bluuebunny/crossref_metadata_2025 huggingface dataset:
CLDN6: From Traditional Barrier Function to Emerging Roles in Cancers
Authors: Qu Huinan , Jin Qiu , Quan Chengshi
Published: December 2021

Claudins (CLDNs) are the most important tight junction proteins, which are mainly expressed in endothelial cells or epithelial cells in a tissue-specific manner. As a member of the CLDNs family, CLDN6 is highly expressed in fetal tissues such as the stomach, pancreas, lung, and kidney, but is not expressed in corresponding adult tissues. The expression of CLDN6 is regulated by a variety of factors, including but not limited to stimuli and transcription factors, DNA methylation, and post-translational modifications. CLDN6 has been found to have a key role in the formation of barriers, especially the lung epithelial barrier and the epidermal permeability barrier (EPB). Importantly, the roles of CLDN6 in cancers have gained focus and are being investigated in recent years. Strong evidence indicates that the altered expression of CLDN6 is linked to the development of various cancers. Malignant phenotypes of tumors affected by CLDN6 include proliferation and apoptosis, migration and invasion, and drug resistance, which are regulated by CLDN6-mediated key signaling pathways. Given the important role in tumors and its low or no expression in normal tissues, CLDN6 is an ideal target for tumor therapy. This review aims to provide an overview of the structure and regulation of CLDN6, and its traditional barrier function, with a special emphasis on its emerging roles in cancers, including its impact on the malignant phenotypes, signal-modulating effects, the prognosis of tumor patients, and clinical applications in cancers.
Transcriptomic Insights on the Preventive Action of Apple (cv Granny Smith) Skin Wounding on Superficial Scald Development
Authors: Cainelli Nadia , Forestan Cristian , Angeli Dario , Villegas Tomas , Costa Fabrizio , Botton Alessandro , Rasori Angela , Bonghi Claudio , Ruperti Benedetto
Published: December 2021

Superficial scald is a post-harvest chilling storage injury leading to browning of the surface of the susceptible cv Granny Smith apples. Wounding of skins has been reported to play a preventive role on scald development however its underlying molecular factors are unknown. We have artificially wounded the epidermal and sub-epidermal layers of apple skins consistently obtaining the prevention of superficial scald in the surroundings of the wounds during two independent vintages. Time course RNA-Seq analyses of the transcriptional changes in wounded versus unwounded skins revealed that two transcriptional waves occurred. An early wave included genes up-regulated by wounding already after 6 h, highlighting a specific transcriptional rearrangement of genes connected to the biosynthesis and signalling of JA, ethylene and ABA. A later transcriptional wave, occurring after three months of cold storage, included genes up-regulated exclusively in unwounded skins and was prevented from its occurrence in wounded skins. A significant portion of these genes was related to decay of tissues and to the senescence hormones ABA, JA and ethylene. Such changes suggest a wound-inducible reversed hormonal balance during post-harvest storage which may explain the local inhibition of scald in wounded tissues, an aspect that will need further studies for its mechanistic explanation.
Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases
Authors: Ramos-Martínez Ivan Emmanuel , Rodríguez María Carmen , Cerbón Marco , Ramos-Martínez Juan Carlos , Ramos-Martínez Edgar Gustavo
Published: December 2021

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.
Polyethylene Films Containing Plant Extracts in the Polymer Matrix as Antibacterial and Antiviral Materials
Authors: Ordon Magdalena , Zdanowicz Magdalena , Nawrotek Paweł , Stachurska Xymena , Mizielińska Małgorzata
Published: December 2021

Low density polyethylene (LDPE) films covered with active coatings containing mixtures of rosemary, raspberry, and pomegranate CO2 extracts were found to be active against selected bacterial strains that may extend the shelf life of food products. The coatings also offer antiviral activity, due to their influence on the activity of Φ6 bacteriophage, selected as a surrogate for SARS-CoV-2 particles. The mixture of these extracts could be incorporated into a polymer matrix to obtain a foil with antibacterial and antiviral properties. The initial goal of this work was to obtain active LDPE films containing a mixture of CO2 extracts of the aforementioned plants, incorporated into an LDPE matrix via an extrusion process. The second aim of this study was to demonstrate the antibacterial properties of the active films against Gram-positive and Gram-negative bacteria, and to determine the antiviral effect of the modified material on Φ6 bacteriophage. In addition, an analysis was made on the influence of the active mixture on the polymer physicochemical features, e.g., mechanical and thermal properties, as well as its color and transparency. The results of this research indicated that the LDPE film containing a mixture of raspberry, rosemary, and pomegranate CO2 extracts incorporated into an LDPE matrix inhibited the growth of Staphylococcus aureus. This film was also found to be active against Bacillus subtilis. This modified film did not inhibit the growth of Escherichia coli and Pseudomonas syringae cells; however, their number decreased significantly. The LDPE active film was also found to be active against Φ6 particles, meaning that the film had antiviral properties. The incorporation of the mixture of CO2 extracts into the polymer matrix affected its mechanical properties. It was observed that parameters describing mechanical properties decreased, although did not affect the transition of LDPE significantly. Additionally, the modified film exhibited barrier properties towards UV radiation. Modified PE/CO2 extracts films could be applied as a functional food packaging material with antibacterial and antiviral properties.
Explainable AI for Psychological Profiling from Behavioral Data: An Application to Big Five Personality Predictions from Financial Transaction Records
Authors: Ramon Yanou , Farrokhnia R.A. , Matz Sandra C. , Martens David
Published: December 2021

