bluuebunny/crossref_metadata_2025 huggingface dataset:
The Significance of Military Expenditure, Tourism, and Exports for Sustainable Economic Growth
Authors: Aziz Ghazala , Alsaggaf Majid Ibrahim , Khan Mohd Saeed
Published: December 2021

The current empirical study addresses the recent economics of Saudi Arabia such as the uncertainty of economic growth and dependence on oil export. For this purpose, labor, capital, oil price, terrorism, military expenditure, tourism, and exports are added to the analysis. ARDL long-run and short-run analyses are used, and the results of the study have revealed that labor is negatively related to economic growth, which suggests that efforts should be done to reduce dependence on international labor through the installation of production facilities in those countries where labor is cheap. Also, it is noted that capital, tourism, and non-oil exports enhance economic growth, whereas oil price is the main problem for the economic growth of the country. These results suggest that the diversification of exports to non-oil products is a good strategy to boost economic growth. Alongside, domestic tourism should be promoted to enhance its share in economic activities. The current study helps the policy makers to open new earning avenues such as enhanced tourism sectors and modernized industries which help in technology exports.
Evolutionary and Ecological Explanations for the Elevational Flexibility of Several East African Bird Species Complexes
Authors: Fjeldså Jon , Bowie Rauri C. K.
Published: December 2021

Africa’s montane areas are broken up into several large and small units, each isolated as forest-capped “sky islands” in a “sea” of dry lowland savanna. Many elements of their biota, including montane forest birds, are shared across several disjunct mountains, yet it has been difficult to rigorously define an Afromontane forest avifauna, or determine its evolutionary relationships with the birds of the surrounding lowland forests. In order to trace the historical relationship between lowland and highland avifaunas, we review cases of species or groups of closely related species with breeding populations at different elevations, and use phylogeographic methods to explore the historical connections between such populations within the biodiversity hotspot of East Africa. The study reveals several idiosyncratic patterns, but also a prominent number of cases of gene flow between populations in southern areas, mainly around the Malawi Rift, and mountains and coastal forests to the north, close to the equator. This may reflect more continuous past distributions through northern Mozambique and coastal Tanzania, or seasonal migrations between areas with different rainfall regimes. Over time, these distributional dynamics have resulted in a higher persistence of lineages, and an accumulation of forest-dependent lineages within the Eastern Arc Mountains of Tanzania and the northern part of the coastal forest mosaic.
Genome Analysis of Lagocephalus sceleratus: Unraveling the Genomic Landscape of a Successful Invader
Authors: Danis Theodoros , Papadogiannis Vasileios , Tsakogiannis Alexandros , Kristoffersen Jon B. , Golani Daniel , Tsaparis Dimitris , Sterioti Aspasia , Kasapidis Panagiotis , Kotoulas Georgios , Magoulas Antonios , Tsigenopoulos Costas S. , Manousaki Tereza
Published: December 2021

The Tetraodontidae family encompasses several species which attract scientific interest in terms of their ecology and evolution. The silver-cheeked toadfish (Lagocephalus sceleratus) is a well-known “invasive sprinter” that has invaded and spread, in less than a decade, throughout the Eastern and part of the Western Mediterranean Sea from the Red Sea through the Suez Canal. In this study, we built and analysed the first near-chromosome level genome assembly of L. sceleratus and explored its evolutionary landscape. Through a phylogenomic analysis, we positioned L. sceleratus closer to T. nigroviridis, compared to other members of the family, while gene family evolution analysis revealed that genes associated with the immune response have experienced rapid expansion, providing a genetic basis for studying how L. sceleratus is able to achieve highly successful colonisation. Moreover, we found that voltage-gated sodium channel (NaV 1.4) mutations previously connected to tetrodotoxin resistance in other pufferfishes are not found in L. sceleratus, highlighting the complex evolution of this trait. The high-quality genome assembly built here is expected to set the ground for future studies on the species biology.
Sex Differences in Substance Use Disorders: A Neurobiological Perspective
Authors: Cornish Jennifer L. , Prasad Asheeta A.
Published: December 2021

Clinical studies provide fundamental knowledge of substance use behaviors (substance of abuse, patterns of use, relapse rates). The combination of neuroimaging approaches reveal correlation between substance use disorder (SUD) and changes in neural structure, function, and neurotransmission. Here, we review these advances, placing special emphasis on sex specific findings from structural neuroimaging studies of those dependent on alcohol, nicotine, cannabis, psychostimulants, or opioids. Recent clinical studies in SUD analyzing sex differences reveal neurobiological changes that are differentially impacted in common reward processing regions such as the striatum, hippocampus, amygdala, insula, and corpus collosum. We reflect on the contribution of sex hormones, period of drug use and abstinence, and the potential impact of these factors on the interpretation of the reported findings. With the overall recognition that SUD impacts the brains of females and males differentially, it is of fundamental importance that future research is designed with sex as a variable of study in this field. Improved understanding of neurobiological changes in males and females in SUD will advance knowledge underlying sex-specific susceptibility and the neurobiological impact in these disorders. Together these findings will inform future treatments that are tailor designed for improved efficacy in females and males with SUD.
The Elevated Expressions of Anti-lipopolysaccharide Factors After Priming Stimulation Confer Lastingly Humoral Protection in Crab Eriocheir sinensis
Authors: Wang Weilin , Li Yan , Fan Siqi , Lian Xingye , Cao Wanqing , Song Xiaorui , Yi Qilin , Wang Lingling , Song Linsheng
Published: December 2021

