bluuebunny/crossref_metadata_2025 huggingface dataset:
Peri- and Post-Menopausal Women with Schizophrenia and Related Disorders Are a Population with Specific Needs: A Narrative Review of Current Theories
Authors: González-Rodríguez Alexandre , Guàrdia Armand , Monreal José Antonio
Published: August 2021

Background: While gender differences in antipsychotic response have been recognized, the potential role of menopause in changing drug efficacy and clinical outcome in schizophrenia related disorders has been understudied. We aimed to review the relevant literature to test whether optimizing menopausal and post-menopausal treatment and addressing specific health needs of this stage in life will improve outcome. Methods: Non-systematic narrative review using the PubMed database (1900–July 2021) focusing on randomized controlled trial results addressing our question. Forty-nine studies met our criteria. Results: Premenopausal women show significantly better antipsychotic response than postmenopausal women. Hormone replacement therapies (HRT) should be used in postmenopausal women with schizophrenia with caution. Raloxifene, combined with antipsychotics, is effective for psychotic and cognitive symptoms in postmenopausal women with schizophrenia and related disorders. Medical comorbidities increase after menopause, but the influence of comorbidities on clinical outcomes has been poorly investigated. Preventive strategies include weighing risks and benefits of treatment, preventing medical comorbidities, and enhancing psychosocial support. Ideal treatment settings for this population warrant investigation. Conclusions: Antipsychotic dose adjustment at menopause is recommended for schizophrenia. Raloxifene may play an important role in permitting dose reduction and lessening adverse effects. Prevention of comorbidities will help to reduce the mortality rate.
Patient-Reported Outcomes following Genetic Testing for Familial Hypercholesterolemia, Breast and Ovarian Cancer Syndrome, and Lynch Syndrome: A Systematic Review
Authors: Hendricks-Sturrup Rachele M. , Joseph Lucson , Lu Christine Y.
Published: August 2021

Background: Patient-reported outcomes (PROs) and PRO measures (PROMs) are real-world evidence that can help capture patient experiences and perspectives regarding a clinical intervention such as genetic testing. Objective: To identify and capture methods and qualitative PRO themes among studies reporting PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Methods: A systematic review was conducted via PubMed/MEDLINE, EMBASE, and Yale University’s TRIP Medical Databases on articles published by April 2021. Results: We identified 24 studies published between 1996 and 2021 representing 4279 participants that reported PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Studies collected and reported PROs from validated PROM instruments (n = 12; 50%), validated surveys (n = 7; 26%), and interviews (n = 10; 42%). PRO themes ranged across all collection methods (e.g., psychological, knowledge, coping and satisfaction, concern about stigma/discrimination, etc.). Conclusions: Important gaps identified include (1) most studies (n = 18; 75%) reported PROs following genetic testing for breast and ovarian cancer, and (2) populations reporting PROs overall were largely of White/Caucasian/Northern European/Anglo-Saxon descent. We offer recommendations and describe real-world implications for the field moving forward.
Potential Use of Pharmacogenetics to Reduce Drug-Induced Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
Authors: Wilke Russell A.
Published: August 2021

Syndrome of inappropriate antidiuretic hormone (SIADH) is a common cause of hyponatremia, and many cases represent adverse reactions to drugs that alter ion channel conductance within the peptidergic nerve terminals of the posterior pituitary. The frequency of drug-induced SIADH increases with age; as many as 20% of patients residing in nursing homes have serum sodium levels below 135 mEq/L. Mild hyponatremia is associated with cognitive changes, gait instability, and falls. Severe hyponatremia is associated with cerebral edema, seizures, permanent disability, and/or death. Although pharmacogenetic tests are now being deployed for some drugs capable of causing SIADH (e.g., antidepressants, antipsychotics, and opioid analgesics), the implementation of these tests has been based upon the prior known association of these drugs with other serious adverse drug reactions (e.g., electrocardiographic abnormalities). Work is needed in large observational cohorts to quantify the strength of association between pharmacogene variants and drug-induced SIADH so that decision support can be developed to identify patients at high risk.
A Novel Tool for a Challenging Disease: Stasis Leg Ulcers Assessed Using QFlow in Triggered Angiography Noncontrast Enhanced Magnetic Resonance Imaging
Authors: Chen Chien-Wei , Fang Yueh-Fu , Tseng Yuan-Hsi , Wong Min-Yi , Lin Yu-Hui , Hsu Yin-Chen , Lin Bor-Shyh , Huang Yao-Kuang
Published: August 2021