Every step we take in the digital world leaves behind a record of our behavior; a digital footprint. Research has suggested that algorithms can translate these digital footprints into accurate estimates of psychological characteristics, including personality traits, mental health or intelligence. The mechanisms by which AI generates these insights, however, often remain opaque. In this paper, we show how Explainable AI (XAI) can help domain experts and data subjects validate, question, and improve models that classify psychological traits from digital footprints. We elaborate on two popular XAI methods (rule extraction and counterfactual explanations) in the context of Big Five personality predictions (traits and facets) from financial transactions data (N = 6408). First, we demonstrate how global rule extraction sheds light on the spending patterns identified by the model as most predictive for personality, and discuss how these rules can be used to explain, validate, and improve the model. Second, we implement local rule extraction to show that individuals are assigned to personality classes because of their unique financial behavior, and there exists a positive link between the model’s prediction confidence and the number of features that contributed to the prediction. Our experiments highlight the importance of both global and local XAI methods. By better understanding how predictive models work in general as well as how they derive an outcome for a particular person, XAI promotes accountability in a world in which AI impacts the lives of billions of people around the world.
Cognitive Impairment in Acute Heart Failure: Narrative Review
Authors: Ventoulis Ioannis , Arfaras-Melainis Angelos , Parissis John , Polyzogopoulou Eftihia
Published: December 2021

Cognitive impairment (CI) represents a common but often veiled comorbidity in patients with acute heart failure (AHF) that deserves more clinical attention. In the AHF setting, it manifests as varying degrees of deficits in one or more cognitive domains across a wide spectrum ranging from mild CI to severe global neurocognitive disorder. On the basis of the significant negative implications of CI on quality of life and its overwhelming association with poor outcomes, there is a compelling need for establishment of detailed consensus guidelines on cognitive screening methods to be systematically implemented in the population of patients with heart failure (HF). Since limited attention has been drawn exclusively on the field of CI in AHF thus far, the present narrative review aims to shed further light on the topic. The underlying pathophysiological mechanisms of CI in AHF remain poorly understood and seem to be multifactorial. Different pathophysiological pathways may come into play, depending on the clinical phenotype of AHF. There is some evidence that cognitive decline closely follows the perturbations incurred across the long-term disease trajectory of HF, both along the time course of stable chronic HF as well as during episodes of HF exacerbation. CI in AHF remains a rather under recognized scientific field that poses many challenges, since there are still many unresolved issues regarding cognitive changes in patients hospitalized with AHF that need to be thoroughly addressed.
Relationship between Indices of Vascular Function and Presence of Overt Cardiovascular Disease among Persons with Poorly Controlled Type 2 Diabetes
Authors: Antoniou Sofia , Naka Katerina K. , Papadakis Marios , Bechlioulis Aris , Makriyiannis Dimitrios , Tsatsoulis Agathocles , Michalis Lampros K. , Tigas Stelios
Published: December 2021

The aim of this study was to assess the factors associated with impaired vascular function in patients with poorly controlled type 2 diabetes (DM2) with and without overt cardiovascular disease (CVD). Ninety-five patients with DM2 and poor glycemic control were recruited and divided into two groups: Group 1, with known CVD (n = 38), and Group 2, without CVD (n = 57). Patients in Group 2 were further subdivided into those with short (<5 years, group 2b) and long (>5 years, group 2a) diabetes duration. Subclinical markers of atherosclerosis were assessed. Glycemic control was similar in the two groups (HbA1c: 9.2% (1.5) vs. 9.4% (1.8), p = 0.44). In Group 1, lower FMD (3.13 (2.16)% vs. 4.7 (3.4)%, p < 0.05) and higher cIMT (1.09 (0.3) mm vs. 0.96 (0.2) mm, p < 0.05) was seen compared with Group 2, whereas PWV was similar (12.1 (3.4) vs. 11.3 (3.0) m/s, p = 0.10). Patients in Group 2b had significantly lower PWV and cIMT and higher FMD compared to Group 1 (p < 0.05). Among patients with poorly controlled T2D, more pronounced vascular dysfunction was present in those with overt macrovascular disease. In patients with T2D without known CVD, vascular dysfunction was associated with disease duration. The use of vascular indices for cardiovascular risk stratification in patients with T2D requires further study.
Intra-Cochlear Current Spread Correlates with Speech Perception in Experienced Adult Cochlear Implant Users
Authors: Joly Charles-Alexandre , Reynard Pierre , Hermann Ruben , Seldran Fabien , Gallego Stéphane , Idriss Samar , Thai-Van Hung
Published: December 2021

