bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual Variation Does Not Regulate Foraging Response to Humidity in Harvester Ant Colonies
Authors: Nova Nicole , Pagliara Renato , Gordon Deborah M.
Published: January 2022

Differences among groups in collective behavior may arise from responses that all group members share, or instead from differences in the distribution of individuals of particular types. We examined whether the collective regulation of foraging behavior in colonies of the desert red harvester ant (Pogonomyrmex barbatus) depends on individual differences among foragers. Foragers lose water while searching for seeds in hot, dry conditions, so colonies regulate foraging activity in response to humidity. In the summer, foraging activity begins in the early morning when humidity is high, and ends at midday when humidity is low. We investigated whether individual foragers within a colony differ in the decision whether to leave the nest on their next foraging trip as humidity decreases, by tracking the foraging trips of marked individuals. We found that individuals did not differ in response to current humidity. No ants were consistently more likely than others to stop foraging when humidity is low. Each day there is a skewed distribution of trip number: only a few individuals make many trips, but most individuals make few trips. We found that from one day to the next, individual foragers do not show any consistent tendency to make a similar number of trips. These results suggest that the differences among colonies in response to humidity, found in previous work, are due to behavioral responses to current humidity that all workers in a colony share, rather than to the distribution within a colony of foragers that differ in response.
Screening and Identification of Survival-Associated Splicing Factors in Lung Squamous Cell Carcinoma
Authors: Chen Min , Zhu Rui , Zhang Fangzhou , Zhu Liucun
Published: January 2022

Lung squamous cell carcinoma (LUSC) is a disease with high morbidity and mortality. Many studies have shown that aberrant alternative splicing (AS) can lead to tumorigenesis, and splicing factors (SFs) serve as an important function during AS. In this research, we propose an analysis method based on synergy to screen key factors that regulate the initiation and progression of LUSC. We first screened alternative splicing events (ASEs) associated with survival in LUSC patients by bivariate Cox regression analysis. Then an association network consisting of OS-ASEs, SFs, and their targeting relationship was constructed to identify key SFs. Finally, 10 key SFs were selected in terms of degree centrality. The validation on TCGA and cross-platform GEO datasets showed that some SFs were significantly differentially expressed in cancer and paracancer tissues, and some of them were associated with prognosis, indicating that our method is valid and accurate. It is expected that our method would be applied to a wide range of research fields and provide new insights in the future.
Potential Risks for Seahorse Stock Enhancement: Insight From the Declivity of Genetic Levels With Hatchery Management
Authors: Luo Wei , Wu Qing , Zhang Xiaoyang , Wei Yuling , Liao Min , Gao Tong , Zhang Yibo , Zhang Shoudong , Chen Pengyu , Guo Zhonggang , Xiong Yinlin , Xu Zhou , Du Zongjun
Published: January 2022

Stock enhancement is one of the potential management strategies for the fishery. To better understand the impaction of stock enhancement, we simulated an experiment for lined seahorse (Hippocampus erectus) and evaluated the genetic structure after stock enhancement. In this study, we found the numbers of alleles (NA) and heterozygosity (HO) of stock enhancement strains were lower than those of the wild collections, while the inbreeding coefficient (FIS) and relatedness index were higher. Within the 3 generations of stock enhancement strain, the NA, HO and polymorphism information content (PIC) didn’t change significantly. In addition, the FST value indicated that the genetic differentiation between the stock enhancement strains and the first wild collection reached an intermediate level, which could lead to substructuring in wild populations. Overall, these findings revealed a potential genetic risk associated with the release of hatchery strains into wild populations.
Investigating Molecular Signatures Underlying Trapeziometacarpal Osteoarthritis Through the Evaluation of Systemic Cytokine Expression
Authors: Ratneswaran Anusha , Rockel Jason S. , Antflek Daniel , Matelski John J. , Shestopaloff Konstantin , Kapoor Mohit , Baltzer Heather
Published: January 2022

Purpose

Non-operative management of trapeziometacarpal osteoarthritis (TMOA) demonstrates only short-term symptomatic alleviation, and no approved disease modifying drugs exist to treat this condition. A key issue in these patients is that radiographic disease severity can be discordant with patient reported pain, illustrating the need to identify molecular mediators of disease. This study characterizes the biochemical profile of TMOA patients to elucidate molecular mechanisms driving TMOA progression.

Methods

Plasma from patients with symptomatic TMOA undergoing surgical (n=39) or non-surgical management (n=44) with 1-year post-surgical follow-up were compared using a targeted panel of 27 cytokines. Radiographic (Eaton-Littler), anthropometric, longitudinal pain (VAS, TASD, quick DASH) and functional (key pinch, grip strength) data were used to evaluate relationships between structure, pain, and systemic cytokine expression. Principal Component Analysis was used to identify clusters of patients.

Results

Patients undergoing surgery had greater BMI as well as higher baseline quick DASH, TASD scores. Systemically, these patients could only be distinguished by differing levels of Interleukin-7 (IL-7), with an adjusted odds ratio of 0.22 for surgery for those with increased levels of this cytokine. Interestingly, PCA analysis of all patients (regardless of surgical status) identified a subset of patients with an “inflammatory” phenotype, as defined by a unique molecular signature consisting of thirteen cytokines.

