bluuebunny/crossref_metadata_2025 huggingface dataset:
CD11c+CD163+ Cells and Signal Transducer and Activator of Transcription 3 (STAT3) Expression Are Common in Melanoma Leptomeningeal Disease
Authors: Najem Hinda , Marisetty Anantha , Horbinski Craig , Long James , Huse Jason T. , Glitza Oliva Isabella C. , Ferguson Sherise D. , Kumthekar Priya U. , Wainwright Derek A. , Chen Peiwen , Lesniak Maciej S. , Burks Jared K. , Heimberger Amy B.
Published: October 2021

Leptomeningeal disease (LMD) in melanoma patients is associated with significant neurological sequela and has a dismal outcome, with survival measured typically in weeks. Despite the therapeutic benefit of targeted therapies and immunotherapies for Stage IV melanoma, patients with LMD do not typically benefit. A deeper understanding of the tumor microenvironment (TME) of LMD may provide more appropriate therapeutic selection. A retrospective analysis of subjects who underwent surgical resection with LMD (n=8) were profiled with seven color multiplex staining to evaluate the expression of the global immune suppressive hub - the signal transducer and activator of transcription 3 (STAT3) and for the presence of CD3+ T cells, CD68+ monocyte-derived cells, CD163+ immune suppressive macrophages, and CD11c+ cells [potential dendritic cells (DCs)] in association with the melanoma tumor marker S100B and DAPI for cellular nuclear identification. High-resolution cellular imaging and quantification was conducted using the Akoya Vectra Polaris. CD11c+ cells predominate in the TME (10% of total cells), along with immunosuppressive macrophages (2%). Another potential subset of DCs co-expressing CD11c+ and the CD163+ immunosuppressive marker is frequently present (8/8 of specimens, 8%). Occasional CD3+ T cells are identified, especially in the stroma of the tumor (p=0.039). pSTAT3 nuclear expression is heterogeneous in the various immune cell populations. Occasional immune cluster interactions can be seen in the stroma and on the edge. In conclusion, the TME of LMD is largely devoid of CD3+ T cells but is enriched in immune suppression and innate immunity.
Case Report: Lenalidomide as a Second-Line Treatment for Bortezomib-Ineffective Nephrotic Syndrome Caused by LCDD: 2 Case Reports and a Literature Review
Authors: Zhang Xin , Yu Xiao-juan , Wang Su-xia , Zhou Fu-de , Zhao Ming-hui
Published: October 2021

Background: Light-chain deposition disease (LCDD) is a rare systemic disorder characterized by the deposition of monoclonal light chains in organs. The kidney is a prominent target of light-chain deposition, with a median time to end-stage renal disease (ESRD) of 2.7 years and 5-year ESRD-free survival of 37%. The therapeutic management of LCDD remains ill-defined. In addition to bortezomib-based therapy as first-line therapy, the effect of lenalidomide on LCDD is rarely reported.

Case Presentation: This study describes two male LCDD patients in their 60s with nephrotic syndrome and moderately impaired renal function. One patient had monoclonal IgGλ with underlying MGRS, and another had monoclonal IgGκ with underlying monoclonal gammopathy that developed into symptomatic MM during follow-up. The hallmarks of this disease were consistent with previous reports. Both patients initially received BCD therapy, but no hematological response was observed. Consequently, the nephrotic syndrome was refractory. Sequential Rd therapy was initiated, and partial hematological response and nephrotic remission were observed in the IgGλ patient but absent in the IgGκ patient.

Conclusion: Limited reports have demonstrated the effect of lenalidomide in LCDD. We report the outcome of lenalidomide in two cases of bortezomib-resistant LCDD. This treatment might be a beneficial supplement for those unresponsive or intolerant to bortezomib in LCDD, but the effect should be prospectively investigated.
Pathogenesis of Behçet's Syndrome: Genetic, Environmental and Immunological Factors
Authors: Mattioli Irene , Bettiol Alessandra , Saruhan-Direskeneli Güher , Direskeneli Haner , Emmi Giacomo
Published: October 2021

Behçet's syndrome (BS) is a rare systemic vasculitis, characterized by a wide range of different clinical involvements and unpredictable phases of recurrence and remission. BS can be described as a multifactorial disease with an incompletely known etiopathogenesis; in fact, though presenting some peculiar features, such as its typical geographic distribution and the strong association with the well-known genetic predisposing factor HLA-B*51, the cause behind the onset and progression of the disease remains currently not fully understood. Besides genetic HLA and non-HLA predisposing associations and epigenetic influence, environmental factors also play an important role in the pathogenesis of the disease, and among these, infectious agents (both bacterial and viral) and specific microbiome alterations are considered of particular relevance in BS pathogenesis. BS has been included for decades among autoimmune diseases, in light of evidence showing T- and B-cell aberrant responses. However, because of recurrent mucocutaneous lesions and episodes of inflammation without antigen-specific T-cell or autoantibody responses, BS has also been classified among autoinflammatory disorders. Nevertheless, differently from autoinflammatory diseases, BS mildly responds to therapies targeting IL-1, its onset is not usually in childhood, and has high neutrophilic vasculitic involvement. Finally, given the association with HLA class I alleles, similar to spondyloarthropathies, the concept of BS as a major histocompatibility complex (MHC) I -opathy has been introduced. Understanding the complex etiopathogenesis of BS is essential to identify modifiable risk factors of BS occurrence or exacerbation and to develop targeted therapies. This review summarizes current evidence on the main genetic, environmental and immunological factors contributing to BS development.
Diagnostic Values of Dermatoscopy and CD31 Expression in Cutaneous Lymphangioma Circumscriptum
Authors: Lu Lixia , Yan Siyu , Chen Mingliang , Huang Xiaoyan , Su Juan
Published: October 2021

Background: Cutaneous lymphangioma circumscriptum is characterized by clusters of deep-seated, vesicle-like papules. Cutaneous lymphangioma circumscriptum (CLC) is not a tumor but rather a congenital malformation of superficial lymphatics.