Evidence of immune memory in invertebrates (immune priming) has accumulated in various organisms, and both cellular and humoral immune reactions are speculated to be involved in immune priming. However, there is a lack of understanding of the molecular mechanisms involved. In the present study, the protective effect of primed haemolymph was further validated by the increased survival rate of naïve crabs receiving a transfusion of primed haemolymph. By proteomic analysis, there were 474 proteins identified from the primed haemolymph, and most of them were functionally annotated in transport and metabolism classes. A total of 70 proteins were found to be differentially expressed in haemolymph at 12 hours and 7 days after priming stimulation with Aeromonas hydrophila, among which anti-lipopolysaccharide factor 1 (EsALF-1) and 3 (EsALF-3) were identified as the most significant (p < 0.05). After being challenged with A. hydrophila, EsALF-1 and EsALF-3 were highly expressed at both mRNA (in haemocytes) and protein (in haemolymph) levels compared with blank crabs, and the mRNA expressions of components in the EsTLR1-EsMyd88-EsPelle-EsALF pathway also increased significantly (p < 0.05). The EsALF-3 and EsMyd88 were even significantly higher expressed in response to the second A. hydrophila challenge, but their expressions all decreased (p < 0.05) when EsTLR1 was knocked down by RNAi. After the naïve crabs received an injection with the recombinant protein of EsALF-1 (rEsALF-1) or EsALF-3 (rEsALF-3), their survival rate increased significantly (p < 0.05) upon A. hydrophila stimulation. In contrast, the survival rate of the primed crabs reduced significantly (p < 0.05) after they received an injection with the antibody of EsALF-1 or EsALF-3. The enhanced expressions of EsALF-1 and EsALF-3 after A. hydrophilap riming stimulation could sustain for four weeks. All the results suggested that the EsTLR1-mediated productions of EsALF-1 and EsALF-3 in haemolymph played an indispensable role in the month-long humoral immune protection induced by A. hydrophila, which provides solid evidence of immune priming in crabs and a valuable reference for further understanding immune memory in invertebrates.
Angioedema Without Wheals: Challenges in Laboratorial Diagnosis
Authors: Grumach Anete S. , Veronez Camila L. , Csuka Dorottya , Farkas Henriette
Published: December 2021

Angioedema is a prevailing symptom in different diseases, frequently occurring in the presence of urticaria. Recurrent angioedema without urticaria (AE) can be hereditary (HAE) and acquired (AAE), and several subtypes can be distinguished, although clinical presentation is quite similar in some of them. They present with subcutaneous and mucosal swellings, affecting extremities, face, genitals, bowels, and upper airways. AE is commonly misdiagnosed due to restricted access and availability of appropriate laboratorial tests. HAE with C1 inhibitor defect is associated with quantitative and/or functional deficiency. Although bradykinin-mediated disease results mainly from disturbance in the kallikrein–kinin system, traditionally complement evaluation has been used for diagnosis. Diagnosis is established by nephelometry, turbidimetry, or radial immunodiffusion for quantitative measurement of C1 inhibitor, and chromogenic assay or ELISA has been used for functional C1-INH analysis. Wrong handling of the samples can lead to misdiagnosis and, consequently, mistaken inappropriate approaches. Dried blood spot (DBS) tests have been used for decades in newborn screening for certain metabolic diseases, and there has been growing interest in their use for other congenital conditions. Recently, DBS is now proposed as an efficient tool to diagnose HAE with C1 inhibitor deficiency, and its use would improve the access to outbound areas and family members. Regarding HAE with normal C1 inhibitor, complement assays’ results are normal and the genetic sequencing of target genes, such as exon 9 ofF12andPLG, is the only available method. New methods to measure cleaved high-molecular-weight kininogen and activated plasma kallikrein have emerged as potential biochemical tests to identify bradykinin-mediated angioedema. Validated biomarkers of kallikrein–kinin system activation could be helpful in differentiating mechanisms of angioedema. Our aim is to focus on the capability to differentiate histaminergic AE from bradykinin-mediated AE. In addition, we will describe the challenges developing specific tests like direct bradykinin measurements. The need for quality tests to improve the diagnosis is well represented by the variability of results in functional assays.
Single-Cell Regulatory Network Inference and Clustering Identifies Cell-Type Specific Expression Pattern of Transcription Factors in Mouse Sciatic Nerve
Authors: Li Mingchao , Min Qing , Banton Matthew C. , Dun Xinpeng
Published: December 2021

