bluuebunny/crossref_metadata_2025 huggingface dataset:
Pipeline Embolization Device for the Treatment of Ruptured Intracerebral Aneurysms: A Multicenter Retrospective Study
Authors: Zhong Weiying , Kuang Hong , Zhang Ping , Yang Xinjian , Luo Bin , Maimaitili Aisha , Zhao Yuanli , Song Donglei , Guan Sheng , Zhang Hongqi , Wang Yang , Wang Donghai , Su Wandong , Wang Yunyan
Published: September 2021

Background and Purpose: The utilization of flow diversion for ruptured intracerebral aneurysms (IAs) is still limited. We aimed to demonstrate our multicenter experience using the pipeline embolization device (PED) for ruptured IAs that were difficult to treat by clipping and coiling.

Methods: Thirty-eight patients with ruptured IAs who underwent PED treatment from 2015 to 2020 were retrospectively reviewed. Factors associated with procedure-related stroke (ischemic and hemorrhagic) and clinical and angiography outcomes were analyzed.

Results: There were 14 (36.8%) saccular IAs, 12 (31.6%) blister-like IAs, and 12 (31.6%) dissecting IAs. Perforator involvement was noted in 10 (26.3%) IAs. Early PED placement ( ≤ 15 days) and adjunctive coiling treatment were performed in 27 (71.1%) and 22 (57.9%) cases, respectively. The overall rate of stroke-related complications was 31.6% (12/38) (including rates of 10.5% for procedure-related hemorrhagic complications and 15.8% for procedure-related infarction). The mortality rate was 13.2% (5/38), and 84.2% of patients (32/38) had favorable outcomes. Thirty-two (84.2%) patients underwent follow-up angiographic evaluations; of these, 84.4% (27 patients) had complete occlusion and 15.6% had incomplete obliteration. Multivariate analysis revealed that early PED placement was not associated with a high risk of procedure-related stroke or an unfavorable outcome. Adjunctive coiling exhibited an association with procedure-related stroke (p = 0.073). Procedure-related hemorrhagic complications were significantly associated with an unfavorable outcome (p = 0.003). Immediate contrast stasis in the venous phase was associated with complete occlusion during follow-up (p = 0.050).

Conclusion: The PED is a feasible and effective treatment to prevent rebleeding and achieve aneurysm occlusion, but it is associated with a substantial risk of periprocedural hemorrhage and ischemic complications in acute ruptured IAs. Therefore, the PED should be used selectively for acutely ruptured IAs. Additionally, adjunctive coiling might increase procedure-related stroke; however, it may reduce aneurysm rebleeding in acutely ruptured IAs. Patients with immediate contrast stasis in the venous phase were more likely to achieve total occlusion. A prospective study with a larger sample size should be performed to verify our results.
Effects of Symmetry and Apparent Distance in a Parasagittal-Mirror Variant of the Rubber Hand Illusion Paradigm
Authors: de Silva Jhana , Chen Haiwen , Isaac Sasha , White Rebekah C. , Davies Martin , Aimola Davies Anne M.
Published: September 2021

When I see my face in a mirror, its apparent position (behind the glass) is not one that my own face could be in. I accept the face I see as my own because I have an implicit understanding of how mirrors work. The situation is different if I look at the reflection of my right hand in a parasagittal mirror (parallel to body midline) when my left hand is hidden behind the mirror. It is as if I were looking through a window at my own left hand. The experience of body ownership has been investigated using rubber hand illusion (RHI) paradigms, and several studies have demonstrated ownership of a rubber hand viewed in a frontal mirror. Our “proof of concept” study was the first to combine use of a parasagittal mirror and synchronous stroking of both a prosthetic hand (viewed in the mirror) and the participant’s hand, with a manipulation of distance between the hands. The strength of the RHI elicited by our parasagittal-mirror paradigm depended not on physical distance between the hands (30, 45, or 60 cm) but on apparent distance between the prosthetic hand (viewed in the mirror) and the participant’s hand. This apparent distance was reduced to zero when the prosthetic hand and participant’s hand were arranged symmetrically (e.g., 30 cm in front of and behind the mirror). Thus, the parasagittal-mirror paradigm may provide a distinctive way to assess whether competition for ownership depends on spatial separation between the prosthetic hand and the participant’s hand.
Association of Malnutrition, Left Ventricular Ejection Fraction Category, and Mortality in Patients Undergoing Coronary Angiography: A Cohort With 45,826 Patients
Authors: Mai Ziling , Huang Zhidong , Lai Wenguang , Li Huanqiang , Wang Bo , Huang Sumei , Shi Yingming , Yu Sijia , Hu Qizheng , Liu Jin , Zhang Lingyu , Liu Yong , Chen Jiyan , Liang Yan , Zhong Shilong , Chen Shiqun
Published: September 2021

Background: The regulatory effect of the left ventricular ejection fraction (LVEF) categories on the association of malnutrition and all-cause mortality in patients undergoing coronary angiography (CAG) have not been adequately addressed.

Methods: Forty-five thousand eight hundred and twenty-six patients consecutively enrolled in the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936) from January 2008 to July 2018 who underwent coronary angiography (CAG). The Controlling Nutritional Status (CONUT) score was applied to 45,826 CAG patients. The hazard ratios of mortality across combined LVEF and/or malnutrition categories were estimated by Cox regression models. Variables adjusted for in the Cox regression models included: age, gender, hypertension (HT), DM, PCI, coronary artery disease (CAD), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TRIG), chronic kidney disease (CKD), statins, atrial fibrillation (AF), anemia, and stroke. Population attributable risk (PAR) was estimated for eight groups stratified by nutritional status and LVEF categories.