Objectives: The study aimed to describe the dermoscopic features of CLC and investigate the reason why marked blood components in CLC. Moreover, this study sought to increase awareness of the clinical characteristics of CLC and provide insights into CLC diagnosis.

Methods: A representative sample of patients with CLC with demographic information and pathological and dermoscopical results was analyzed. The immunohistochemistry of lymphangioma specimens with CD31 and D2-40 was performed. The clinical manifestations of CLC, demographic information, and the results of immunohistochemistry were statistically analyzed to validate the correlation.

Results: Besides the pattern of frog spawn-like blisters, lymphangioma also presented as either transparent or pigmented with dark-red to whitish/yellowish shades. Moreover, lymphangioma manifested as a pattern of dermatofibroma. Furthermore, CD31 was detected in the flattened endothelium and only present in dilated spaces containing enough blood or lymph components.

Limitations: This study is limited by its retrospective nature and statistical power.

Conclusion: Dermoscopy is useful for the diagnosis of CLC. CD31 positive staining and cystic-dilated spaces showed flattened inner and outer endothelia are the diagnostic features in hypopyon-like shape and blisters resembling frog spawn patterns in CLC. These features can assist in the diagnosis of CLC.
Legacy Metal Contaminants and Excess Nutrients in Low Flow Estuarine Embayments Alter Composition and Function of Benthic Bacterial Communities
Authors: Birrer Simone C. , Wemheuer Franziska , Dafforn Katherine A. , Gribben Paul E. , Steinberg Peter D. , Simpson Stuart L. , Potts Jaimie , Scanes Peter , Doblin Martina A. , Johnston Emma L.
Published: October 2021

Coastal systems such as estuaries are threatened by multiple anthropogenic stressors worldwide. However, how these stressors and estuarine hydrology shape benthic bacterial communities and their functions remains poorly known. Here, we surveyed sediment bacterial communities in poorly flushed embayments and well flushed channels in Sydney Harbour, Australia, using 16S rRNA gene sequencing. Sediment samples were collected monthly during the Austral summer-autumn 2014 at increasing distance from a large storm drain in each channel and embayment. Bacterial communities differed significantly between sites that varied in proximity to storm drains, with a gradient of change apparent for sites within embayments. We explored this pattern for embayment sites with analysis of RNA-Seq gene expression patterns and found higher expression of multiple genes involved in bacterial stress response far from storm drains, suggesting that bacterial communities close to storm drains may be more tolerant of localised anthropogenic stressors. Several bacterial groups also differed close to and far from storm drains, suggesting their potential utility as bioindicators to monitor contaminants in estuarine sediments. Overall, our study provides useful insights into changes in the composition and functioning of benthic bacterial communities as a result of multiple anthropogenic stressors in differing hydrological conditions.
Host-Induced Gene Silencing of a Multifunction Gene Sscnd1 Enhances Plant Resistance Against Sclerotinia sclerotiorum
Authors: Ding Yijuan , Chen Yangui , Yan Baoqin , Liao Hongmei , Dong Mengquan , Meng Xinran , Wan Huafang , Qian Wei
Published: October 2021

Sclerotinia sclerotiorum is a devastating necrotrophic fungal pathogen and has a substantial economic impact on crop production worldwide. Magnaporthe appressoria-specific (MAS) proteins have been suggested to be involved in the appressorium formation in Magnaporthe oryzae. Sscnd1, an MAS homolog gene, is highly induced at the early infection stage of S. sclerotiorum. Knock-down the expression of Sscnd1 gene severely reduced the virulence of S. sclerotiorum on intact rapeseed leaves, and their virulence was partially restored on wounded leaves. The Sscnd1 gene-silenced strains exhibited a defect in compound appressorium formation and cell integrity. The instantaneous silencing of Sscnd1 by tobacco rattle virus (TRV)-mediated host-induced gene silencing (HIGS) resulted in a significant reduction in disease development in tobacco. Three transgenic HIGS Arabidopsis lines displayed high levels of resistance to S. sclerotiorum and decreased Sscnd1 expression. Production of specific Sscnd1 siRNA in transgenic HIGS Arabidopsis lines was confirmed by stem-loop qRT-PCR. This study revealed that the compound appressorium-related gene Sscnd1 is required for cell integrity and full virulence in S. sclerotiorum and that Sclerotinia stem rot can be controlled by expressing the silencing constructs of Sscnd1 in host plants.
Enhanced Production of Pterostilbene in Escherichia coli Through Directed Evolution and Host Strain Engineering
Authors: Yan Zhi-Bo , Liang Jing-Long , Niu Fu-Xing , Shen Yu-Ping , Liu Jian-Zhong
Published: October 2021

