs to receive reasonable attention, and assist radiologist to confidently diagnose the benignity or malignancy.
Development of a Margin Determination Framework for Tumor-Tracking Radiation Therapy With Intraoperatively Implanted Fiducial Markers
Authors: Kim Jihun , Han Min Cheol , Chang Jee Suk , Hong Chae-Seon , Kim Kyung Hwan , Byun Hwa Kyung , Park Ryeong Hwang , Koom Woong Sub , Park Seong Yong , Kim Jin Sung
Published: October 2021

Purpose

To develop an internal target volume (ITV) margin determination framework (or decision-supporting framework) for treating multiple lung metastases using CyberKnife Synchrony with intraoperatively implanted fiducial markers (IIFMs). The feasibility of using non-ideally implanted fiducial markers (a limited number and/or far from a target) for tracking-based lung stereotactic ablative radiotherapy (SABR) was investigated.

Methods

In the developed margin determination framework, an optimal set of IIFMs was determined to minimize a tracking uncertainty-specific ITV (ITVtracking) margin (margin required to cover target-to-marker motion discrepancy), i.e., minimize the motion discrepancies between gross tumor volume (GTV) and the selected set of fiducial markers (FMs). The developed margin determination framework was evaluated in 17 patients with lung metastases. To automatically calculate the respiratory motions of the FMs, a template matching-based FM tracking algorithm was developed, and GTV motion was manually measured. Furthermore, during-treatment motions of the selected FMs were analyzed using log files and compared with those calculated using 4D CTs.

Results

For 41 of 42 lesions in 17 patients (97.6%), an optimal set of the IIFMs was successfully determined, requiring an ITVtracking margin less than 5 mm. The template matching-based FM tracking algorithm calculated the FM motions with a sub-millimeter accuracy compared with the manual measurements. The patient respiratory motions during treatment were, on average, significantly smaller than those measured at simulation for the patient cohort considered.

Conclusion

Use of the developed margin determination framework employing CyberKnife Synchrony with a limited number of IIFMs is feasible for lung SABR.
Prophylactic Heme Arginate Infusion for Acute Intermittent Porphyria
Authors: Kuo Hung-Chou , Lin Chia-Ni , Tang Yi-Fen
Published: October 2021

Objectives: This study aimed to evaluate the efficacy of long-term weekly prophylactic heme arginate (HA) infusions in reducing attack frequency and severity in female AIP patients.

Methods: We report the results of five female AIP patients with frequent recurrent attacks (>9/year) before and after institution of weekly prophylaxis with heme arginate (3 mg/kg body weight). All five cases had confirmed disease-associated mutations in the porphobilinogen deaminase gene, and all had received genetic and clinical counseling about AIP.

Results: In the five included patients, average annual attack rate (AAR) in the year prior to HA prophylaxis was 11.82 (range 9.03–17.06), and average total HA usage was 32.60 doses (range: 13.71–53.13). After 2.58–14.64 years of HA prophylaxis, average AAR was reduced to 2.23 (range 0.00–5.58), and attack severity (i.e., doses required per attack) was reduced from 2.81 to 1.39 doses/attack. Liver and renal function remained stable during weekly administration of HA prophylaxis. The most common complications were port-A catheter-related events. No other complications or safety concerns occurred with long-term use of HA prophylaxis.

Conclusion: Our study demonstrated women with AIP receiving weekly prophylactic HA infusions resulted in fewer episodes that required acute HA treatment while maintaining stable renal and liver function. Weekly prophylactic HA infusions effectively prevent frequent porphyric attacks and reduce attack severity.
The Multimodal MOPr/DOPr Agonist LP2 Reduces Allodynia in Chronic Constriction Injured Rats by Rescue of TGF-β1 Signalling
Authors: Fidilio Annamaria , Grasso Margherita , Turnaturi Rita , Caruso Giuseppe , Spitale Federica Maria , Vicario Nunzio , Parenti Rosalba , Spoto Salvatore , Musso Nicolò , Marrazzo Agostino , Chiechio Santina , Caraci Filippo , Pasquinucci Lorella , Parenti Carmela
Published: October 2021

Neuropathic pain is one of the most disabling forms of chronic pain and it is characterized by hyperalgesia and allodynia linked to an aberrant processing of pain transmission and to neuroinflammation. Transforming growth factor-β1 (TGF-β1) is an anti-inflammatory cytokine, which protects against neuroinflammation. It has been demonstrated that TGF-β1 and opioid receptors signalling crosstalk results in an improvement of endogenous opioid analgesia, but it is not known whether mu opioid peptide receptor (MOPr) or delta opioid peptide receptor (DOPr) agonists can positively modulate TGF-β1 pathway. In the present study, we examined the correlation between anti-allodynic effect of LP2, a dual-target MOPr/DOPr agonist, and TGF-β1 signalling in the chronic constriction injury (CCI) model. We detected a significant decrease of active TGF-β1 and of its type II receptor TGFβ-R2 levels in the spinal cord from CCI rats and a selective deficit of TGF-β1 in microglia cells both at days 11 and 21 post-ligature, as assessed by immunofluorescence analysis. LP2, when administered from the 11 days post-ligature to 21 days, was able to reduce CCI-induced mechanical allodynia by rescue of TGF-β1 and TGFβ-R2 levels. Our data suggest that the rescue of TGF-β1 signalling by dual-target MOPr/DOPr agonist LP2 could be mediated by DOPr activation in spinal microglia, thus the dual-target approach could represent a novel pharmacological approach to increase the analgesic efficacy of MOPr agonists.
How to Measure Grana – Ultrastructural Features of Thylakoid Membranes of Plant Chloroplasts
Authors: Mazur Radosław , Mostowska Agnieszka , Kowalewska Łucja
Published: October 2021