Results: In our study, 42,181(92%) of patients were LVEF ≥ 40%, of whom, 41.55 and 9.34% were in mild and moderate or severe malnutrition status, respectively, while 46.53 and 22.28% in mild and moderate or severe malnutritional status among patients with LVEF < 40%. During a median follow-up time of 4.5 years (percentile 2.8–7.1), 5,350 (11.7%) patients died. After fully adjustment, there is no difference of mortality on malnutrition in LVEF < 40% group (mild, moderate and severe vs. normal, HR (95%CI): [1.00 (0.83–0.98)], [1.20 (0.95–1.51)], [1.41 (0.87–2.29)], respectively, p for trend =0.068), but malnutrition was related to markedly increased risk of mortality in LVEF ≥ 40% group (mild, moderate, and severe vs. normal, HR (95%CI): [1.21 (1.12–1.31)], [1.56 (1.40–1.74)], and [2.20(1.67–2.90)], respectively, p for trend < 0.001, and p for interaction < 0.001). Patients with LVEF ≥ 40% had a higher malnutrition-associated risk of mortality and a higher PAR than those with LVEF < 40%.

Conclusions: Malnutrition is common in CAG patients and it has a greater effect on all-cause mortality and a higher PAR in patients with LVEF ≥ 40% than LVEF < 40%.
Transcriptomic Analysis Reveals a Sex-Dimorphic Influence of GAT-2 on Murine Liver Function
Authors: Fu Jian , Zhang Qingzhuo , Wu Zebiao , Hong Changming , Zhu Congrui
Published: September 2021

Accumulating evidence shows that the γ-amino butyric acid (GABA)ergic system affects the functions of different organs, and liver is one of the most sex-dimorphic organs in animals. However, whether and how the GABAergic system influences liver function in a sex-specific manner at the intrinsic molecular level remains elusive. In this study, firstly, we find that the levels of GABA are significantly increased in the livers of female mice with GABA transporter (GAT)-2 deficiency (KO) whereas it only slightly increased in male GAT-2 KO mice. Apart from the amino acid profiles, the expressions of toll-like receptors (TLRs) also differ in the livers of female and male KO mice. Moreover, RNA-seq results show 2,227 differentially expressed genes (DEGs) in which 1,030 are upregulated whereas 1,197 that are downregulated in the livers of female KO mice. Notably, oxidative phosphorylation, non-alcoholic fatty liver disease, Huntington's disease, and peroxisome proliferator-activated receptor (PPAR) signaling pathways are highly enriched by GAT-2 deficiency, indicating that these pathways probably meditate the effects of GAT-2 on female liver functions, on the other hand, only 1,233 DEGs, including 474 are upregulated and 759 are downregulated in the livers of male KO mice. Interestingly, retinol metabolism, PPAR signaling pathway, and tuberculosis pathways are substantially enriched by GAT-2 deficiency, suggesting that these pathways may be responsible for the effects of GAT-2 on male liver functions. Collectively, our results reveal the sex-dimorphic effects of GAT-2 in guiding liver functions, and we propose that targeting the GABAergic system (e.g., GATs) in a sex-specific manner could provide previously unidentified therapeutic opportunities for liver diseases.
The Differences Between Multifocal and Unifocal Papillary Thyroid Carcinoma in Unilateral Lobe: A Meta-Analysis
Authors: Zhang Ting , He Liang , Wang Zhihong , Dong Wenwu , Sun Wei , Zhang Ping , Zhang Hao
Published: September 2021

Background

As many inconsistent reports on the clinical manifestations and prognosis between unilateral unifocal PTC (UUPTC) and unilateral multifocal PTC (UMPTC), identifying the difference should guide management. The purpose of this study was to investigate other additional differences between UUPTC and UMPTC in addition to their difference in the number of cancer foci.

Data Sources

A systematic literature search was conducted in the PubMed and Web of Science databases for relevant studies published before December 31, 2020. Their reference lists were also reviewed.

Review Methods

Two reviewers independently extracted data and assessed the quality of eligible studies. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included. Data were analyzed using the RevMan 5.3 software.

Results

Fifteen studies comprising 9,665 patients were selected for the meta-analysis. UMPTC occurred in 10% to 36% of all PTC cases. There were no significant differences between UMPTC and UUPTC patients in age, gender, tumor size, and extrathyroidal extension (ETE). However, significant differences (P < 0.05) between UMPTC and UUPTC patients were observed in central lymph node metastasis (CLNM), lateral lymph node metastasis (LLNM), tumor-node-metastasis (TNM) stage I+II, TNM stage III+IV, the recurrence/persistence of the UMPTC group after total thyroidectomy and overall recurrence/persistence.

