bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-Effectiveness Analysis of Immunotherapy in Patient with Allergic Rhinitis
Authors: Park Joon Yong , Kim Yoon-Sook , Kim Jin Kook , Cho Jae Hoon
Published: August 2021

Background and Objectives All treatments must be effective and affordable. Although it is clear that immunotherapy is effective in patients with allergic rhinitis, no cost-effectiveness analysis has been conducted in Korea.Subjects and Method We compared 10 years of total treatment costs (medical expense+ transportation cost+time cost) with medications and symptoms scores assuming that adult patients with allergic rhinitis are treated only with symptomatic medication (medication model) or immunotherapy (subcutaneous or sublingual) plus symptomatic medication [subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) models, respectively]. For cost-effectiveness analysis, related papers and domestic medical statistics were used.Results The total treatment costs for the first 3 years were ₩3330199, ₩6605557, and ₩7130467 for the Medication model, SCIT model and SLIT model, respectively. The total treatment costs for the 10-year period were ₩7996087, ₩8588624, and ₩9113534 for the medication model, SCIT model, and SCIT model, respectively. The cumulative symptoms plus medications scores decreased 0.44 times in both immunotherapy models compared to the medication model. Conclusion The initial cost of immunotherapy is more expensive than symptomatic medication, but the total cost for 10 years is similar. In addition, immunotherapy can reduce symptoms by more than half. Therefore, it is a cost-effective treatment for allergic rhinitis.
A Case of the Hamartoma of Middle Ear Presenting with the Aplasia of Ipsilateral Internal Carotid Artery
Authors: Kim Sangjun , Pak Min Gyoung , Jeong Sung Wook
Published: August 2021

Hamartoma is a benign congenital tumor made of an abnormal mixture of normal tissues. It is a kind of developmental anomaly, in which the tissues are arranged with an excess growth of one or more of its components. Hamartoma is usually found in the lung, hypothalamus, and colon, but very rarely found in the head and neck areas. Symptoms are caused by the tumor tissue pressing against other tissues or organs. Surgical removal is the treatment modality of choice for hamartomas causing symptoms. The aplasia of unilateral internal carotid artery (ICA) is a rare congenital anomaly. ICA aplasia can cause structural change of the middle ear space. A 5 year-old female patient was presented with large hamartoma in the middle ear and the aplasia of the ipsilateral ICA. The mass was successfully removed without any complications. Authors report this case with a brief literature review.
Single-Cell Imaging Reveals That Staphylococcus aureus Is Highly Competitive Against Pseudomonas aeruginosa on Surfaces
Authors: Niggli Selina , Wechsler Tobias , Kümmerli Rolf
Published: August 2021

Pseudomonas aeruginosa and Staphylococcus aureus frequently occur together in polymicrobial infections, and their interactions can complicate disease progression and treatment options. While interactions between P. aeruginosa and S. aureus have been extensively described using planktonic batch cultures, little is known about whether and how individual cells interact with each other on solid substrates. This is important because both species frequently colonize surfaces to form aggregates and biofilms in infections. Here, we performed single-cell time-lapse fluorescence microscopy, combined with automated image analysis, to describe interactions between P. aeruginosa PAO1 with three different S. aureus strains (Cowan I, 6850, JE2) during microcolony growth on agarose surfaces. While P. aeruginosa is usually considered the dominant species, we found that the competitive balance tips in favor of S. aureus on surfaces. We observed that all S. aureus strains accelerated the onset of microcolony growth in competition with P. aeruginosa and significantly compromised P. aeruginosa growth prior to physical contact. Upon direct contact, JE2 was the most competitive S. aureus strain, simply usurping P. aeruginosa microcolonies, while 6850 was the weakest competitor itself suppressed by P. aeruginosa. Moreover, P. aeruginosa reacted to the assault of S. aureus by showing increased directional growth and expedited expression of quorum sensing regulators controlling the synthesis of competitive traits. Altogether, our results reveal that quantitative single-cell live imaging has the potential to uncover microbial behaviors that cannot be predicted from batch culture studies, and thereby contribute to our understanding of interactions between pathogens that co-colonize host-associated surfaces during polymicrobial infections.
Fluid Secretion by Malpighian Tubules of Rhodnius prolixus: Neuroendocrine Control With New Insights From a Transcriptome Analysis
Authors: Orchard Ian , Leyria Jimena , Al-Dailami Areej , Lange Angela B.
Published: August 2021