Imaging characteristics of stasis leg ulcers (SLUs) are not easily demonstrated through existing diagnostic tools. Early diagnosis and treatment are crucial. This pilot study was conducted to assess the quantitative flow (QFlow) in triggered angiography noncontrast enhanced (TRANCE) magnetic resonance imaging (MRI) to identify the hemodynamics of victims with stasis leg ulcers (SLUs). This study included 33 patients with SLUs and 14 healthy controls (HC). The 33 patients with SLUs were divided into a reflux (15 patients) and a nonreflux group (18 patients). QFlow was done in the reflux, the nonreflux, and the HC. The stroke volume (SV), forward flow volume (FFV), absolute flow volume (AFV), mean flow (MF), and mean velocity (MV) were higher in the reflux than in the HC group in most segments, namely the external iliac vein (EIV), popliteal vein (PV), and great saphenous vein (GSV) (SV, p = 0.008; FFV, p = 0.008; absolute stroke volume (ASV), p = 0.008; MF, p = 0.002; MV, p = 0.009). No differences in the QFlow patterns were found in the GSV segment between the nonreflux group and the HC. Excellent performance in discriminating SLU with superficial venous reflux was reported for SV in the EIV and the PV (area under the curve (AUC) = 0.851 and 0.872), FFV in the EIV and PV (AUC = 0.854 and 0.869), ASV in the EIV and PV (AUC = 0.848 and 0.881), and MF in the EIV and PV (AUC = 0.866 and 0.868). The cutoff levels of SV/FFV/ASV/MF in the EIV/FV/PV/GSV for discriminating the SLU with superficial venous reflux were identified (p < 0.005). In conclusion, SLUs present different QFlow patterns by different etiology. The QFlow parameters of all vessel segments were higher in the morbid limbs of the reflux group than HC. The GSV segment of the nonreflux group displayed a pattern like the HC.
Increased Prevalence of Celiac Disease in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis
Authors: Imrei Marcell , Németh Dávid , Szakács Zsolt , Hegyi Péter , Kiss Szabolcs , Alizadeh Hussain , Dembrovszky Fanni , Pázmány Piroska , Bajor Judit , Párniczky Andrea
Published: August 2021

Objectives: Immune regulation seems to be altered in cystic fibrosis (CF), thus potentially predisposing patients to developing autoimmune diseases (AID). In this meta-analysis, we aimed to evaluate the prevalence of celiac disease (CeD) among CF patients as by far the most commonly reported autoimmune disease in this population and, secondly, to review the observations on other, less frequently studied autoimmune diseases. Methods: We conducted a systematic literature search for studies that discussed AIDs among CF patients. Following standard selection and data collection, we calculated pooled raw prevalence with 95% confidence intervals (CI) for biopsy-verified CeD and seropositivity. Results: Out of the 21 eligible studies, 15 reported on CeD. Pooled prevalence of biopsy-verified CeD was 1.8% (CI 1.1–2.7%) according to a homogeneous dataset from six prospective, consecutive screening studies, while it proved to be 2.3% (CI 1.1–4.7%) according to a heterogeneous dataset from the other studies. Tissue transglutaminase IgA positivity was detected in 4.5% of CF cases (CI 2.8–6.9%), while tissue transglutaminase IgA–endomysial antibody IgA double positivity was found in 2.4% of them (CI 1.5–3.9%). Findings on other AIDs were strongly limited. Conclusions: The pooled prevalence of CeD in CF seemed to be more than twice as high compared to the global prevalence; therefore, routine screening of CeD could be considered in CF.
Molecular Determination of mirRNA-126 rs4636297, Phosphoinositide-3-Kinase Regulatory Subunit 1-Gene Variability rs7713645, rs706713 (Tyr73Tyr), rs3730089 (Met326Ile) and Their Association with Susceptibility to T2D
Authors: Mir Rashid , Elfaki Imadeldin , Duhier Faisel M. Abu , Alotaibi Maeidh A. , AlAlawy Adel Ibrahim , Barnawi Jameel , Babakr Abdullatif Taha , Mir Mohammad Muzaffar , Mirghani Hyder , Hamadi Abdullah , Dabla Pradeep Kumar
Published: August 2021

Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different (p-value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, p-value < 0.05. In addition results showed that there were significant differences (p-value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a p-values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, p-value < 0.05. We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity.
Prediction of Hemorrhagic Transformation after Ischemic Stroke Using Machine Learning
Authors: Choi Jeong-Myeong , Seo Soo-Young , Kim Pum-Jun , Kim Yu-Seop , Lee Sang-Hwa , Sohn Jong-Hee , Kim Dong-Kyu , Lee Jae-Jun , Kim Chulho
Published: August 2021

Hemorrhagic transformation (HT) is one of the leading causes of a poor prognostic marker after acute ischemic stroke (AIS). We compared the performances of the several machine learning (ML) algorithms to predict HT after AIS using only structured data. A total of 2028 patients with AIS, who were admitted within seven days of symptoms onset, were included in this analysis. HT was defined based on the criteria of the European Co-operative Acute Stroke Study-II trial. The whole dataset was randomly divided into a training and a test dataset with a 7:3 ratio. Binary logistic regression, support vector machine, extreme gradient boosting, and artificial neural network (ANN) algorithms were used to assess the performance of predicting the HT occurrence after AIS. Five-fold cross validation and a grid search technique were used to optimize the hyperparameters of each ML model, which had its performance measured by the area under the receiver operating characteristic (AUROC) curve. Among the included AIS patients, the mean age and number of male subjects were 69.6 years and 1183 (58.3%), respectively. HT was observed in 318 subjects (15.7%). There were no significant differences in corresponding variables between the training and test dataset. Among all the ML algorithms, the ANN algorithm showed the best performance in terms of predicting the occurrence of HT in our dataset (0.844). Feature scaling including standardization and normalization, and the resampling strategy showed no additional improvement of the ANN’s performance. The ANN-based prediction of HT after AIS showed better performance than the conventional ML algorithms. Deep learning may be used to predict important outcomes for structured data-based prediction.
Discrimination of Exudative Pleural Effusions Based on Pleural Adenosine Deaminase (ADA)-C-Reactive Protein (CRP) Levels, and Their Combination: An Observational Prospective Study
Authors: Perlepe Garifallia , Varsamas Charalampos , Petinaki Efthymia , Antonopoulos Dionysios , Daniil Zoe , Gourgoulianis Konstantinos I.
Published: August 2021