Conclusion

Overall, this study demonstrated that circulating cytokines are capable of distinguishing TMOA disease severity, and identified IL-7 as a target capable of differentiating disease severity with higher levels associated with a decreased likelihood of TMOA needing surgical intervention. It also identified a cluster of patients who segregate based on a molecular signature of select cytokines.
Role of Lipid Rafts in Pathogen-Host Interaction - A Mini Review
Authors: Kulkarni Rakesh , Wiemer Erik A. C. , Chang Wen
Published: January 2022

Lipid rafts, also known as microdomains, are important components of cell membranes and are enriched in cholesterol, glycophospholipids and receptors. They are involved in various essential cellular processes, including endocytosis, exocytosis and cellular signaling. Receptors are concentrated at lipid rafts, through which cellular signaling can be transmitted. Pathogens exploit these signaling mechanisms to enter cells, proliferate and egress. However, lipid rafts also play an important role in initiating antimicrobial responses by sensing pathogens via clustered pathogen-sensing receptors and triggering downstream signaling events such as programmed cell death or cytokine production for pathogen clearance. In this review, we discuss how both host and pathogens use lipid rafts and associated proteins in an arms race to survive. Special attention is given to the involvement of the major vault protein, the main constituent of a ribonucleoprotein complex, which is enriched in lipid rafts upon infection with vaccinia virus.
Interleukin-25-Mediated-IL-17RB Upregulation Promotes Cutaneous Wound Healing in Diabetic Mice by Improving Endothelial Cell Functions
Authors: Zhang Fang , Liu Ye , Wang Shiqi , Yan Xin , Lin Yue , Chen Deyan , Tan Qian , Wu Zhiwei
Published: January 2022

Diabetic foot ulcer (DFU) frequently leads to non-traumatic amputation and finally even death. However, the mechanism of DFU is not fully understood. Interleukin 25 (IL-25), an alarmin cytokine that responds to tissue injury, has been reported to participate in tissue regeneration and maintaining glucose homeostasis. However, the role of IL-25 in diabetic wound healing remains unknown. Here, we showed that interleukin 17 receptor B (IL-17RB), the functional receptor of IL-25, was significantly inhibited in the wound skin of both diabetic patients with DFU and streptozotocin (STZ)-induced diabetic mice. Topical administration of recombinant IL-25 protein improved angiogenesis and collagen deposition in the wound bed and thus ameliorated delayed diabetic wound healing. IL-25 increased endothelial-specific CD31 expression in diabetic wounds and exogenous IL-25 protected endothelial cells from high glucose-impaired cell migration and tube formation in vitro. We further revealed that IL-25-mediated-IL-17RB signaling rescued the downregulation of Wnt/β-catenin pathway both in vivo in diabetic mice and in vitro in HUVECs and induced the phosphorylation of AKT and ERK 1/2 in HUVECs under high glucose conditions. This study defines a positive regulatory role of IL-25-mediated-IL-17RB signaling in diabetic wound healing and suggests that induction of IL-25-mediated-IL-17RB signaling may be a novel therapeutic strategy for treating poor healing diabetic wounds.
Gut Microbiome and Bile Acid Metabolism Induced the Activation of CXCR5+ CD4+ T Follicular Helper Cells to Participate in Neuromyelitis Optica Spectrum Disorder Recurrence
Authors: Cheng Xi , Zhou Luyao , Li Zhibin , Shen Shishi , Zhao Yipeng , Liu Chunxin , Zhong Xiaonan , Chang Yanyu , Kermode Allan G. , Qiu Wei
Published: January 2022

From the perspective of the role of T follicular helper (Tfh) cells in the destruction of tolerance in disease progression, more attention has been paid to their role in autoimmunity. To address the role of Tfh cells in neuromyelitis optica spectrum disorder (NMOSD) recurrence, serum C-X-C motif ligand 13 (CXCL13) levels reflect the effects of the Tfh cells on B-cell-mediated humoral immunity. We evaluated the immunobiology of the CXCR5+CD4+ Tfh cells in 46 patients with NMOSD, including 37 patients with NMOSD with an annual recurrence rate (ARR) of<1 and 9 patients with NMOSD with an ARR of ≥1. Herein, we reported several key observations. First, there was a lower frequency of circulating Tfh cells in patients with an ARR of<1 than in those with an ARR of ≥1 (P< 0.05). Second, the serum CXCL13 levels were downregulated in individuals with an ARR<1 (P< 0.05), processing the ability to promote Tfh maturation and chemotaxis. Third, the level of the primary bile acid, glycoursodeoxycholic acid (GUDCA), was higher in patients with NMOSD with an ARR of<1 than in those with NMOSD with an ARR of ≥1, which was positively correlated with CXCL13. Lastly, the frequency of the Tfh precursor cells decreased in the spleen of keyhole limpet haemocyanin-stimulated animals following GUDCA intervention. These findings significantly broaden our understanding of Tfh cells and CXCL13 in NMOSD. Our data also reveal the potential mechanism of intestinal microbiota and metabolites involved in NMOSD recurrence.
From Active to Non-active Giant Cell Arteritis: Longitudinal Monitoring of Patients on Glucocorticoid Therapy in Combination With Leflunomide
Authors: Kuret Tadeja , Frank-Bertoncelj Mojca , Lakota Katja , Žigon Polona , Thallinger Gerhard G. , Kopitar Andreja N. , Čučnik Saša , Tomšič Matija , Hočevar Alojzija , Sodin-Šemrl Snežna
Published: January 2022