Rhodnius prolixus (the kissing bug and a major vector of Chagas disease) is an obligate blood feeder that in the case of the fifth instar consumes up to 10 times its unfed body weight in a single 20-minute feed. A post-prandial diuresis is initiated, within minutes of the start of gorging, in order to lower the mass and concentrate the nutrients of the meal. Thus, R. prolixus rapidly excretes a fluid that is high in NaCl content and hypo-osmotic to the hemolymph, thereby eliminating 50% of the volume of the blood meal within 3 hours of gorging. In R. prolixus, as with other insects, the Malpighian tubules play a critical role in diuresis. Malpighian tubules are not innervated, and their fine control comes under the influence of the neuroendocrine system that releases amines and neuropeptides as diuretic or antidiuretic hormones. These hormones act upon the Malpighian tubules via a variety of G protein-coupled receptors linked to second messenger systems that influence ion transporters and aquaporins; thereby regulating fluid secretion. Much has been discovered about the control of diuresis in R. prolixus, and other model insects, using classical endocrinological studies. The post-genomic era, however, has brought new insights, identifying novel diuretic and antidiuretic hormone-signaling pathways whilst also validating many of the classical discoveries. This paper will focus on recent discoveries into the neuroendocrine control of the rapid post-prandial diuresis in R. prolixus, in order to emphasize new insights from a transcriptome analysis of Malpighian tubules taken from unfed and fed bugs.
Inflammatory Protein Profiles in Plasma of Candidaemia Patients and the Contribution of Host Genetics to Their Variability
Authors: Matzaraki Vasiliki , Le Kieu T. T. , Jaeger Martin , Aguirre-Gamboa Raúl , Johnson Melissa D. , Sanna Serena , Rosati Diletta , Franke Lude , Zhernakova Alexandra , Fu Jingyuan , Withoff Sebo , Jonkers Iris , Li Yang , Joosten Leo A. B. , Netea Mihai G. , Wijmenga Cisca , Kumar Vinod
Published: August 2021

Circulatory inflammatory proteins play a significant role in anti-Candidahost immune defence. However, little is known about the genetic variation that contributes to the variability of inflammatory responses in response toC. albicans. To systematically characterize inflammatory responses inCandidainfection, we profiled 91 circulatory inflammatory proteins in peripheral blood mononuclear cells (PBMCs) stimulated withC. albicansyeast isolated from 378 individuals of European origin from the 500 Functional Genomics (500FG) cohort of the Human Functional Genomics Project (HFGP) and Lifelines Deep cohort. To identify the genetic factors that determine variation in inflammatory protein responses, we correlated genome-wide single nucleotide polymorphism (SNP) genotypes with protein abundance (protein quantitative trait loci, pQTLs) produced by theCandida-stimulated PBMCs. Furthermore, we investigated whether differences in survival of candidaemia patients can be explained by modulating levels of inflammatory proteins. We identified five genome-wide significant pQTLs that modulate IL-8, MCP-2, MMP-1, and CCL3 in response toC. albicans. In addition, our genetic analysis suggested thatGADD45Gfrom rs10114707 locus that reached genome-wide significance could be a potential core gene that regulates a cytokine network uponCandidainfection. Last but not least, we observed that a trans-pQTL marked from SNP rs7651677 at chromosome 3 that influences urokinase plasminogen activator (uPA) is strongly associated with patient survival (Psurvival= 3.52 x 10-5, OR 3). Overall, our genetic analysis showed that genetic variation determines the abundance of circulatory proteins in response toCandidainfection.
Activation Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells Promoting the Discrimination Between Active Tuberculosis and Latent Tuberculosis Infection
Authors: Luo Ying , Xue Ying , Mao Liyan , Lin Qun , Tang Guoxing , Song Huijuan , Liu Wei , Tong Shutao , Hou Hongyan , Huang Min , Ouyang Renren , Wang Feng , Sun Ziyong
Published: August 2021

Background

Rapid and effective discrimination between active tuberculosis (ATB) and latent tuberculosis infection (LTBI) remains a challenge. There is an urgent need for developing practical and affordable approaches targeting this issue.

Methods

Participants with ATB and LTBI were recruited at Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort) based on positive T-SPOT results from June 2020 to January 2021. The expression of activation markers including HLA-DR, CD38, CD69, and CD25 was examined on Mycobacterium tuberculosis (MTB)-specific CD4+ T cells defined by IFN-γ, TNF-α, and IL-2 expression upon MTB antigen stimulation.

Results

A total of 90 (40 ATB and 50 LTBI) and another 64 (29 ATB and 35 LTBI) subjects were recruited from the Qiaokou cohort and Caidian cohort, respectively. The expression patterns of Th1 cytokines including IFN-γ, TNF-α, and IL-2 upon MTB antigen stimulation could not differentiate ATB patients from LTBI individuals well. However, both HLA-DR and CD38 on MTB-specific cells showed discriminatory value in distinguishing between ATB patients and LTBI individuals. As for developing a single candidate biomarker, HLA-DR had the advantage over CD38. Moreover, HLA-DR on TNF-α+ or IL-2+ cells had superiority over that on IFN-γ+ cells in differentiating ATB patients from LTBI individuals. Besides, HLA-DR on MTB-specific cells defined by multiple cytokine co-expression had a higher ability to discriminate patients with ATB from LTBI individuals than that of MTB-specific cells defined by one kind of cytokine expression. Specially, HLA-DR on TNF-α+IL-2+ cells produced an AUC of 0.901 (95% CI, 0.833–0.969), with a sensitivity of 93.75% (95% CI, 79.85–98.27%) and specificity of 72.97% (95% CI, 57.02–84.60%) as a threshold of 44% was used. Furthermore, the performance of HLA-DR on TNF-α+IL-2+ cells for differential diagnosis was obtained with validation cohort data: 90.91% (95% CI, 72.19–97.47%) sensitivity and 68.97% (95% CI, 50.77–82.73%) specificity.

