bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Versus Blood: A Systematic Review on the Concordance Between Peripheral and Central Kynurenine Pathway Measures in Psychiatric Disorders
Authors: Skorobogatov Katrien , De Picker Livia , Verkerk Robert , Coppens Violette , Leboyer Marion , Müller Norbert , Morrens Manuel
Published: September 2021

Objective

Disturbances in the kynurenine pathway have been implicated in the pathophysiology of psychotic and mood disorders, as well as several other psychiatric illnesses. It remains uncertain however to what extent metabolite levels detectable in plasma or serum reflect brain kynurenine metabolism and other disease-specific pathophysiological changes. The primary objective of this systematic review was to investigate the concordance between peripheral and central (CSF or brain tissue) kynurenine metabolites. As secondary aims we describe their correlation with illness course, treatment response, and neuroanatomical abnormalities in psychiatric diseases.

Methods

We performed a systematic literature search until February 2021 in PubMed. We included 27 original research articles describing a correlation between peripheral and central kynurenine metabolite measures in preclinical studies and human samples from patients suffering from neuropsychiatric disorders and other conditions. We also included 32 articles reporting associations between peripheral KP markers and symptom severity, CNS pathology or treatment response in schizophrenia, bipolar disorder or major depressive disorder.

Results

For kynurenine and 3-hydroxykynurenine, moderate to strong concordance was found between peripheral and central concentrations not only in psychiatric disorders, but also in other (patho)physiological conditions. Despite discordant findings for other metabolites (mainly tryptophan and kynurenic acid), blood metabolite levels were associated with clinical symptoms and treatment response in psychiatric patients, as well as with observed neuroanatomical abnormalities and glial activity.

Conclusion

Only kynurenine and 3-hydroxykynurenine demonstrated a consistent and reliable concordance between peripheral and central measures. Evidence from psychiatric studies on kynurenine pathway concordance is scarce, and more research is needed to determine the validity of peripheral kynurenine metabolite assessment as proxy markers for CNS processes. Peripheral kynurenine and 3-hydroxykynurenine may nonetheless represent valuable predictive and prognostic biomarker candidates for psychiatric disorders.
PTP4A3 Is a Prognostic Biomarker Correlated With Immune Infiltrates in Papillary Renal Cell Carcinoma
Authors: Song Qian , Zheng Yutian , Wu Junzhou , Wang Sheng , Meng Lin , Yao Qian , Li Zhongwu , Lian Shenyi
Published: September 2021

PTP4A3 plays an important role in the tumorigenesis and metastasis of multiple tumors, but its prognostic role in renal cancer is not well understood. We utilized the Oncomine and Tumor Immunoassay Resource databases to examine the differential expression of PTP4A3 in tumor tissues and normal tissues in breast, urinary tract, gastrointestinal tract and skin. Using the GEPIA and PrognoScan databases, the independent prognostic role of PTP4A3 was confirmed in clear cell renal cell cancer and papillary renal cell cancer. Expression of PTP4A3 were obviously higher in tumor tissue compare with normal tissues (P=0.028). We haven’t found the associations of PTP4A3 and clinicopathological features in our IHC cohort. Ectopic expression of PTP4A3 promotes proliferation, migration and invasion and increased the mRNA level of TGFB1 in RCC cell lines. Immunohistochemical staining indicated that the expression of PTP4A3 associates with CD3+ (P =0.037)/CD8+ (P =0.037) intratumor TILs, not with invasive margins in renal cancer. Comprehensive analysis of immune infiltration in the TIMER database correlated PTP4A3 expression with the infiltration of B cells, CD8+ T cells, CD4+ T cells and neutrophils in both clear cell renal cell carcinoma and papillary renal cell carcinoma. PTP4A3 expression was associated with the infiltration of dendritic cells in papillary renal cell carcinoma. We further confirmed that the infiltration of B cells and CD8+ T cells was associated with poor prognosis in papillary renal cell carcinoma patients, consistent with the prognostic role of PTP4A3 in papillary renal cell carcinoma. PTP4A3 expression correlated genes involved in B cells, monocytes, M1 macrophages, Th2 and Treg cells in papillary renal cell carcinoma. These results suggest PTP4A3 as a prognostic factor with a role in regulating immune cell infiltration in papillary renal cell carcinoma.
Endocervical Regulatory T Cells Are Associated With Decreased Genital Inflammation and Lower HIV Target Cell Abundance
Authors: Ssemaganda Aloysious , Cholette Francois , Perner Michelle , Kambaran Cheli , Adhiambo Wendy , Wambugu Peter M. , Gebrebrhan Henok , Lee Amy , Nuhu Faisal , Mwatelah Ruth S. , Jahan Naima , Omole Tosin E. , Wanjiru Tabitha , Gitau Apollo , Kimani Joshua , McKinnon Lyle R.
Published: September 2021

Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127lowTregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8vs2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8vs6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillusdominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10CD4+ T cells per log10Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study
Authors: Sun Shuhui , Chen Zhiwei , Zhang Danting , Xu Wenwen , Wu Wanlong , Sun Fangfang , Gu Liyang , Chen Jie , Li Jiajie , Li Ting , Wang Xiaodong , Ye Shuang
Published: September 2021

Objectives

The aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.