In the present study, we longitudinally monitored leukocyte subsets, expression of neutrophil surface adhesion molecules (CD62L and CD11b) and serum analytes in therapy-naïve patients with active giant cell arteritis (GCA). We collected blood samples at the baseline, and at weeks 1, 4, 12, 24, and 48 of follow-up, and evaluated short- and long-term effects of glucocorticoids (GC) vs. GC and leflunomide. Our aim was to identify candidate biomarkers that could be used to monitor disease activity and predict an increased risk of a relapse. Following high doses of GC, the numbers of CD4+ T-lymphocytes and B-lymphocytes transiently increased and then subsided when GC dose tapering started at week 4. In contrast, the numbers of neutrophils significantly increased during the follow-up time of 12 weeks compared to pre-treatment time. Neutrophil CD62L rapidly diminished after initiation of GC therapy, however its expression remained low at week 48, only in patients under combinatorial therapy with leflunomide. Levels of acute phase reactant SAA and IL-6 decreased significantly after treatment with GC and leflunomide, while levels of IL-8, IL-18, and CHI3L1 did not change significantly during the follow-up period. CHI3L1 was associated with signs of transmural inflammation and vessel occlusion and might therefore serve as a marker of fully developed active GCA, and a promising therapeutic target. Patients with relapses had higher levels of IL-23 at presentation than patients without relapses (p = 0.021). Additionally, the levels of IL-23 were higher at the time of relapse compared to the last follow-up point before relapse. IL-23 might present a promising biomarker of uncontrolled and active disease and could give early indication of upcoming relapses.
Specific Denitrifying and Dissimilatory Nitrate Reduction to Ammonium Bacteria Assisted the Recovery of Anammox Community From Nitrite Inhibition
Authors: Qiao Xuejiao , Zhang Liyu , Qiu Zhiguang , Wang Li , Wu Yang , Deng Chunfang , Su Jia , Zhang Xue , Wang Yuexing , Li Bing , Zhou Lijie , Ma Anthony Y. W. , Zhuang Wei-Qin , Yu Ke
Published: January 2022

The anaerobic ammonium oxidation (anammox) by autotrophic anaerobic ammonia-oxidizing bacteria (AnAOB) is a biological process used to remove reactive nitrogen from wastewater. It has been repeatedly reported that elevated nitrite concentrations can severely inhibit the growth of AnAOB, which renders the anammox process challenging for industrial-scale applications. Both denitrifying (DN) and dissimilatory nitrate reduction to ammonium (DNRA) bacteria can potentially consume excess nitrite in an anammox system to prevent its inhibitory effect on AnAOB. However, metabolic interactions among DN, DNRA, and AnAOB bacteria under elevated nitrite conditions remain to be elucidated at metabolic resolutions. In this study, a laboratory-scale anammox bioreactor was used to conduct an investigation of the microbial shift and functional interactions of AnAOB, DN, and DNRA bacteria during a long-term nitrite inhibition to eventual self-recovery episode. The relative abundance of AnAOB first decreased due to high nitrite concentration, which lowered the system’s nitrogen removal efficiency, but then recovered automatically without any external interference. Based on the relative abundance variations of genomes in the inhibition, adaptation, and recovery periods, we found that DN and DNRA bacteria could be divided into three niche groups: type I (types Ia and Ib) that includes mainly DN bacteria and type II and type III that include primarily DNRA bacteria. Type Ia and type II bacteria outcompeted other bacteria in the inhibition and adaptation periods, respectively. They were recognized as potential nitrite scavengers at high nitrite concentrations, contributing to stabilizing the nitrite concentration and the eventual recovery of the anammox system. These findings shed light on the potential engineering solutions to maintain a robust and efficient industrial-scale anammox process.
A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder
Authors: Guo Pan , Chen Shasha , Wang Hao , Wang Yaogang , Wang Ju
Published: January 2022

Background

During the past years, clinical and epidemiological studies have indicated a close relationship between Alzheimer's disease (AD) and other mental disorders like major depressive disorder (MDD). At the same time, a number of genes genetically associated with AD or MDD have been detected. However, our knowledge on the mechanisms that link the two disorders is still incomplete, and controversies exist. In such a situation, a systematic analysis on these genes could provide clues to understand the molecular features of two disorders and their comorbidity.

Methods

In this study, we compiled the genes reported to be associated with AD or MDD by a comprehensive search of human genetic studies and genes curated in disease-related database. Then, we investigated the features of the shared genes between AD and MDD using the functional enrichment analysis. Furthermore, the major biochemical pathways enriched in the AD- or MDD-associated genes were identified, and the cross talks between the pathways were analyzed. In addition, novel candidate genes related to AD and MDD were predicted in the context of human protein-protein interactome.