Pterostilbene is a derivative of resveratrol with a higher bioavailability and biological activity, which shows antioxidant, anti-inflammatory, antitumor, and antiaging activities. Here, directed evolution and host strain engineering were used to improve the production of pterostilbene in Escherichia coli. First, the heterologous biosynthetic pathway enzymes of pterostilbene, including tyrosine ammonia lyase, p-coumarate: CoA ligase, stilbene synthase, and resveratrol O-methyltransferase, were successively directly evolved through error-prone polymerase chain reaction (PCR). Four mutant enzymes with higher activities of in vivo and in vitro were obtained. The directed evolution of the pathway enzymes increased the pterostilbene production by 13.7-fold. Then, a biosensor-guided genome shuffling strategy was used to improve the availability of the precursor L-tyrosine of the host strain E. coli TYR-30 used for the production of pterostilbene. A shuffled E. coli strain with higher L-tyrosine production was obtained. The shuffled strain harboring the evolved pathway produced 80.04 ± 5.58 mg/l pterostilbene, which is about 2.3-fold the highest titer reported in literatures.
Parallel Pandemics Illustrate the Need for One Health Solutions
Authors: Tucker Claire , Fagre Anna , Wittemyer George , Webb Tracy , Abworo Edward Okoth , VandeWoude Sue
Published: October 2021

African Swine Fever (ASF) was reported in domestic pigs in China in 2018. This highly contagious viral infection with no effective vaccine reached pandemic proportions by 2019, substantially impacting protein availability in the same region where the COVID-19 pandemic subsequently emerged. We discuss the genesis, spread, and wide-reaching impacts of this epidemic in a vital livestock species, noting parallels and potential contributions to ignition of COVID-19. We speculate about impacts of these pandemics on global public health infrastructure and suggest intervention strategies using a cost: benefit approach for low-risk, massive-impact events. We note that substantive changes in how the world reacts to potential threats will be required to overcome catastrophes driven by climate change, food insecurity, lack of surveillance infrastructure, and other gaps. A One Health approach creating collaborative processes connecting expertise in human, animal, and environmental health is essential for combating future global health crises.
Adaptations of Vibrio parahaemolyticus to Stress During Environmental Survival, Host Colonization, and Infection
Authors: Pazhani Gururaja Perumal , Chowdhury Goutam , Ramamurthy Thandavarayan
Published: October 2021

Vibrio parahaemolyticus (Vp) is an aquatic Gram-negative bacterium that may infect humans and cause gastroenteritis and wound infections. The first pandemic of Vp associated infection was caused by the serovar O3:K6 and epidemics caused by the other serovars are increasingly reported. The two major virulence factors, thermostable direct hemolysin (TDH) and/or TDH-related hemolysin (TRH), are associated with hemolysis and cytotoxicity. Vp strains lacking tdh and/or trh are avirulent and able to colonize in the human gut and cause infection using other unknown factors. This pathogen is well adapted to survive in the environment and human host using several genetic mechanisms. The presence of prophages in Vp contributes to the emergence of pathogenic strains from the marine environment. Vp has two putative type-III and type-VI secretion systems (T3SS and T6SS, respectively) located on both the chromosomes. T3SS play a crucial role during the infection process by causing cytotoxicity and enterotoxicity. T6SS contribute to adhesion, virulence associated with interbacterial competition in the gut milieu. Due to differential expression, type III secretion system 2 (encoded on chromosome-2, T3SS2) and other genes are activated and transcribed by interaction with bile salts within the host. Chromosome-1 encoded T6SS1 has been predominantly identified in clinical isolates. Acquisition of genomic islands by horizontal gene transfer provides enhanced tolerance of Vp toward several antibiotics and heavy metals. Vp consists of evolutionarily conserved targets of GTPases and kinases. Expression of these genes is responsible for the survival of Vp in the host and biochemical changes during its survival. Advanced genomic analysis has revealed that various genes are encoded in Vp pathogenicity island that control and expression of virulence in the host. In the environment, the biofilm gene expression has been positively correlated to tolerance toward aerobic, anaerobic, and micro-aerobic conditions. The genetic similarity analysis of toxin/antitoxin systems of Escherichia coli with VP genome has shown a function that could induce a viable non-culturable state by preventing cell division. A better interpretation of the Vp virulence and other mechanisms that support its environmental fitness are important for diagnosis, treatment, prevention and spread of infections. This review identifies some of the common regulatory pathways of Vp in response to different stresses that influence its survival, gut colonization and virulence.
ΔCT Value of Amplified Refractory Mutation System Predicts Efficacy of EGFR-TKIs in Advanced Non–Small-Cell Lung Cancer: A Multi-Center Retrospective Study
Authors: Chen Min , Huang Wenqi , Yang Dongyong , Huang Jincheng , Li Gong , Wang Xiaoqing , Xiao Nanjie , Zhang Weijian , Guan Jian , Wang Shuang , Liu Laiyu
Published: October 2021

Purpose: This multi-center retrospective study determines whether the ΔCT value of the Amplified Refractory Mutation System (ARMS) predicts the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant advanced non–small-cell lung cancer (NSCLC).

Patients and methods: Patients who harbored an exon 19 deletion (19Del) or L858R mutation detected by the ARMS and previously received treatment of EGFR-TKIs as a monotherapy were enrolled. A total of 108 NSCLC patients in four hospitals were enrolled. We divided the patients into a high ΔCT group (Group H) and a low ΔCT group (Group L) by the Martingale residuals analysis and log-rank test. The primary outcome was progression-free survival (PFS). Univariate analysis and multivariable regression were applied to compare the PFS between the groups.