Methods

A retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.

Results

Out of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0–1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% vs. 21% and 40% vs. 9%, respectively, both p<0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (>=3) were much higher in the high-inflammation group (60% vs. 26%), while biological agents, i.e., rituximab and tocilizumab, showed better “drug survival” for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.

Conclusions

ASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.
Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases
Authors: Ramprasath Tharmarajan , Han Young-Min , Zhang Donghong , Yu Chang-Jiang , Zou Ming-Hui
Published: September 2021

Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.
From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack
Authors: Fuhrmann Verena , Huang Huey-Jy , Akarsu Aysegul , Shilovskiy Igor , Elisyutina Olga , Khaitov Musa , van Hage Marianne , Linhart Birgit , Focke-Tejkl Margarete , Valenta Rudolf , Sekerel Bulent Enis
Published: September 2021

Peanuts and tree nuts are two of the most common elicitors of immunoglobulin E (IgE)-mediated food allergy. Nut allergy is frequently associated with systemic reactions and can lead to potentially life-threatening respiratory and circulatory symptoms. Furthermore, nut allergy usually persists throughout life. Whether sensitized patients exhibit severe and life-threatening reactions (e.g., anaphylaxis), mild and/or local reactions (e.g., pollen-food allergy syndrome) or no relevant symptoms depends much on IgE recognition of digestion-resistant class I food allergens, IgE cross-reactivity of class II food allergens with respiratory allergens and clinically not relevant plant-derived carbohydrate epitopes, respectively. Accordingly, molecular allergy diagnosis based on the measurement of allergen-specific IgE levels to allergen molecules provides important information in addition to provocation testing in the diagnosis of food allergy. Molecular allergy diagnosis helps identifying the genuinely sensitizing nuts, it determines IgE sensitization to class I and II food allergen molecules and hence provides a basis for personalized forms of treatment such as precise prescription of diet and allergen-specific immunotherapy (AIT). Currently available forms of nut-specific AIT are based only on allergen extracts, have been mainly developed for peanut but not for other nuts and, unlike AIT for respiratory allergies which utilize often subcutaneous administration, are given preferentially by the oral route. Here we review prevalence of allergy to peanut and tree nuts in different populations of the world, summarize knowledge regarding the involved nut allergen molecules and current AIT approaches for nut allergy. We argue that nut-specific AIT may benefit from molecular subcutaneous AIT (SCIT) approaches but identify also possible hurdles for such an approach and explain why molecular SCIT may be a hard nut to crack.
Host Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities
Authors: Llibre Alba , Dedicoat Martin , Burel Julie G. , Demangel Caroline , O’Shea Matthew K. , Mauro Claudio
Published: September 2021

Mycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of theMycobacterium tuberculosiscomplex (causing tuberculosis),Mycobacterium leprae(causing leprosy), and non-tuberculous mycobacterial pathogens includingMycobacterium ulcerans.Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines.
Profile of Immunoglobulin G N-Glycome in COVID-19 Patients: A Case-Control Study
Authors: Hou Haifeng , Yang Huan , Liu Pengcheng , Huang Changwu , Wang Meng , Li Yuejin , Zhu Mingsong , Wang Jing , Xu Yuan , Wang Youxin , Ma Qingwei , Li Dong , Liao Pu , Wang Wei
Published: September 2021

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in acute immune responses. In severe cases, a low level of IgG sialylation contributes to the ADCC-regulated enhancement of inflammatory cytokines. The decreases in sialylation and galactosylation play a role in COVID-19 pathogenesis via the activation of the lectin-initiated alternative complement pathway. IgG N-glycosylation underlines the complex clinical phenotypes of SARS-CoV-2 infection.
Effective Strain of BFRP for Confined Heat-Damaged Concrete Cylinders
Authors: Ouyang Li-Jun , Wei Xiao-Xiao , Ding Bin , Gao Wan-Yang
Published: September 2021