Broader intra-cochlear current spread (ICCS) implies higher cochlear implant (CI) channel interactions. This study aimed to investigate the relationship between ICCS and speech intelligibility in experienced CI users. Using voltage matrices collected for impedance measurements, an individual exponential spread coefficient (ESC) was computed. Speech audiometry was performed to determine the intelligibility at 40 dB Sound Pressure Level (SPL) and the 50% speech reception threshold: I40 and SRT50 respectively. Correlations between ESC and either I40 or SRT50 were assessed. A total of 36 adults (mean age: 50 years) with more than 11 months (mean: 34 months) of CI experience were included. In the 21 subjects for whom all electrodes were active, ESC was moderately correlated with both I40 (r = −0.557, p = 0.009) and SRT50 (r = 0.569, p = 0.007). The results indicate that speech perception performance is negatively affected by the ICCS. Estimates of current spread at the closest vicinity of CI electrodes and prior to any activation of auditory neurons are indispensable to better characterize the relationship between CI stimulation and auditory perception in cochlear implantees.
Fecal Microbiota Transplant in Severe and Non-Severe Clostridioides difficile Infection. Is There a Role of FMT in Primary Severe CDI?
Authors: Popa Daniel , Neamtu Bogdan , Mihalache Manuela , Boicean Adrian , Banciu Adela , Banciu Daniel Dumitru , Moga Doru Florian Cornel , Birlutiu Victoria
Published: December 2021

Background: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI. Methods: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI. Results: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode. Conclusions: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.
Protective Role of an Initial Low-Dose Septic Challenge against Lethal Sepsis in Neonatal Mice: A Pilot Study
Authors: Nakasone Ruka , Ashina Mariko , Kido Takumi , Miyauchi Harunori , Saito Masafumi , Inoue Shigeaki , Shinohara Masakazu , Nozu Kandai , Fujioka Kazumichi
Published: December 2021

Neonatal sepsis is characterized by systemic bacterial invasion followed by a massive inflammatory response. At present, no therapeutic strategy has been found that significantly reduces the mortality of neonatal sepsis. We aimed to investigate the protective role of an initial low-dose septic challenge for the prevention of subsequent lethal sepsis in a mouse model. A stock cecal slurry (CS) solution was prepared from adult ceca. The LD83 (1.5 mg CS/g) was used for all animals. An initial challenge of normal saline (NS) or 0.5 mg CS/g (non-lethal dose) was administered at four days of age, then 1.5 mg CS/g was administered intraperitoneally at seven days of age (72 h post-initial challenge), and survival was monitored. Initial exposure to NS (n = 10) resulted in 90% mortality following exposure to the LD83 CS dose in contrast to an initial exposure to CS (n = 16), which significantly decreased mortality to 6% (p < 0.0001), reduced blood bacterial counts, attenuated inflammatory responses, and suppressed lipid mediators. Initial exposure to a non-lethal CS dose prior to exposure to a lethal CS dose significantly reduces sepsis mortality, a protective effect that might be mediated by modulating abnormal systemic inflammatory responses.
Blood Cultures for the Diagnosis of Infective Endocarditis: What Is the Benefit of Prolonged Incubation?
Authors: Fihman Vincent , Faury Hélène , Moussafeur Amina , Huguet Raphaelle , Galy Adrien , Gallien Sébastien , Lim Pascal , Lepeule Raphaël , Woerther Paul-Louis
Published: December 2021

To assess the need for prolonged incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis (IE), we conducted a retrospective cohort study of 6109 sets of two blood culture bottles involving 1211 patients admitted to the Henri Mondor University Hospital for suspicion of IE between 1 January 2016 and 31 December 2019. Among the 322 patients with IE, 194 had positive blood cultures in our centre. Only one patient with a time-to-positivity blood culture of more than 120 h (5 days) was found. The main cause for the 22 patients with positive blood cultures after five days was contamination with Cutibacterium acnes. Our results do not support extending the duration of incubation of blood culture bottles beyond five days for the diagnosis of infectious endocarditis, with the exception of patients with risk factors for C. acnes infection.
The Diagnostic Value of Pulsar Perimetry, Optical Coherence Tomography, and Optical Coherence Tomography Angiography in Pre-Perimetric and Perimetric Glaucoma
Authors: Chen Hung-Chih , Chou Michael Chia-Yen , Lee Ming-Tsung , Lee Chia-Yi , Yang Che-Ning , Liu Chin-Hsin , Chao Shih-Chun
Published: December 2021

The purpose of this article is to investigate the diagnostic value of Pulsar perimetry (PP), optical coherence tomography (OCT), and optical coherence tomography angiography (OCTA) in pre-perimetric glaucoma (PPG) and perimetric glaucoma (PG). This retrospective cross-sectional study included 202 eyes (145 eyes in the control group, 40 eyes in the PPG group, and 17 eyes in the PG group) from 105 subjects. The results were analyzed by paired t-tests and Wilcoxon signed-rank test. The area under the curve (AUC), sensitivity, and specificity were used to evaluate the diagnostic accuracy. Pearson correlation was used to investigate the relationships of each parameter. The most sensitive parameters for differentiating the control group from the PPG group by using Pulsar, OCT, and OCTA were square loss variance of PP (AUC = 0.673, p < 0.001), superior ganglion cell complex thickness (AUC = 0.860, p < 0.001), and superior-hemi retina thickness (AUC = 0.817, p < 0.001). In the PG group, the most sensitive parameters were mean defect of PP (AUC = 0.885, p < 0.001), whole image of ganglion cell complex thickness (AUC = 0.847, p < 0.001), and perifoveal retina thickness (AUC = 0.833, p < 0.001). The mean defect of PP was significantly correlated with vascular parameters (radial peripapillary capillary (RPC), p = 0.008; vessel density of macular superficial vascular complex (VDms), p = 0.001; vessel density of macular deep vascular complex (VDmd), p = 0.002). In conclusion, structural measurements using OCT were more sensitive than vascular measurements of OCTA and functional measurements of PP for PPG, while PP was more sensitive than the structural and vascular measurements for PG. The mean defect of PP was also shown to be highly correlated with the reduction of vessel density.
Race/Ethnicity Is Not Independently Associated with Risk of Adverse Waitlist Removal among Patients with HCC Exception Points
Authors: Goyes Daniela , Nsubuga John Paul , Medina-Morales Esli , Barba Romelia , Patwardhan Vilas , Saberi Behnam , Fricker Zachary , Bonder Alan
Published: December 2021