Conclusion

UMPTC patients are more likely to have CLNM, LLNM, more advanced TNM stage, and recurrence/persistence than UUPTC patients. Compared with UUPTC, UMPTC patients should undergo central lymph node dissection, and pay more attention to LLNM, TNM stage and recurrence/persistence during the follow-up.
Psychosocial Stress and Age Influence Depression and Anxiety-Related Behavior, Drive Tumor Inflammatory Cytokines and Accelerate Prostate Cancer Growth in Mice
Authors: Bellinger Denise L. , Dulcich Melissa S. , Molinaro Christine , Gifford Peter , Lorton Dianne , Gridley Daila S. , Hartman Richard E.
Published: September 2021

Prostate cancer (PCa) prevalence is higher in older men and poorer coping with psychosocial stressors effect prognosis. Yet, interactions between age, stress and PCa progression are underexplored. Therefore, we characterized the effects of age and isolation combined with restraint (2 h/day) for 14 days post-tumor inoculation on behavior, tumor growth and host defense in the immunocompetent, orthotopic RM-9 murine PCa model. All mice were tumor inoculated. Isolation/restraint increased sympathetic and hypothalamic-pituitary-adrenal cortical activation, based on elevated serum 3-methoxy-4-hydroxyphenylglycol/norepinephrine ratios and corticosterone levels, respectively. Elevated zero maze testing revealed age-related differences in naïve C57Bl/6 mice, and increased anxiety-like behavior in tumor-bearing mice. In open field testing, old stressed mice were less active throughout the 30-min test than young non-stressed and stressed, and old non-stressed mice, suggesting greater anxiety in old stressed mice. Old (18 month) mice demonstrated more depression-like behavior than young mice with tail suspension testing, without effects of isolation/restraint stress. Old mice developed larger tumors, despite similar tumor expression of tumor vascular endothelial growth factor or transforming growth factor-beta1 across age. Tumor chemokine/cytokine expression, commonly prognostic for poorer outcomes, were uniquely age- and stress-dependent, underscoring the need for PCa research in old animals. Macrophages predominated in RM-9 tumors. Macrophages, and CD4+ and CD4+FoxP3+ T-cell tumor infiltration were greater in young mice than in old mice. Stress increased macrophage infiltration in old mice. Conversely, stress reduced intratumoral CD4+ and CD4+FoxP3+ T-cell numbers in young mice. CD8+ T-cell infiltration was similar across treatment groups. Our findings support that age- and psychological stress interacts to affect PCa outcomes by interfering with neural-immune mechanisms and affecting behavioral responses.
Prognostic Value of Plasma Epstein-Barr Virus DNA Levels Pre- and Post-Neoadjuvant Chemotherapy in Patients With Nasopharyngeal Carcinoma
Authors: Zhu Lisheng , Ouyang Tao , Xiong Ying , Ba Li , Li Qiuting , Qiu Mengjun , Zou Zhenwei , Peng Gang
Published: September 2021

Background

In this study, we evaluated the prognostic value of the plasma levels of Epstein-Barr virus (EBV) DNA in patients with nasopharyngeal carcinoma (NPC) at different treatment stages.

Methods

We retrospectively analyzed the Data of 206 patients with NPC. Pre-neoadjuvant chemotherapy (pre-NACT), post-NACT, post-radiotherapy, and post-treatment plasma EBV DNA levels were used to establish prognostic nomograms. The concordance index (C-index) and calibration curves were used to compare the prognostic accuracy of the nomograms. The results were confirmed in a validation cohort consisting of patients who were tested for EBV DNA levels at all four stages of treatment. The Kaplan-Meier method was used to calculate the progression-free survival (PFS) and overall survival (OS). Survival differences were calculated using the log-rank test.

Results

EBV DNA-positive patients had worse 3-year PFS and 5-year OS than EBV DNA-negative patients; this was true for pre-NACT (PFS: 82.7% vs. 57.3%, P < 0.001; OS: 90.9% vs. 68.7%, P = 0.08) and post-NACT (PFS: 85.0% vs. 50.6%, P < 0.001; OS: 91.7% vs. 65.7%; P = 0.001) EBV DNA levels but not for post-radiotherapy (PFS: 72.2% vs. 60.9%, P = 0.192; OS: 73.1% vs. 77.2%, P = 0.472) or post-treatment (PFS: 77.3% vs. 59.2%, P = 0.063; OS: 77.5% vs. 79.7%, P = 0.644) levels. Nomograms combining pre-NACT and post-NACT EBV DNA levels had a superior prognostic ability than those of post-radiotherapy and post-treatment EBV DNA levels.

Conclusion

Pre-NACT EBV DNA levels combined with post-NACT EBV DNA levels can more reliably predict survival outcomes in patients with NPC.
Melanoma in Adolescents and Young Adults: Evaluation of the Characteristics, Treatment Strategies, and Prognostic Factors in a Monocentric Retrospective Study
Authors: Del Fiore Paolo , Russo Irene , Ferrazzi Beatrice , Monico Alessandro Dal , Cavallin Francesco , Filoni Angela , Tropea Saveria , Russano Francesco , Di Prata Claudia , Buja Alessandra , Collodetto Alessandra , Spina Romina , Carraro Sabrina , Cappellesso Rocco , Nicolè Lorenzo , Chiarion-Sileni Vanna , Pigozzo Jacopo , Dall’Olmo Luigi , Rastrelli Marco , Vecchiato Antonella , Benna Clara , Menin Chiara , Di Carlo Daniela , Bisogno Gianni , Dei Tos Angelo Paolo , Alaibac Mauro , Mocellin Simone
Published: September 2021