Advances in single-cell RNA sequencing technologies and bioinformatics methods allow for both the identification of cell types in a complex tissue and the large-scale gene expression profiling of various cell types in a mixture. In this report, we analyzed a single-cell RNA sequencing (scRNA-seq) dataset for the intact adult mouse sciatic nerve and examined cell-type specific transcription factor expression and activity during peripheral nerve homeostasis. In total, we identified 238 transcription factors expressed in nine different cell types of intact mouse sciatic nerve. Vascular smooth muscle cells have the lowest number of transcription factors expressed with 17 transcription factors identified. Myelinating Schwann cells (mSCs) have the highest number of transcription factors expressed, with 61 transcription factors identified. We created a cell-type specific expression map for the identified 238 transcription factors. Our results not only provide valuable information about the expression pattern of transcription factors in different cell types of adult peripheral nerves but also facilitate future studies to understand the function of key transcription factors in the peripheral nerve homeostasis and disease.
A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome
Authors: Jiang Yanbo , Patton Mary H. , Zakharenko Stanislav S.
Published: December 2021

Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages. Consequently, the development of therapies continues to be stagnant, and overall prognosis is poor. The main obstacle to improving the treatment of schizophrenia is its multicausal, polygenic etiology, which is difficult to model. Clinical observations and the emergence of preclinical models of rare but well-defined genomic lesions that confer substantial risk of schizophrenia (e.g., 22q11.2 microdeletion) have highlighted the role of the thalamus in the disease. Here we review the literature on the molecular, cellular, and circuitry findings in schizophrenia and discuss the leading theories in the field, which point to abnormalities within the thalamus as potential pathogenic mechanisms of schizophrenia. We posit that synaptic dysfunction and oscillatory abnormalities in neural circuits involving projections from and within the thalamus, with a focus on the thalamocortical circuits, may underlie the psychotic (and possibly other) symptoms of schizophrenia.
Working Memory and Language Contribution to Verbal Learning and Memory in Drug-Resistant Unilateral Focal Temporal Lobe Epilepsy
Authors: Bolocan Monica , Iacob Claudia I. , Avram Eugen
Published: December 2021

We aimed to investigate the working memory (WM) and language separate contributions to verbal learning and memory in patients with unilateral drug-resistant temporal lobe epilepsy (drTLE); additionally, we explored the mediating role of WM on the relationship between the number of antiepileptic drugs (AEDs) and short-term verbal memory. We retrospectively enrolled 70 patients with left (LTLE; n = 44) and right (RTLE; n = 26) drTLE. About 40 similar (age and education) healthy controls were used to determine impairments of groups at WM, language (naming and verbal fluency), and verbal learning and memory (five trials list-learning, story memory—immediate recall). To disentangle the effect of learning from the short-term memory, we separately analyzed performances at the first trial, last trial, and delayed-recall list-learning measures, in addition to the total learning capacity (the sum of the five trials). Correlation and regression analyses were used to assess the contribution of potential predictors while controlling for main clinical and demographic variables, and ascertain the mediating role of WM. All patients were impaired at WM and story memory, whereas only LTLE showed language and verbal learning deficits. In RTLE, language was the unique predictor for the most verbal learning performances, whereas WM predicted the results at story memory. In LTLE, WM was the sole predictor for short-term verbal learning (list-learning capacity; trial 1) and mediated the interaction between AED number and the performance at these measures, whereas language predicted the delayed-recall. Finally, WM confounded the performance at short-term memory in both groups, although at different measures. WM is impaired in drTLE and contributes to verbal memory and learning deficits in addition to language, mediating the relationship between AED number and short-term verbal memory in LTLE. Clinicians should consider this overlap when interpreting poor performance at verbal learning and memory in drTLE.
Transverse Sinus Stenosis in Venous Pulsatile Tinnitus Patients May Lead to Brain Perfusion and White Matter Changes
Authors: Li Xiaoshuai , Xu Ning , Meng Xuxu , Dai Chihang , Qiu Xiaoyu , Ding Heyu , Lv Han , Zeng Rong , Xie Jing , Zhao Pengfei , Yang Zhenghan , Gong Shusheng , Wang Zhenchang
Published: December 2021

Objective: Transverse sinus stenosis (TSS) is associated with various symptoms, but whether it can lead to pathological brain changes is unclear. This study aimed to investigate brain changes in venous pulsatile tinnitus (PT) patients with TSS.

Materials and Methods: In this study, fifty-five consecutive venous PT patients and fifty age- and gender-matched healthy controls (HCs) were investigated. In CT venography, the combined conduit score (CCS) was used to assess the degree of TSS in venous PT patients. Magnetic resonance venography was used to assess TSS in HCs. All the participants had undergone arterial spin labeling and structural MRI scans.

Results: Two patients without TSS and ten HCs with TSS were excluded. Fifty-three venous PT patients with TSS and 40 HCs without TSS were included in this study. All the patients had unilateral cases: 16 on the left and 37 on the right. Based on the CCS, the patients were divided into high-degree TSS (a score of 1–2) (n = 30) and low-degree TSS groups (a score of 3–4) (n = 23). In the whole brain and gray matter, the patients with high-degree TSS showed decreased cerebral blood flow (CBF) compared with patients with low-degree TSS as well as HCs (P < 0.05), and no significant difference in CBF was found in patients with low-degree TSS and HCs (P > 0.05). In white matter (WM) regions, the patients with high-degree TSS exhibited decreased CBF relative to the HCs (P < 0.05). The incidence of cloud-like WM hyperintensity was significantly higher in the above two patient groups than in the HC group (P < 0.05).