Result: The Martingale residuals analysis and log-rank test were applied to find the cutoff ΔCT value (0.8). In the 108 patients we enrolled, 59 were in group L and 49 were in group H. Patients’ demographics and clinical characteristics, including age, sex, smoking history, pathology, mutation sites, TNM stage, and line of TKIs therapy, were not significantly different between group L and group H. The median PFS was 11.1 months in group L and 6.9 months in group H, and the difference showed statistical significance (p < 0.001). Moreover, the objective response rates (ORRs) in group L was significantly higher than in group H (61.0 vs 34.7%, p = 0.002). The median OS was 25.0 months in group L and 20.0 months in group H (p = 0.046).

Conclusion: The ΔCT value of ARMS could be an efficacy predictor for EGFR-TKI treatment in advanced EGFR-mutant NSCLC.
Identification of Negative BOLD Responses in Epilepsy Using Windkessel Models
Authors: Suarez Alejandro , Valdés-Hernández Pedro A. , Bernal Byron , Dunoyer Catalina , Khoo Hui Ming , Bosch-Bayard Jorge , Riera Jorge J.
Published: October 2021

Alongside positive blood oxygenation level–dependent (BOLD) responses associated with interictal epileptic discharges, a variety of negative BOLD responses (NBRs) are typically found in epileptic patients. Previous studies suggest that, in general, up to four mechanisms might underlie the genesis of NBRs in the brain: (i) neuronal disruption of network activity, (ii) altered balance of neurometabolic/vascular couplings, (iii) arterial blood stealing, and (iv) enhanced cortical inhibition. Detecting and classifying these mechanisms from BOLD signals are pivotal for the improvement of the specificity of the electroencephalography–functional magnetic resonance imaging (EEG-fMRI) image modality to identify the seizure-onset zones in refractory local epilepsy. This requires models with physiological interpretation that furnish the understanding of how these mechanisms are fingerprinted by their BOLD responses. Here, we used a Windkessel model with viscoelastic compliance/inductance in combination with dynamic models of both neuronal population activity and tissue/blood O2 to classify the hemodynamic response functions (HRFs) linked to the above mechanisms in the irritative zones of epileptic patients. First, we evaluated the most relevant imprints on the BOLD response caused by variations of key model parameters. Second, we demonstrated that a general linear model is enough to accurately represent the four different types of NBRs. Third, we tested the ability of a machine learning classifier, built from a simulated ensemble of HRFs, to predict the mechanism underlying the BOLD signal from irritative zones. Cross-validation indicates that these four mechanisms can be classified from realistic fMRI BOLD signals. To demonstrate proof of concept, we applied our methodology to EEG-fMRI data from five epileptic patients undergoing neurosurgery, suggesting the presence of some of these mechanisms. We concluded that a proper identification and interpretation of NBR mechanisms in epilepsy can be performed by combining general linear models and biophysically inspired models.
Background Activity Findings in End-Stage Renal Disease With and Without Comorbid Diabetes: An Electroencephalogram Study
Authors: Jatupornpoonsub Tirapoot , Thimachai Paramat , Supasyndh Ouppatham , Wongsawat Yodchanan
Published: October 2021

Renal failure and diabetes can induce cerebral complications, including encephalopathy, for which attentional and cognitive impairment are common symptoms. It is possible that renal failure with comorbid diabetes may induce more severe encephalopathy due to multiple pathogenic mechanisms. This concept was supported by the main findings of this study, which showed that EEG background activity between end-stage renal disease with and without comorbid diabetes was significantly different in relative power of delta in the eyes-open condition in frontoparietal regions; theta in the eyes-closed condition in all regions; beta in the parieto-occipital regions in both eye conditions; the delta/theta ratio in both eye conditions in frontoparietal regions; and the theta/beta ratio in all regions in the eyes-closed condition. These findings may increase awareness of comorbid cerebral complications in clinical practice. Moreover, the delta/theta ratio is recommended as an optimal feature to possibly determine the severity of encephalopathy.
Autistic Spectrum Disorder Detection and Structural Biomarker Identification Using Self-Attention Model and Individual-Level Morphological Covariance Brain Networks
Authors: Wang Zhengning , Peng Dawei , Shang Yongbin , Gao Jingjing
Published: October 2021

Autism spectrum disorder (ASD) is a range of neurodevelopmental disorders, which brings enormous burdens to the families of patients and society. However, due to the lack of representation of variance for diseases and the absence of biomarkers for diagnosis, the early detection and intervention of ASD are remarkably challenging. In this study, we proposed a self-attention deep learning framework based on the transformer model on structural MR images from the ABIDE consortium to classify ASD patients from normal controls and simultaneously identify the structural biomarkers. In our work, the individual structural covariance networks are used to perform ASD/NC classification via a self-attention deep learning framework, instead of the original structural MR data, to take full advantage of the coordination patterns of morphological features between brain regions. The self-attention deep learning framework based on the transformer model can extract both local and global information from the input data, making it more suitable for the brain network data than the CNN- structural model. Meanwhile, the potential diagnosis structural biomarkers are identified by the self-attention coefficients map. The experimental results showed that our proposed method outperforms most of the current methods for classifying ASD patients with the ABIDE data and achieves a classification accuracy of 72.5% across different sites. Furthermore, the potential diagnosis biomarkers were found mainly located in the prefrontal cortex, temporal cortex, and cerebellum, which may be treated as the early biomarkers for the ASD diagnosis. Our study demonstrated that the self-attention deep learning framework is an effective way to diagnose ASD and establish the potential biomarkers for ASD.
Both Underweight and Obesity Are Associated With an Increased Risk of Coronavirus Disease 2019 (COVID-19) Severity
Authors: Ye Pian , Pang Ran , Li Ling , Li Hua-Rong , Liu Shuang-Lin , Zhao Lei
Published: October 2021

Introduction: As coronavirus Disease 2019 (COVID-19) has evolved into a global pandemic, increasing numbers of reports have linked obesity to more severe COVID-19 illness and death. However, almost all the studies focused on an increased risk of mortality or intensive care unit (ICU) admission among hospitalized obese patients with COVID-19. Is obesity also associated with the incidence of acute lung injury (ALI) in the patients with COVID-19? How about underweight patients? The answer is lacking. Therefore, our following research will answer the above two questions.