Conclusions

We demonstrated that HLA-DR on MTB-specific cells was a potentially useful biomarker for accurate discrimination between ATB and LTBI.
HIV Antibody Profiles in HIV Controllers and Persons With Treatment-Induced Viral Suppression
Authors: Kammers Kai , Chen Athena , Monaco Daniel R. , Hudelson Sarah E. , Grant-McAuley Wendy , Moore Richard D. , Alter Galit , Deeks Steven G. , Morrison Charles S. , Eller Leigh A. , Blankson Joel N. , Laeyendecker Oliver , Ruczinski Ingo , Eshleman Susan H. , Larman H. Benjamin
Published: August 2021

Introduction

Low HIV viral load is associated with delayed disease progression and reduced HIV transmission. HIV controllers suppress viral load to low levels in the absence of antiretroviral treatment (ART). We used an antibody profiling system, VirScan, to compare antibody reactivity and specificity in HIV controllers, non-controllers with treatment-induced viral suppression, and viremic non-controllers.

Methods

The VirScan library contains 3,384 phage-displayed peptides spanning the HIV proteome. Antibody reactivity to these peptides was measured in plasma from a Discovery Cohort that included 13 elite controllers, 27 viremic controllers, 12 viremic non-controllers, and 21 non-controllers who were virally suppressed on ART. Antibody reactivity to selected peptides was also assessed in an independent cohort of 29 elite controllers and 37 non-controllers who were virally suppressed on ART (Validation Cohort) and in a longitudinal cohort of non-controllers.

Results

In the Discovery Cohort, 62 peptides were preferentially targeted in HIV controllers compared to non-controllers who were virally suppressed on ART. These specificities were not significantly different when comparing controllers versus viremic non-controllers. Aggregate reactivity to these peptides was also high in elite controllers from the independent Validation Cohort. The 62 peptides formed seven clusters of homologous epitopes in env, gag, integrase, and vpu. Reactivity to one of these clusters located in gag p17 was inversely correlated with viral load set point in an independent cohort of non-controllers.

Conclusions

Antibody reactivity was low in non-controllers suppressed on ART, but remained high in viremic controllers despite viral suppression. Antibodies in controllers and viremic non-controllers were directed against epitopes in diverse HIV proteins; higher reactivity against p17 peptides was associated with lower viral load set point. Further studies are needed to determine if these antibodies play a role in regulation of HIV viral load.
Single-Molecule Insights Into the Dynamics of Replicative Helicases
Authors: Spinks Richard R. , Spenkelink Lisanne M. , Dixon Nicholas E. , van Oijen Antoine M.
Published: August 2021

Helicases are molecular motors that translocate along single-stranded DNA and unwind duplex DNA. They rely on the consumption of chemical energy from nucleotide hydrolysis to drive their translocation. Specialized helicases play a critically important role in DNA replication by unwinding DNA at the front of the replication fork. The replicative helicases of the model systems bacteriophages T4 and T7, Escherichia coli and Saccharomyces cerevisiae have been extensively studied and characterized using biochemical methods. While powerful, their averaging over ensembles of molecules and reactions makes it challenging to uncover information related to intermediate states in the unwinding process and the dynamic helicase interactions within the replisome. Here, we describe single-molecule methods that have been developed in the last few decades and discuss the new details that these methods have revealed about replicative helicases. Applying methods such as FRET and optical and magnetic tweezers to individual helicases have made it possible to access the mechanistic aspects of unwinding. It is from these methods that we understand that the replicative helicases studied so far actively translocate and then passively unwind DNA, and that these hexameric enzymes must efficiently coordinate the stepping action of their subunits to achieve unwinding, where the size of each step is prone to variation. Single-molecule fluorescence microscopy methods have made it possible to visualize replicative helicases acting at replication forks and quantify their dynamics using multi-color colocalization, FRAP and FLIP. These fluorescence methods have made it possible to visualize helicases in replication initiation and dissect this intricate protein-assembly process. In a similar manner, single-molecule visualization of fluorescent replicative helicases acting in replication identified that, in contrast to the replicative polymerases, the helicase does not exchange. Instead, the replicative helicase acts as the stable component that serves to anchor the other replication factors to the replisome.
CSF and Plasma Cholinergic Markers in Patients With Cognitive Impairment
Authors: Karami Azadeh , Darreh-Shori Taher , Schultzberg Marianne , Eriksdotter Maria
Published: August 2021

Introduction

Alzheimer’s disease (AD) is the most prevalent form of dementia with symptoms of deteriorating cognitive functions and memory loss, partially as a result of a decrease in cholinergic neurotransmission. The disease is incurable and treatment with cholinesterase inhibitors (ChEIs) is symptomatic. Choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine (ACh), has been proven recently to be present in both cerebrospinal fluid (CSF) and plasma. As ChAT plays a role in regulating the extracellular ACh levels, it may have an impact on prognosis and cognitive performance in AD patients.

Objectives

To measure ChAT activity and its protein concentration in CSF and plasma from patients with AD, mild cognitive impairment (MCI), or Subjective cognitive impairment (SCI).

Methods

Plasma and CSF samples were obtained from 21 AD, 32 MCI, and 30 SCI patients. The activity and protein levels of ChAT and acetylcholinesterase (AChE), the enzyme catalyzing the hydrolysis of ACh, were analyzed using an integrated activity and protein concentration ELISA-like assay. A Cholinergic Index was calculated as the ratio of ChAT to AChE activities in CSF. The data were analyzed in relation to dementia biomarkers and cognitive performance of the patients.