Conclusion: TSS in venous PT patients may lead to decreased CBF and cloud-like WM hyperintensity. These neuroimaging findings may provide new insights into pathological TSS in venous PT.
Closing the Loop With Cortical Sensing: The Development of Adaptive Deep Brain Stimulation for Essential Tremor Using the Activa PC+S
Authors: Fra̧czek Tomasz M. , Ferleger Benjamin I. , Brown Timothy E. , Thompson Margaret C. , Haddock Andrew J. , Houston Brady C. , Ojemann Jeffrey G. , Ko Andrew L. , Herron Jeffrey A. , Chizeck Howard J.
Published: December 2021

Deep Brain Stimulation (DBS) is an important tool in the treatment of pharmacologically resistant neurological movement disorders such as essential tremor (ET) and Parkinson's disease (PD). However, the open-loop design of current systems may be holding back the true potential of invasive neuromodulation. In the last decade we have seen an explosion of activity in the use of feedback to “close the loop” on neuromodulation in the form of adaptive DBS (aDBS) systems that can respond to the patient's therapeutic needs. In this paper we summarize the accomplishments of a 5-year study at the University of Washington in the use of neural feedback from an electrocorticography strip placed over the sensorimotor cortex. We document our progress from an initial proof of hardware all the way to a fully implanted adaptive stimulation system that leverages machine-learning approaches to simplify the programming process. In certain cases, our systems out-performed current open-loop approaches in both power consumption and symptom suppression. Throughout this effort, we collaborated with neuroethicists to capture patient experiences and take them into account whilst developing ethical aDBS approaches. Based on our results we identify several key areas for future work. “Graded” aDBS will allow the system to smoothly tune the stimulation level to symptom severity, and frequent automatic calibration of the algorithm will allow aDBS to adapt to the time-varying dynamics of the disease without additional input from a clinician. Additionally, robust computational models of the pathophysiology of ET will allow stimulation to be optimized to the nuances of an individual patient's symptoms. We also outline the unique advantages of using cortical electrodes for control and the remaining hardware limitations that need to be overcome to facilitate further development in this field. Over the course of this study we have verified the potential of fully-implanted, cortically driven aDBS as a feasibly translatable treatment for pharmacologically resistant ET.
Hierarchical Spatio-Temporal Modeling of Naturalistic Functional Magnetic Resonance Imaging Signals via Two-Stage Deep Belief Network With Neural Architecture Search
Authors: Ren Yudan , Xu Shuhan , Tao Zeyang , Song Limei , He Xiaowei
Published: December 2021

Naturalistic functional magnetic resonance imaging (NfMRI) has become an effective tool to study brain functional activities in real-life context, which reduces the anxiety or boredom due to difficult or repetitive tasks and avoids the problem of unreliable collection of brain activity caused by the subjects’ microsleeps during resting state. Recent studies have made efforts on characterizing the brain’s hierarchical organizations from fMRI data by various deep learning models. However, most of those models have ignored the properties of group-wise consistency and inter-subject difference in brain function under naturalistic paradigm. Another critical issue is how to determine the optimal neural architecture of deep learning models, as manual design of neural architecture is time-consuming and less reliable. To tackle these problems, we proposed a two-stage deep belief network (DBN) with neural architecture search (NAS) combined framework (two-stage NAS-DBN) to model both the group-consistent and individual-specific naturalistic functional brain networks (FBNs), which reflected the hierarchical organization of brain function and the nature of brain functional activities under naturalistic paradigm. Moreover, the test-retest reliability and spatial overlap rate of the FBNs identified by our model reveal better performance than that of widely used traditional methods. In general, our model provides a promising method for characterizing hierarchical spatiotemporal features under the natural paradigm.
Home-Based Transcranial Direct Current Stimulation for the Treatment of Symptoms of Depression and Anxiety in Temporal Lobe Epilepsy: A Randomized, Double-Blind, Sham-Controlled Clinical Trial
Authors: Mota Suelen Mandelli , Amaral de Castro Luiza , Riedel Patrícia Gabriela , Torres Carolina Machado , Bragatti José Augusto , Brondani Rosane , Secchi Thais Leite , Sanches Paulo Roberto Stefani , Caumo Wolnei , Bianchin Marino Muxfeldt
Published: December 2021