Methods: We collected and analyzed epidemiologic, demographic, clinical, and laboratory data from 193 confirmed cases of COVID-19 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, between January 1, 2020, and March 13, 2020. They were followed up until April 15, 2020. Underweight was defined by body mass index (BMI) lower than 18.5 kg/m2, normal weight by 18.5−23.9 kg/m2, overweight by 24.0−27.9 kg/m2, and obesity as ≥28 kg/m2.

Results: Among these patients, 5.70% were underweight, 58.03% were normal weight, 27.98% were overweight, and 8.29% were obese. Underweight patients were more likely to have a headache (P = 0.029). Obese patients were more likely than other groups to experience a decline in lymphocyte counts (P = 0.038), an increase in C-reactive protein (CRP; P = 0.023), bilateral multiple mottling, and ground glass opacity in the lungs (P = 0.007). Besides, the proportion of patients receiving human immunoglobulin + systematic corticosteroids treatment is the highest among the obese group compared with other BMI groups. After adjusting for potential confounders, underweight patients had a 6.483-fold higher (P = 0.012), and obese patients showed a 5.965-fold higher odds for developing ALI than normal-weight patients (P = 0.022). In addition, underweight patients were 3.255 times more likely than normal-weight patients to develop secondary infections (P = 0.041).

Conclusions: Our study showed that both underweight and obese patients with COVID-19 tend to develop ALI compared with normal-weight patients. Underweight patients were more likely to develop a secondary infection than other patients.
Overall Neutrophil-to-Lymphocyte Ratio and SUVmax of Nodal Metastases Predict Outcome in Head and Neck Cancer Before Chemoradiation
Authors: Werner Jonas , Strobel Klaus , Lehnick Dirk , Rajan Gunesh P.
Published: October 2021

Introduction

This study investigates the pretherapeutic neutrophil-to-lymphocyte ratio (NLR) with markers of tumor metabolism in 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and their potential prognostic value in head and neck cancer patients prior to primary chemoradiation.

Materials and Methods

NLR and metabolic markers of primary tumor and nodal metastases including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were retrospectively assessed in a consecutive cohort of head and neck squamous cell cancer patients undergoing primary chemoradiation. The main outcome measure was survival.

Results

The study included 90 patients of which 74 had lymph node metastases at diagnosis. Median follow-up time of nodal positive patients (n=74) was 26.5 months (IQR 18–44). The NLR correlated significantly with metabolic markers of the primary tumor (TLG: rs=0.47, P<0.001; MTV: rs=0.40, P<0.001; SUVmax: rs=0.34, P=0.003), but much less with FDG-PET/CT surrogate markers of metabolic activity in nodal metastases (TLG: rs=0.15, P=0.19; MTV: rs=0.25, P=0.034; SUVmax: rs=0.06, P=0.63).

For nodal positive cancer patients, multivariate analysis showed that an increased NLR (HR=1.19, 95% CI=1.04-1.37, P=0.012) and SUVmax of lymph node metastasis (HR=1.09; 95% CI=0.99-1.19; P=0.081) are independently predictive of disease-specific survival. High NLR had a negative prognostic value for overall survival (HR=1.16, 95% CI=1.02-1.33, P=0.021).

Conclusion

NLR correlates positively with metabolic markers of the primary tumor, suggestive of an unspecific inflammatory response in the host as a possible reflection of increased metabolism of the primary tumor. SUVmax of lymph node metastases and the NLR, however, show no correlation and are independently predictive of disease-specific survival. Therefore, their addition could be used to improve survival prediction in nodal positive head and neck cancer patients undergoing primary chemoradiation.
Outcomes of Recurrent Nasopharyngeal Carcinoma Patients Treated With Salvage Surgery: A Meta-Analysis
Authors: Feng Yekai , Dai Zhimei , Yan Ruicheng , Li Feng , Zhong Xiaosheng , Ye Haoxin , Chen Caiqing , Fan Shaochong , Qing Cheng , Pan Yong , Sun Haiying
Published: October 2021

Objective

To assess the efficacy of treatment outcomes of salvage surgery for recurrent nasopharyngeal carcinoma (rNPC).

Methods

We conducted a detailed search of the literatures in biomedical databases published from January 1990 to December 2020. The main research features and results of interest were retrieved from the articles that met the selection criteria for meta-analysis.

Results

A total of 21 articles with 778 patients were included, 17 of which met the meta-analysis inclusion criteria. The pooled 2-year overall survival (OS), 5-year OS, and 2-year disease-free survival (DFS) were 71%, 50% and 61%, respectively. Subgroup analysis was conducted with postoperative adjuvant therapy. The pooled 2-year OS, 5-year OS and 2-year DFS of the postoperative adjuvant therapy group compared with the surgery alone group were 69% vs 72%, 44% vs 56%, and 77% vs 54%, respectively. Univariate and multivariate analyses were performed on 178 patients with detailed individual postoperative survival data in 10 articles. On multivariate analysis, recurrent T (RT) stage and adjuvant therapy were independent predictors of outcomes.