The “Veneto Cancer Registry” records melanoma as the most common cancer diagnosed in males and the third common cancer in females under 50 years of age in the Veneto Region (Italy). While melanoma is rare in children, it has greater incidence in adolescents and young adults (AYA), but literature offers only few studies specifically focused on AYA melanoma. The aim of this study was to describe the characteristics, surgical treatment, and prognosis of a cohort of AYA melanoma in order to contribute to the investigation of this malignancy and provide better patient care. This retrospective cohort study included 2,752 Caucasian patients (702 AYA and 2,050 non-AYA patients) from the Veneto Region who were over 15 years of age at diagnosis, and who received diagnosis and/or treatment from our institutions between 1998 and 2014. Patients were divided in adolescents and youth (15-25 years), young adults (26-39 years) and adults (more than 39 years) for the analysis. We found statistically significant differences in gender, primary site, Breslow thickness, ulceration, pathologic TNM classification (pTNM) stage and tumor subtype among the age groups. Disease-specific survival and disease-free survival were also different among the age groups. Our findings suggest that the biological behavior of melanoma in young people is different to that in adults, but not such as to represent a distinct pathological entity. Additional and larger prospective studies should be performed to better evaluate potential biological and cancer-specific differences between AYAs and the adult melanoma population.
Electrochemotherapy as a Trigger to Overcome Primary Resistance to Anti-PD-1 Treatment: A Case Report of Melanoma of the Scalp
Authors: Quaresmini Davide , Di Lauro Alessandra , Fucci Livia , Strippoli Sabino , De Risi Ivana , Sciacovelli Angela Monica , Albano Anna , Achille Gaetano , Montepara Massimo , Russo Sabino , Tassone Gabriella , Guida Michele
Published: September 2021

Background

Immunotherapy with immune checkpoint inhibitors is one of the main therapies for advanced melanoma. Nevertheless, albeit remarkable, immunotherapy results are still unsatisfactory as more than half of patients progress, and resistance to treatment still has a dramatic impact on clinical outcomes. Local treatments such as radiotherapy or electrochemotherapy (ECT), in addition to local control with palliative intent, have been shown to release tumoral neoantigens that can stimulate a robust systemic antitumor immune response.

Case Presentation

We report the case of a patient with multiple nodular melanoma lesions of the scalp initially treated with local ECT. Soon after the procedure, multiple new lesions appeared close to the treated ones, therefore the patient started a systemic treatment with the anti-PD-1 nivolumab. The lesions of the scalp did not respond to immunotherapy, presenting a loco-regional spreading. To control the bleeding and painful lesions, we performed a second ECT, while continuing systemic immunotherapy. The treated lesions responded to the second procedure, while the other lesions continued progressing in number and dimension. Unexpectedly, after 2 months from the second ECT, the patient presented a progressive shrinkage of both treated and untreated lesions until complete remission. Concomitantly, he developed immune-related adverse events including grade 4 thyroid toxicity, grade 2 vitiligo-like depigmentation and grade 2 pemphigoid. At present, after 18 months from the first ECT and 14 months from the starting of anti-PD-1 immunotherapy, the patient is in good clinical condition and complete remission of disease still persists.

Conclusion

This case highlights the potential role of ECT in increasing tumor immunogenicity and consequently in inducing a powerful immune response overcoming primary resistance to checkpoint inhibitor immunotherapy.
Advanced Nano-Carriers for Anti-Tumor Drug Loading
Authors: Xiang Jia , Zhao Rui , Wang Bo , Sun Xinran , Guo Xu , Tan Songwen , Liu Wenjie
Published: September 2021

Chemotherapy is one of the important means of tumor therapy. However, most of the anti-tumor drugs that currently used in clinic are hydrophobic non-specific drugs, which seriously affect the efficacy of drugs. With the development of nanotechnology, drug efficacy can be improved by selecting appropriate biodegradable nanocarriers for achieving the controlled release, targeting and higher bioavailability of drugs. This paper reviewed the research progress of anti-tumor drug nanoparticle carriers, which mainly summarized the materials used for anti-tumor drug nanoparticle carriers and their effects in anti-tumor drugs, as well as the targeted drug delivery methods of anti-tumor drugs based on nanocarriers.
Association of Fluid Balance and Survival of Pediatric Patients Treated With Extracorporeal Membrane Oxygenation
Authors: Rajapreyar Prakadeshwari , Castaneda Lauren , Thompson Nathan E. , Petersen Tara L. , Hanson Sheila J.
Published: September 2021

The effect of positive fluid balance (FB) on extracorporeal membrane oxygenation (ECMO) outcomes in pediatric patients remains unknown. We sought to evaluate if positive FB in pediatric intensive care unit (PICU) patients with respiratory and/or cardiac failure necessitating ECMO was associated with increased morbidity or mortality. This was a multicenter retrospective cohort study of data from the deidentified PEDiatric ECMO Outcomes Registry (PEDECOR). Patients entered into the database from 2014 to 2017, who received ECMO support, were included. A total of 168 subjects met the study criteria. Univariate analysis showed no significant difference in total FB on ECMO days 1–5 between survivors and non-survivors [median 90 ml/kg (IQR 18–208.5) for survivors vs. median 139.7 ml/kg (IQR 11.2–300.6) for non-survivors, p = 0.334]. There was also no difference in total FB on ECMO days 1–5 in patients with no change in functional outcome as reflected by the Pediatric Outcome Performance Category (POPC) score vs. those who had worsening in POPC score ≥2 at hospital discharge [median 98 ml/kg (IQR 18–267) vs. median 130 ml/kg (IQR 13–252), p = 0.91]. Subjects that required 50 ml/kg or more of blood products over the initial 5 days of ECMO support had an increased rate of mortality with an odds ratio of 5.8 (95% confidence interval of 2.7–12.3; p = 0.048). Our study showed no association of the noted FB with survival after ECMO cannulation. This FB trend was also not associated with POPC at hospital discharge, MV duration, or ECMO duration. The amount of blood product administered was found to be a significant predictor of mortality.
The Role of the Carnitine/Organic Cation Transporter Novel 2 in the Clinical Outcome of Patients With Locally Advanced Esophageal Carcinoma Treated With Oxaliplatin
Authors: Sun Dongfeng , Chen Qingfa , Gai Zhibo , Zhang Fengxia , Yang Xiaoqing , Hu Wensi , Chen Chengyu , Yang Guangjie , Hörmann Severin , Kullak-Ublick Gerd. A. , Visentin Michele
Published: September 2021