(1) Background: Malignant (MPE), parapneumonic (PPE) and tuberculous (TPE) pleural effusions constitute common causes of pleurisy. Discriminating among them is usually challenging. C-reactive protein (CRP) and adenosine deaminase (ADA) pleural levels (p-CRP, p-ADA) have been used as differentiators in many studies showing promising results. This study aims to evaluate the diagnostic value of p-CRP, p-ADA levels and their combination among the three categories. (2) Methods: A prospective study of 100 patients with MPE (n = 59), PPE (n = 34) and TPE (n = 7) from a single centre was performed. p-CRP levels were evaluated between PPE and non-PPE and between complicated (CPPE) and non-complicated PPE. ADA levels were also measured to classify patients among MPE and non- MPE. Eventually, the combination of p-CRP and p-ADA values was used as a discrimination factor among PPE, MPE and TPE. (3) Results: ROC analysis revealed that p-CRP with a cut-off value: 4.4 mg/dL can successfully differentiate PPE (AUC = 0.998). The cut-off level of 10 mg/dL can predict CPPE with sensitivity: 63%, specificity: 71.4%, positive predictive value (PPV): 89%, and negative predictive value (NPV): 33%. Furthermore, patients with ADA levels ≤ 32 U/L were more likely to belong to the malignant group sensitivity: 93%, specificity: 78%, PPV: 85.9%, and NPV: 88.9%. Discriminant analysis showed that the combination of p-CRP and p-ADA levels can discriminate PPE, MPE and TPE in 93% of cases. (4) Conclusion: This study provides evidence that p-CRP and p-ADA levels could be possibly used in clinal practice in order to establish a diagnosis among MPE, PPE and TPE.
Emotional Dysregulation, Temperament and Lifetime Suicidal Ideation among Youths with Mood Disorders
Authors: Janiri Delfina , Moccia Lorenzo , Conte Eliana , Palumbo Laura , Chieffo Daniela Pia Rosaria , Fredda Giulia , Menichincheri Renato Maria , Balbi Andrea , Kotzalidis Georgios D. , Sani Gabriele , Janiri Luigi
Published: August 2021

Background: Psychopathological dimensions contributing to suicidal ideation in young age are poorly understood. We aimed to investigate the involvement of emotional dysregulation and temperament in suicide risk in a sample of accurately selected young patients with mood disorders and a matched sample of healthy controls (HC). Methods: We assessed 50 young patients (aged 14–25 years) with DSM-5 bipolar or depressive disorders for clinical and psychopathological characteristics and 82 age and sex, educational level, and smoking habits-matched HC. Emotional dysregulation and temperament were assessed using the Difficulties in Emotion Regulation Scale (DERS) and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire (TEMPS-A-39), respectively. We tested their associations with suicidal ideation, using standard univariate/bivariate methods, preceded by overall multivariate analysis. Results: In the group of patients, 24 (48%) reported lifetime suicide ideation (LSI). Patients with LSI scored higher on emotional dysregulation (p < 0.001) and cyclothymic (p < 0.001), irritable (p = 0.01), and hyperthymic temperaments (p = 0.003) than HC. Patients with LSI specifically presented with more emotional dysregulation (p < 0.001) and cyclothymic temperament (p = 0.001), than patients without LSI (N = 26). Conclusions: Temperamental features, in particular cyclothymic temperament, and emotion dysregulation may represent independent factors for increased vulnerability to lifetime suicidal ideation in young adults with mood disorders.
Effect of COVID-19-Related Lockdown οn Hospital Admissions for Asthma and COPD Exacerbations: Associations with Air Pollution and Patient Characteristics
Authors: Sigala Ioanna , Giannakas Timoleon , Giannakoulis Vassilis G. , Zervas Efthimios , Brinia Aikaterini , Gianiou Niki , Asimakos Andreas , Dima Efi , Kalomenidis Ioannis , Katsaounou Paraskevi
Published: August 2021