Conclusions

This meta-analysis indicated that recurrent NPC patients can obtain survival benefits from salvage surgery. Accurately assessing the RT stage of the tumor and choosing the appropriate surgical method are important to the success of the surgery. Although the prognostic factors influencing outcome have been studied, conclusive data on the survival benefits are still lacking. Random controlled trials (RCTs) to compare surgery alone and postoperative adjuvant therapy are needed in patients with positive margin status after salvage surgery.
Preparation of MSZ Hydrogel and Its Treatment of Colitis
Authors: Wu Yanhong , Li Shangyong , Jin Mengfei , Li Dandan , Zhou Zihan , Hou Haiqing , Han Yantao
Published: October 2021

In order to control the release of mesalazine (MSZ) in the gastrointestinal tract to achieve better pharmacological effects in the colon, in this study, MSZ was added to hydroxypropyl-β-cyclodextrin (HP-β-CD) to form a water-soluble HP-β-CD/MSZ inclusion complex. Then, the inclusion compound was loaded into the structure of the bilayer polyelectrolyte complex microsphere formed by alginate (Alg), chitosan (Cs), and kappa carrageenan (κ-Car) as the hydrogel carrier, and the hydrogel beads with colon-specific release MSZ after oral administration were formed. The formed hydrogel beads have different swelling capabilities in different pH media and have the greatest swelling degree under pH 7.4. The encapsulation efficiency and drug loading of hydrogel beads can reach up to 83.23 and 18.31%, respectively, and the size of hydrogel beads can be reduced to less than 1 mm after drying, so that the size of oral administration can be reached. In vivo experiments also showed that the formed hydrogel beads had a better therapeutic effect on colitis than free drugs, and the microspheres were biodegradable, so the double-layer pH-sensitive microspheres could be effectively used in colon-targeting drug delivery.
FDX1 can Impact the Prognosis and Mediate the Metabolism of Lung Adenocarcinoma
Authors: Zhang Zeyu , Ma Yarui , Guo Xiaolei , Du Yingxi , Zhu Qing , Wang Xiaobing , Duan Changzhu
Published: October 2021

Background: Lung cancer has emerged as one of the most common cancers in recent years. The mitochondrial electron transport chain (ETC) is closely connected with metabolic pathways and inflammatory response. However, the influence of ETC-associated genes on the tumor immune response and the pathogenesis of lung cancer is not clear and needs further exploration.

Methods: The RNA-sequencing transcriptome and clinical characteristic data of LUAD were downloaded from the Cancer Genome Atlas (TCGA) database. The LASSO algorithm was used to build the risk signature, and the prediction model was evaluated by the survival analysis and receiver operating characteristic curve. We explored the function of FDX1 through flow cytometry, molecular biological methods, and liquid chromatography–tandem mass spectrometry/mass spectrometry (LC–MS/MS).

Results: 12 genes (FDX1, FDX2, LOXL2, ASPH, GLRX2, ALDH2, CYCS, AKR1A1, MAOB, RDH16, CYBB, and CYB5A) were selected to build the risk signature, and the risk score was calculated with the coefficients from the LASSO algorithm. The 1-year, 3-year, and 5-year area under the curve (AUC) of ROC curves of the dataset were 0.7, 0.674, and 0.692, respectively. Univariate Cox analysis and multivariate Cox regression analysis indicated that the risk signature is an independent risk factor for LUAD patients. Among these genes, we focused on the FDX1 gene, and we found that knockdown of FDX1 neither inhibited tumor cell growth nor did it induce apoptosis or abnormal cell cycle distribution. But FDX1 could promote the ATP production. Furthermore, our study showed that FDX1 was closely related to the glucose metabolism, fatty acid oxidation, and amino acid metabolism.

Conclusion: Collectively, this study provides new clues about carcinogenesis induced by ETC-associated genes in LUAD and paves the way for finding potential targets of LUAD.
Identification and Validation of Genomic Regions Associated With Charcoal Rot Resistance in Tropical Maize by Genome-Wide Association and Linkage Mapping
Authors: Rashid Zerka , Kaur Harleen , Babu Veerendra , Singh Pradeep Kumar , Harlapur Sharanappa I. , Nair Sudha K.
Published: October 2021