It is widely accepted that concrete columns confined with fiber-reinforced polymer (FRP) jackets exhibit significant increases in strength and ductility with reference to the unconfined case. Existing experimental studies have indicated that the hoop rupture strains measured in the FRP jackets are significantly lower than the material strain capacity determined by the flat coupon tensile tests. An FRP efficiency factor is then usually used to define the ratio of the average hoop rupture strain to the material strain capacity of the FRP jackets, which governs the lateral FRP confinement as well as the peak strength and ultimate strain of the FRP-confined concrete under axial compression. FRP jackets are also expected to be a promising solution to repair damaged RC columns after fire exposure. However, there is lacking research on the behavior of FRP-confined fire or heat-damaged concrete columns. In particular, the FRP efficiency factor of FRP-confined fire or heat-damaged concrete columns has not yet been established. The study presents the results of an experimental study aimed to investigate the effects of the historical high temperature and the layer of basalt FRP (BFRP) jackets on the efficiency factor of BFRP for the confined heat-damaged concrete cylinders. A sum of 51 standard concrete cylinders is prepared and tested under axial compression. The parameters varied between tests are the historical high temperature (200°C, 400°C, 600°C, or 800°C) that is used to produce the heat damage of concrete cylinders and the number of layers of BFRP jackets (2, 3, or 4). The test results have indicated that the efficiency factor of BFRP jackets increases with the historical high temperature but decreases slightly with the increase in the BFRP layers. A new temperature-dependent design equation for the BFRP efficiency factor of the confined heat-damaged concrete is proposed to consider the effects of the parameters mentioned above and can be used for practical design.
Effect of Dynamic Circuit Pressures Monitoring on the Lifespan of Extracorporeal Circuit and the Efficiency of Solute Removal During Continuous Renal Replacement Therapy
Authors: Li Peiyun , Zhang Ling , Lin Li , Tang Xin , Guan Mingjing , Wei Tiantian , Chen Lixin
Published: September 2021

Objective: To observe the effects of dynamic pressure monitoring on the lifespan of the extracorporeal circuit and the efficiency of solute removal during continuous renal replacement therapy (CRRT).

Materials and Methods: A prospective observational study was performed at the West China Hospital of Sichuan University in the ICU. Analyses of the downloaded pressure data recorded by CRRT machines and the solute removal efficiencies, calculated by 2*Ce/(Cpre+Cpost), where Ce, Cpre, and Cpost are the concentrations of the effluent, pre-filter blood, and post-filter blood, respectively, were performed. Samples were collected at 0, 2, 6, 12, and 24 h when continuous veno-venous hemodiafiltration (CVVHDF) was used after the initiation of CRRT. Measurements in concentrations of creatinine, blood urea nitrogen, and β2-microglobulin in the plasma and effluent were recorded.

Results: Extracorporeal circuits characterized by moderate-to-severe (M–S) access outflow dysfunction (AOD) events, defined as access outflow pressure less than or equal to −200 mmHg for more than 5 min, had shorter median lifespans with no anticoagulation (32.3 vs. 10.90 h, P = 0.001) compared with the no M–S AOD events group. The significant outcome also existed in regional citrate anticoagulation (RCA) (72 vs. 42.47 h, P = 0.02). Moreover, Cox regression analysis revealed that the lack of M–S AOD events, RCA, or CVVHDF independently prolonged the circuit lifespan. All tested solutes removal efficiencies started to decline at 12 h. Furthermore, efficiencies of all solutes removal dropped obviously at 24 h when TMP ≥ 150 mmHg.

Conclusion: RCA and CVVHDF predicted a longer circuit lifespan. M–S AOD events were associated with a shorter circuit lifespan when RCA or no anticoagulant was used. Replacement of extracorporeal circuit could be considered when running time of filter lasted up to 24 h with TMP ≥ 150 mmHg.
Past and Present Approaches to Diagnosis of Active Pulmonary Tuberculosis
Authors: Namuganga Anna Ritah , Chegou Novel N. , Mayanja-Kizza Harriet
Published: September 2021

Tuberculosis disease continues to contribute to the mortality burden globally. Due to the several shortcomings of the available diagnostic methods, tuberculosis disease continues to spread. The difficulty to obtain sputum among the very ill patients and the children also affects the quick diagnosis of tuberculosis disease. These challenges warrant investigating different sample types that can provide results in a short time. Highlighted in this review are the approved pulmonary tuberculosis diagnostic methods and ongoing research to improve its diagnosis. We used the PRISMA guidelines for systematic reviews to search for studies that met the selection criteria for this review. In this review we found out that enormous biosignature research is ongoing to identify host biomarkers that can be used as predictors of active PTB disease. On top of this, more research was also being done to improve already existing diagnostic tests. Host markers required more optimization for use in different settings given their varying sensitivity and specificity in PTB endemic and non-endemic settings.
Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study
Authors: Kronborg Thit Mynster , Ytting Henriette , Hobolth Lise , Møller Søren , Kimer Nina
Published: September 2021

Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.
Case Report: Eculizumab and ECMO Rescue Therapy of Severe ARDS in Goodpasture Syndrome
Authors: Sobotta Michael , Moerer Onnen , Gross Oliver
Published: September 2021

Introduction:Goodpasture's syndrome is a life-threatening autoimmune type IV collagen disease characterized by the presence anti–glomerular basement membrane antibodies, rapid progressive glomerulonephritis and/or pulmonary hemorrhage.