Results

We obtained 650 AD-associated genes, 447 MDD-associated genes, and 77 shared genes between AD and MDD. The functional analysis revealed that biological processes involved in cognition, neural development, synaptic transmission, and immune-related processes were enriched in the common genes, indicating a complex mechanism underlying the comorbidity of the two diseases. In addition, we conducted the pathway enrichment analysis and found 102 shared pathways between AD and MDD, which involved in neuronal development, endocrine, cell growth, and immune response. By using the pathway cross-talk analysis, we found that these pathways could be roughly clustered into four modules, i.e., the immune response-related module, the neurodevelopmental module, the cancer or cell growth module, and the endocrine module. Furthermore, we obtained 37 novel candidate genes potentially related to AD and MDD with node degrees > 5.0 by mapping the shared genes to human protein-protein interaction network (PPIN). Finally, we found that 37 novel candidate genes are significantly expressed in the brain.

Conclusion

These results indicated shared biological processes and pathways between AD and MDD and provided hints for the comorbidity of AD and MDD.
Active Middle Ear Implant Evoked Auditory Brainstem Response Intensity-Latency Characteristics
Authors: Fröhlich Laura , Müller Alexander , Kropp Miriam H. , Mir-Salim Parwis , Dziemba Oliver , Oberhoffner Tobias , Plontke Stefan K. , Rahne Torsten
Published: January 2022

Objective

To analyze intensity-latency functions of intraoperative auditory evoked brainstem responses (ABRs) to stimulation by the Vibrant Soundbridge (VSB) active middle ear implant with respect to coupling efficiency, VSB evoked ABR thresholds, and coupling modality [oval window (OW) placement vs. Incus placement and vs. round window (RW) placement].

Study Design

Exploratory study.

Setting

Bi-centric study at tertiary referral centers.

Patients

Twenty-four patients (10 female, 14 male, mean age: 58 years) who received a VSB.

Outcome Measures

Wave-V intensity-latency functions of intraoperative VSB evoked ABRs using a modified audio processor programmed to preoperative bone conduction thresholds for stimulation. Threshold level correction to coupling efficiency and ABR thresholds. Individual plots and exponential function fits.

Results

After ABR threshold level correction, the latency functions could be aligned. A large variance of latencies was observed at individual threshold level. Wave-V latency was longest in the Incus placement subgroup (9.73 ms, SD: 1.04) as compared to OW placement subgroup (9.47 ms, SD: 1.05), with the shortest latency in the RW placement subgroup (8.99 ms, SD: 0.68). For increasing stimulation levels, the variance decreased with intensity-latency function slopes converging toward a steady-state (saturation) latency caused by saturation of audio processor (stimulation) gain. Latency saturation was reached at a stimulation level of 50 dB nHL for the OW placement subgroup, 35 dB nHL for the Incus placement subgroup, and 30 dB nHL for the RW placement subgroup. The latency and saturation results indicated decreased dynamic range for RW placement, i.e., reverse stimulation.

Conclusions

VSB evoked ABR wave-V intensity-latency function slopes were similar to acoustic stimulation at high stimulation levels with a shift toward longer latencies caused by audio processor signal delay. Saturation of latencies occurred for higher stimulation levels due to saturation of audio processor gain. Thus, the analysis of VSB evoked intensity-latency functions appears to allow for the objective assessment of a patient's individual dynamic range. This can further improve diagnostics as well as intraoperative and postoperative quality control.
Morphological and Hemodynamic Characteristics Associated With the Rupture of Multiple Intracranial Aneurysms
Authors: Tang Xiaoyu , Zhou Longjiang , Wen Lili , Wu Qi , Leng Xiaochang , Xiang Jianping , Zhang Xin
Published: January 2022

Background and Purpose

The objective of this study was to identify the morphological and hemodynamic factors associated with the rupture of multiple intracranial aneurysms regardless of patient-related factors and establish a statistical model for aneurysm rupture risk assessment.

Methods

The digital subtraction angiography (DSA) data of 104 mirror intracranial aneurysms in 52 consecutive patients were retrospectively analyzed in this study. 21 morphological parameters and hemodynamic parameters were calculated by 3-dimensional reconstruction and computational fluid dynamics (CFD) simulation. Significant differences (p < 0.05) between the two groups were subsequently tested with the multivariate logistic regression to identify the independent risk factors. A prediction model was established based on the independent risk factors. The receiver operating characteristics (ROCs) were generated to estimate the prediction performance. A cohort of patients with multiple intracranial aneurysms admitted in our institute from January 2021 to October 2021 was introduced to verify the value of the model.

Results

Significant differences between the ruptured and unruptured aneurysms were found in 15 out of 19 parameters. Bleb formation, neck width, and size ratio were independent factors in the multivariate logistic regression. A prediction model based on the three independent risk factors was established: Odds = −1.495 – 0.707 × (Neckwidth) + 3.061 × (Blebformation) + 2.1 × (SR) (bleb formation: Yes = 1, No = 0). The area under the curve (AUC) value of the model was 0.901. In the validation cohort, the prediction model showed satisfying performance in assessing multiple aneurysm rupture risk with a sensitivity of 100% and specificity of 88.46%.