We conducted a retrospective observational study to assess the hospitalization rates for acute exacerbations of asthma and COPD (chronic obstructive pulmonary disease) during the first imposed lockdown in Athens, Greece. Patient characteristics and the concentration of eight air pollutants [namely, NO (nitrogen monoxide), NO2 (nitrogen dioxide), CO (carbon monoxide), PM2.5 (particulate matter 2.5), PM10 (particulate matter 10), O3 (ozone), SO2 (sulfur dioxide) and benzene] were considered. A total of 153 consecutive hospital admissions were studied. Reduced admissions occurred in the Lockdown period compared to the Pre-lockdown 2020 (p < 0.001) or the Control 2019 (p = 0.007) period. Furthermore, the concentration of 6/8 air pollutants positively correlated with weekly hospital admissions in 2020 and significantly decreased during the lockdown. Finally, admitted patients for asthma exacerbation during the lockdown were younger (p = 0.046) and less frequently presented respiratory failure (p = 0.038), whereas patients with COPD presented higher blood eosinophil percentage (p = 0.017) and count (p = 0.012). Overall, admissions for asthma and COPD exacerbations decreased during the lockdown. This might be partially explained by reduction of air pollution during this period while medical care avoidance behavior, especially among elderly patients cannot be excluded. Our findings aid in understanding the untold impact of the pandemic on diseases beyond COVID-19, focusing on patients with obstructive diseases.
Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies
Authors: M. Kholosy Waleed , Derieppe Marc , van den Ham Femke , Ober Kim , Su Yan , Custers Lars , Schild Linda , M. J. van Zogchel Lieke , M. Wellens Lianne , R. Ariese Hendrikus , Szanto Celina L. , Wienke Judith , Dierselhuis Miranda P. , van Vuurden Dannis , Dolman Emmy M. , Molenaar Jan J.
Published: August 2021

Cancer immunotherapy has transformed the landscape of adult cancer treatment and holds a great promise to treat paediatric malignancies. However, in vitro test coculture systems to evaluate the efficacy of immunotherapies on representative paediatric tumour models are lacking. Here, we describe a detailed procedure for the establishment of an ex vivo test coculture system of paediatric tumour organoids and immune cells that enables assessment of different immunotherapy approaches in paediatric tumour organoids. We provide a step-by-step protocol for an efficient generation of patient-derived diffuse intrinsic pontine glioma (DIPG) and neuroblastoma organoids stably expressing eGFP-ffLuc transgenes using defined serum-free medium. In contrast to the chromium-release assay, the new platform allows for visualization, monitoring and robust quantification of tumour organoid cell cytotoxicity using a non-radioactive assay in real-time. To evaluate the utility of this system for drug testing in the paediatric immuno-oncology field, we tested our in vitro assay using a clinically used immunotherapy strategy for children with high-risk neuroblastoma, dinutuximab (anti-GD2 monoclonal antibody), on GD2 proficient and deficient patient-derived neuroblastoma organoids. We demonstrated the feasibility and sensitivity of our ex vivo coculture system using human immune cells and paediatric tumour organoids as ex vivo tumour models. Our study provides a novel platform for personalized testing of potential anticancer immunotherapies for aggressive paediatric cancers such as neuroblastoma and DIPG.
Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?
Authors: Proske Pia , Distelmaier Laura , Aramayo-Singelmann Carmen , Koliastas Nikolaos , Iannaccone Antonella , Papathanasiou Maria , Temme Christian , Klump Hannes , Lenz Veronika , Koldehoff Michael , Carpinteiro Alexander , Reinhardt Hans , Köninger Angela , Röth Alexander , Yamamoto Raina , Dührsen Ulrich , Alashkar Ferras
Published: August 2021

Background: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.
Nepenthes Extract Induces Selective Killing, Necrosis, and Apoptosis in Oral Cancer Cells
Authors: Yang Kun-Han , Tang Jen-Yang , Chen Yan-Ning , Chuang Ya-Ting , Tsai I-Hsuan , Chiu Chien-Chih , Li Li-Jie , Chien Tsu-Ming , Cheng Yuan-Bin , Chang Fang-Rong , Yen Ching-Yu , Chang Hsueh-Wei
Published: August 2021

Ethyl acetate Nepenthes extract (EANT) from Nepenthes thorellii × (ventricosa × maxima) shows antiproliferation and apoptosis but not necrosis in breast cancer cells, but this has not been investigated in oral cancer cells. In the present study, EANT shows no cytotoxicity to normal oral cells but exhibits selective killing to six oral cancer cell lines. They were suppressed by pretreatment of the antioxidant inhibitor N-acetylcysteine (NAC), demonstrating that EANT-induced cell death was mediated by oxidative stress. Concerning high sensitivity to EANT, Ca9-22 and CAL 27 oral cancer cells were chosen for exploring detailed selective killing mechanisms. EANT triggers a mixture of necrosis and apoptosis as determined by annexin V/7-aminoactinmycin D analysis. Still, they show differential switches from necrosis at a low (10 μg/mL) concentration to apoptosis at high (25 μg/mL) concentration of EANT in oral cancer cells. NAC induces necrosis but suppresses annexin V-detected apoptosis in oral cancer cells. Necrostatin 1 (NEC1), a necroptosis inhibitor, moderately suppresses necrosis but induces apoptosis at 10 μg/mL EANT. In contrast, Z-VAD-FMK, a pancaspase inhibitor, slightly causes necrosis but suppresses apoptosis at 10 μg/mL EANT. Furthermore, the flow cytometry-detected pancaspase activity is dose-responsively increased but is suppressed by NAC and ZVAD, although not for NEC1 in oral cancer cells. EANT causes several oxidative stress events such as reactive oxygen species, mitochondrial superoxide, and mitochondrial membrane depolarization. In response to oxidative stresses, the mRNA for antioxidant signaling, such as nuclear factor erythroid 2-like 2 (NFE2L2), catalase (CAT), heme oxygenase 1 (HMOX1), and thioredoxin (TXN), are overexpressed in oral cancer cells. Moreover, EANT also triggers DNA damage, as detected by γH2AX and 8-oxo-2′-deoxyguanosine adducts. The dependence of oxidative stress is validated by the evidence that NAC pretreatment reverts the changes of cellular and mitochondrial stress and DNA damage. Therefore, EANT exhibits antiproliferation involving an oxidative stress-dependent necrosis/apoptosis switch and DNA damage in oral cancer cells.
Is Low Heart Rate Variability Associated with Emotional Dysregulation, Psychopathological Dimensions, and Prefrontal Dysfunctions? An Integrative View
Authors: Cattaneo Lorena Angela , Franquillo Anna Chiara , Grecucci Alessandro , Beccia Laura , Caretti Vincenzo , Dadomo Harold
Published: August 2021