We conducted a double-blind randomized clinical trial in order to examine the effects and the safety of home-based transcranial direct current stimulation (tDCS) on depressive and anxious symptoms of patients with temporal lobe epilepsy (TLE). We evaluated 26 adults with TLE and depressive symptoms randomized into two different groups: active tDCS (tDCSa) and Sham (tDCSs). The patients were first submitted to 20 sessions of tDCS for 20 min daily, 5 days a week for 4 weeks and then received a maintenance tDCS application in the research laboratory once a week for 3 weeks. The intensity of the current was 2 mA, applied bilaterally over the dorsolateral prefrontal cortex, with the anode positioned on the left side and the cathode on the right side. Participants were evaluated on days 1, 15, 30, and 60 of the study using the Beck Depression Inventory II (BDI). A follow-up evaluation was performed 1 year after the end of treatment. They were also evaluated for quality of life and for anxious symptoms as secondary outcomes. The groups did not differ in clinical, socioeconomic or psychometric characteristics at the initial assessment. There was no statistically significant difference between groups regarding reported adverse effects, seizure frequency or dropouts. On average, between the 1st and 60th day, the BDI score decreased by 43.93% in the active group and by 44.67% in the Sham group (ΔBDIfinal – initial = −12.54 vs. −12.20, p = 0.68). The similar improvement in depressive symptoms observed in both groups was attributed to placebo effect and interaction between participants and research group and not to tDCS intervention per se. In our study, tDCS was safe and well tolerated, but it was not effective in reducing depressive or anxiety symptoms in patients with temporal lobe epilepsy.

Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT03871842].
Eye Tracking in Driver Attention Research—How Gaze Data Interpretations Influence What We Learn
Authors: Ahlström Christer , Kircher Katja , Nyström Marcus , Wolfe Benjamin
Published: December 2021

Eye tracking (ET) has been used extensively in driver attention research. Amongst other findings, ET data have increased our knowledge about what drivers look at in different traffic environments and how they distribute their glances when interacting with non-driving related tasks. Eye tracking is also the go-to method when determining driver distraction via glance target classification. At the same time, eye trackers are limited in the sense that they can only objectively measure the gaze direction. To learn more about why drivers look where they do, what information they acquire foveally and peripherally, how the road environment and traffic situation affect their behavior, and how their own expertise influences their actions, it is necessary to go beyond counting the targets that the driver foveates. In this perspective paper, we suggest a glance analysis approach that classifies glances based on their purpose. The main idea is to consider not only the intention behind each glance, but to also account for what is relevant in the surrounding scene, regardless of whether the driver has looked there or not. In essence, the old approaches, unaware as they are of the larger context or motivation behind eye movements, have taken us as far as they can. We propose this more integrative approach to gain a better understanding of the complexity of drivers' informational needs and how they satisfy them in the moment.
Dietary Salt Intake and Gastric Cancer Risk: A Systematic Review and Meta-Analysis
Authors: Wu Bo , Yang Dehua , Yang Shuhan , Zhang Guangzhe
Published: December 2021

The results of prospective cohort studies regarding the role of salt intake and subsequent gastric cancer risk are inconsistent. Thus, we performed a systematic review and meta-analysis to summarize the strength of the association of salt intake with gastric cancer morbidity and mortality. PubMed, EmBase, and Cochrane Library were systematically searched to identify eligible studies published throughout September 2021. The effect estimates with 95% confidence intervals (CIs) for gastric cancer morbidity or mortality in each study were applied to calculate the pooled results; these analyses were performed using the random-effects model. Twenty-six prospective cohort studies involving 4,956,350 individuals were selected; these studies reported 19,301 cases of gastric cancer and 2,871 cases of gastric cancer-associated mortality. High (RR: 1.25; 95%CI: 1.10–1.41; P = 0.001) or moderate (RR: 1.20; 95%CI: 1.04–1.38; P = 0.012) salt intake was associated with a greater risk of gastric cancer. High pickled food intake was associated with an increased gastric cancer risk (RR: 1.28; 95%CI: 1.05–1.57; P = 0.017), while moderate pickled foods intake had no significant effect on gastric cancer risk (RR: 1.10; 95%CI: 0.88–1.37; P = 0.390). Neither high (RR: 1.14; 95%CI: 0.95–1.36; P = 0.161) nor moderate (RR: 1.10; 95%CI: 0.87–1.40; P = 0.436) salted fish intake were associated with gastric cancer risk. A high intake of processed meat was significantly associated with a higher risk of gastric cancer (RR: 1.24; 95%CI: 1.03–1.49; P = 0.023), while moderate processed meat intake had no significant effect on the gastric cancer risk (RR: 1.01; 95%CI: 0.92–1.11; P = 0.844). High (RR: 1.04; 95%CI: 0.90–1.19; P = 0.626) and moderate (RR: 1.02; 95%CI: 0.94–1.11; P = 0.594) miso-soup intake had no effects on the gastric cancer risk. High intakes of salt, pickled food, and processed meat are associated with significantly increased risks of gastric cancer; these increased risks are also seen when participants consumed moderate amounts of salt.
Case Report: Five Adult Cases of H3K27-Altered Diffuse Midline Glioma in the Spinal Cord
Authors: Gu Quanquan , Huang Yajing , Zhang Hao , Jiang Biao
Published: December 2021

Background

Diffuse midline glioma with H3K27-altered (DMG-H3K27a) is a novel tumor entity of the pediatric-type diffuse high-grade tumor in the latest WHO CNS 5. It mostly affects children and is only rarely found in adults. The tumor has a high level of aggressiveness, with a rapid progression and bad prognosis. In adults, the spinal cord is the most common site of DMG-H3K27a. Rare adult cases of primary DMG-H3K27a in the spinal cord were reported in this study, together with clinico-histopathologico-radiographic data.