Results

The CSF ChAT activity was significantly higher (55–67%) in MCI patients compared to AD and SCI cases. The CSF Cholinergic Index was 41 and 22% lower in AD patients than in MCI and SCI subjects, respectively. This index correlated positively with the Aβ42/p-tau ratio in CSF in SCI but negatively with that in AD and MCI. The ChAT activity and protein levels in plasma exhibited significant differences with the pattern of AD>>MCI>SCI.

Conclusion

This is the first study investigating soluble levels of the key cholinergic enzyme, ChAT, in both plasma and CSF of individuals at different clinical stages of dementia. Although further validation is needed, the overall pattern of the results suggests that in the continuum of AD, the cholinergic signaling exhibits an inverse U-shape dynamic of changes in the brain that greatly differs from the changes observed in the plasma compartment.
Multi-Head Attention-Based Long Short-Term Memory for Depression Detection From Speech
Authors: Zhao Yan , Liang Zhenlin , Du Jing , Zhang Li , Liu Chengyu , Zhao Li
Published: August 2021

Depression is a mental disorder that threatens the health and normal life of people. Hence, it is essential to provide an effective way to detect depression. However, research on depression detection mainly focuses on utilizing different parallel features from audio, video, and text for performance enhancement regardless of making full usage of the inherent information from speech. To focus on more emotionally salient regions of depression speech, in this research, we propose a multi-head time-dimension attention-based long short-term memory (LSTM) model. We first extract frame-level features to store the original temporal relationship of a speech sequence and then analyze their difference between speeches of depression and those of health status. Then, we study the performance of various features and use a modified feature set as the input of the LSTM layer. Instead of using the output of the traditional LSTM, multi-head time-dimension attention is employed to obtain more key time information related to depression detection by projecting the output into different subspaces. The experimental results show the proposed model leads to improvements of 2.3 and 10.3% over the LSTM model on the Distress Analysis Interview Corpus-Wizard of Oz (DAIC-WOZ) and the Multi-modal Open Dataset for Mental-disorder Analysis (MODMA) corpus, respectively.
Combination of Matching Responsive Stimulations of Hippocampus and Subiculum for Effective Seizure Suppression in Temporal Lobe Epilepsy
Authors: Zhang Fang , Yang Yufang , Zheng Yongte , Zhu Junming , Wang Ping , Xu Kedi
Published: August 2021

Responsive neural stimulation (RNS) is considered a promising neural modulation therapy for refractory epilepsy. Combined stimulation on different targets may hold great promise for improving the efficacy of seizure control since neural activity changed dynamically within associated brain targets in the epileptic network. Three major issues need to be further explored to achieve better efficacy of combined stimulation: (1) which nodes within the epileptogenic network should be chosen as stimulation targets? (2) What stimulus frequency should be delivered to different targets? and (3) Could the efficacy of RNS for seizure control be optimized by combined different stimulation targets together? In our current study, Granger causality (GC) method was applied to analyze epileptogenic networks for finding key targets of RNS. Single target stimulation (100 μA amplitude, 300 μs pulse width, 5s duration, biphasic, charge-balanced) with high frequency (130 Hz, HFS) or low frequency (5 Hz, LFS) was firstly delivered by our lab designed RNS systems to CA3, CA1, subiculum (SUB) of hippocampi, and anterior nucleus of thalamus (ANT). The efficacy of combined stimulation with different groups of frequencies was finally assessed to find out better combined key targets with optimal stimulus frequency. Our results showed that stimulation individually delivered to SUB and CA1 could shorten the average duration of seizures. Different stimulation frequencies impacted the efficacy of seizure control, as HFS delivered to CA1 and LFS delivered to SUB, respectively, were more effective for shortening the average duration of electrographic seizure in Sprague-Dawley rats (n = 3). Moreover, the synchronous stimulation of HFS in CA1 combined with LFS in SUB reduced the duration of discharge significantly in rats (n = 6). The combination of responsive stimulation at different targets may be an inspiration to optimize stimulation therapy for epilepsy.
Transcranial Magnetic Stimulation in Tremor Syndromes: Pathophysiologic Insights and Therapeutic Role
Authors: Frey Jessica , Hess Christopher W. , Kugler Liam , Wajid Manahil , Wagle Shukla Aparna
Published: August 2021

Transcranial magnetic stimulation (TMS) is a painless, non-invasive, and established brain stimulation technique to investigate human brain function. Over the last three decades, TMS has shed insight into the pathophysiology of many neurological disorders. Tremor is an involuntary, rhythmic oscillatory movement disorder commonly related to pathological oscillations propagatedviathe cerebello-thalamo-cortical pathway. Although tremor is the most common movement disorder and recent imaging studies have enhanced our understanding of the critical pathogenic networks, the underlying pathophysiology of different tremor syndromes is complex and still not fully understood. TMS has been used as a tool to further our understanding of tremor pathophysiology. In addition, repetitive TMS (rTMS) that can modulate brain functions through plasticity effects has been targeted to the tremor network to gain potential therapeutic benefits. However, evidence is available for only a few studies that included small patient samples with limited clinical follow-up. This review aims to discuss the role of TMS in advancing the pathophysiological understanding as well as emerging applications of rTMS for treating individual tremor syndromes. The review will focus on essential tremor, Parkinson's disease tremor, dystonic tremor syndrome, orthostatic tremor, and functional tremor.
Stuttering: A Disorder of Energy Supply to Neurons?
Authors: Alm Per A.
Published: August 2021