(1) Background: Since 2015, exception points have been awarded to appropriate candidates after six months of waitlist time to allow more equitable access to liver transplants regardless of hepatocellular carcinoma status. However, it remains unknown whether racial disparities in outcomes among waitlisted patients remain after the introduction of a 6-month waiting period for exception points. (2) Methods: Using the United Network for Organ Sharing database, we identified 2311 patients diagnosed with hepatocellular carcinoma listed for liver transplant who received exception points from 2015 to 2019. The outcome of interest was waitlist survival defined as the composite outcome of death or removal for clinical deterioration. Competing risk analysis was used to identify factors associated with death or removal for clinical deterioration. The final model adjusted for age, sex, race/ethnicity, blood type, diabetes, obesity, laboratory MELD score, tumor size, AFP, locoregional therapies, UNOS region, and college education. (3) Results: No difference was found in the risk of adverse waitlist removal among ethnic/racial groups.
Pulmonary Vein Isolation Outcome Degree Is a New Score for Efficacy of Atrial Fibrillation Catheter Ablation
Authors: Jurcevic Ruzica , Angelkov Lazar , Tasic Nebojsa , Tomovic Milosav , Kojic Dejan , Otasevic Petar , Bojic Milovan
Published: December 2021

This study introduces the pulmonary vein isolation outcome degree (PVIOD) as a new semiquantitative measure for the efficacy of atrial fibrillation (AF) catheter ablation and reports the determination of predictors associated with PVIOD. The median follow-up periods of 117 patients after the first and last ablation were, respectively, 82 (IQR 15) and 72 (IQR 30) months. PVIOD 1 included 32.5% of patients, those with successful single pulmonary vein isolation (PVI); PVIOD 2 included 29.1% of subjects, those with success after multiple procedures; PVIOD 3 comprised 14.5% of patients, those with clinical success; and PVIOD 4 included 23.9% of cases, those with procedural and clinical failure. In the multivariate ordinal logistic regression analysis, PVIOD 1–4 were independently associated with longstanding persistent AF with paroxysmal AF as the referent category (odds ratio (OR), 3.5; 95% confidence interval (95% CI), 1.1–10.7 (p = 0.031)), left atrial (LA) diameter (OR, 1.2; 95% CI, 1.1–1.3 (p = 0.001)) and left ventricular ejection fraction (LVEF) (OR, 0.9; 95% CI, 0.86–1.0 (p = 0.038)). LA size > 41 mm, LVEF ≤ 50% and longstanding persistent AF are strong predictors of AF recurrence. PVIOD 1–4 offer the most exact long-term prognosis of PVI. The purpose of the present article is to expand the quantitative measure of procedural success in the medical and biological fields.
Epidemiology of Antepartum Stillbirths in Austria—A Population-Based Study between 2008 and 2020
Authors: Muin Dana Anaïs , Helmer Hanns , Leitner Hermann , Neururer Sabrina
Published: December 2021

(1) Background: Across Europe, the incidence of antepartum stillbirth varies greatly, partly because of heterogeneous definitions regarding gestational weeks and differences in legislation. With this study, we sought to provide a comprehensive overview on the demographics of antepartum stillbirth in Austria, defined as non-iatrogenic fetal demise ≥22+0 gestational weeks (/40). (2) Methods: We conducted a population-based study on epidemiological characteristics of singleton antepartum stillbirth in Austria between January 2008 and December 2020. Data were derived from the validated Austrian Birth Registry. (3) Results: From January 2008 through December 2020, the antepartum stillbirth rate ≥20+0/40 was 3.10, ≥22+0/40 3.14, and ≥24+0/40 2.83 per 1000 births in Austria. The highest incidence was recorded in the federal states of Vienna, Styria, and Lower and Upper Austria, contributing to 71.9% of all stillbirths in the country. In the last decade, significant fluctuations in incidence were noted: from 2011 to 2012, the rate significantly declined from 3.40 to 3.07‰, whilst it significantly increased from 2.76 to 3.49‰ between 2019 and 2020. The median gestational age of antepartum stillbirth in Austria was 33+0 (27+2–37+4) weeks. Stillbirth rates ≤26/40 ranged from 164.98 to 334.18‰, whilst the lowest rates of 0.58–8.4‰ were observed ≥36/40. The main demographic risk factors were maternal obesity and low parity. (4) Conclusions: In Austria, the antepartum stillbirth rate has remained relatively stable at 2.83–3.10 per 1000 births for the last decade, despite a significant decline in 2012 and an increase in 2020.
Association between the Level of Physical Activity and Health-Related Quality of Life in Type 1 Diabetes Mellitus. A Preliminary Study
Authors: Domínguez-Domínguez Adrián , Martínez-Guardado Ismael , Domínguez-Muñoz Francisco Javier , Barrios-Fernandez Sabina , Morenas-Martín Jesús , Garcia-Gordillo Miguel Angel , Carlos-Vivas Jorge
Published: December 2021