Conclusion

Bleb formation, neck width, and size ratio were independently associated with aneurysm rupture status. The prediction model may help in identifying the aneurysm with high rupture risk.
Translocation of Phthalates From Food Packaging Materials Into Minced Beef
Authors: Baranenko Denis , Boulkrane Mohamed Said , Borisova Irina , Astafyeva Bazhena , Lu Weihong , Abd El-Aty A. M.
Published: January 2022

There has been increased concern regarding the potential human health risks associated with exposure to phthalates. Research indicates that food intake is the most critical exposure pathway for phthalates. This study aimed to investigate packaged beef samples for the presence of dimethyl terephthalate (DMTP), di-n-butyl phthalate (DnBP), and diisooctyl phthalate (DiOP) and to assess their translocation from the common form of food packaging procured from various Saint-Petersburg and Leningrad region shops. The packaging samples include paper and different types of plastic. Phthalates were extracted by dichloromethane and analyzed by gas chromatography coupled with mass spectrometry (GC-MS). While DnBP had the highest mean values in beef from 34.5 to 378.5 μg·kg−1, DiOP displayed the lowest mean values from LOD to 37 μg·kg−1. The larger contact area and the presence of distributed fat on the surface of the minced meat resulted in significantly higher phthalate translocation than beef slices. Further, DMTP was not detected in any samples. However, the examined food packages do not meet the requirements of Russian, EU and USA legislation, as DnBP migrates to meat. Calculated maximum DnBP daily intake of 0.167 μg·kg−1·day−1 for chilled minced beef in vacuum packaging did not exceed tolerable daily intake (TDI) level. The most alarming results are concerning the phthalates presence in beef farmed in the Leningrad region and not subjected to any plastic packaging. A full-scale study is warranted to determine the pathways and sources of phthalates migration in the food chain.
Systematic In Vitro Evaluation of a Library of Approved and Pharmacologically Active Compounds for the Identification of Novel Candidate Drugs for KMT2A-Rearranged Leukemia
Authors: Karsa Mawar , Ronca Emma , Bongers Angelika , Mariana Anna , Moles Ernest , Failes Timothy W. , Arndt Greg M. , Cheung Laurence C. , Kotecha Rishi S. , Kavallaris Maria , Haber Michelle , Norris Murray D. , Henderson Michelle J. , Xiao Lin , Somers Klaartje
Published: January 2022

Patients whose leukemias harbor a rearrangement of the Mixed Lineage Leukemia (MLL/KMT2A) gene have a poor prognosis, especially when the disease strikes in infants. The poor clinical outcome linked to this aggressive disease and the detrimental treatment side-effects, particularly in children, warrant the urgent development of more effective and cancer-selective therapeutics. The aim of this study was to identify novel candidate compounds that selectively target KMT2A-rearranged (KMT2A-r) leukemia cells. A library containing 3707 approved drugs and pharmacologically active compounds was screened for differential activity against KMT2A-r leukemia cell lines versus KMT2A-wild type (KMT2A-wt) leukemia cell lines, solid tumor cells and non-malignant cells by cell-based viability assays. The screen yielded SID7969543, an inhibitor of transcription factor Nuclear Receptor Subfamily 5 Group A Member 1 (NR5A1), that limited the viability of 7 out of 11 KMT2A-r leukemia cell lines including 5 out of 7 lines derived from infants, without affecting KMT2A-wt leukemia cells, solid cancer lines, non-malignant cell lines, or peripheral blood mononuclear cells from healthy controls. The compound also significantly inhibited growth of leukemia cell lines with a CALM-AF10 translocation, which defines a highly aggressive leukemia subtype that shares common underlying leukemogenic mechanisms with KMT2A-r leukemia. SID7969543 decreased KMT2A-r leukemia cell viability by inducing caspase-dependent apoptosis within hours of treatment and demonstrated synergy with established chemotherapeutics used in the treatment of high-risk leukemia. Thus, SID7969543 represents a novel candidate agent with selective activity against CALM-AF10 translocated and KMT2A-r leukemias that warrants further investigation.
Real-Life Data From the Largest Pediatric Familial Mediterranean Fever Cohort
Authors: Öztürk Kübra , Coşkuner Taner , Baglan Esra , Sönmez Hafize Emine , Yener Gülçin Otar , Çakmak Figen , Demirkan Fatma Gül , Tanatar Ayşe , Karadag Serife Gül , Ozdel Semanur , Demir Ferhat , Çakan Mustafa , Aktay Ayaz Nuray , Sözeri Betül
Published: January 2022

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease manifesting phenotypic heterogeneity. It is a clinically diagnosed disease supported by MEditerranean FeVer (MEFV) gene mutation analysis. However, the phenotype-genotype correlation is not yet established clearly. We aimed to determine the clinical findings, phenotype-genotype correlation, and treatment outcomes within a large pediatric FMF cohort. The medical charts of children with FMF who were diagnosed and followed up at the eight pediatric rheumatology units were reviewed retrospectively. All patients in the cohort were analyzed for sequence variants in exon 2,3,5 and 10 of the MEFV gene. Patients without any mutations or with polymorphisms including R202Q were excluded. A total of 3,454 children were involved in the study. The mean ± standard deviation of current age, age at symptom onset, and age at diagnosis were 12.1 ± 5.2, 5.1 ± 3.8, and 7.3 ± 4.0 years, respectively. Of 3,454 patients, 88.2% had abdominal pain, 86.7% had fever, 27.7% had arthritis, 20.2% had chest pain, 23% had myalgia, and 13.1% had erysipelas-like erythema. The most common MEFV mutation patterns were homozygous (32.5%) and heterozygous (29.9%) mutations of exon 10. Homozygous M694V was present in 969 patients (28.1%). Allele frequencies of common mutations were M694V (55.3%), M680I (11.3%), V726A (7.6%), and E148Q (7.2%). Children carrying homozygous or compound heterozygous exon 10 mutations had an earlier age of disease onset (4.6 vs. 5.6 years, p = 0.000) and a higher number of attacks per year (11.1 vs. 9.6, p = 0.001). Although 8% of the patients had a family history of amyloidosis, 0.3% (n = 11) had the presence of amyloidosis. M694V homozygosity was detected in nine patients who developed amyloidosis. Colchicine resistance was present in 4.2% of our patients. In this largest pediatric cohort reviewed and presented to date, patients with exon 10 mutations, particularly the M694V homozygous mutation, have been demonstrated earlier disease onset, annual attack count, and more frequent colchicine-resistant cases. Although E148Q is considered as a polymorphism in some populations, it was identified as a disease-causing mutation in our cohort. Secondary amyloidosis is still happening in adults however, it is extremely rare among children, presumably due to increased awareness, tight control, and the availability of anti-IL1 agents in colchicine-resistant cases.
Diet Therapy in Eosinophilic Esophagitis. Focus on a Personalized Approach
Authors: Votto Martina , De Filippo Maria , Lenti Marco Vincenzo , Rossi Carlo Maria , Di Sabatino Antonio , Marseglia Gian Luigi , Licari Amelia
Published: January 2022