Stuttering is a disorder characterized by intermittent loss of volitional control of speech movements. This hypothesis and theory article focuses on the proposal that stuttering may be related to an impairment of the energy supply to neurons. Findings from electroencephalography (EEG), brain imaging, genetics, and biochemistry are reviewed: (1) Analyses of the EEG spectra at rest have repeatedly reported reduced power in the beta band, which is compatible with indications of reduced metabolism. (2) Studies of the absolute level of regional cerebral blood flow (rCBF) show conflicting findings, with two studies reporting reduced rCBF in the frontal lobe, and two studies, based on a different method, reporting no group differences. This contradiction has not yet been resolved. (3) The pattern of reduction in the studies reporting reduced rCBF corresponds to the regional pattern of the glycolytic index (GI; Vaishnavi et al., 2010). High regional GI indicates high reliance on non-oxidative metabolism, i.e., glycolysis. (4) Variants of the gene ARNT2 have been associated with stuttering. This gene is primarily expressed in the brain, with a pattern roughly corresponding to the pattern of regional GI. A central function of the ARNT2 protein is to act as one part of a sensor system indicating low levels of oxygen in brain tissue and to activate appropriate responses, including activation of glycolysis. (5) It has been established that genes related to the functions of the lysosomes are implicated in some cases of stuttering. It is possible that these gene variants result in a reduced peak rate of energy supply to neurons. (6) Lastly, there are indications of interactions between the metabolic system and the dopamine system: for example, it is known that acute hypoxia results in an elevated tonic level of dopamine in the synapses. Will mild chronic limitations of energy supply also result in elevated levels of dopamine? The indications of such interaction effects suggest that the metabolic theory of stuttering should be explored in parallel with the exploration of the dopaminergic theory.
A Distinct Clinicopathological Feature and Prognosis of Young Gastric Cancer Patients Aged ≤ 45 Years Old
Authors: Huang Qian , Zheng Xiufeng , Jiao Yang , Lei Yanna , Li Xiaoying , Bi Feng , Guo Fukun , Wang Gang , Liu Ming
Published: August 2021

Purpose

The aim of this retrospective study was to probe into clinicopathological features and prognosis of early-onset gastric cancer (EOGC) patients aged ≤ 45 years old.

Methods

This study selected 154 young gastric cancer patients aged ≤ 45 years old and 158 elderly gastric cancer patients aged > 50 years old admitted to West China Hospital of Sichuan University in 2009-2019 as the research object. These patients were further divided into two groups according to whether tumor can be resected radically. The following parameters were analyzed: age, gender, helicobacter pylori (HP) infection status, Her-2 status, pathological type and stage, chemotherapy, tumor differentiation degree, overall survival (OS).

Results

More than 3,000 patients with gastric carcinoma were screened, and 154 young gastric cancer patients aged ≤ 45 years old were identified as EOGC. Among them, the number of female patients in EOGC group was significantly higher than that of males, accounting for 63.6%. In addition, EOGC were associated with diffuse Laur´en type and poorly differentiated tumors. Interestingly, the Kaplan–Meier method showed that the OS of unresectable EOGC group was significantly lower than that of unresectable LOGC group (P = 0.0005) and chemotherapy containing paclitaxel tended to be more effective in the young people (P = 0.0511). Nevertheless, there was no significant difference in OS between young and elderly patients with gastric cancer in the radical resection group (P = 0.3881).

Conclusion

EOGC patients have a worse prognosis than late-onset gastric cancer (LOGC) patients with advanced unresectable gastric cancer. Palliative surgery or chemotherapy containing paclitaxel may improve the OS of unresectable young individuals with gastric cancer. Additional randomized controlled trials are required for guiding clinical practice.
Imaging Hallmarks of the Tumor Microenvironment in Glioblastoma Progression
Authors: Walsh John J. , Parent Maxime , Akif Adil , Adam Lucas C. , Maritim Samuel , Mishra Sandeep K. , Khan Muhammad H. , Coman Daniel , Hyder Fahmeed
Published: August 2021

Glioblastoma progression involves multifaceted changes in vascularity, cellularity, and metabolism. Capturing such complexities of the tumor niche, from the tumor core to the periphery, by magnetic resonance imaging (MRI) and spectroscopic imaging (MRSI) methods has translational impact. In human-derived glioblastoma models (U87, U251) we made simultaneous and longitudinal measurements of tumor perfusion (Fp), permeability (Ktrans), and volume fractions of extracellular (ve) and blood (vp) spaces from dynamic contrast enhanced (DCE) MRI, cellularity from apparent diffusion coefficient (ADC) MRI, and extracellular pH (pHe) from an MRSI method called Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). Spatiotemporal patterns of these parameters during tumorigenesis were unique for each tumor. While U87 tumors grew faster, Fp, Ktrans, and vp increased with tumor growth in both tumors but these trends were more pronounced for U251 tumors. Perfused regions between tumor periphery and core with U87 tumors exhibited higher Fp, but Ktrans of U251 tumors remained lowest at the tumor margin, suggesting primitive vascularization. Tumor growth was uncorrelated with ve, ADC, and pHe. U87 tumors showed correlated regions of reduced ve and lower ADC (higher cellularity), suggesting ongoing proliferation. U251 tumors revealed that the tumor core had higher ve and elevated ADC (lower cellularity), suggesting necrosis development. The entire tumor was uniformly acidic (pHe 6.1-6.8) early and throughout progression, but U251 tumors were more acidic, suggesting lower aerobic glycolysis in U87 tumors. Characterizing these cancer hallmarks with DCE-MRI, ADC-MRI, and BIRDS-MRSI will be useful for exploring tumorigenesis as well as timely therapies targeted to specific vascular and metabolic aspects of the tumor microenvironment.
Primary Cilia–Related Pathways Moderate the Development and Therapy Resistance of Glioblastoma
Authors: Li Minghao , Zhang Jiaxun , Zhou Haonan , Xiang Rong
Published: August 2021