Several studies have suggested a correlation between heart rate variability (HRV), emotion regulation (ER), psychopathological conditions, and cognitive functions in the past two decades. Specifically, recent data seem to support the hypothesis that low-frequency heart rate variability (LF-HRV), an index of sympathetic cardiac control, correlates with worse executive performances, worse ER, and specific psychopathological dimensions. The present work aims to review the previous findings on these topics and integrate them from two main cornerstones of this perspective: Porges’ Polyvagal Theory and Thayer and Lane’s Neurovisceral Integration Model, which are necessary to understand these associations better. For this reason, based on these two approaches, we point out that low HRV is associated with emotional dysregulation, worse cognitive performance, and transversal psychopathological conditions. We report studies that underline the importance of considering the heart-brain relation in order to shed light on the necessity to implement psychophysiology into a broader perspective on emotions, mental health, and good cognitive functioning. This integration is beneficial not only as a theoretical ground from which to start for further research studies but as a starting point for new theoretical perspectives useful in clinical practice.
Analysis of Forest Landscape Restoration Based on Landscape Connectivity: A Case Study in the Yi River Basin, China, during 2015–2020
Authors: Bian Ziqi , Liu Lyuyi , Ding Shengyan
Published: August 2021

Landscape connectivity has widely been recognized as one of the key objectives in studies of forest landscape management, ecological conservation and construction. Protecting virgin forests and afforesting marginal cropland are two long-term ecological projects in China. However, along with rapid urbanization and industrialization in China, the relationship between landscape connectivity and forest landscape restoration (FLR) has not been fully explored. The emergent question concerns whether the connectivity of a restored forest landscape could benefit the local flora and fauna. We evaluated the status of FLR in the Yi River watershed based on remote sensing images during 2015–2020. The forest landscape connectivity (FLC) was investigated using landscape connectivity indicators, applying the theory of landscape connectivity. We also examined the variations of FLC under different landform types (hills and low mountains) according to distance threshold values ranging from 100 m to 20,000 m. The most appropriate distance thresholds for analyzing FLC in hills and low mountains are 500 m and 100 m, respectively. The results showed that in this period, the FLC in low mountains was increased, whereas that of hills was decreased. The contributions for reforested patches on the improvement of the FLC were evaluated. In hills, patches that made “very high” and “high” contributions to improve the FLC occupied 15.6% of the total reforested area, whereas the proportion in low mountains was 25.5%. The results indicated that although rainfed cropland patches have been converted to forest patches, some of them have made small contributions to the FLC. Through this case study, we hope to have confirmed that landscape connectivity analysis could be used as a criterion for selecting important patches in the planning of FLR. Moreover, we have introduced this implementable method for future ecological restoration management programs.
Comparison of Models for Spatial Distribution and Prediction of Cadmium in Subtropical Forest Soils, Guangdong, China
Authors: Ding Xiaogang , Zhao Zhengyong , Xing Zisheng , Li Shengting , Li Xiaochuan , Liu Yanmei
Published: August 2021

Cadmium (Cd) is a toxic metal and found in various soils, including forest soils. The great spatial heterogeneity in soil Cd makes it difficult to determine its distribution. Both traditional soil surveys and spatial modeling have been used to study the natural distribution of Cd. However, traditional methods are highly labor-intensive and expensive, while modeling is often encumbered by the need to select the proper predictors. In this study, based on intensive soil sampling (385 soil pits plus 64 verification soil pits) in subtropical forests in Yunfu, Guangdong, China, we examined the impacting factors and the possibility of combining existing soil information with digital elevation model (DEM)-derived variables to predict the Cd concentration at different soil depths along the landscape. A well-developed artificial neural network model (ANN), multi-variate analysis, and principal component analysis were used and compared using the same dataset. The results show that soil Cd concentration varied with soil depth and was affected by the top 0–20 cm soil properties, such as soil sand or clay content, and some DEM-related variables (e.g., slope and vertical slope position, varying with depth). The vertical variability in Cd content was found to be correlated with metal contents (e.g., Cu, Zn, Pb, Ni) and Cd contents in the layer immediately above. The selection of candidate predictors differed among different prediction models. The ANN models showed acceptable accuracy (around 30% of predictions have a relative error of less than 10%) and could be used to assess the large-scale Cd impact on environmental quality in the context of intensifying industrialization and climate change, particularly for ecosystem management in this region or other regions with similar conditions.
Linking Morphological Spatial Pattern Analysis and Circuit Theory to Identify Ecological Security Pattern in the Loess Plateau: Taking Shuozhou City as an Example
Authors: Yang Ronglei , Bai Zhongke , Shi Zeyu
Published: August 2021