Eosinophilic esophagitis (EoE) is a chronic allergic disease defined by a marked eosinophilic inflammation and symptoms of esophageal dysfunction. EoE is a heterogeneous disease and severely impacts the quality of life of affected patients. The current therapeutic management of EoE is based on two cornerstones: medication and diet therapy, both effective but limited by several critical issues. The choice of one or the other therapy might depend on the different disease phenotypes (allergic vs. non-allergic, inflammatory vs. fibro-stenotic), patient's age (adult vs. childhood-onset), food habits, patient/family preference, and familiar financial resource. Diet therapy is a successful treatment but limited by low patient adherence, the need for several endoscopies, food restrictions, psychosocial impact, and potential nutritional deficiencies. All these limitations could be effectively overcome with multidisciplinary and personalized management. This review summarizes the most recent evidence on the dietary elimination approaches and will provide a practical guide to clinicians in managing and implementing dietary therapy for patients with EoE.
Evolution of a Paradigm Switch in Diagnosis and Treatment of HPV-Driven Head and Neck Cancer—Striking the Balance Between Toxicity and Cure
Authors: Tawk Bouchra , Debus Jürgen , Abdollahi Amir
Published: January 2022

More than a decade after the discovery of p16 immunohistochemistry (IHC) as a surrogate for human papilloma virus (HPV)-driven head and neck squamous cell carcinoma (HNSCC), p16-IHC has become a routinely evaluated biomarker to stratify oropharyngeal squamous cell carcinoma (OPSCC) into a molecularly distinct subtype with favorable clinical prognosis. Clinical trials of treatment de-escalation frequently use combinations of biomarkers (p16-IHC, HPV-RNA in situ hybridization, and amplification of HPV-DNA by PCR) to further improve molecular stratification. Implementation of these methods into clinical routine may be limited in the case of RNA by the low RNA quality of formalin-fixed paraffin-embedded tissue blocks (FFPE) or in the case of DNA by cross contamination with HPV-DNA and false PCR amplification errors. Advanced technological developments such as investigation of tumor mutational landscape (NGS), liquid-biopsies (LBx and cell-free cfDNA), and other blood-based HPV immunity surrogates (antibodies in serum) may provide novel venues to further improve diagnostic uncertainties. Moreover, the value of HPV/p16-IHC outside the oropharynx in HNSCC patients needs to be clarified. With regards to therapy, postoperative (adjuvant) or definitive (primary) radiochemotherapy constitutes cornerstones for curative treatment of HNSCC. Side effects of chemotherapy such as bone-marrow suppression could lead to radiotherapy interruption and may compromise the therapy outcome. Therefore, reduction of chemotherapy or its replacement with targeted anticancer agents holds the promise to further optimize the toxicity profile of systemic treatment. Modern radiotherapy gradually adapts the dose. Higher doses are administered to the visible tumor bulk and positive lymph nodes, while a lower dose is prescribed to locoregional volumes empirically suspected to be invaded by tumor cells. Further attempts for radiotherapy de-escalation may improve acute toxicities, for example, the rates for dysphagia and feeding tube requirement, or ameliorate late toxicities like tissue scars (fibrosis) or dry mouth. The main objective of current de-intensification trials is therefore to reduce acute and/or late treatment-associated toxicity while preserving the favorable clinical outcomes. Deep molecular characterization of HPV-driven HNSCC and radiotherapy interactions with the tumor immune microenvironment may be instructive for the development of next-generation de-escalation strategies.
Efficacy and Safety of Chinese Herbal Medicine Xiao Yao San in Functional Gastrointestinal Disorders: A meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Liu Qian , Shi Zongming , Zhang Tao , Jiang Tianyuan , Luo Xiaoying , Su Xiaolan , Yang Yang , Wei Wei
Published: January 2022

Background and Aims: Functional gastrointestinal disorders are now named disorders of gut-brain interaction (DGBI) according to the Rome IV criteria, characterized by the interaction of gastrointestinal symptoms and dysregulation of central nervous systems. Xiao-Yao-San (XYS) is effective in the treatment of gastrointestinal symptoms in China, especially in patients with concurrent mood disorders. A meta-analysis was designed to evaluate the efficacy and safety of Xiao-Yao-San for FGIDs.