Methods:Here, we describe new therapeutic options, which take recent advances in unraveling Goodpasture's pathogenesis into account.

Results:In a 17-year old male, severe Goodpasture's syndrome resulted in acute respiratory distress syndrome (ARDS). Within 1 day after hospital admission, the patient required extracorporeal membrane oxygenation (ECMO). Despite steroid-pulse and plasmapheresis, ARDS further deteriorated. Eleven days after admission, the patient was in a pre-final stage. At last, we decided to block the complement-driven lung damage by Eculizumab. Three days after, lung-failure has stabilized in a way allowing us to initiate Cyclophosphamide-therapy. As mechanical ventilation further triggers Goodpasture-epitope exposure, the patient was taken from pressure support - breathing spontaneously by the help of maintaining ECMO therapy. After a total of 24 days, ECMO could be stopped and pulmonary function further recovered.

Conclusions:In conclusion, our findings suggest that life-threatening organ-damage in Goodpasture's syndrome can be halted by Eculizumab as well as by lung-protective early withdrawal from pressure support by the help of ECMO. Both therapeutic options serve as new tools in otherwise hopeless situations to prevent further organ-damage and to gain time until the established immunosuppressive therapy works in otherwise lethal autoimmune-diseases.
Pharmacist-Led Education for Final Year Medical Students: A Pilot Study
Authors: Mokrzecki Sophie , Pain Tilley , Mallett Andrew , Perks Stephen
Published: September 2021

Background: Prescribing is a core skillset for medical officers. Prescribing errors or deficiencies can lead to patient harm and increased healthcare costs. There is an undefined role for pharmacist-led education to final year medical students to improve prescribing skills.

Aim: Assess if pharmacist-led education on prescription writing improves the quality and safety of final year medical students' prescribing skills.

Method: 

Participants and Intervention: Final year medical students were randomised into tutorial (TG) or non-tutorial groups (NTG) and assessed pre- and post- intervention. TG received education by a clinical pharmacist and pharmacy educator using case-based learning. NTG received no additional training as per usual practice. Following the pre-test, all students completed a 3-week tertiary hospital medical ward placement. Students completed the post-test following placement and after the TG participated in the intervention.

Student Assessment: Assessment included writing Schedule 4 (S4, prescription only), Schedule 8 (S8, controlled drug), S4 streamline (S4SL), and Mixed case (S4 and S8) prescriptions.

Results: At baseline, there were no significant differences between TG and NTG for overall scores or proportion of passes. Post intervention scores significantly improved in TG (p = 0.012) whereas scores significantly decreased in the NTG (p = 0.004). The overall proportion of passes was significantly higher in the TG than NTG (p < 0.001).

Conclusion: Education by a clinical pharmacist improved short-term prescribing skills of final year medical students in this study. Students learning primarily experientially from peers and rotational supervisors showed decreased prescribing skills. We propose pharmacist-led education on prescription writing should be further evaluated in larger studies across more student cohorts and for longer periods of follow up time to clarify whether such an educational model could be included in future medical school curricula.
Memristive Hodgkin-Huxley Spiking Neuron Model for Reproducing Neuron Behaviors
Authors: Fang Xiaoyan , Duan Shukai , Wang Lidan
Published: September 2021

The Hodgkin-Huxley (HH) spiking neuron model reproduces the dynamic characteristics of the neuron by mimicking the action potential, ionic channels, and spiking behaviors. The memristor is a nonlinear device with variable resistance. In this paper, the memristor is introduced to the HH spiking model, and the memristive Hodgkin-Huxley spiking neuron model (MHH) is presented. We experimentally compare the HH spiking model and the MHH spiking model by applying different stimuli. First, the individual current pulse is injected into the HH and MHH spiking models. The comparison between action potentials, current densities, and conductances is carried out. Second, the reverse single pulse stimulus and a series of pulse stimuli are applied to the two models. The effects of current density and action time on the production of the action potential are analyzed. Finally, the sinusoidal current stimulus acts on the two models. The various spiking behaviors are realized by adjusting the frequency of the sinusoidal stimulus. We experimentally demonstrate that the MHH spiking model generates more action potential than the HH spiking model and takes a short time to change the memductance. The reverse stimulus cannot activate the action potential in both models. The MHH spiking model performs smoother waveforms and a faster speed to return to the resting potential. The larger the external stimulus, the faster action potential generated, and the more noticeable change in conductances. Meanwhile, the MHH spiking model shows the various spiking patterns of neurons.
Evaluation of Structural Changes and Molecular Mechanism Induced by High Hydrostatic Pressure in Enterobacter sakazakii
Authors: Liao Qiaoming , Tao Han , Li Yali , Xu Yi , Wang Hui-Li
Published: September 2021