Located in an ecologically fragile area in China’s eastern part of the Loess Plateau, Shuozhou City has faced environmental challenges imposed by frequent urban expansion and mining activities in recent years. As ecological security patterns (ESP) identification and optimization are significant to regional biodiversity and ecosystem services, this study combined morphological spatial pattern analysis (MSPA) and circuit theory to construct and optimize regional ESP. Results show the number and area of ecological sources in the study area decreased from 21 to 20 between 2010 and 2017. The total area of ecological sources fell from 1923.35 km2 to 1869.37 km2, with their proportion in the study area dropped from 18.14% to 17.64%. From 2010 to 2017, the number of obstacles increases from 63 to 80, mainly consisting of farmland, unused land, transportation land, and construction land. The area of obstacles reached 10.17 km2 in 2017. A framework of “one protection area, two regulation areas, and three restoration areas” is proposed to optimize the ESP of the study zone. This study explored a combination of ESP analysis tools and focused on improving regional ecosystem service and biodiversity. It will support local urban planning and provide a reference for similar studies in resource-based cities.
Tracheal Repair with Human Umbilical Cord Mesenchymal Stem Cells Differentiated in Chondrocytes Grown on an Acellular Amniotic Membrane: A Pre-Clinical Approach
Authors: Baggio Simeoni Paulo Ricardo , Simeoni Rossana Baggio , Bispo Machado Júnior Paulo André , de Almeida Meila Bastos , Dziedzic Dilcele Silva Moreira , da Rosa Nádia Nascimento , Ferreira Stricker Priscila E. , dos Santos Miggiolaro Anna Flávia Ribeiro , Naves Guilherme , Neto Nelson Bergonse , de Noronha Lucia , Francisco Julio Cesar , Teixeira de Carvalho Katherine Athayde , Guarita-Souza Luiz Cesar
Published: August 2021

Acellular amniotic membrane (AM) has been studied, with promising results on the reconstruction of lesioned tissues, and has become an attractive approach for tracheal repair. This study aimed to evaluate the repair of the trachea with human umbilical cord mesenchymal stem cells (hucMSCs) differentiated in chondrocytes, grown on an experimental model. Tracheal defects were induced by surgical tracheostomy in 30 New Zealand rabbits, and the acellular amniotic membrane, with or without cells, was covering the defect. The hucMSCs were isolated and cultivated with chondrogenic differentiation over the culture of 14 days, and then grown on the AM. In this study, the AM was biocompatible and hucMSCs differentiated into chondrocytes. Our results demonstrated an important role for AM with cultured cells in the promotion of immature collagen, known to produce tissue regeneration. In addition, cartilaginous tissue was found at the tracheal defects, demonstrated by immunohistology results. This study suggests that this biomaterial implantation can be an effective future therapeutic alternative for patients with tracheal injury.
Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects
Authors: Lőrincz Hajnalka , Csige Imre , Harangi Mariann , Szentpéteri Anita , Seres Ildikó , Szabó Zoltán , Paragh György , Somodi Sándor
Published: August 2021

Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m2) were enrolled in our study. Serum fetuin-A and RBP4 were measured by ELISA. Lipoprotein subfractions were distributed by Lipoprint gelelectrophoresis. Results: Serum fetuin-A and RBP4 were unexpectedly lower in obese patients (p < 0.01 and p < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; p < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; p = 0.02), apolipoprotein AI (apoAI) (r = 0.33; p < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; p = 0.05), and large HDL subfraction levels (r = 0.3; p = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; p = 0.025), apoAI (r = 0.23; p = 0.01), VLDL subfraction (r = 0.37; p < 0.001), intermediate HDL subfraction (r = 0.23; p = 0.01), and small HDL subfraction (r = 0.21; p = 0.02) concentrations, as well as C-peptide levels in overall participants. Backward stepwise multiple regression analysis showed that serum fetuin-A concentration is best predicted by RBP4 and large HDL subfraction. In model 2, VLDL subfraction was the independent predictor of serum RBP4 level. Conclusions: Our data may indicate a potential role of fetuin-A and RBP4 in impaired lipoprotein metabolism associated with obesity.
The Genetic Variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) as Possible Risk Factors of Psoriasis Development
Authors: Bartosińska Joanna , Zmorzyński Szymon , Sarecka-Hujar Beata , Raczkiewicz Dorota , Wojcierowska-Litwin Magdalena , Korszeń-Pilecka Iwona , Michalak-Stoma Anna , Kowal Małgorzata , Bartosiński Jarosław , Filip Agata , Krasowska Dorota , Chodorowska Grażyna
Published: August 2021