Methods: We searched randomized controlled trials in seven databases from their inception till November 22, 2021. Pooled analysis included therapeutic efficacy, symptom score, Self-Rating Anxiety Scale (SAS) score, Self-Rating Depression Scale (SDS) score, and the recurrence rate. Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis (TSA) were performed.

Results: A total of 48 RCTs were eligible for inclusion (n = 4,403). Meta-analysis results showed that XYS could improve the effective rate of FGIDs compared with western drugs [RR = 1.23; (95%CI, 1.19–1.27); p < 0.00001], and XYS combined with western medicine could also improve the effective rate [RR = 1.26; (95%CI, 1.21–1.33); p < 0.00001]. In addition, XYS could reduce the symptom score [SMD = −1.07; (95%CI −1.42, -0.72); Z = 6.03; p < 0.00001], SAS score [MD = −6.24; (95%CI −7.48, −4.99); Z = 9.81; p < 0.00001] and SDS score [MD = -6.70; (95%CI −8.18, −5.21); Z = 8.83; p < 0.00001] of FGIDs patients, and reduce the recurrence rate [MD = -6.70; (95%CI −8.18, −5.21); Z = 8.83; p < 0.00001]. XYS was safe in most cases and no serious adverse events were observed in any of the included trials. TAS showed adequate “information size” for the primary outcome, and further confirmed the efficacy of XYS in the treatment of FGIDs.

Conclusion: XYS could improve symptoms and reduce recurrence rates in FGIDs patients, and XYS may be a potential candidate for the treatment of FGIDs. However, due to the limited quality of current studies, more long-term, randomized, double-blinded clinical trials are needed in future studies.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=284308, identifier CRD42021284308.
Multilayer-Aggregation Functional Network for Identifying Brain Fatigue and Diseases
Authors: Cui Wen-Kuo , Qi Xin-Rui , Sun Yu , Yan Gang
Published: January 2022

Recent years have witnessed increasing interest of applying network science methodologies to analyze brain activity data. Owing to the noninvasiveness, low cost and high sampling rate, electroencephalogram (EEG) recordings have been widely used as a proxy for probing the internal states of human brains. Previous correlation-based functional networks (CFN) mainly focused on the covariance or coherence between readings from electrodes attached to different regions, largely overlooking local temporal properties of these electrical activities. Here, we propose a method to construct multilayer-aggregation functional network (MAFN) which is able to capture both temporal and topological characteristics from EEG data. We extract features from these MAFNs and incorporate them into each of 12 classification algorithms, aiming to detect mental fatigue and two brain diseases, schizophrenia and epilepsy. The results demonstrate that MAFNs consistently outperform CFN and dynamic version of CFN. In comparison to functional networks based on weighted phase lag index (wPLI), MAFNs also achieve higher or comparable accuracy in most classifiers. Moreover, the nodal features of MAFNs allow us to identify the important positions of EEG electrodes for different brain states or diseases. These findings together offer not only a framework for classifying normal and abnormal brain activities but also a general method for constructing more informative functional networks from multiple time series data.
Genome-Wide Identification and Expression Profiling of DUF221 Gene Family Provides New Insights Into Abiotic Stress Responses in Potato
Authors: Zaynab Madiha , Peng Jiaofeng , Sharif Yasir , Albaqami Mohammed , Al-Yahyai Rashid , Fatima Mahpara , Nadeem Muhammad Azhar , Khan Khalid Ali , Alotaibi Saqer S. , Alaraidh Ibrahim A. , Shaikhaldein Hassan O. , Li Shuangfei
Published: January 2022

The domain of the unknown function 221 proteins regulate several processes in plants, including development, growth, hormone transduction mechanism, and abiotic stress response. Therefore, a comprehensive analysis of the potato genome was conducted to identify the deafness-dystonia peptide (DDP) proteins’ role in potatoes. In the present study, we performed a genome-wide analysis of the potato domain of the unknown function 221 (DUF221) genes, including phylogenetic inferences, chromosomal locations, gene duplications, gene structures, and expression analysis. In our results, we identified 10 DDP genes in the potato genome. The phylogenetic analysis results indicated that StDDPs genes were distributed in all four clades, and clade IV was the largest clade. The gene duplication under selection pressure analysis indicated various positive and purifying selections in StDDP genes. The putative stu-miRNAs from different families targeting StDDPs were also predicted in the present study. Promoter regions of StDDP genes contain different cis-acting components involved in multiple stress responses, such as phytohormones and abiotic stress-responsive factors. The analysis of the tissue-specific expression profiling indicated the StDDPs gene expression in stem, root, and leaf tissues. We subsequently observed that StDDP4, StDDP5, and StDDP8 showed higher expressions in roots, stems, and leaves. StDDP5 exhibited high expression against heat stress response, and StDDP7 showed high transcript abundance against salt stress in potatoes. Under abscisic acid (ABA) and indole acetic acid (IAA) treatments, seven StDDP genes’ expressions indicated that ABA and IAA performed important roles in immunity response. The expression profiling and real-time qPCR of stems, roots, and leaves revealed StDDPs’ significant role in growth and development. These expression results of DDPs are primary functional analysis and present basic information for other economically important crops.
The Effects of Open Innovation Based on Mergers and Acquisitions on Innovative Behavior of Enterprises: Evidence From Chinese Listed Enterprises
Authors: Wu Min , Luo Tao , Tian Yihao
Published: January 2022