The contamination of infant milk and powder with Enterobacter sakazakii poses a risk to human health and frequently caused recalls of affected products. This study aims to explore the inactivation mechanism of E. sakazakii induced by high hydrostatic pressure (HHP), which, unlike conventional heat treatment, is a nonthermal technique for pasteurization and sterilization of dairy food without deleterious effects. The mortality of E. sakazakii under minimum reaction conditions (50 MPa) was 1.42%, which was increased to 33.12% under significant reaction conditions (400 MPa). Scanning electron microscopy (SEM) and fluorescent staining results showed that 400 MPa led to a loss of physical integrity of cell membranes as manifested by more intracellular leakage of nucleic acid, intracellular protein and K+. Real-time quantitative PCR (RT-qPCR) analysis presents a downregulation of three functional genes (glpK, pbpC, and ompR), which were involved in cell membrane formation, indicating a lower level of glycerol utilization, outer membrane protein assembly, and environmental tolerance. In addition, the exposure of E. sakazakii to HHP modified oxidative stress, as reflected by the high activity of catalase and super oxide dismutase. The HHP treatment lowered down the gene expression of flagellar proteins (fliC, flgI, fliH, and flgK) and inhibited biofilm formation. These results determined the association of genotype to phenotype in E. sakazakii induced by HHP, which was used for the control of food-borne pathogens.
Prediction of Biochemical Recurrence-Free Survival of Prostate Cancer Patients Leveraging Multiple Gene Expression Profiles in Tumor Microenvironment
Authors: Zhou Rui , Feng Yuanfa , Ye Jianheng , Han Zhaodong , Liang Yuxiang , Chen Qingbiao , Xu Xiaoming , Huang Yuhan , Jia Zhenyu , Zhong Weide
Published: September 2021

Tumor-adjacent normal (TAN) tissues, which constitute tumor microenvironment and are different from healthy tissues, provide critical information at molecular levels that can be used to differentiate aggressive tumors from indolent tumors. In this study, we analyzed 52 TAN samples from the Cancer Genome Atlas (TCGA) prostate cancer patients and developed a 10-gene prognostic model that can accurately predict biochemical recurrence-free survival based on the profiles of these genes in TAN tissues. The predictive ability was validated using TAN samples from an independent cohort. These 10 prognostic genes in tumor microenvironment are different from the prognostic genes detected in tumor tissues, indicating distinct progression-related mechanisms in two tissue types. Bioinformatics analysis showed that the prognostic genes in tumor microenvironment were significantly enriched by p53 signaling pathway, which may represent the crosstalk tunnels between tumor and its microenvironment and pathways involving cell-to-cell contact and paracrine/endocrine signaling. The insight acquired by this study has advanced our knowledge of the potential role of tumor microenvironment in prostate cancer progression.
The Progress in the Treatment of Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
Authors: Luo Fangzhou , Li Mengxia , Ding Jun , Zheng Shusen
Published: September 2021

Hepatocellular carcinoma (HCC) is one of most prevalent cancer and is a serious healthcare issue worldwide. Portal vein tumor thrombus (PVTT) is a frequent complication and remains as the blockage in the treatment of HCC with high recurrence rate and poor prognosis. There is still no global consensus or standard guideline on the management of HCC with PVTT. In western countries, Sorafenib and Lenvatinib are recommended as the first-line treatment options for HCC patients with PVTT where this condition is now regarded as BCLC Stage C regardless of PVTT types. However, there is growing evidence that supports the close relationship of the extent of PVTT to the prognosis of HCC. Besides the targeted therapy, more aggressive treatment modalities have been proposed and practiced in the clinic which may improve the prognosis of HCC patients with PVTT and prolong the patients’ survival time, such as transarterial chemoembolization, radiotherapy, hepatic resection, liver transplantation, and various combination therapies. Herein, we aim to review and summarize the advances in the treatment of HCC with PVTT.
Reasonable Timing of Radiotherapy for Stage IV Non-Small-Cell Lung Cancer During Targeted Therapy Based on Tumour Volume Change
Authors: Li Qingsong , Liang Na , Zhang Xia , Zhang Yi , Ouyang Weiwei , Su Shengfa , Ma Zhu , Hu Yinxiang , Geng Yichao , Chen Xiaxia , Lu Bing
Published: September 2021

Purpose

The aim of this study was to investigate the reasonable timing of radiotherapy for stage IV non-small-cell lung cancer (NSCLC) with EGFR-positive mutations during targeted therapy based on tumour volume change (TVC).