Type 1 Diabetes Mellitus (T1D) is a chronic autoimmune disease characterized by the selective destruction of the beta cells of the pancreas causing an absolute deficiency of insulin for life. This pathology carries associated risks so that it is essential to measure Health-Related Quality of Life (HRQoL) in this population. The aim was to analyse associations between the level of physical activity and HRQoL in people with T1D. The sample consisted of 172 participants with T1D diagnoses, between 18 and 49 years (31.29 ± 8.17). The participants answered different questionnaires related to physical activity (IPAQ) and HRQoL (EsDQOL, ViDa1, 15D, and EQ-5D-5L). The results showed significant correlations between the level of physical activity and HRQoL. Vigorous physical activity had an impact on the HRQoL questionnaires, such as the well-being dimension (rho = 0.349; p < 0.001) of the ViDa1 questionnaire. A significant correlation between total physical activity and levels of anxiety and depression was observed: anxiety (15D) (rho = 0.328; p < 0.001) and anxiety/depression (EQ-5D-5L) (rho = 0.324; p < 0.001). The present study showed associations between higher levels of physical activity and higher HRQoL parameters in the population with T1D, which can be erected as a reason for exercise prescription in these patients.
Extramedullary Hematopoiesis of the Liver and Spleen
Authors: Cenariu Diana , Iluta Sabina , Zimta Alina-Andreea , Petrushev Bobe , Qian Liren , Dirzu Noemi , Tomuleasa Ciprian , Bumbea Horia , Zaharie Florin
Published: December 2021

Hematopoiesis is the formation of blood cellular components and, consequently, immune cells. In a more complete definition, this process refers to the formation, growth, maturation, and specialization of blood cells, from the hematopoietic stem cell, through the hematopoietic progenitor cells, to the s pecialized blood cells. This process is tightly regulated by several elements of the bone marrow microenvironment, such as growth factors, transcription factors, and cytokines. During embryonic and fetal development, hematopoiesis takes place in different organs: the yolk sac, the aorta–gonad mesonephros region, the lymph nodes, and not lastly, the fetal liver and the spleen. In the current review, we describe extramedullary hematopoiesis of the spleen and liver, with an emphasis on myeloproliferative conditions.
NTBC Treatment Monitoring in Chilean Patients with Tyrosinemia Type 1 and Its Association with Biochemical Parameters and Liver Biomarkers
Authors: Fuenzalida Karen , Leal-Witt María Jesús , Guerrero Patricio , Hamilton Valerie , Salazar María Florencia , Peñaloza Felipe , Arias Carolina , Cornejo Verónica
Published: December 2021

Treatment and follow-up in Hereditary Tyrosinemia type 1 (HT-1) patients require comprehensive clinical and dietary management, which involves drug therapy with NTBC and the laboratory monitoring of parameters, including NTBC levels, succinylacetone (SA), amino acids, and various biomarkers of liver and kidney function. Good adherence to treatment and optimal adjustment of the NTBC dose, according to clinical manifestations and laboratory parameters, can prevent severe liver complications such as hepatocarcinogenesis (HCC). We analyzed several laboratory parameters for 15 HT-1 patients over one year of follow-up in a cohort that included long-term NTBC-treated patients (more than 20 years), as well as short-term patients (one year). Based on this analysis, we described the overall adherence by our cohort of 70% adherence to drug and dietary treatment. A positive correlation was found between blood and plasma NTBC concentration with a conversion factor of 2.57. Nonetheless, there was no correlation of the NTBC level with SA levels, αFP, liver biomarkers, and amino acids in paired samples analysis. By separating according to the range of the NTBC concentration, we therefore determined the mean concentration of each biochemical marker, for NTBC ranges above 15–25 μmol/L. SA in urine and αFP showed mean levels within controlled parameters in our group of patients. Future studies analyzing a longer follow-up period, as well as SA determination in the blood, are encouraged to confirm the present findings.
Differential Expression of Glucose Transporter Proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the Placenta of Macrosomic, Small-for-Gestational-Age and Growth-Restricted Foetuses
Authors: Stanirowski Paweł Jan , Szukiewicz Dariusz , Majewska Agata , Wątroba Mateusz , Pyzlak Michał , Bomba-Opoń Dorota , Wielgoś Mirosław
Published: December 2021

Placental transfer of glucose constitutes one of the major determinants of the intrauterine foetal growth. The objective of the present study was to evaluate the expression of glucose transporter proteins GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in the placenta of macrosomic, small-for-gestational-age (SGA) and growth-restricted foetuses (FGR). A total of 70 placental tissue samples were collected from women who delivered macrosomic ≥4000 g (n = 26), SGA (n = 11), growth-restricted (n = 13) and healthy control neonates (n = 20). Computer-assisted quantitative morphometry of stained placental sections was performed to determine the expression of selected GLUT proteins. Immunohistochemical staining identified the presence of all glucose transporters in the placental tissue. Quantitative morphometric analysis performed for the vascular density-matched placental samples revealed a significant decrease in GLUT-1 and increase in GLUT-3 protein expression in pregnancies complicated by FGR as compared to other groups (p < 0.05). In addition, expression of GLUT-8 was significantly decreased among SGA foetuses (p < 0.05). No significant differences in GLUTs expression were observed in women delivering macrosomic neonates. In the SGA group foetal birth weight (FBW) was negatively correlated with GLUT-3 (rho = −0.59, p < 0.05) and positively with GLUT-12 (rho = 0.616, p < 0.05) placental expression. In addition, a positive correlation between FBW and GLUT-12 expression in the control group (rho = 0.536, p < 0.05) was noted. In placentas derived from FGR-complicated pregnancies the expression of two major glucose transporters GLUT-1 and GLUT-3 is altered. On the contrary, idiopathic foetal macrosomia is not associated with changes in the placental expression of GLUT-1, GLUT-3, GLUT-8 and GLUT-12 proteins.
An Analysis of IL-10, IL-17A, IL-17RA, IL-23A and IL-23R Expression and Their Correlation with Clinical Course in Patients with Psoriasis
Authors: Kutwin Magdalena , Migdalska-Sęk Monika , Brzeziańska-Lasota Ewa , Zelga Piotr , Woźniacka Anna
Published: December 2021