Esophageal cancer is the ninth most common malignancy worldwide, ranking sixth in mortality. Platinum-based chemotherapy is commonly used for treating locally advanced esophageal cancer, yet it is ineffective in a large portion of patients. There is a need for reliable molecular markers with direct clinical application for a prospective selection of patients who can benefit from chemotherapy and patients in whom toxicity is likely to outweigh the benefit. The cytotoxic activity of platinum derivatives largely depends on the uptake and accumulation into cells, primarily by organic cation transporters (OCTs). The aim of the study was to investigate the impact of OCT expression on the clinical outcome of patients with esophageal cancer treated with oxaliplatin. Twenty patients with esophageal squamous cell carcinoma (SCC) were prospectively enrolled and surgical specimens used for screening OCT expression level by western blotting and/or immunostaining, and for culture of cancer cells. Sixty-seven patients with SCC who received oxaliplatin and for whom follow-up was available were retrospectively assessed for organic cation/carnitine transporter 2 (OCTN2) expression by real time RT-PCR and immunostaining. OCTN2 staining was also performed in 22 esophageal adenocarcinomas. OCTN2 function in patient-derived cancer cells was evaluated by assessing L-carnitine uptake and sensitivity to oxaliplatin. The impact of OCTN2 on oxaliplatin activity was also assessed in HEK293 cells overexpressing OCTN2. OCTN2 expression was higher in tumor than in normal tissues. In patient-derived cancer cells and HEK293 cells, the expression of OCTN2 sensitized to oxaliplatin. Patients treated with oxaliplatin who had high OCTN2 level in the tumor tissue had a reduced risk of recurrence and a longer survival time than those with low expression of OCTN2 in tumor tissue. In conclusion, OCTN2 is expressed in esophageal cancer and it is likely to contribute to the accumulation and cytotoxic activity of oxaliplatin in patients with esophageal carcinoma treated with oxaliplatin.
Andrographolide Sulfonate Is a Promising Treatment to Combat Methicillin-resistant Staphylococcus aureus and Its Biofilms
Authors: Zhang Lulu , Wen Bo , Bao Mei , Cheng Yungchi , Mahmood Tariq , Yang Weifeng , Chen Qing , Lv Lang , Li Li , Yi Jianfeng , Xie Ning , Lu Cheng , Tan Yong
Published: September 2021

Methicillin-resistant Staphylococcus aureus (MRSA) is a drug-resistant pathogen threatening human health and safety. Biofilms are an important cause of its drug resistance and pathogenicity. Inhibition and elimination of biofilms is an important strategy for the treatment of MRSA infection. Andrographolide sulfonate (AS) is an active component of the traditional herbal medicine Andrographis paniculata. This study aims to explore the inhibitory effect and corresponding mechanisms of AS on MRSA and its biofilms. Three doses of AS (6.25, 12.5, and 25 mg/ml) were introduced to MRSA with biofilms. In vitro antibacterial testing and morphological observation were used to confirm the inhibitory effect of AS on MRSA with biofilms. Real-time PCR and metabonomics were used to explore the underlying mechanisms of the effect by studying the expression of biofilm-related genes and endogenous metabolites. AS displayed significant anti-MRSA activity, and its minimum inhibitory concentration was 50 μg/ml. Also, AS inhibited biofilms and improved biofilm permeability. The mechanisms are mediated by the inhibition of the expression of genes, such as quorum sensing system regulatory genes (agrD and sarA), microbial surface components–recognizing adhesion matrix genes (clfA and fnbB), intercellular adhesion genes (icaA, icaD, and PIA), and a gene related to cellular eDNA release (cidA), and the downregulation of five biofilm-related metabolites, including anthranilic acid, D-lactic acid, kynurenine, L-homocitrulline, and sebacic acid. This study provided valuable evidence for the activity of AS against MRSA and its biofilms and extended the methods to combat MRSA infection.
CD3D, GZMK, and KLRB1 Are Potential Markers for Early Diagnosis of Rheumatoid Arthritis, Especially in Anti-Citrullinated Protein Antibody-Negative Patients
Authors: Lu Junqin , Bi Yihui , Zhu Yapeng , Huipeng Shi , Duan Wenxiu , Zhou Jian
Published: September 2021