As microtubule-based structures, primary cilia are typically present on the cells during the G0 or G1-S/G2 phase of the cell cycle and are closely related to the development of the central nervous system. The presence or absence of this special organelle may regulate the central nervous system tumorigenesis (e.g., glioblastoma) and several degenerative diseases. Additionally, the development of primary cilia can be regulated by several pathways. Conversely, primary cilia are able to regulate a few signaling transduction pathways. Therefore, development of the central nervous system tumors in conjunction with abnormal cilia can be regulated by up- or downregulation of the pathways related to cilia and ciliogenesis. Here, we review some pathways related to ciliogenesis and tumorigenesis, aiming to provide a potential target for developing new therapies at genetic and molecular levels.
Effect of TTN Mutations on Immune Microenvironment and Efficacy of Immunotherapy in Lung Adenocarcinoma Patients
Authors: Wang Zhe , Wang Chunguang , Lin Shengcheng , Yu Xin
Published: August 2021

Immune checkpoint inhibitors (ICIs) effectively treat lung adenocarcinoma (LUAD) with fewer side effects. However, for LUAD patients, the lack of predictive markers for ICIs makes their clinical benefits less than ideal. Despite reports suggesting that a TTN (titin) mutation plays an important role in immunotherapy of solid tumors and gastric cancer, the relationship between the TTN mutation and LUAD immunotherapy has not been determined. We collected a LUAD cohort with whole-exome sequencing (WES) and immunotherapy prognosis. The ICI cohort was used to explore the relationship between TTN mutation status and prognosis. Then, the Cancer Genome Atlas (TCGA)-LUAD and Chen-LUAD cohorts were downloaded from the cbioportal website. We also used CIBERSORT, gene-set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA) to evaluate the proportion of immune cells and the degree of pathway activation in LUAD patients, respectively. DDR signaling pathways obtained from the Molecular Signatures Database (MSigDB), tumor mutation burden (TMB), and NAL were used to evaluate the immunogenicity of LUAD patients. In the ICI cohort, TTN-mutant (TTN-MT) had significantly longer overall survival (OS) than TTN-wildtype (TTN-WT) (P = 0.009). Univariate and multivariate COX models showed that TTN mutation status can independently predict immunotherapy prognosis. Notably, the results of tumor immune microenvironment (TIME) analysis showed that TTN-MT patients had inflammatory TIME, which showed enriched activated immune cells and higher immune scores. Immunogenicity analysis showed higher immunogenicity in TTN-MT patients, which indicated high levels of gene mutations in TMB, NAL, and DDR pathways. GSEA and ssGSEA results showed that TTN-MT was substantially enriched in chemokine secretion, inflammatory factor secretion, and antigen presentation. Some pathways related to immunosuppression and immune depletion were significantly downregulated. TTN-MT is associated with significantly prolonged OS in LUAD patients. Additionally, TTN-MT is related to high immunogenicity and inflammatory TIME, suggesting that TTN-MT may be a potential predictive marker for patients with LUAD to accept ICIs.
Modeling Climate Impacts on Tree Growth to Assess Tree Vulnerability to Drought During Forest Dieback
Authors: Valeriano Cristina , Gazol Antonio , Colangelo Michele , González de Andrés Ester , Camarero J. Julio
Published: August 2021

Forest dieback because of drought is a global phenomenon threatening particular tree populations. Particularly vulnerable stands are usually located in climatically stressing locations such as xeric sites subjected to seasonal drought. These tree populations show a pronounced loss of vitality, growth decline, and high mortality in response to extreme climate events such as heat waves and droughts. However, dieback events do not uniformly affect stands, with some trees showing higher symptoms of drought vulnerability than other neighboring conspecifics. In this study, we investigated if trees showing different vulnerabilities to dieback showed lower growth rates (Grs) and higher sensitivities to the climate in the past using dendroecology and the Vaganov-Shashkin (VS) process-based growth model. We studied two Pinus pinaster stands with contrasting Grs showing recent dieback in the Iberian System, north-eastern Spain. We compared coexisting declining (D) and non-declining (ND) trees with crown defoliation values above and below the 50% threshold, respectively. The mean growth rate was lower in D than in ND trees in the two stands. The two vigor classes showed a growth divergence prior to the dieback onset and different responsiveness to climate. The ND trees were more responsive to changes in spring water balance and soil moisture than D trees, indicating a loss of growth responsiveness to the climate in stressed trees. Such an interaction between water availability and vigor was reflected by the VS-model simulations, which provided evidence for the observation that growth was mainly limited by low soil moisture in both sites. Such an interaction between water availability and vigor was reflected by the VS-model simulations, which provided evidence for the observation that growth was mainly limited by low soil moisture in both sites. The presented comparisons indicated different stand vulnerabilities to drought contingent on-site conditions. Further research should investigate the role played by environmental conditions and individual features such as access to soil water or hydraulic traits and implement them in process-based growth models to better forecast dieback.
Lens orientalis Contributes Quantitative Trait Loci and Candidate Genes Associated With Ascochyta Blight Resistance in Lentil
Authors: Dadu Rama Harinath Reddy , Bar Ido , Ford Rebecca , Sambasivam Prabhakaran , Croser Janine , Ribalta Federico , Kaur Sukhjiwan , Sudheesh Shimna , Gupta Dorin
Published: August 2021