Granum is a basic structural unit of the thylakoid membrane network of plant chloroplasts. It is composed of multiple flattened membranes forming a stacked arrangement of a cylindrical shape. Grana membranes are composed of lipids and tightly packed pigment-protein complexes whose primary role is the catalysis of photosynthetic light reactions. These membranes are highly dynamic structures capable of adapting to changing environmental conditions by fine-tuning photochemical efficiency, manifested by the structural reorganization of grana stacks. Due to a nanometer length scale of the structural granum features, the application of high-resolution electron microscopic techniques is essential for a detailed analysis of the granum architecture. This mini-review overviews recent approaches to quantitative grana structure analyses from electron microscopy data, highlighting the basic manual measurements and semi-automated workflows. We outline and define structural parameters used by different authors, for instance, granum height and diameter, thylakoid thickness, end-membrane length, Stacking Repeat Distance, and Granum Lateral Irregularity. This article also presents insights into efficient and effective measurements of grana stacks visualized on 2D micrographs. The information on how to correctly interpret obtained data, taking into account the 3D nature of grana stacks projected onto 2D space of electron micrograph, is also given. Grana ultrastructural observations reveal key features of this intriguing membrane arrangement, broadening our knowledge of the thylakoid network’s remarkable plasticity.
God Helps Those Who Help Themselves: How Recipients’ Efforts Perception Affects Donation
Authors: Jin Fei , Zheng Zhengyu , Wu Banggang
Published: October 2021

This research examines how recipients’ efforts to get out of the plight affect the empathy they evoke and the subsequent help they receive from donors. Through three experiments, we find that the higher the efforts made by the recipients to get out of the plight, the stronger the donors’ willingness to donate. This effect is moderated by the need severity of the recipients. The more serious the plight is, the stronger the impact of the degree of efforts on the willingness to donate. This research makes theoretical contributions to charitable giving and provides implications for non-profit organizations on describing recipients’ efforts to get out of their plight.
Psychological Difficulties Mediate and Self-Efficacy Moderates the Relationship Between Family Cumulative Risk and Hope Among Chinese Children From Low-Income Families
Authors: Yin Xiayun , Wang Dongfang , Li Zhihua , Huang Yuesheng
Published: October 2021

This longitudinal study investigated the role of psychological difficulties and self-efficacy in the relationship between family cumulative risk and hope among children from low-income families. The participants were 392 Chinese children from low-income families; the study extended for 2 years, and participants completed data that were collected with the following questionnaires: the Family Cumulative Risk Index, Children's Hope Scale, Strengths and Difficulties Questionnaire-Difficulties subscale, and General Self-efficacy Scale. The results demonstrated that psychological difficulties played a mediating role in the relationship between family cumulative risk and hope; specifically, family cumulative risk predicted hope of children via psychological difficulties. Self-efficacy moderated the relationship between psychological difficulties and hope. This moderation supported “a drop in the ocean effect”; the protective effect of high self-efficacy worked only when psychological difficulties were at low levels. When psychological difficulties were at high levels, the buffering effect of self-efficacy on family cumulative risk was gradually weakened and eventually lost.
Family Functioning in the Time of COVID-19 Among Economically Vulnerable Families: Risks and Protective Factors
Authors: He Minxuan , Cabrera Natasha , Renteria Jone , Chen Yu , Alonso Angelica , McDorman S. Alexa , Kerlow Marina A. , Reich Stephanie M.
Published: October 2021