Patients and Methods

Simulation Computed Tomography Scan (SCTS) measurements were taken to test TVC in patients with stage IV NSCLC during targeted therapy at intervals of 10 days. The SCTS measurement was terminated when the tumour volume shrinkage rate in the latter simulation compared with the previous simulation was ≤5% or when the time after treatment was 90 days. Then, primary tumour radiotherapy was performed. Related parameters of the radiotherapy plan were compared between the implementation and simulation plans.

Results

Twenty-seven patients were enrolled in the analysis. After treatment, shrinkage of the primary tumour was observed in all patients, but the rate and speed were inconsistent. The average tumour volume decreased obviously within 40 days and was significantly different every 10 days (P ≤ 0.001). The average volume decreased slowly and tended to be stable (P>0.05) after 40 days. After the termination of SCTSs, 21 patients accepted primary tumour radiotherapy. No patients experienced grade 3+ acute radiation toxicity. The implementation radiotherapy plan was significantly better than that before treatment (all P<0.05) but not better than that on the 40th day after treatment (all P>0.05).

Conclusions

To obtain a high radiation dose and control radiation toxicity, the 40th day after targeted therapy may be a reasonable time to start radiotherapy for stage IV NSCLC with EGFR-positive mutations.

Clinical Trial Registration

https://www.clinicaltrials.gov/ct2/show/NCT03258671, identifier, NCT03258671.
Rectal Cancer Treatment Management: Deep-Learning Neural Network Based on Photoacoustic Microscopy Image Outperforms Histogram-Feature-Based Classification
Authors: Leng Xiandong , Amidi Eghbal , Kou Sitai , Cheema Hassam , Otegbeye Ebunoluwa , Chapman William Jr , Mutch Matthew , Zhu Quing
Published: September 2021

We have developed a novel photoacoustic microscopy/ultrasound (PAM/US) endoscope to image post-treatment rectal cancer for surgical management of residual tumor after radiation and chemotherapy. Paired with a deep-learning convolutional neural network (CNN), the PAM images accurately differentiated pathological complete responders (pCR) from incomplete responders. However, the role of CNNs compared with traditional histogram-feature based classifiers needs further exploration. In this work, we compare the performance of the CNN models to generalized linear models (GLM) across 24 ex vivo specimens and 10 in vivo patient examinations. First order statistical features were extracted from histograms of PAM and US images to train, validate and test GLM models, while PAM and US images were directly used to train, validate, and test CNN models. The PAM-CNN model performed superiorly with an AUC of 0.96 (95% CI: 0.95-0.98) compared to the best PAM-GLM model using kurtosis with an AUC of 0.82 (95% CI: 0.82-0.83). We also found that both CNN and GLMs derived from photoacoustic data outperformed those utilizing ultrasound alone. We conclude that deep-learning neural networks paired with photoacoustic images is the optimal analysis framework for determining presence of residual cancer in the treated human rectum.
Case Report: Ocular Manifestations and Treatments of Ciliary Body Involvement by Lymphoma
Authors: Di Yu , Ye Junjie , Han Ruoan , Li Mengda , Zhang Bilei
Published: September 2021

Purpose

To describe the ocular clinical features, histopathological findings, and treatment outcomes of lymphomas involving the ciliary body.

Methods

We demonstrate three cases of ciliary body involvement by lymphoma from 2013 to 2019 in Peking Union Medical College Hospital (PUMCH). All patients underwent examinations including best corrected visual acuity (BCVA), slit-lamp microscopy, indirect ophthalmoscope, ultrasound biomicroscopy (UBM), and diagnostic vitrectomy. In addition, cytopathology, immunohistochemistry, gene rearrangement, cytometric immunophenotypic, or in-situ hybridization were used for determining the pathological type of lymphoma.

Results

The patients were a 25-year-old man, a 52-year-old woman, and a 54-year-old man. Two patients had unilateral involvement, and one patient had bilateral involvement. All patients presented with anterior uveitis and elevated intraocular pressure. Ciliary body masses or infiltration were found in 3 patients. Two patients had diffuse large B-cell lymphoma and one patient had natural killer/T-cell lymphoma. All patients received 0.4 mg methotrexate intravitreal injections, and the ciliary body lesions regressed completely.