Australian lentil production is affected by several major biotic constraints including Ascochyta blight (AB), caused by Ascochyta lentis, a devastating fungal disease. Cultivation of AB resistant cultivars, alongside agronomic management including fungicide application, is the current most economically viable control strategy. However, the breakdown of AB resistance in cultivars, such as Northfield and Nipper, suggests the need for introgression of new and diverse resistance genes. Successful introgression entails an understanding of the genetic basis of resistance. In this context, a biparental mapping population derived from a cross between a recently identified AB resistant accession ILWL 180 (Lens orientalis) and a susceptible cultivar ILL 6002 was produced. A genetic linkage map was constructed from single-nucleotide polymorphism markers generated using a genotyping-by-sequencing transcript approach. Genetic dissection of the mapping population revealed a major quantitative trait loci (QTL) region nested with three QTLs on linkage group 5 and explained 9.5–11.5 percent (%) of phenotypic variance for AB resistance. Another QTL was identified on LG2 with phenotypic variance of 9.6%. The identified QTL regions harbored putative candidate genes potentially associated with defense responses to A. lentis infection. The QTL analysis and the candidate gene information are expected to contribute to the development of diagnostic markers and enable marker-assisted resistance selection in lentil breeding programmes.
When Does the Leader’s Positive Expression Get a Positive Response From Members? The Three-Way Interaction Effects of Perceived Deep/Surface Acting, Positive Affect, and Quality of Leader-Member Exchange on Work Engagement
Authors: Hong Sung Hyoun , Kim Min Soo
Published: August 2021

Although researchers have argued that a leader’s positive affective display effectively induces work motivation among members, it has not always resulted in desirable outcomes. This research addresses these critical issues and explains why individuals react differently, by considering the three-way interaction of the characteristics of expression, the positive affect of the members, and quality of leader-member exchange (LMX). To verify our hypotheses, 698days from 47 leaders and 146 members were collected through the Experience Sampling Method. The analysis was conducted using HLM, and the results showed that, for members with high quality LMX, the positive effect of perceived deep acting on work engagement was strengthened when positive affect was high, and the negative effect of perceived surface acting was weakened when positive affect was high. On the other hand, members with low-quality LMX showed a stronger positive effect of perceived deep acting on work engagement when positive affect was high, and the negative effect of perceived deep acting was mitigated when positive affect was low. These results demonstrate that quality of LMX serves as a context of the affective display between leaders and members, and the effect of displaying positive affect relies on members’ perception of the characteristics of the expression and the affective state.
Climate Denial Fuels Climate Change Discussions More Than Local Climate-Related Disasters
Authors: Shah Miti , Seraj Sarah , Pennebaker James W.
Published: August 2021

Most scientists agree that climate change is the largest existential threat of our time. Despite the magnitude of the threat, surprisingly few climate-related discussions take place on social media. What factors drive online discussions about climate change? In this study, we examined the occurrence of Reddit discussions around three types of climate-related events: natural disasters (e.g., hurricanes, wildfires), political events (i.e., 2016 United States Presidential election), and policy events (i.e., United States’ withdrawal from Paris Climate Agreement, release of IPCC report). The objective was to understand how different types of events influence collective action as measured by discussions of climate change. Six large US cities were selected based on the occurrence of at least one locally-relevant natural disaster since 2014. Posts (N = 4.4 million) from subreddits of the selected cities were collected to obtain a six-month period before and after local natural disasters as well as climate-related political and policy events (which applied equally to all cities). Climate change discussions increased significantly for all three types of events, with the highest discussion during the 2016 elections. Further, discussions returned to baseline levels within 2 months following natural disasters and policy events but continued at elevated rates for up to 4 months following the 2016 elections. The findings suggest that collective discussions on climate change are driven more by political leaders’ controversial positions than life-threatening local natural disasters themselves. Implications for collective action are discussed.
Sorry, Not Sorry: Effects of Different Types of Apologies and Self-Monitoring on Non-verbal Behaviors
Authors: Yamamoto Kyoko , Kimura Masanori , Osaka Miki
Published: August 2021