The ongoing COVID-19 crisis has been particularly harmful to economically vulnerable families with young children. We surveyed 247 low-income mothers and fathers from 142 families in the United States about changes in their family life following the economic and social restrictions imposed by the pandemic. We examined the associations between pandemic-related risk factors such as economic stressors (e.g., loss of job) and social stressors (e.g., exposure to the virus) on family functioning (e.g., parents’ mental health, parent engagement, and children’s socioemotional behaviors) and the degree to which coparenting support and parents’ positivity protected families from the negative effects of these stressors on their wellbeing. We found both positive and negative associations. Mothers and fathers who reported more economic stressors since the pandemic also observed that their children behaved more prosocially and that fathers experienced more mental health difficulties during the pandemic. Mothers and fathers who reported more social stressors reported that they were less engaged with their children and their children exhibited more behavior problems compared to before the pandemic. We also found that mothers and fathers who reported feeling more positive also reported feeling less depressed and stressed during the pandemic and observed that their children had more prosocial behaviors compared to before the pandemic. Compared to before the pandemic, mothers and fathers who reported a more supportive coparenting relationship also reported more parent engagement and observed more prosocial behaviors in their children. In terms of protective factors, high levels of parent positivity during the pandemic protected mothers (less mental health difficulties) whereas high levels of coparenting support protected fathers (less mental health difficulties) from the negative effects of economic stress on their mental health during the pandemic. These findings highlight family processes that could promote resilience in mothers and fathers in the face of pandemic-related economic and social stressors.
Pandemic-Related Stress Symptoms Among Norwegian Parents of Adolescents in Grades 6 to 8
Authors: Idsoe Thormod , Dyregrov Atle , Janson Harald , Nærde Ane
Published: October 2021

We investigated pandemic-related stress symptoms during the first COVID-19 lockdown period in spring 2020 among parents of adolescents that were 11 to 13 years old in the study period. We also investigated whether parental stress symptoms were associated with family situation and family activities during lockdown. Altogether 147 couples reported about their own trauma-related stress symptoms following the outbreak of the pandemic. Among the respondents, 9.5% of the mothers and 10.2% of the fathers had scores over cutoff on the screener (IES-6) measuring stress symptoms, a non-significant gender difference. Scores on the screener were not associated with family contamination or lockdown consequences. Family activities during lockdown did not impact the pandemic stress symptom levels. Whereas, the experience of the COVID-19 pandemic pose a stressor to most people, it is unlikely to be a criterion A event for other than directly affected families.
The Psychometric Properties of the Stress and Anxiety to Viral Epidemics-6 Items: A Test in the U.S. General Population
Authors: Lee Sangha , Lee Jihoon , Yoo Soyoung , Suh Sooyeon , Chung Seockhoon , Lee Sherman A.
Published: October 2021

Objectives: Many individuals around the world are suffering from psychological distress due to the COVID-19 outbreak. The aim of this study is to explore the validity and reliability of the English version of Stress and Anxiety to Viral Epidemics-6 (SAVE-6), which measures the anxiety response of the general population to the viral epidemic.

Methods: A cross-sectional web-based study with self-reporting measures was conducted. A total of 314 United States residents were recruited via online platform in exchange for payment. The participants were asked to an anonymous questionnaire, collecting information on demographics, psychiatric history, SAVE-6, Patient Health Questionnaire-4 (PHQ-4), and the Coronavirus Anxiety Scale.

Results: The result from confirmatory factor analysis (CFA) demonstrated that a single-factor model [χ(9)2 = 11.53, p = 0.24] yielded excellent fit for all of indices [χ2/df ratio = 1.28; CFI = 1.00; TLI = 1.00; SRMR = 0.02; RMSEA = 0.03 (0.00, 0.07; 90% CI)] and yielded strong internal consistency reliability (Cronbach's α = 0.88). The results from multigroup CFAs showed that there were no gender differences [Δχ(6)2 = 3.20, p = 0.78, ns] and no race differences [Δχ(6)2=3.60, p = 0.73, ns] between the models, along with excellent model fits.

Conclusions: The results of this study support the reliability and validity of SAVE-6 with strong psychometric properties for the English version of the U.S. population.
Schoolteachers' Resilience Does but Self-Efficacy Does Not Mediate the Influence of Stress and Anxiety Due to the COVID-19 Pandemic on Depression and Subjective Well-Being
Authors: Cho Inn-Kyu , Lee Jihoon , Kim Kyumin , Lee Joohee , Lee Sangha , Yoo Soyoung , Suh Sooyeon , Chung Seockhoon
Published: October 2021

Objectives: In the current coronavirus disease (COVID-19) pandemic, schoolteachers experience stress from addressing students or performing school tasks that may result in burnout. This study aimed to observe whether teachers' stress and anxiety due to the pandemic can influence their depression or psychological well-being and examine whether their resilience or self-efficacy mediates this association.

Methods: During March 4–15, 2021, 400 teachers participated and responded voluntarily to an online survey that included the Stress and Anxiety to Viral Epidemics-9 items (SAVE-9), the Teacher-Efficacy Scale, the Brief Resilience Scale (BRS), the WHO-5 Well-Being Index, and the Patients Health Questionnaire-9 items.

Results: High psychological well-being of teachers in COVID-19 pandemic era was expected by a low SAVE-9 score (aOR = 0.95; 95% CI, 0.91–0.99), a high level of self-efficacy (aOR = 1.03; 95% CI, 1.01–1.06), and a high BRS score (aOR = 1.18; 95% CI, 1.10–1.27). Moreover, teachers' resilience mediated the effects of stress and anxiety from the COVID-19 pandemic on their subjective well-being or depression.

Conclusions: Schoolteachers' subjective well-being and depression were influenced by high levels of stress and anxiety of the viral epidemic, and their resilience mediated this relationship in this COVID-19 pandemic era.