Conclusion

Lymphomatous involvement of the ciliary body usually presents as an atypical anterior chamber reaction. Vitreous biopsy should be considered in these patients for diagnosis. Methotrexate intravitreal injection combine with chemotherapy or radiotherapy, might extend the survival time and preserve visual acuity for patients with ciliary body involvement by lymphoma.
Radiotherapy Response Assessment of Multiple Myeloma: A Dual-Energy CT Approach With Virtual Non-Calcium Images
Authors: Fervers Philipp , Celik Erkan , Bratke Grischa , Maintz David , Baues Christian , Ruffing Simon , Pollman-Schweckhorst Philip , Kottlors Jonathan , Lennartz Simon , Große Hokamp Nils
Published: September 2021

Background

Life expectancy of patients with multiple myeloma (MM) has increased over the past decades, underlining the importance of local tumor control and avoidance of dose-dependent side effects of palliative radiotherapy (RT). Virtual noncalcium (VNCa) imaging from dual-energy computed tomography (DECT) has been suggested to estimate cellularity and metabolic activity of lytic bone lesions (LBLs) in MM.

Objective

To explore the feasibility of RT response monitoring with DECT-derived VNCa attenuation measurements in MM.

Methods

Thirty-three patients with 85 LBLs that had been irradiated and 85 paired non-irradiated LBLs from the same patients were included in this retrospective study. Irradiated and non-irradiated LBLs were measured by circular regions of interest (ROIs) on conventional and VNCa images in a total of 216 follow-up measurements (48 before and 168 after RT). Follow-ups were rated as therapy response, stable disease, or local progression according to the MD Anderson criteria. Receiver operating characteristic (ROC) analysis was performed to discriminate irradiated vs. non-irradiated and locally progressive vs. stable/responsive LBLs using absolute attenuation post-irradiation and percentage attenuation change for patients with pre-irradiation DECT, if available.

Results

Attenuation of LBLs decreased after RT depending on the time that had passed after irradiation [absolute thresholds for identification of irradiated LBLs 30.5–70.0 HU [best area under the curve [AUC] 0.75 (0.59–0.91)] and -77.0 to -22.5 HU [best AUC 0.85 (0.65–1.00)]/-50% and -117% to -167% proportional change of attenuation on conventional and VNCa images, respectively]. VNCa CT was significantly superior for identification of RT effects in LBLs with higher calcium content [best VNCa AUC 0.96 (0.91–1.00), best conventional CT AUC 0.64 (0.45–0.83)]. Thresholds for early identification of local irradiation failure were >20.5 HU on conventional CT [AUC 0.78 (0.68–0.88)] and >-27 HU on VNCa CT [AUC 0.83 (0.70–0.96)].

Conclusion

Therapy response of LBLs after RT can be monitored by VNCa imaging based on regular myeloma scans, which yields potential for optimizing the lesion-specific radiation dose for local tumor control. Decreasing attenuation indicates RT response, while above threshold attenuation of LBLs precedes local irradiation failure.
The Microbiome Tumor Axis: How the Microbiome Could Contribute to Clonal Heterogeneity and Disease Outcome in Pancreatic Cancer
Authors: Basu Meghna , Philipp Lisa-Marie , Baines John F. , Sebens Susanne
Published: September 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant cancers. It is characterized by a poor prognosis with a 5-year survival rate of only around 10% and an ongoing increase in death rate. Due to the lack of early and specific symptoms, most patients are diagnosed at an advanced or even metastasized stage, essentially limiting curative treatment options. However, even curative resection of the primary tumor and adjuvant therapy often fails to provide a long-term survival benefit. One reason for this dismal situation can be seen in the evolution of therapy resistances. Furthermore, PDAC is characterized by high intratumor heterogeneity, pointing towards an abundance of cancer stem cells (CSCs), which are regarded as essential for tumor initiation and drug resistance. Additionally, it was shown that the gut microbiome is altered in PDAC patients, promotes Epithelial-Mesenchymal-Transition (EMT), determines responses towards chemotherapy, and affects survival in PDAC patients. Given the established links between CSCs and EMT as well as drug resistance, and the emerging role of the microbiome in PDAC, we postulate that the composition of the microbiome of PDAC patients is a critical determinant for the abundance and plasticity of CSC populations and thus tumor heterogeneity in PDAC. Unravelling this complex interplay might pave the way for novel treatment strategies.
Anticancer Effects and Mechanisms of OSW-1 Isolated From Ornithogalum saundersiae: A Review
Authors: Zhan Zhixin , Liu Ziqiang , Lai Jiacheng , Zhang Chaochao , Chen Yong , Huang Haiyan
Published: September 2021