Charcoal rot is a post-flowering stalk rot (PFSR) disease of maize caused by the fungal pathogen, Macrophomina phaseolina. It is a serious concern for smallholder maize cultivation, due to significant yield loss and plant lodging at harvest, and this disease is expected to surge with climate change effects like drought and high soil temperature. For identification and validation of genomic variants associated with charcoal rot resistance, a genome-wide association study (GWAS) was conducted on CIMMYT Asia association mapping panel comprising 396 tropical-adapted lines, especially to Asian environments. The panel was phenotyped for disease severity across two locations with high disease prevalence in India. A subset of 296,497 high-quality SNPs filtered from genotyping by sequencing was correcting for population structure and kinship matrices for single locus mixed linear model (MLM) of GWAS analysis. A total of 19 SNPs were identified to be associated with charcoal rot resistance with P-value ranging from 5.88 × 10−06 to 4.80 × 10−05. Haplotype regression analysis identified 21 significant haplotypes for the trait with Bonferroni corrected P ≤ 0.05. For validating the associated variants and identifying novel QTLs, QTL mapping was conducted using two F2:3 populations. Two QTLs with overlapping physical intervals, qMSR6 and qFMSR6 on chromosome 6, identified from two different mapping populations and contributed by two different resistant parents, were co-located with the SNPs and haplotypes identified at 103.51 Mb on chromosome 6. Similarly, several SNPs/haplotypes identified on chromosomes 3, 6 and 8 were also found to be physically co-located within QTL intervals detected in one of the two mapping populations. The study also noted that several SNPs/haplotypes for resistance to charcoal rot were located within physical intervals of previously reported QTLs for Gibberella stalk rot resistance, which opens up a new possibility for common disease resistance mechanisms for multiple stalk rots.
Genome-Wide Characterization and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Fig (Ficus carica L.)
Authors: Song Miaoyu , Wang Haomiao , Wang Zhe , Huang Hantang , Chen Shangwu , Ma Huiqin
Published: October 2021

The basic helix–loop–helix (bHLH) transcription factor family is the second largest transcription factor family in plants, and participates in various plant growth and development processes. A total of 118 bHLH genes were identified from fig (Ficus carica L.) by whole-genome database search. Phylogenetic analysis with Arabidopsis homologs divided them into 25 subfamilies. Most of the bHLHs in each subfamily shared a similar gene structure and conserved motifs. Seventy-two bHLHs were found expressed at fragments per kilobase per million mapped (FPKM) > 10 in the fig fruit; among them, 15 bHLHs from eight subfamilies had FPKM > 100 in at least one sample. bHLH subfamilies had different expression patterns in the female flower tissue and peel during fig fruit development. Comparing green and purple peel mutants, 13 bHLH genes had a significantly different (≥ 2-fold) expression. Light deprivation resulted in 68 significantly upregulated and 22 downregulated bHLH genes in the peel of the fruit. Sixteen bHLH genes in subfamily III were selected by three sets of transcriptomic data as candidate genes related to anthocyanin synthesis. Interaction network prediction and yeast two-hybrid screening verified the interaction between FcbHLH42 and anthocyanin synthesis-related genes. The transient expression of FcbHLH42 in tobacco led to an apparent anthocyanin accumulation. Our results confirm the first fig bHLH gene involved in fruit color development, laying the foundation for an in-depth functional study on other FcbHLH genes in fig fruit quality formation, and contributing to our understanding of the evolution of bHLH genes in other horticulturally important Ficus species.
Identification of Transcription Factor Genes and Functional Characterization of PlMYB1 From Pueraria lobata
Authors: Shen Guoan , Wu Ranran , Xia Yaying , Pang Yongzhen
Published: October 2021

Kudzu, Pueraria lobata, is a traditional Chinese food and medicinal herb that has been commonly used since ancient times. Kudzu roots are rich sources of isoflavonoids, e.g., puerarin, with beneficial effects on human health. To gain global information on the isoflavonoid biosynthetic regulation network in kudzu, de novo transcriptome sequencings were performed using two genotypes of kudzu with and without puerarin accumulation in roots. RNAseq data showed that the genes of the isoflavonoid biosynthetic pathway were significantly represented in the upregulated genes in the kudzu with puerarin. To discover regulatory genes, 105, 112, and 143 genes encoding MYB, bHLH, and WD40 transcription regulators were identified and classified, respectively. Among them, three MYB, four bHLHs, and one WD40 gene were found to be highly identical to their orthologs involved in flavonoid biosynthesis in other plants. Notably, the expression profiles of PlMYB1, PlHLH3-4, and PlWD40-1 genes were closely correlated with isoflavonoid accumulation profiles in different tissues and cell cultures of kudzu. Over-expression of PlMYB1 in Arabidopsis thaliana significantly increased the accumulation of anthocyanins in leaves and proanthocyanidins in seeds, by activating AtDFR, AtANR, and AtANS genes. Our study provided valuable comparative transcriptome information for further identification of regulatory or structural genes involved in the isoflavonoid pathway in P. lobata, as well as for bioengineering of bioactive isoflavonoid compounds.
Growth Patterns in Seedling Roots of the Pincushion Cactus Mammillaria Reveal Trends of Intra- and Inter-Specific Variation
Authors: González-Sánchez José de Jesús , Santiago-Sandoval Itzel , Lara-González José Antonio , Colchado-López Joel , Cervantes Cristian R. , Vélez Patricia , Reyes-Santiago Jerónimo , Arias Salvador , Rosas Ulises
Published: October 2021

Genetic mechanisms controlling root development are well-understood in plant model species, and emerging frontier research is currently dissecting how some of these mechanisms control root development in cacti. Here we show the patterns of root architecture development in a gradient of divergent lineages, from populations to species in Mammillaria. First, we show the patterns of variation in natural variants of the species Mammillaria haageana. Then we compare this variation to closely related species within the Series Supertexta in Mammillaria (diverging for the last 2.1 million years) in which M. haageana is inserted. Finally, we compared these patterns of variation to what is found in a set of Mammillaria species belonging to different Series (diverging for the last 8 million years). When plants were grown in controlled environments, we found that the variation in root architecture observed at the intra-specific level, partially recapitulates the variation observed at the inter-specific level. These phenotypic outcomes at different evolutionary time-scales can be interpreted as macroevolution being the cumulative outcome of microevolutionary phenotypic divergence, such as the one observed in Mammillaria accessions and species.
An Asymmetric Investigation of Remittance and Trade Openness Impact on Inequality: Evidence From Selected South Asian Countries
Authors: Fang Liu , Qamruzzaman Md.
Published: October 2021