Early diagnosis and monitoring of rheumatoid arthritis (RA) progress are critical for effective treatment. In clinic, the detection of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are usually combined to diagnose early RA. However, the poor specificity of RF and high heterogeneity of ACPA make the early diagnosis of RA still challenging. Bioinformatics analysis based on high-throughput omics is an emerging method to identify novel and effective biomarkers, which has been widely used in many diseases. Herein, utilizing an integrated strategy based on expression correlation analysis and weighted gene coexpression network analysis (WGCNA), we identified 76 RA-trait different expression genes (DEGs). Combined with protein-protein interaction (PPI) network construction and clustering, new hub genes associated in RA synovia, CD3D, GZMK, and KLRB1, were identified. We verified the specificity of these genes in the synovium of RA patients through three external datasets. We also observed high sensitivity and specificity of them for ACPA-negative patients. CD3D, GZMK, and KLRB1 are potentially key mediators of RA pathogenesis and markers for RA diagnosis.
Multidimensional MRI for Characterization of Subtle Axonal Injury Accelerated Using an Adaptive Nonlocal Multispectral Filter
Authors: Benjamini Dan , Bouhrara Mustapha , Komlosh Michal E. , Iacono Diego , Perl Daniel P. , Brody David L. , Basser Peter J.
Published: September 2021

Multidimensional MRI is an emerging approach that simultaneously encodes water relaxation (T1 and T2) and mobility (diffusion) and replaces voxel-averaged values with subvoxel distributions of those MR properties. While conventional (i.e., voxel-averaged) MRI methods cannot adequately quantify the microscopic heterogeneity of biological tissue, using subvoxel information allows to selectively map a specific T1-T2-diffusion spectral range that corresponds to a group of tissue elements. The major obstacle to the adoption of rich, multidimensional MRI protocols for diagnostic or monitoring purposes is the prolonged scan time. Our main goal in the present study is to evaluate the performance of a nonlocal estimation of multispectral magnitudes (NESMA) filter on reduced datasets to limit the total acquisition time required for reliable multidimensional MRI characterization of the brain. Here we focused and reprocessed results from a recent study that identified potential imaging biomarkers of axonal injury pathology from the joint analysis of multidimensional MRI, in particular voxelwise T1-T2 and diffusion-T2 spectra in human Corpus Callosum, and histopathological data. We tested the performance of NESMA and its effect on the accuracy of the injury biomarker maps, relative to the co-registered histological reference. Noise reduction improved the accuracy of the resulting injury biomarker maps, while permitting data reduction of 35.7 and 59.6% from the full dataset for T1-T2 and diffusion-T2 cases, respectively. As successful clinical proof-of-concept applications of multidimensional MRI are continuously being introduced, reliable and robust noise removal and consequent acquisition acceleration would advance the field towards clinically-feasible diagnostic multidimensional MRI protocols.
Recognition of Multiscale Dense Gel Filament-Droplet Field in Digital Holography With Mo-U-Net
Authors: Pang Zhentao , Zhang Hang , Wang Yu , Zhang Letian , Wu Yingchun , Wu Xuecheng
Published: September 2021

Accurate particle detection is a common challenge in particle field characterization with digital holography, especially for gel secondary breakup with dense complex particles and filaments of multi-scale and strong background noises. This study proposes a deep learning method called Mo-U-net which is adapted from the combination of U-net and Mobilenetv2, and demostrates its application to segment the dense filament-droplet field of gel drop. Specially, a pruning method is applied on the Mo-U-net, which cuts off about two-thirds of its deep layers to save its training time while remaining a high segmentation accuracy. The performances of the segmentation are quantitatively evaluated by three indices, the positive intersection over union (PIOU), the average square symmetric boundary distance (ASBD) and the diameter-based prediction statistics (DBPS). The experimental results show that the area prediction accuracy (PIOU) of Mo-U-net reaches 83.3%, which is about 5% higher than that of adaptive-threshold method (ATM). The boundary prediction error (ASBD) of Mo-U-net is only about one pixel-wise length, which is one third of that of ATM. And Mo-U-net also shares a coherent size distribution (DBPS) prediction of droplet diameters with the reality. These results demonstrate the high accuracy of Mo-U-net in dense filament-droplet field recognition and its capability of providing accurate statistical data in a variety of holographic particle diagnostics. Public model address: https://github.com/Wu-Tong-Hearted/Recognition-of-multiscale-dense-gel-filament-droplet-field-in-digital-holography-with-Mo-U-net.
Improved Dielectric Properties and Grain Boundary Effect of Phenanthrene Under High Pressure
Authors: Wang Xiaofeng , Wang Qinglin , Qin Tianru , Zhang Guozhao , Zhang Haiwa , Sang Dandan , Wang Cong , Li Jianfu , Wang Xiaoli , Liu Cailong
Published: September 2021

In situ impedance measurements, Raman measurements and theoretical calculations were performed to investigate the electrical transport and vibrational properties of polycrystalline phenanthrene. Two phase transitions were observed in the Raman spectra at 2.3 and 5.9 GPa, while phenanthrene transformed into an amorphous phase above 12.1 GPa. Three discontinuous changes in bulk and grain boundary resistance and relaxation frequency with pressure were attributed to the structural phase transitions. Grain boundaries were found to play a dominant role in the carrier transport process of phenanthrene. The dielectric performance of phenanthrene was effectively improved by pressure. A significant mismatch between Z″ and M″ peaks was observed, which was attributed to the localized electronic conduction in phenanthrene. Theoretical calculations showed that the intramolecular interactions were enhanced under compression. This study offers new insight into the electrical properties as well as grain boundary effect in organic semiconductors at high pressure.
Investigation of the Sympathetic Regulation in Delayed Onset Muscle Soreness: Results of an RCT
Authors: Fleckenstein Johannes , Neuberger Elmo W. I. , Bormuth Philipp , Comes Fabio , Schneider Angelika , Banzer Winfried , Fischer Lorenz , Simon Perikles
Published: September 2021