For centuries, cancer has been a lingering dark cloud floating on people’s heads. With rapid population growth and aging worldwide, cancer incidence and mortality are growing rapidly. Despite major advances in oncotherapy including surgery, radiation and chemical therapy, as well as immunotherapy and targeted therapy, cancer is expected be the leading cause of premature death in this century. Nowadays, natural compounds with potential anticancer effects have become an indispensable natural treasure for discovering clinically useful agents and made remarkable achievements in cancer chemotherapy. In this regards, OSW-1, which was isolated from the bulbs of Ornithogalum saundersiae in 1992, has exhibited powerful anticancer activities in various cancers. However, after almost three decades, OSW-1 is still far from becoming a real anticancer agent for its anticancer mechanisms remain unclear. Therefore, in this review we summarize the available evidence on the anticancer effects and mechanisms of OSW-1 in vitro and in vivo, and some insights for researchers who are interested in OSW-1 as a potential anticancer drug. We conclude that OSW-1 is a potential candidate for anticancer drugs and deserves further study.
Pediatric COVID-19: Report From Indonesian Pediatric Society Data Registry
Authors: Pudjiadi Antonius H. , Putri Nina Dwi , Sjakti Hikari Ambara , Yanuarso Piprim Basarah , Gunardi Hartono , Roeslani Rosalina Dewi , Pasaribu Ade Djanwardi , Nurmalia Lies Dewi , Sambo Catharine Mayung , Ugrasena I Dewa Gede , Soeroso Santoso , Firman Armijn , Muryawan Heru , Setyanto Darmawan Budi , Citraresmi Endah , Effendi Jaya Ariheriyanto , Habibah Lathiefatul , Octaviantie Prillye Deasy , Utami Indriyanti Natasya Ayu , Prawira Yogi , Kaswandani Nastiti , Alam Anggraini , Kadafi Kurniawan Taufiq , Pulungan Aman B.
Published: September 2021

Background: Indonesia has a high number of COVID-19 cases and mortalities relative to not only among the Asia Pacific region but the world. Children were thought to be less affected by the virus compared to adults. Most of the public data reported combined data between adults and children. The Indonesian Pediatric Society (IPS) was involved in the COVID-19 response, especially in the area of child health. One of IPS's activities is collecting data registries from each of their chapters to provide a better understanding of COVID-19 in children.

Objective: The objective of this study was to share the data of suspected and confirmed COVID-19 cases in children from IPS's COVID-19 data registry.

Method: This is a retrospective study from the IPS's COVID-19 registry data. We collected the data of COVID-19 in children during March to December 2020 from each of the IPS chapters. We analyzed the prevalence, case fatality rate (CFR), age groups, diagnosis, and comorbidities of the children diagnosed with COVID-19.

Result: As of December 21, 2020, there were 35,506 suspected cases of children with COVID-19. In total, there were 522 deaths, with a case fatality ratio (CFR) of 1.4. There were 37,706 confirmed cases with 175 fatalities (CFR 0.46). The highest mortality in confirmed COVID-19 cases was from children ages 10–18 years (42 out of 159 cases: 26%). The most common comorbidity and diagnosis found were malignancy (17.3%) and respiratory failure (54.5%).

Conclusion: The CFR of confirmed COVID-19 cases in children in Indonesia is high and should be a major public concern.
Myocardial Expression of Estrogen Receptor-mRNA Is Associated With Lower Markers of Post-operative Organ Damage in Young Patients With Congenital Cardiac Defect
Authors: Rouatbi Hatem , Farhat Nesrine , Heying Ruth , Vazquez-Jimenez Jaime F. , Parent Anne-Simone , Seghaye Marie-Christine
Published: September 2021

Background:Estrogen receptors (ERs) relate to cardio-protection in adults, but their role in younger patients is not known. We aimed to assess the myocardial expression of ERα- and ERβ- mRNA in young patients with congenital cardiac disease and to analyze their putative protective role.

Patients and Methods:Twenty children and young adults (seven females and 13 males) with a median age of 13.8 years (interquartile range: 12.3 years) were enrolled in this prospective study. The myocardial expression of ER-mRNA and genes involved in inflammation, growth, and stress response was assessed by real-time PCR and was correlated to post-operative (po) outcome.

Results:ER-mRNA was detected in the myocardium of all patients, independently of gender and age. The expression of ER-mRNA correlated with that of mRNA coding for brain natriuretic peptide and for all cytokines tested. A higher ERα-mRNA expression correlated with lower troponin T concentrations at 24 h po (p= 0.032), higher PaO2/FiO2ratio at 4 h po (p= 0.059), lower fluid retention at 4 h po (p= 0.048), and lower aspartate aminotransferase (AST) levels at 24 h po (p= 0.047). A higher ERβ-mRNA expression was also correlated with lower fluid retention at 24 h po (p= 0.048).

Patients in whom the levels of ERα- and ERβ-mRNA were >P50 had lower troponin T (p= 0.003, respectively) and lower AST concentrations at 24 h po (p= 0.043, respectively) than the others.

Conclusions:The expression of ERα- and ERβ-mRNA is present in the myocardium of children and young adults with congenital cardiac defect and is associated with lower markers of po organ damage. This suggests that ERs may provide perioperative organ protection in this population.