Being one of the most common dermatological inflammatory disorders, psoriasis is a frequent subject of research. It is considered to be a T cell-dependent immune disease whose pathogenesis is influenced by cytokines, such as IL-10, IL-17A, IL-17RA, IL-23A and IL-23R. The present study examines whether the expression of selected genes is correlated with the clinical course of psoriasis, assessed by the PASI, BSA and DLQI scales. Skin biopsies and blood from 60 patients with psoriasis and 24 healthy controls were obtained for RNA isolation. These were subjected to RT-PCR for IL-10, IL-17A, IL-17RA, IL-23A and IL-23R genes. The results were presented as an RQ value. IL-17A and IL-23R expression levels were higher in psoriatic skin compared to controls, while IL-10 expression was lower. A positive correlation was also found between RQ for IL-23A and PASI index. Psoriatic skin is characterised by elevated expression of IL-17A and IL-23R and decreased expression of IL-10. This indicates that the selected cytokines may be one of the factors involved in the pathogenesis and pathomechanism of psoriasis, but more studies need to be made before we can elucidate the exact reason for the unbalance in cytokine expression levels.
Risk Factors of Aggressive Clinical Presentation in Patients with Angiographically Aggressive Cranial Dural Arteriovenous Fistulas
Authors: Wen Hung-Yu , Chen Hsien-Chung , Yang Shun-Tai
Published: December 2021

Compared to nonaggressive cranial dural arteriovenous fistulae (cDAVF), aggressive cDAVF carries leptomeningeal venous drainage (LVD) and has approximately 15% annual risk of hemorrhagic and non-hemorrhagic aggressive neurological presentations. In terms of aggressive clinical presentations, the previous classification does not adequately differentiate the higher risk group from the lower risk group. Herein, we retrospectively collected a series of patients with aggressive cDAVF and explored the risk factors for differentiating the higher-risk group from the lower-risk group with aggressive clinical presentations. We retrospectively collected patients with aggressive cDAVF from March 2011 to March 2019. The risk of aggressive clinical presentation was recorded. Risk factors were included in the analysis for aggressive clinical presentations. From March 2011 to March 2019, 37 patients had aggressive cDAVF. Among them, 24 presented with aggressive clinical presentation (20, hemorrhagic presentation; four, non-hemorrhagic presentation). In patients presenting with hemorrhage, four patients experienced early rebleeding after diagnosis. In the univariate analysis, risk location, directness of LVD, exclusiveness of LVD, and venous strain were significantly different in patients with aggressive clinical presentation. In the multivariate analysis, exclusiveness of LVD and venous strain were observed, with a significant difference between patients with aggressive clinical presentation and those with benign clinical presentation. Among patients with angiographically aggressive cDAVFs, approximately 65% presented with aggressive clinical presentations in our series. Among all potential risk factors, patients with exclusiveness of LVD and venous strain have even higher risk and should be treated aggressively and urgently.
The Complex Role of C-Reactive Protein in Systemic Lupus Erythematosus
Authors: Enocsson Helena , Karlsson Jesper , Li Hai-Yun , Wu Yi , Kushner Irving , Wetterö Jonas , Sjöwall Christopher
Published: December 2021

C-reactive protein (CRP) is well-known as a sensitive albeit unspecific biomarker of inflammation. In most rheumatic conditions, the level of this evolutionarily highly conserved pattern recognition molecule conveys reliable information regarding the degree of ongoing inflammation, driven mainly by interleukin-6. However, the underlying causes of increased CRP levels are numerous, including both infections and malignancies. In addition, low to moderate increases in CRP predict subsequent cardiovascular events, often occurring years later, in patients with angina and in healthy individuals. However, autoimmune diseases characterized by the Type I interferon gene signature (e.g., systemic lupus erythematosus, primary Sjögren’s syndrome and inflammatory myopathies) represent exceptions to the general rule that the concentrations of CRP correlate with the extent and severity of inflammation. In fact, adequate levels of CRP can be beneficial in autoimmune conditions, in that they contribute to efficient clearance of cell remnants and immune complexes through complement activation/modulation, opsonization and phagocytosis. Furthermore, emerging data indicate that CRP constitutes an autoantigen in systemic lupus erythematosus. At the same time, the increased risks of cardiovascular and cerebrovascular diseases in patients diagnosed with systemic lupus erythematosus and rheumatoid arthritis are well-established, with significant impacts on quality of life, accrual of organ damage, and premature mortality. This review describes CRP-mediated biological effects and the regulation of CRP release in relation to aspects of cardiovascular disease and mechanisms of autoimmunity, with particular focus on systemic lupus erythematosus.
Mismatch Negativity and P3a Impairment through Different Phases of Schizophrenia and Their Association with Real-Life Functioning
Authors: Giordano Giulia M. , Giuliani Luigi , Perrottelli Andrea , Bucci Paola , Di Lorenzo Giorgio , Siracusano Alberto , Brando Francesco , Pezzella Pasquale , Fabrazzo Michele , Altamura Mario , Bellomo Antonello , Cascino Giammarco , Comparelli Anna , Monteleone Palmiero , Pompili Maurizio , Galderisi Silvana , Maj Mario ,   The Italian Network for Research on Psychoses
Published: December 2021