Sports-related pain and injury is directly linked to tissue inflammation, thus involving the autonomic nervous system (ANS). In the present experimental study, we disable the sympathetic part of the ANS by applying a stellate ganglion block (SGB) in an experimental model of delayed onset muscle soreness (DOMS) of the biceps muscle. We included 45 healthy participants (female 11, male 34, age 24.16 ± 6.67 years [range 18–53], BMI 23.22 ± 2.09 kg/m2) who were equally randomized to receive either (i) an SGB prior to exercise-induced DOMS (preventive), (ii) sham intervention in addition to DOMS (control/sham), or (iii) SGB after the induction of DOMS (rehabilitative). The aim of the study was to determine whether and to what extent sympathetically maintained pain (SMP) is involved in DOMS processing. Focusing on the muscular area with the greatest eccentric load (biceps distal fifth), a significant time × group interaction on the pressure pain threshold was observed between preventive SGB and sham (p= 0.034). There was a significant effect on pain at motion (p= 0.048), withpost hocstatistical difference at 48 h (preventive SGB Δ1.09 ± 0.82 cm VAS vs. sham Δ2.05 ± 1.51 cm VAS;p= 0.04). DOMS mediated an increase in venous cfDNA -as a potential molecular/inflammatory marker of DOMS- within the first 24 h after eccentric exercise (time effectp= 0.018), with a peak at 20 and 60 min. After 60 min, cfDNA levels were significantly decreased comparing preventive SGB to sham (unpairedt-testp= 0.008). At both times, 20 and 60 min, cfDNA significantly correlated with observed changes in PPT. The 20-min increase was more sensitive, as it tended toward significance at 48 h (r= 0.44;p= 0.1) and predicted the early decrease of PPT following preventive stellate blocks at 24 h (r= 0.53;p= 0.04). Our study reveals the broad impact of the ANS on DOMS and exercise-induced pain. For the first time, we have obtained insights into the sympathetic regulation of pain and inflammation following exercise overload. As this study is of a translational pilot character, further research is encouraged to confirm and specify our observations.
Credibility Assessment of a Subject-Specific Mathematical Model of Blood Volume Kinetics for Prediction of Physiological Response to Hemorrhagic Shock and Fluid Resuscitation
Authors: Parvinian Bahram , Bighamian Ramin , Scully Christopher George , Hahn Jin-Oh , Pathmanathan Pras
Published: September 2021

Subject-specific mathematical models for prediction of physiological parameters such as blood volume, cardiac output, and blood pressure in response to hemorrhage have been developed. In silico studies using these models may provide an effective tool to generate pre-clinical safety evidence for medical devices and help reduce the size and scope of animal studies that are performed prior to initiation of human trials. To achieve such a goal, the credibility of the mathematical model must be established for the purpose of pre-clinical in silico testing. In this work, the credibility of a subject-specific mathematical model of blood volume kinetics intended to predict blood volume response to hemorrhage and fluid resuscitation during fluid therapy was evaluated. A workflow was used in which: (i) the foundational properties of the mathematical model such as structural identifiability were evaluated; (ii) practical identifiability was evaluated both pre- and post-calibration, with the pre-calibration results used to determine an optimal splitting of experimental data into calibration and validation datasets; (iii) uncertainty in model parameters and the experimental uncertainty were quantified for each subject; and (iv) the uncertainty was propagated through the blood volume kinetics model and its predictive capability was evaluated via validation tests. The mathematical model was found to be structurally identifiable. Pre-calibration identifiability analysis led to splitting the 180 min of time series data per subject into 50 and 130 min calibration and validation windows, respectively. The average root mean squared error of the mathematical model was 12.6% using the calibration window of (0 min, 50 min). Practical identifiability was established post-calibration after fixing one of the parameters to a nominal value. In the validation tests, 82 and 75% of the subject-specific mathematical models were able to correctly predict blood volume response when predictive capability was evaluated at 180 min and at the time when amount of infused fluid equals fluid loss.
Vitamin D, Thyroid Hormones and Cardiovascular Risk: Exploring the Components of This Novel Disease Triangle
Authors: Vassalle Cristina , Parlanti Alessandra , Pingitore Alessandro , Berti Sergio , Iervasi Giorgio , Sabatino Laura
Published: September 2021

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.
Anthropometric Markers With Specific Cut-Offs Can Predict Anemia Occurrence Among Malaysian Young Adults
Authors: Dutta Sulagna , Karkada Ivan Rolland , Sengupta Pallav , Chinni Suresh V.
Published: September 2021

Objective:Anemia bears a high global prevalence with about 1.6 billion people living with this affliction. Malaysia carries the burden of 13.8% anemia prevalence which urges for extensive research directed to its prediction and amelioration. This is the first study that aims to (a) propose simple non-invasive predictive anthropometric markers and their specific cut-off values for early prediction of anemia among the young adults in Malaysia, (b) provide anemia prevalence based on both gender and ethnicity among young adults of Malaysia.

Method:The present cross-sectional study included 245 participants (113 men and 132 women) aged between 18 and 30 years. Anthropometric parameters were measured following the standard protocols. Blood samples were collected and hemoglobin levels were determined using the HemoCue haemoglobinometer (Hb 201+ System, Angelhom, Sweden) to detect the presence of anemia. The receiver operating characteristics (ROC) curve was employed to assess and compare the efficacy of anthropometric indices in the prediction of anemia. Data were analyzed using SPSS (v. 22.0, IBM, Chicago, IL, USA) and MedCalc (v. 19.05, Ostend, Belgium).