Methods

From January 2016 to December 2020, we conducted a retrospective study of five adults with primary DMG-H3K27a in the spinal cord, analyzing their clinical, pathohistological, and radiographic datasets from the first diagnosis to follow-up.

Results

All five patients were diagnosed for the first time and were given full treatment. In three of the five patients, post-operative follow-up revealed tumor recurrence. The longest survival of the five patients was 45 months at the time of report submission, while the longest progression-free survival (PFS) following surgery was 20 months. Immunohistochemical studies showed the tumors featured aggressive behavior (grade 4) and were positive for the H3K27M mutation. The radiographic appearances were varied, but they were all initially mistaken as benign. DMG-H3K27a in the spinal cord was characterized by isointense/hyperintense on T1WI and isointense/hyperintense on T2WI, as well as cystic necrosis and peripheral spinal cord edema, as well as central canal enlargement and other types of enhancement.

Conclusion

This is the first case report focusing on adult DMG-H3K27a of the pediatric-type diffuses high-grade gliomas in the spinal cord. In our cases, we discovered the following: 1) adults had a better prognosis with a longer PFS compared with prior pediatric reports; 2) despite aggressive behavior under the microscope, radiographic appearances of the tumors were less aggressive; and 3) adjuvant treatment, including TCM, may have played a role in the prognosis.
CD146 as a Prognostic-Related Biomarker in ccRCC Correlating With Immune Infiltrates
Authors: Lv Zheng , Feng Hua-Yi , Tao Wang , Li Hong-Zhao , Zhang Xu
Published: December 2021

Backgrounds

CD146 is highly expressed in various malignant tumors and associated with the poor prognosis. However, the role of CD146 in clear cell renal cell carcinoma (ccRCC) is still unknown. This study aimed to identify the role of CD146 in ccRCC by integrated bioinformatics analysis.

Methods

CD146 mRNA expression and methylation data in ccRCC was examined using the TIMER, UALCAN, and MethSurv databases. CD146 expression in paraffin-embedded tissues (140 cancer samples and 140 paracancer tissues) from our cohort were examined by immunohistochemistry assay. The LinkedOmics database was used to study the signaling pathways related to CD146 expression. TIMER and TISIDB were used to analyze the correlations among CD146, CD146-coexpressed genes, tumor-infiltrating immune cells, and immunomodulators. The relationship between CD146 and drug response in renal cancer cell lines was analyzed by the CTRP and CCLE databases.

Results

The mRNA and protein levels of CD146 were elevated in ccRCC tissues than that in paracancer tissues. The DNA methylation of CD146 in ccRCC tissues were lower than that in normal tissues. Importantly, high CD146 expression was associated with poor prognosis in patients with ccRCC. Furthermore, multivariate Cox regression analysis showed that CD146 was an independent prognostic factor in ccRCC. GO and KEGG pathway analyses indicated the co-expressed genes of CD146 were mainly related to a variety of immune-related pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, and leukocyte transendothelial migration. Our data demonstrated that the expression and methylation status of CD146 were strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Further, the sensitivity and resistance of renal cancer cell lines to some drugs were related to CD146 expression.

Conclusions

Our study highlights the clinical significance of CD146 in ccRCC and provides novel insights into the immune function of CD146 in the tumor microenvironment.
Anesthesia Techniques and Long-Term Oncological Outcomes
Authors: Ramirez Maria F. , Cata Juan P.
Published: December 2021

Despite advances in cancer treatments, surgery remains one of the most important therapies for solid tumors. Unfortunately, surgery promotes angiogenesis, shedding of cancer cells into the circulation and suppresses anti-tumor immunity. Together this increases the risk of tumor metastasis, accelerated growth of pre-existing micro-metastasis and cancer recurrence. It was theorized that regional anesthesia could influence long-term outcomes after cancer surgery, however new clinical evidence demonstrates that the anesthesia technique has little influence in oncologic outcomes. Several randomized controlled trials are in progress and may provide a better understanding on how volatile and intravenous hypnotics impact cancer progression. The purpose of this review is to summarize the effect of the anesthesia techniques on the immune system and tumor microenvironment (TME) as well as to summarize the clinical evidence of anesthesia techniques on cancer outcomes.
Aurora Kinase A as a Diagnostic and Prognostic Marker of Malignant Mesothelioma
Authors: Guo Zhenying , Shen Li , Li Ningning , Wu Xiaoxiao , Wang Canming , Gu Zheng , Chen Zhongjian , Liu Junping , Mao Weimin , Han Yuchen
Published: December 2021

Background

Malignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM.

Methods

The expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values.

Results

346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix–receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes—AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA—may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively.

Conclusion

Aurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.
Causes of Melena and Effective Examination Strategies in Children
Authors: Iwama Itaru , Yoshida Masashi , Hara Tomoko , Nambu Ryusuke
Published: December 2021

Background and Aim: Melena, or tarry black stool, is not a rare symptom encountered in pediatric clinical practice, and the bleeding source varies from the upper gastrointestinal tract to the small intestine. Endoscopy is effective in identifying bleeding, but it does not always identify the source of bleeding. Endoscopic examination in children is commonly challenging, and there are no detailed reports about the causes of melena in children. This observational study aimed to validate the cause of melena in children and to investigate more effective and less burdensome examination methods.