Finding the factors driving enterprise innovation behavior from multiple dimensions is of great significance for promoting enterprise innovation. Open innovation based on overseas mergers and acquisitions (M&A) has become one of the main ways for enterprises to obtain knowledge and technology. However, there is still no agreement on whether open innovation based on overseas M&A can promote innovation behavior of enterprises. Based on data from M&A transaction and enterprise patent of China’s Shanghai and Shenzhen A-share listed companies from 2011 to 2018, this study constructs a propensity score matching and difference-in-difference model from the perspective of innovation performance and innovation investment empirically studies the influence of open innovation mode based on overseas M&A on the innovation behavior of enterprises and finds that open innovation based on overseas M&A can significantly promote the innovation performance and innovation investment. Meanwhile dynamic effects test shows this promotion effect is sustainable; it reaches the maximum in the year of overseas M&A and decreases in the next two years. In addition, the impacts are heterogeneous due to enterprise ownership and enterprise technology intensity. The findings extends the scope of understanding innovation behavior of enterprises from overseas M&A and provide solid evidence of significant business implications for the promotion of entrepreneurial innovation.
Socio-Psychological and Design Features Related to Transport Choices: A Focus Group Research in the Metropolitan Area of Cagliari (Sardinia, Italy)
Authors: Manca Sara , Tirotto Francesca Ausilia , Mura Nicola , Fornara Ferdinando
Published: January 2022

Due to the environmental and health impact of the private transport sector, social scientists have largely focused on psychosocial and contextual factors associated with people's choice over transport means. This study aims to contribute to this line of research by applying a user-centered approach, with the objective of taking into account the specific environmental and social context of the metropolitan area of Cagliari city (Sardinia, Italy). To accomplish this aim, four groups of people were matched according to their shared starting point: car users vs. public transport users (Study 1), and light-rail users vs. non-light-rail users (Study 2). Groups were interviewed using a focus group method. Participants were invited to discuss their everyday travel experiences and to exchange their ideas on different sustainable (e.g., bicycles and public transport) and less sustainable (i.e., private cars) means of transport. Both consolidated drivers/barriers in the field of environmental psychology (e.g., perceived behavioral control, social norms) and public transportation design features (e.g., lighting) have been investigated. Other than highlighting the importance of socio-psychological factors to promote more sustainable transport choices like in previous studies, the present research offers an insight into how these aspects and factors are shaped and experienced in the narratives of residents.
Understanding the Effects of Emergency Experience on Online First-Aid Learning Intention: The Mediating Role of Psychological Distances and Prosociality
Authors: Zhang Shuo , Guo Huijing , Ju Xiaofeng , Ma Jiantao
Published: January 2022

The fast-paced lifestyle resulting from China's rapid economic development has caused more than 500 million sudden cardiac deaths in 2020. Online first-aid education for the public is considered a key potential solution to avoid such incidents and would have great practical value. This study focuses on understanding the impact of past first-aid experience on the intention for online learning of first-aid knowledge and skills from the perspective of individual psychological factors based on the construction level and prosociality theories. More specifically, it tests the mediating roles of psychological distances and prosociality, which reflect psychological status, in the relationship between experience and learning intention along with a series of associated demographic variables. Primary data collected via a survey are analyzed through regression analysis. The results show that first-aid experience has a significant positive impact on online first-aid learning intention. In addition, psychological distances from first-aid events, and prosociality, play mediating roles in the relationship between first-aid experience and learning intention. Thus, this study contributes to understanding first-aid learning intention by revealing the impact of the individual factors of psychological distances and prosociality.
COVID-19 Exposure, Stress, and Mental Health Outcomes: Results From a Needs Assessment Among Low Income Adults in Central North Carolina
Authors: Kaniuka Andréa R. , Cramer Robert J. , Wilsey Corrine N. , Langhinrichsen-Rohling Jennifer , Mennicke Annelise , Patton Alexandra , Zarwell Meagan , McLean Carmen P. , Harris Yu-Jay , Sullivan Sharon , Gray Glori
Published: January 2022

This study focuses on identifying COVID-19 related exposure, stress, and mental health concerns in the larger Charlotte, North Carolina region, an area with many low-income and under resourced communities. A community-academic partnership conducted a regional COVID-19 needs assessment. Low-income adults (N = 156) completed an online-administered survey of demographic information, COVID-19 exposure, stress, coping-related factors, and mental health. Frequency data showed that common COVID-19 related stressors included job exposure, lost job/income, and increased home responsibilities. Frequency data further showed elevated screening risk rates for mental health concerns were observed for post-traumatic stress (83.3%), depression (52.2%), problematic drinking (50.0%), generalized anxiety (43.0%), and suicide (40.4%). Bivariate correlation and multivariate regression models identified robust mental health risk factors including COVID-19 related stress affecting close persons, fear/worry reaction to the pandemic, and use of venting as a coping strategy; protective factors included active coping and problem-focused coping beliefs. Findings are discussed with respect to informing regional public health efforts during the pandemic.