Advances in genotypic technologies enable identification of possible associations between genetic variants of certain genes and increased risk of developing plaque psoriasis or psoriatic arthritis. The aim of the study was to analyze the NOTCH3 (6746T>C) (rs1044009) and PSMA6 (-8C>G) (rs1048990) polymorphisms and their role in genetic susceptibility to psoriasis. The study included 158 psoriatic patients and 100 healthy controls. The frequencies of the NOTCH3 genotypes differed between the psoriatic patients and healthy controls (p = 0.050). No differences were found in the distribution of PSMA6 genotypes and alleles between the psoriatic patients and healthy controls. The studied psoriatic patients presented a higher frequency of the CC genotype of PSMA6 compared to the healthy controls (8.8% vs. 2%, respectively). Psoriatic arthritis was more frequent among patients with the CC genotype of PSMA6 (p = 0.059). CC homozygosity of NOTCH3 was more commonly observed in the studied psoriatic patients than in the healthy controls (OR = 4.76, p= 0.032). The obtained data suggest that genetic variants of NOTCH3 (6746T>C) and PSMA6 (-8C>G) genes may play significant roles in psoriatic patients. Further studies are necessary to unequivocally determine their role as genetic risk factors of psoriasis development.
Metabolic Health, Obesity, and Renal Function: 2013–2018 National Health and Nutrition Examination Surveys
Authors: Adair Kathleen E. , Bowden Rodney G. , Funderburk LesLee K. , Forsse Jeffrey S. , Ylitalo Kelly R.
Published: August 2021

Rising rates of metabolic syndrome, obesity, and mortality from chronic kidney disease (CKD) have prompted further investigation into the association between metabolic phenotypes and CKD. Purpose: To report the frequency of strictly defined metabolic phenotypes, renal function within each phenotype, and individual risk factors associated with reduced renal function. We utilized the 2013–2018 National Health and Nutrition Examination Surveys (NHANES) and complex survey sample weighting techniques to represent 220 million non-institutionalized U.S. civilians. Metabolic health was defined as having zero of the risk factors defined by the National Cholesterol Education Program with the exception of obesity, which was defined as BMI ≥ 30 kg/m2 in non-Asians and BMI ≥ 25 kg/m2 in Asians. The metabolically healthy normal (MUN) phenotype comprised the highest proportion of the population (38.40%), whereas the metabolically healthy obese (MHO) was the smallest (5.59%). Compared to the MHN reference group, renal function was lowest in the strictly defined MUN (B = −9.60, p < 0.001) and highest in the MHO (B = 2.50, p > 0.05), and this persisted when an increased number of risk factors were used to define metabolic syndrome. Systolic blood pressure had the strongest correlation with overall eGFR (r = −0.25, p < 0.001), and individuals with low HDL had higher renal function compared to the overall sample. The MUN phenotype had the greatest association with poor renal function. While the MHO had higher renal function, this may be due to a transient state caused by renal hyperfiltration. Further research should be done to investigate the association between dyslipidemia and CKD.
Contributions to a Discussion of Spinosaurus aegyptiacus as a Capable Swimmer and Deep-Water Predator
Authors: Gimsa Jan , Gimsa Ulrike
Published: August 2021

The new findings on Spinosaurus’ swim tail strongly suggest that Spinosaurus was a specialized deep-water predator. However, the tail must be seen in the context of the propelled body. The comparison of the flow characteristics of Spinosaurus with geometrically similar animals and their swimming abilities under water must take their Reynolds numbers into account and provide a common context for the properties of Spinosaurus’ tail and dorsal sail. Head shape adaptations such as the head crest reduced hydrodynamic disturbance and facilitated stealthy advance, especially when hunting without visual contact, when Spinosaurus could have used its rostral integumentary mechanoreceptors for prey detection. The muscular neck permitted ‘pivot’ feeding, where the prey’s escape abilities were overcome by rapid dorsoventral head movement, facilitated by crest-mediated lower friction.
Sensitive Detection of Heregulin-α from Biological Samples Using a Disposable Stochastic Sensor Based on Plasma Deposition of GNPs–AgPs’ Nanofilms on Silk
Authors: Gheorghe Sorin Sebastian , Cioates Negut Catalina , Badulescu Marius , Stefan-van Staden Raluca Ioana
Published: August 2021

A composite material comprised of graphene nanoplatelet and silver particles (GNPs–AgPs) was used for the deposition of GNPs–AgPs’ nanofilms with cold plasma on silk. α-Cyclodextrin was used as a modifier of the active surface of the disposable sensor. The disposable stochastic sensor was used in screening tests for the assay of heregulin-α in whole blood and tissue samples. The disposable stochastic sensor showed a low limit of determination (4.10 fg mL−1) and can be used with high sensitivity on a wide concentration range (4.10 fg mL−1–0.04 µg mL−1). The screening method was validated against ELISA when good correlations (confirmed also by the t-test) were obtained.
BNT162b2 SARS-CoV-2 Vaccination Elicits High Titers of Neutralizing Antibodies to Both B.1 and P.1 Variants in Previously Infected and Uninfected Subjects
Authors: Vicenti Ilaria , Gatti Francesca , Scaggiante Renzo , Boccuto Adele , Zago Daniela , Basso Monica , Dragoni Filippo , Parisi Saverio , Zazzi Maurizio
Published: August 2021