Methods: We retrospectively reviewed the clinical records of 55 patients who underwent examination for melena.

Results: In this research, 38 patients had underlying diseases such as malignancy and severe mental and physical disorders. The bleeding source was identified in 39 patients. The most common final diagnosis was duodenal ulcer (n = 22), and the other diagnoses were gastric ulcer, esophagitis, and esophageal varices. The upper gastrointestinal tract was the most common source of bleeding (n = 34). In five patients, the bleeding source was the small intestine. Vomiting, abnormal abdominal ultrasonography findings, and a hemoglobin level of ≤ 3 g/dL than the lower normal limit were significant factors indicating that the bleeding source can be found on esophagogastroduodenoscopy.

Conclusions: The upper gastrointestinal tract was the most common bleeding source of melena in children. As in adults, esophagogastroduodenoscopy is the primary endoscopic method of choice. Furthermore, small bowel capsule endoscopy may be useful in identifying the bleeding source in children without upper gastrointestinal lesions.
Cajanol Sensitizes A2780/Taxol Cells to Paclitaxel by Inhibiting the PI3K/Akt/NF-κB Signaling Pathway
Authors: Sui Ming , Yang Hairong , Guo Mingqi , Li Wenle , Gong Zheng , Jiang Jing , Li Peiling
Published: December 2021

Ovarian cancer is the second most common gynecological malignancy, and one of the most deadly. The bottleneck restricting the treatment of ovarian cancer is its multi-drug resistance to chemotherapy. Cajanol is an isoflavone from pigeon pea (Cajanus cajan) that has been reported to have anti-tumor activity. In this work, we evaluate the effect of cajanol in reversing paclitaxel resistance of the A2780/Taxol ovarian cancer cell line in vitro and in vivo, and we discuss its mechanism of action. We found that 8 μM cajanol significantly restored the sensitivity of A2780/Taxol cells to paclitaxel, and in vivo experiments demonstrated that the combination of 0.5 mM/kg paclitaxel and 2 mM/kg cajanol significantly inhibited the growth of A2780/Taxol metastatic tumors in mice. Flow cytometry, fluorescence quantitative PCR, western blotting and immunohistochemical staining methods were used to study the mechanism of reversing paclitaxel resistance with cajanol. First, we determined that cajanol inhibits paclitaxel efflux in A2780/Taxol cells by down-regulating permeability glycoprotein (P-gp) expression, and further found that cajanol can inhibit P-gp transcription and translation through the PI3K/Akt/NF-κB pathway. The results of this work are expected to provide a new candidate compound for the development of paclitaxel sensitizers.
Comparison Between Pressure Swing Adsorption and Liquid Oxygen Enrichment Techniques in the Atacama Large Millimeter/Submillimeter Array Facility at the Chajnantor Plateau (5,050 m)
Authors: Lopez Ivan , Aravena Reinaldo , Soza Daniel , Morales Alicia , Riquelme Silvia , Calderon-Jofré Rodrigo , Moraga Fernando A.
Published: December 2021

The Chilean workforce has over 200,000 people that are intermittently exposed to altitudes over 4,000 m. In 2012, the Ministry of Health provided a technical guide for high-altitude workers that included a series of actions to mitigate the effects of hypoxia. Previous studies have shown the positive effect of oxygen enrichment at high altitudes. The Atacama Large Millimeter/submillimeter Array (ALMA) radiotelescope operates at 5,050 m [Array Operations Site (AOS)] and is the only place in the world where pressure swing adsorption (PSA) and liquid oxygen technologies have been installed at a large scale. These technologies reduce the equivalent altitude by increasing oxygen availability. This study aims to perform a retrospective comparison between the use of both technologies during operation in ALMA at 5,050 m. In each condition, variables such as oxygen (O2), temperature, and humidity were continuously recorded in each AOS rooms, and cardiorespiratory variables were registered. In addition, we compared portable O2 by using continuous or demand flow during outdoor activities at very high altitudes. The outcomes showed no differences between production procedures (PSA or liquid oxygen) in regulating oxygen availability at AOS facilities. As a result, big-scale installations have difficulties reaching the appropriate O2 concentration due to leaks in high mobility areas. In addition, the PSA plant requires adequacy and maintenance to operate at a very high altitude. A continuous flow of 2–3 l/min of portable O2 is recommended at 5,050 m.
Differential Variation in Non-structural Carbohydrates in Root Branch Orders of Fraxinus mandshurica Rupr. Seedlings Across Different Drought Intensities and Soil Substrates
Authors: Ji Li , Liu Yue , Wang Jun , Lu Zhimin , Zhang Lijie , Yang Yuchun
Published: December 2021