Impairment in functioning since the onset of psychosis and further deterioration over time is a key aspect of subjects with schizophrenia (SCZ). Mismatch negativity (MMN) and P3a, indices of early attention processing that are often impaired in schizophrenia, might represent optimal electrophysiological candidate biomarkers of illness progression and poor outcome. However, contrasting findings are reported about the relationships between MMN-P3a and functioning. The study aimed to investigate in SCZ the influence of illness duration on MMN-P3a and the relationship of MMN-P3a with functioning. Pitch (p) and duration (d) MMN-P3a were investigated in 117 SCZ and 61 healthy controls (HCs). SCZ were divided into four illness duration groups: ≤ 5, 6 to 13, 14 to 18, and 19 to 32 years. p-MMN and d-MMN amplitude was reduced in SCZ compared to HCs, independently from illness duration, psychopathology, and neurocognitive deficits. p-MMN reduction was associated with lower “Work skills”. The p-P3a amplitude was reduced in the SCZ group with longest illness duration compared to HCs. No relationship between P3a and functioning was found. Our results suggested that MMN amplitude reduction might represent a biomarker of poor functioning in SCZ.
The Impact of Gestational Diabetes in Pregnancy on the Cardiovascular System of Children at One Year of Age
Authors: Wacker-Gussmann Annette , Schopen Judith , Engelhard Jana , Sitzberger Christina , Lienert Nadine , Ewert Peter , Müller Alexander , Schmidt Georg , Oberhoffer-Fritz Renate , Lobmaier Silvia Maria
Published: December 2021

Gestational diabetes mellitus (GDM) is a common complication in pregnancy. The effect of GDM on the cardiovascular system after birth is still unclear. Between August 2015 and December 2018, 205 pregnant women were included in the prospective controlled observational study. Patients with GDM were assigned to the study group (n = 99), whereas (n = 107) healthy women served as controls. Postnatal follow up of their offspring was performed at 12 months of age. All included children (n = 125) underwent a specific standardized protocol including anthropometric data, such as weight, height, body mass index (BMI), blood pressure (BP) recordings and ultrasound measurements of the abdominal aortic intima-media-thickness (IMT). Furthermore, at least 10 min 3-channel electrocardiogram recording was done to evaluate the autonomic nervous system (ANS) by phase rectified signal averaging. There were no significant differences in anthropometric data between the groups, neither in the blood pressure nor in the intima-media-thickness of the aorta abdominals. However, in the study group, significantly lower average acceleration capacity (AAC) (study group −20.10 ± 3.04 ms, control group −18.87 ± 4.00 ms, p = 0.02) was found, indicating ANS activation at one year of age. Further studies are required to determine if these results are persistent and if these findings have long-term effects.
Skin Manifestations in Psoriatic and HS Patients in Treatment with Biologicals during the COVID-19 Pandemic
Authors: Rosi Elia , Fastame Maria Thais , Di Cesare Antonella , Silvi Gianmarco , Pimpinelli Nicola , Prignano Francesca
Published: December 2021

The Coronavirus Disease 2019 (COVID-19) pandemic, a global public health emergency, has changed dermatology practice and daily routine in just under two years. Much has been written in the literature about COVID-19-associated skin manifestations. Nevertheless, much less has been written regarding skin manifestations in patients affected by severe immune-mediated skin diseases, e.g., psoriasis and hidradenitis suppurativa, undergoing biological treatment during the COVID-19 outbreak. Thus, the aim of this article is to provide the reader with an overview of the cutaneous manifestations during the COVID-19 pandemic in this subset of patients.
A Novel Clinical Score Predicting the Presence of Fatty Pancreas
Authors: Khoury Tawfik , Mari Amir , Sbeit Wisam
Published: December 2021

Background: Fatty pancreas (FP) has become an increasingly encountered entity in recent years. Several studies have shown an association with several disease states. Aims: we aimed to generate a simple non-invasive scoring model to predict the presence of FP. Method: We performed a retrospective cross-sectional analysis at Galilee Medical Center. Inclusion criteria included patients who underwent endoscopic ultrasound (EUS) for hepatobiliary indications and who had either hyperechogenic pancreas consistent with FP or no sonographic evidence of fatty pancreas. Results: We included 569 patients. Among them, 78 patients had FP by EUS and 491 patients did not have FP. On univariate analysis, obesity (odds ratio (OR) 5.11, p < 0.0001), hyperlipidemia (OR 2.86, p = 0.0005), smoking (OR 2.02, p = 0.04), hypertension (OR 2.58, p = 0.0001) and fatty liver (OR 5.94, p < 0.0001) were predictive of FP. On multivariate analysis, obesity (OR 4.02, p < 0.0001), hyperlipidemia (OR 2.22, p = 0.01) and fatty liver (OR 4.80, p < 0.0001) remained significantly associated with FP. We developed a diagnostic score which included three parameters that were significant on multivariate regression analysis, with assignment of weights for each variable according to the OR estimate. A low cut-off score of ≤1 was associated with a negative predictive value (NPV) of 98.1% for FP, whereas a high cut-off score of ≥2 was associated with a positive predictive value (PPV) of 35–56%. Conclusion: We recommend incorporating this simple score as an aid to identify individuals with FP.
Long-Term Efficacy and Safety of Ibrutinib in the Treatment of CLL Patients: A Real Life Experience
Authors: Broccoli Alessandro , Argnani Lisa , Morigi Alice , Nanni Laura , Casadei Beatrice , Pellegrini Cinzia , Stefoni Vittorio , Zinzani Pier Luigi
Published: December 2021