This study examines the effects of different types of apologies and individual differences in self-monitoring on non-verbal apology behaviors involving a server apologizing to a customer. Apologies divide into sincere apologies that reflect genuine recognition of fault, and instrumental apologies, made for achieving a personal goal such as avoiding punishment or rejection by others. Self-monitoring (public-performing and other-directedness) were also examined. Fifty-three female undergraduate students participated in the experiment. Participants were assigned randomly to either a sincere apology condition or an instrumental apology condition. They watched the film clip of the communication between a customer and server and then role-played how they would apologize if they were the server. Participants’ non-verbal behavior during the role-play was videotaped. The results showed an interaction between the apology condition and self-monitoring on non-verbal behaviors. When public-performing was low, gaze avoidance was more likely to occur with a sincere apology than an instrumental apology. There was no difference when the public-performing was high. Facial displays of apology were apparent in the instrumental apology compared to the sincere apology. This tendency became more conspicuous with increased public-performing. Our results indicated that the higher the public-performing, the more participants tried to convey the feeling of apology by combining a direct gaze and facial displays in an instrumental apology. On the other hand, results suggest that lower levels of public-performing elicited less immediacy in offering a sincere apology. Further studies are needed to determine whether these results apply to other conflict resolution situations.
Effects of Passive Leadership in the Digital Age
Authors: Wang Cheng-Hui , Liu Gloria H. W. , Lee Neil Chueh-An
Published: August 2021

Organizations must adapt to the trend of digitalization. Nowadays, social media engagement editors play an increasingly crucial role for organizational growth and prosperity in the digital age. Engagement editors are usually tasked to perform the functions of marketing, content production, and data analysis. They have to manage online communities on behalf of the organization, and encounter online audiences' frequent toxic and aggressive behaviors. Engagement editors thus are prone to emotional stress. Substantial literature has examined the influence of leadership style on employee performance. However, passive leadership is rarely studied. This research investigates (1) whether passive leadership would negatively affect engagement editors' performance (i.e., online interaction with audiences); and (2) how the negativity would be ameliorated by certain organizational policies (i.e., job autonomy) and their individual attributes (i.e., employee resilience) from the conservation of resource perspective. We surveyed 122 engagement editors and used the smartPLS 3.2.9 to analyze the data. This research provides important theoretical and practical implications.
Processing Mandarin Tone 3 Sandhi at the Morphosyntactic Interface: Reduplication and Lexical Compounds
Authors: Gao Feier , Lyu Siqi , Lin Chien-Jer Charles
Published: August 2021

Mandarin tone 3 sandhi is a phonological alternation in which the initial tone 3 (i.e., low tone) syllable changes to a tone 2 (i.e., rising tone) when followed by another tone 3. The present study used across-modal syllable-morpheme matchingexperiment to examine how native speakers process the sandhi sequences derived from verb reduplication and compounding, respectively. Embedded in a visually-presented sentential context, a disyllabic sequence containing a sandhi target was displayed simultaneously with a monosyllabic audio, either a tone 1 (i.e., high-level tone), tone 2 (i.e., rising tone) or tone 3 (i.e., low tone), and participants judged whether the audio syllable matched the visual morpheme. Results showed that the tone 3 sandhi was processed differently in the two constructions. The underlying tone and the surface tone were co-activated and competed with each other in sandhi compounds whereas predominant activation of the underlying tone, over the surface tone, was observed in reduplication. The processing of tone 3 sandhi offers support for distinctive morphological structures: a lexical compound is represented both as a whole-word unit and as a combination of two individual morphemes whereas a verb reduplication is represented and accessed as a monomorphemic unit in the mental lexicon.
Research on Psychache in Suicidal Population: A Bibliometric and Visual Analysis of Papers Published During 1994–2020
Authors: Cheng Yin , Zhao Wei-Wei , Chen Shu-Yan , Zhang Yan-Hong
Published: August 2021

Background: Psychache is a negative introspective experience, which is positively associated with the risk of suicide, independently of depression. It is undeniable that psychache is an important influencing factor to trigger suicide, which can also mediate the effect between depression and suicide variables. Nevertheless, the research tendency and current hotspots on psychache of suicide population have not been systematically investigated based on bibliometric analysis.

Aim: The aim of the study was to analyze the research status, hotspots, and frontiers of psychological pain in the field of suicidology, so as to provide reference for domestic clinical research.

Methods: The literature related to psychache in suicide individuals published from 1994 to 2020 was included and selected from the Web of Science Core Collection database on May 28, 2021. CiteSpace (version 5.7.R2) software was used to visualize and analyze highly cited journals, authors, and articles as well as co-occurrence analysis for countries, institution, authors, and keywords.

Results: A total of 230 articles from the WoS database were included. The number of papers over the years showed an overall upward trend. The United States has made the largest contribution, with the majority of publications (89, 38.70%), followed by Canada (48, 20.87%), Israel (31, 13.48%), China (20, 8.80%), and Portugal (17, 7.39%). The most productive institution was Queen's University. Edwin S. Shneidman has the largest achievement and profound influence, and the most prolific author is Ronald R. Holden. However, the cooperation between institutions and authors was comparatively weak. The current hotspots in this field focus on the studies on the relationships between depression, despair, psychache, and suicide, the risk assessments of psychological pain, and the development of psychological pain scales. Suicide and Life-Threatening Behavior was the most frequently cited journal in this field.

Conclusions: This analysis not only reveals the current research trend and hotspots but also provides some instructive suggestions on the development of psychache in the suicidology. Future work should pay more attention to develop effective psychological pain intervention programs for diverse suicide population. Additionally, longitudinal study can also be conducted to grasp the trajectory changes of psychological pain among suicide individuals.