We aimed to investigate neutralizing antibody titers (NtAbT) to the P.1 and B.1 SARS-CoV-2 variants in a cohort of healthy health care workers (HCW), including 20 previously infected individuals tested at baseline (BLinf, after a median of 298 days from diagnosis) and 21 days after receiving one vaccine dose (D1inf) and 15 uninfected subjects tested 21 days after the second-dose vaccination (D2uninf). All the subjects received BNT162b2 vaccination. D1inf NtAbT increased significantly with respect to BLinf against both B.1 and P.1 variants, with a fold-change significantly higher for P.1. D1inf NtAbT were significantly higher than D2uninf NtAbT, against B.1 and P.1. NtAbT against the two strains were highly correlated. P.1 NtAbT were significantly higher than B.1 NtAbT. This difference was significant for post-vaccination sera in infected and uninfected subjects. A single-dose BNT162b2 vaccination substantially boosted the NtAb response to both variants in the previously infected subjects. NtAb titers to B.1 and P.1 lineages were highly correlated, suggesting substantial cross-neutralization. Higher titers to the P.1 than to the B.1 strain were driven by the post-vaccination titers, highlighting that cross-neutralization can be enhanced by vaccination.
Dynamics of Silurian Plants as Response to Climate Changes
Authors: Pšenička Josef , Bek Jiří , Frýda Jiří , Žárský Viktor , Uhlířová Monika , Štorch Petr
Published: August 2021

The most ancient macroscopic plants fossils are Early Silurian cooksonioid sporophytes from the volcanic islands of the peri-Gondwanan palaeoregion (the Barrandian area, Prague Basin, Czech Republic). However, available palynological, phylogenetic and geological evidence indicates that the history of plant terrestrialization is much longer and it is recently accepted that land floras, producing different types of spores, already were established in the Ordovician Period. Here we attempt to correlate Silurian floral development with environmental dynamics based on our data from the Prague Basin, but also to compile known data on a global scale. Spore-assemblage analysis clearly indicates a significant and almost exponential expansion of trilete-spore producing plants starting during the Wenlock Epoch, while cryptospore-producers, which dominated until the Telychian Age, were evolutionarily stagnate. Interestingly cryptospore vs. trilete-spore producers seem to react differentially to Silurian glaciations—trilete-spore producing plants react more sensitively to glacial cooling, showing a reduction in species numbers. Both our own and compiled data indicate highly terrestrialized, advanced Silurian land-plant assemblage/flora types with obviously great ability to resist different dry-land stress conditions. As previously suggested some authors, they seem to evolve on different palaeo continents into quite disjunct specific plant assemblages, certainly reflecting the different geological, geographical and climatic conditions to which they were subject.
Challenges and Scientific Prospects of the Newest Generation of mRNA-Based Vaccines against SARS-CoV-2
Authors: Calina Daniela , Hernández Antonio F. , Hartung Thomas , Egorov Alexey M. , Izotov Boris Nikolaevich , Nikolouzakis Taxiarchis Konstantinos , Tsatsakis Aristidis , Vlachoyiannopoulos Panayiotis G. , Docea Anca Oana
Published: August 2021

In the context of the current COVID-19 pandemic, traditional, complex and lengthy methods of vaccine development and production would not have been able to ensure proper management of this global public health crisis. Hence, a number of technologies have been developed for obtaining a vaccine quickly and ensuring a large scale production, such as mRNA-based vaccine platforms. The use of mRNA is not a new concept in vaccine development but has leveraged on previous knowledge and technology. The great number of human resources and capital investements for mRNA vaccine development, along with the experience gained from previous studies on infectious diseases, allowed COVID-19 mRNA vaccines to be developed, conditionally approved and commercialy available in less than one year, thanks to decades of basic research. This review critically presents and discusses the COVID-19 mRNA vaccine-induced immunity, and it summarizes the most common anaphylactic and autoimmune adverse effects that have been identified until now after massive vaccination campaigns.
“Success Depends on Your Backbone”—About the Use of Polymers as Essential Materials Forming Orodispersible Films
Authors: Olechno Katarzyna , Basa Anna , Winnicka Katarzyna
Published: August 2021

Polymers constitute a group of materials having a wide-ranging impact on modern pharmaceutical technology. Polymeric components provide the foundation for the advancement of novel drug delivery platforms, inter alia orodispersible films. Orodispersible films are thin, polymeric scraps intended to dissolve quickly when put on the tongue, allowing them to be easily swallowed without the necessity of drinking water, thus eliminating the risk of choking, which is of great importance in the case of pediatric and geriatric patients. Polymers are essential excipients in designing orodispersible films, as they constitute the backbone of these drug dosage form. The type of polymer is of significant importance in obtaining the formulation of the desired quality. The polymers employed to produce orodispersible films must meet particular requirements due to their oral administration and have to provide adequate surface texture, film thickness, mechanical attributes, tensile and folding strength as well as relevant disintegration time and drug release to obtain the final product characterized by optimal pharmaceutical features. A variety of natural and synthetic polymers currently utilized in manufacturing of orodispersible films might be used alone or in a blend. The goal of the present manuscript was to present a review about polymers utilized in designing oral-dissolving films.