This study’s motivation is to explore the relationship pattern between remittance, trade openness, and inequality of selected south Asian countries for the 1976–2018 period. The study performed non-linear tests, including unit root tests, non-linearity applying ordinary least squares (OLS) and BDS tests, non-linear autoregressive distributed lagged (NARDL) tests, and asymmetry causality tests to assess their association. Study findings with non-linear unit root tests suggest that the research variables follow the non-linear process of becoming stationary from non-stationary. The non-linear OLS and BDS test results confirm the existence of non-linearity among research variables, implying rejection of the null hypothesis of “no non-linearity.” Furthermore, the results of the Wald test in NARDL confirm the availability of asymmetric links among variables. Besides this, the results of NARDL confirm the long-run asymmetric relationship between remittances, trade openness, and inequality in all sample nations. Findings suggest that both positive and negative shocks in remittances and trade openness is critical to either instituting or vexing the present state of inequality in the economy in the long term. In the directional relationship with asymmetry causality, the study shows that the feedback hypothesis holds to explain the asymmetric causal effects that are positive shocks in remittances and trade openness toward inequality.
Social Support as a Facilitator of Musical Self-Efficacy
Authors: Orejudo Santos , Zarza-Alzugaray Francisco Javier , Casanova Oscar , McPherson Gary Edward
Published: October 2021

Previous research has shown that musical self-efficacy is one of the predictors of academic achievement, but few studies have analyzed the function of social support in the construction of musical self-efficacy. In this study we analyze the relationship between three sources of support perceived by music students – parents, teachers, and peers – and their influence on levels of self-efficacy for learning and for public performance. We analyze three groups of students under the hypothesis that relationships among those variables can vary with age and the level of education. A total of 444 students enrolled in six Spanish music schools, two music universities, and four advanced music schools, completed the Social Support Scale for Music Students, as well as the General Musical Self-Efficacy Scale. Results reveal significant relationships among the aforementioned variables, with considerable variation according to academic level. For the youngest students enrolled in advanced music schools (conservatorios profesionales), the role of parents and teachers was crucial, especially for predicting self-efficacy for learning, which, in turn, is the best predictor of self-efficacy for public performance. For the 16–18-year-olds enrolled in the same advanced music schools, their peers play a particularly relevant role in reinforcing their self-efficacy for learning. Social support had a negligible influence on the self-efficacy of university-level students, but they did experience a strong relationship between self-efficacy for learning, on the one hand, and public performance, on the other. We interpret these results in view of potential long-term careers in music, relating them with a series of different agents.
Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease
Authors: Hu Shurong , Chen Yiping , Chen Yan , Wang Caihua
Published: October 2021

Mental health is a significant yet overlooked aspect of inflammatory bowel disease (IBD) patient care, with challenges in determining optimal treatments and psychological health resources. The most common psychological conditions in patients with IBD are anxiety and depression. The increased prevalence of these mental disorders appeals to mental screening of each person diagnosed with IBD at initial consultation. There are simple and clinically viable methods available to screen for mental problems. Psychological methods may be as or even more significant as a therapeutic modality. Herein we discuss the three major areas of psychological co-morbidity in IBD: (1) the prevalence and risk factors associated with anxiety and depression disorders for patients with IBD; (2) diagnosis of psychological disorders for patients with IBD; (3) treatment with patients with IBD and mental disorders. The gastroenterologists are encouraged to screen and treat these patients with IBD and mental disorders, which may improve outcomes.
Self-Medication and Antimicrobial Resistance: A Survey of Students Studying Healthcare Programmes at a Tertiary Institution in Ghana
Authors: Owusu-Ofori Alex K. , Darko Eric , Danquah Cynthia A. , Agyarko-Poku Thomas , Buabeng Kwame Ohene
Published: October 2021

Objectives: Antimicrobial resistance (AMR) is one of the biggest challenges facing mankind. Inappropriate uses of antibiotics including self-medication promote the increase and spread of AMR. Self-medication has not been well-studied among students. This study was undertaken to determine students of healthcare programmes self-medication practices and attitudes in relation to AMR.

Materials and Methods: This was a cross-sectional survey that used a pretested self-administered questionnaire to elicit responses from first-year students of healthcare programmes at the Kwame Nkrumah University of Science and Technology, Ghana from January 2018 to August 2019.

Results: Two hundred and eighty students were recruited with 264 of them returning the questionnaire, giving a response rate of 94.3%. Majority were female (68.9%) and participants ages ranged from 16 to 34 years with a mean age (SD) of 19.5 (1.88) years. 136 students (56.2%) had previously purchased antibiotics without a prescription and 78.3% expressed satisfaction with the outcome of self-medication. Amoxicillin (78%) was the most frequent antibiotic bought without a prescription. Majority (76.3%) agreed that self-medication can lead to AMR. Majority (77.0%) believed that antibiotic abuse is a problem in Ghana and 94.8% agreed that the introduction of a course in the University on the rational use of antibiotic will help improve student's knowledge and practices.

Conclusion: Self-medication is common among participants despite their knowledge that inappropriate use of antibiotic may lead to resistance. Innovative ways including the introduction of new curricula may help to improve knowledge and to curb wrong attitudes and practices related to antibiotic misuse and ultimately to overcome the problem of AMR.