Result:The ROC analysis indicates that body mass index (BMI) is the best anthropometric marker with the highest area under the curve (AUC) and specificity (SP) for predicting the presence of anemia in young adults in Malaysia. Thus, the study proposes the optimal cut-off value of BMI for young men of Malaysia as 20.65 kg/m2(AUC: 0.889) and young women of Malaysia as 19.7 kg/m2(AUC: 0.904). The study also reports that Malaysian Indians have the highest prevalence of anemia (26.22%) followed by Malays (21.54%), “Others” (indigenous ethnic group) (20%), and Chinese (14.5%), with an overall higher prevalence of anemia in young adult women (21.96%) than in men (18.6%) of Malaysia.

Conclusion:The proposed anemia-predictive anthropometric markers with optimal cut-off values will aid early detection of anemia among young adults in Malaysia, and given its simple, inexpensive, and intelligible approach, it can be widely used. The ease of anemia prediction together with the reported distribution of anemia prevalence based on gender and ethnicity will facilitate in gauging the necessary extent of strategies of anemia management in the young adult population of Malaysia.
Increases in RPE Rating Predict Fatigue Accumulation Without Changes in Heart Rate Zone Distribution After 4-Week Low-Intensity High-Volume Training Period in High-Level Rowers
Authors: Pind Rasmus , Hofmann Peter , Mäestu Evelin , Vahtra Eno , Purge Priit , Mäestu Jarek
Published: September 2021

Purpose: The aim of this study was to investigate the interaction of training load quantification using heart rate (HR) and rating of perceived exertion (RPE)-based methodology, and the relationship between internal training load parameters and subjective training status (Fatigue) in high-level rowers during volume increased low-intensity training period.

Methods: Training data from 19 high-level rowers (age 23.5 ± 5.9 years; maximal oxygen uptake 58.9 ± 5.8 ml·min−1·kg−1) were collected during a 4-week volume increased training period. All individual training sessions were analyzed to quantify training intensity distribution based on the HR time-in-zone method (i.e., HR Z1, HR Z2, and HR Z3) determined by the first and second ventilatory thresholds (VT1/VT2). Internal training load was calculated using session RPE (sRPE) to categorize training load by effort (i.e., sRPE1, sRPE2, and sRPE3). The Recovery-Stress Questionnaire for Athletes (RESTQ-Sport) questionnaire was implemented after every week of the study period.

Results: No differences were found between the respective HR and effort-based zone distributions during the baseline week (p > 0.05). Compared to HR Z1, sRPE1 was significantly lower in weeks 2–4 (p < 0.05), while sRPE2 was higher in weeks 2–3 compared to HR Z2 (p < 0.05) and, in week 4, the tendency (p = 0.06) of the higher amount of sRPE3 compared to HR Z3 was found. There were significant increases in RESTQ-Sport stress scales and decreases in recovery scales mostly during weeks 3 and 4. Increases in the Fatigue scale were associated with the amounts of sRPE2 and sRPE3 (p = 0.011 and p = 0.008, respectively), while no associations with Fatigue were found for HR-based session quantification with internal or external training load variables.

Conclusion: During a low-intensity 4-week training period with increasing volume, RPE-based training quantification indicated a shift toward the harder rating of sessions with unchanged HR zone distributions. Moderate and Hard rated sessions were related to increases in Fatigue. Session rating of perceived exertion and effort-based training load could be practical measures in combination with HR to monitor adaptation during increased volume, low-intensity training period in endurance athletes.
Plant Endophytic Fungus Extract ZNC Improved Potato Immunity, Yield, and Quality
Authors: Cao Juan , Liu Baoyou , Xu Xinning , Zhang Xiaoying , Zhu Changxiang , Li Yang , Ding Xinhua
Published: September 2021

Endophytic fungi play an important role in plant survival and reproduction, but the role of their metabolites in plant growth and immunity, as well as in crop quality formation, is poorly understood. Zhinengcong (ZNC) is a crude ethanol extract from the endophytic fungus Paecilomyces variotii, and previous studies have shown that it can improve the growth and immunity in Arabidopsis thaliana. The aim of the study was to reveal the trade-off balance between plant growth and immunity by evaluating the mechanisms of ZNC on potato growth, yield, and priming immunity against the oomycete Phytophthora infestans indoors and in the field. ZNC maintained a good balance between plant growth and resistance against P. infestans with high activity. It induced the reactive oxygen species (ROS) production, promoted plant growth, yield and quality parameters, enhanced the expression of indoleacetic acid (IAA) related genes, and increased the absorption of nitrogen from the soil. Moreover, the plant endophytic fungus extract ZNC stimulated the pathogen-associated molecular pattern (PAMP) triggered immunity (PTI) pathway and contributed to the ZNC-mediated defense response. Two years of field trials have shown that irrigation with ZNC at one of two optimal concentrations of 1 or 10ng/ml could significantly increase the output by 18.83% or more. The quality of potato tubers was also greatly improved, in which the contents of vitamin C, protein, and starch were significantly increased, especially the sugar content was increased by 125%. Spray application of ZNC onto potato plants significantly reduced the occurrence of potato blight disease with 66.49% of control efficacy at 200ng/ml and increased the potato yield by 66.68% or more in the field. In summary, plant endophytic fungus extract ZNC promoted potato immunity, yield, and quality and presented excellent potential in agricultural applications.