Ibrutinib has demonstrated a significant clinical impact in patients with de novo and relapsed/refractory chronic lymphocytic leukemia (CLL), even in cases with unfavorable cytogenetics and molecular markers. All CLL patients’ data treated at our Institute with ibrutinib have been retrospectively reviewed. Forty-six patients received ibrutinib either as frontline (10) or second or more advanced treatment (36). Five patients presented with TP53 mutations; 11 had the deletion of chromosome 17p; 17 displayed an unmutated immunoglobulin variable heavy chain status. The median number of cycles administered was 26. Among patients treated frontline, the best overall response rate (ORR) was 90.0%. In patients receiving ibrutinib as a second or later line ORR was 97.2%. Median progression-free survival was 28.8 and 21.1 months for patients treated frontline and as second/later line, respectively. Median overall survival was not reached for those treated frontline and resulted in 4.9 years for patients treated as second/later line. Grade 3–4 hematological toxicities were neutropenia, thrombocytopenia, and anemia. Grade 3–4 extrahematological toxicities included diarrhea, cutaneous rash, utero-vesical prolapse, vasculitis, and sepsis. Ibrutinib is effective and well tolerated in CLL. Responses obtained in a real-life setting are durable and the safety profile of the drug is favorable.
How Does Tube Size Affect Patients’ Experiences of Postoperative Sore Throat and Hoarseness? A Randomised Controlled Blinded Study
Authors: Christiansen Pia , Pedersen Caroline Hornnes , Selter Hansjörg , Odder Lillian , Riisager Jette Præstholm , Damgaard Kjeld , Westmark Signe , Bruun Niels Henrik , Melgaard Dorte
Published: December 2021

Sore throat (POST) and hoarseness (PH) are common complaints after endotracheal intubation (EI). The aim of this study was to investigate whether tube size impacts the experiences of POST and PH after EI in patients undergoing elective surgery, as well as to document a possible role of gender. This randomised, controlled, blinded study was conducted at Aalborg University Hospital, Thisted, Denmark or North Denmark Regional Hospital, Denmark. A total of 236 patients (53.4% female, mean age 50.9 years (SD 14.0)) were enrolled from the departments of gynaecology, parenchyma and orthopaedics. The patients were randomised to a tube size of 8.0 or 7.0 for males and 7.0 or 6.0 for females. Tube sizes were known to the anaesthesia staff but blinded for patients, researchers and staff at the postoperative care unit. POST and/or PH was reported 30–60 min before anaesthesia, at 30 min and at 2, 5, 12, 24, 48, 72 and 96 h after anaesthesia. Both female and male patients experienced significantly lower levels of POST and PH after intubation with the smallest tube size. This study demonstrates that a smaller size of tube results in a reduction in POST and PH after EI for both male and female patients.
Rituximab Therapy for Adults with Nephrotic Syndromes: Standard Schedules or B Cell-Targeted Therapy?
Authors: Del Vecchio Lucia , Allinovi Marco , Rocco Paolo , Brando Bruno
Published: December 2021

Rituximab is a chimeric anti-CD20 monoclonal antibody. It acts mainly through complement-dependent cytotoxicity on B cells expressing the CD20 marker. In this review, we analyse the efficacy and possible pitfalls of rituximab to treat nephrotic syndromes by taking into account pharmacological considerations and CD19 marker testing utility. Despite the fact that the drug has been in use for years, efficacy and treatment schedules in adults with nephrotic syndrome are still a matter of debate. Clinical trials have proven the efficacy and safety of rituximab in idiopathic membranous nephropathy. Data from observational studies also showed the efficacy of rituximab in minimal change disease and focal segmental glomerulosclerosis. Rituximab use is now widely recommended by new Kidney Disease Improved Outcome (KDIGO) guidelines in membranous nephropathy and in frequent-relapsing, steroid-dependent minimal change disease or focal segmental glomerulosclerosis. However, rituximab response has a large interindividual variability. One reason could be that rituximab is lost in the urine at a higher extent in patients with nonselective nephrotic proteinuria, exposing patients to different rituximab plasma levels. Moreover, the association between CD19+ levels and clinical response or relapses is not always present, making the use of this marker in clinical practice complex. High resolution flow cytometry has increased the capability of detecting residual CD19+ B cells. Moreover, it can identify specific B-cell subsets (including IgG-switched memory B cells), which can repopulate at different rates. Its wider use could become a useful tool for better understanding reasons of rituximab failure or avoiding unnecessary retreatments.