Non-structural carbohydrates (NSCs) facilitate plant adaptation to drought stress, characterize tree growth and survival ability, and buffer against external disturbances. Previous studies have focused on the distribution and dynamics of NSCs among different plant organs under drought conditions. However, discussion about the NSC levels of fine roots in different root branch orders is limited, especially the relationship between fine root trait variation and NSC content. The objective of the study was to shed light on the synergistic variation in fine root traits and NSC content in different root branch orders under different drought and soil substrate conditions. The 2-year-old Fraxinus mandshurica Rupr. potted seedlings were planted in three different soil substrates (humus, loam, and sandy–loam soil) and subjected to four drought intensities (CK, mild drought, moderate drought, and severe drought) for 2 months. With increasing drought intensity, the biomass of fine roots decreased significantly. Under the same drought intensity, seedlings in sandy–loam soil had higher root biomass, and the coefficient of variation of 5th-order roots (37.4, 44.5, and 53% in humus, loam, and sandy–loam soil, respectively) was higher than that of lower-order roots. All branch order roots of seedlings in humus soil had the largest specific root length (SRL) and specific root surface area (SRA), in addition to the lowest diameter. With increasing drought intensity, the SRL and average diameter (AD) of all root branch orders increased and decreased, respectively. The fine roots in humus soil had a higher soluble sugar (SS) content and lower starch (ST) content compared to the loam and sandy–loam soil. Additionally, the SS and ST contents of fine roots showed decreasing and increasing tendencies with increasing drought intensities, respectively. SS and ST explained the highest degree of the total variation in fine root traits, which were 32 and 32.1%, respectively. With increasing root order, the explanation of the variation in root traits by ST decreased (only 6.8% for 5th-order roots). The observed response in terms of morphological traits of different fine root branch orders of F. mandshurica seedlings to resource fluctuations ensures the maintenance of a low cost-benefit ratio in the root system development.
Transcriptomics Integrated With Metabolomics Reveal the Effects of Ultraviolet-B Radiation on Flavonoid Biosynthesis in Antarctic Moss
Authors: Liu Shenghao , Fang Shuo , Liu Chenlin , Zhao Linlin , Cong Bailin , Zhang Zhaohui
Published: December 2021

Bryophytes are the dominant vegetation in the Antarctic continent. They have suffered more unpleasant ultraviolet radiation due to the Antarctic ozone layer destruction. However, it remains unclear about the molecular mechanism of Antarctic moss acclimation to UV-B light. Here, the transcriptomics and metabolomics approaches were conducted to uncover transcriptional and metabolic profiling of the Antarctic moss Leptobryum pyriforme under UV-B radiation. Totally, 67,290 unigenes with N50 length of 2,055 bp were assembled. Of them, 1,594 unigenes were significantly up-regulated and 3353 unigenes were markedly down-regulated under UV-B radiation. These differentially expressed genes (DEGs) involved in UV-B signaling, flavonoid biosynthesis, ROS scavenging, and DNA repair. In addition, a total of 531 metabolites were detected, while flavonoids and anthocyanins accounted for 10.36% of the total compounds. There were 49 upregulated metabolites and 41 downregulated metabolites under UV-B radiation. Flavonoids were the most significantly changed metabolites. qPCR analysis showed that UVR8-COP1-HY5 signaling pathway genes and photolyase genes (i.e., LpUVR3, LpPHR1, and LpDPL) were significantly up-regulated under UV-B light. In addition, the expression levels of JA signaling pathway-related genes (i.e., OPR and JAZ) and flavonoid biosynthesis-related genes were also significantly increased under UV-B radiation. The integrative data analysis showed that UVR8-mediated signaling, jasmonate signaling, flavonoid biosynthesis pathway and DNA repair system might contribute to L. pyriforme acclimating to UV-B radiation. Therefore, these findings present a novel knowledge for understanding the adaption of Antarctic moss to polar environments and provide a foundation for assessing the impact of global climate change on Antarctic land plants.
Cross-Lagged Analysis of COVID-19-Related Worry and Media Consumption in a Socioeconomically Disadvantaged Sample of Community Adults
Authors: Bounoua Nadia , Goodling Shelly , Sadeh Naomi
Published: December 2021

The COVID-19 pandemic has led to an increase in an array of mental health problems. Previous research has shown that media exposure to stressful situations is often related to anxiety and stress. However, given that most existing work has used cross-sectional designs, less is known about the interplay of media exposure and worry as they unfold during sustained exposure to a collective stressor. The current study examined bidirectional associations between COVID-related worry and media consumption over a three-month period. Participants were 87 community adults, the majority of whom were recruited from communities heavily impacted by the COVID-19 pandemic. For three consecutive months, participants asked to indicate how much time they spent worrying and consuming news about the COVID-19 pandemic on a scale from 1 (“never”) to 5 (“most of the day”). Cross-lagged analyses revealed that Pandemic Worry at Month 1 predicted increases in Pandemic Media Consumption at Month 2, which in turn predicted increases in Pandemic Worry at Month 3. Findings suggest that media consumption may be a maladaptive coping strategy that has the iatrogenic effect of increasing worry. Clarifying the causal associations between anxiety-perpetuating processes and media consumption may have important clinical implications for understanding and treating mental health during health pandemics.