bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review
Authors: De Martinis Massimo , Allegra Alessandro , Sirufo Maria Maddalena , Tonacci Alessandro , Pioggia Giovanni , Raggiunti Martina , Ginaldi Lia , Gangemi Sebastiano
Published: August 2021

Vitamin D (VD) is essential for bone homeostasis, but it is also involved in pleiotropic effects on various organs and tissues. In adults, VD deficiency can cause or exacerbate osteoporosis and induce osteomalacia. However, every tissue and cell in the body has a VD receptor, including the brain, heart, stomach, pancreas, skin, gonads, and immune cells, and a deficiency may modify the function of these organs. Thus, the wide-ranging actions of VD help to explain why a reduction in VD amount has been correlated with numerous chronic diseases. In fact, VD deficiency increases the risk of osteoporosis and several other diseases and complications characterized by impaired bone metabolisms, such as autoimmune diseases, inflammatory bowel diseases, allergy, endocrinological diseases, hematological malignancies, and bone marrow transplantation. This review aims to investigate the link between VD deficiency, osteoporosis, and its concomitant diseases. Further epidemiological and mechanistic studies are necessary in order to ascertain the real role of hypovitaminosis in causing the reported diseases; however, adequate vitamin supplementation and restoration of metabolic normality could be useful for better management of these pathologies.
Targeting Cytokines, Pathogen-Associated Molecular Patterns, and Damage-Associated Molecular Patterns in Sepsis via Blood Purification
Authors: Moriyama Kazuhiro , Nishida Osamu
Published: August 2021

Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system.
PLGA/PLA-Based Long-Acting Injectable Depot Microspheres in Clinical Use: Production and Characterization Overview for Protein/Peptide Delivery
Authors: Butreddy Arun , Gaddam Rajendra Prasad , Kommineni Nagavendra , Dudhipala Narendar , Voshavar Chandrashekhar
Published: August 2021

Over the past few decades, long acting injectable (LAI) depots of polylactide-co-glycolide (PLGA) or polylactic acid (PLA) based microspheres have been developed for controlled drug delivery to reduce dosing frequency and to improve the therapeutic effects. Biopharmaceuticals such as proteins and peptides are encapsulated in the microspheres to increase their bioavailability and provide a long release period (days or months) with constant drug plasma concentration. The biodegradable and biocompatible properties of PLGA/PLA polymers, including but not limited to molecular weight, end group, lactide to glycolide ratio, and minor manufacturing changes, could greatly affect the quality attributes of microsphere formulations such as release profile, size, encapsulation efficiency, and bioactivity of biopharmaceuticals. Besides, the encapsulated proteins/peptides are susceptible to harsh processing conditions associated with microsphere fabrication methods, including exposure to organic solvent, shear stress, and temperature fluctuations. The protein/peptide containing LAI microspheres in clinical use is typically prepared by double emulsion, coacervation, and spray drying techniques. The purpose of this review is to provide an overview of the formulation attributes and conventional manufacturing techniques of LAI microspheres that are currently in clinical use for protein/peptides. Furthermore, the physicochemical characteristics of the microsphere formulations are deliberated.
GDF15 and Cardiac Cells: Current Concepts and New Insights
Authors: Rochette Luc , Dogon Geoffrey , Zeller Marianne , Cottin Yves , Vergely Catherine
Published: August 2021

Growth and differentiation factor 15 (GDF15) belongs to the transforming growth factor-β (TGF-β) superfamily of proteins. Glial-derived neurotrophic factor (GDNF) family receptor α-like (GFRAL) is an endogenous receptor for GDF15 detected selectively in the brain. GDF15 is not normally expressed in the tissue but is prominently induced by “injury”. Serum levels of GDF15 are also increased by aging and in response to cellular stress and mitochondrial dysfunction. It acts as an inflammatory marker and plays a role in the pathogenesis of cardiovascular diseases, metabolic disorders, and neurodegenerative processes. Identified as a new heart-derived endocrine hormone that regulates body growth, GDF15 has a local cardioprotective role, presumably due to its autocrine/paracrine properties: antioxidative, anti-inflammatory, antiapoptotic. GDF15 expression is highly induced in cardiomyocytes after ischemia/reperfusion and in the heart within hours after myocardial infarction (MI). Recent studies show associations between GDF15, inflammation, and cardiac fibrosis during heart failure and MI. However, the reason for this increase in GDF15 production has not been clearly identified. Experimental and clinical studies support the potential use of GDF15 as a novel therapeutic target (1) by modulating metabolic activity and (2) promoting an adaptive angiogenesis and cardiac regenerative process during cardiovascular diseases. In this review, we comment on new aspects of the biology of GDF15 as a cardiac hormone and show that GDF15 may be a predictive biomarker of adverse cardiac events.
Simultaneous Quantification and Speciation of Trace Metals in Paired Serum and CSF Samples by Size Exclusion Chromatography–Inductively Coupled Plasma–Dynamic Reaction Cell–Mass Spectrometry (SEC-DRC-ICP-MS)
Authors: Michalke Bernhard , Berthele Achim , Venkataramani Vivek
Published: August 2021

Background: Transition metals play a crucial role in brain metabolism: since they exist in different oxidation states they are involved in ROS generation, but they are also co-factors of enzymes in cellular energy metabolism or oxidative defense. Methods: Paired serum and cerebrospinal fluid (CSF) samples were analyzed for iron, zinc, copper and manganese as well as for speciation using SEC-ICP-DRC-MS. Brain extracts from Mn-exposed rats were additionally analyzed with SEC-ICP-DRC-MS. Results: The concentration patterns of transition metal size fractions were correlated between serum and CSF: Total element concentrations were significantly lower in CSF. Fe-ferritin was decreased in CSF whereas a LMW Fe fraction was relatively increased. The 400–600 kDa Zn fraction and the Cu-ceruloplasmin fraction were decreased in CSF, by contrast the 40–80 kDa fraction, containing Cu- and Zn-albumin, relatively increased. For manganese, the α-2-macroglobulin fraction showed significantly lower concentration in CSF, whereas the citrate Mn fraction was enriched. Results from the rat brain extracts supported the findings from human paired serum and CSF samples. Conclusions: Transition metals are strictly controlled at neural barriers (NB) of neurologic healthy patients. High molecular weight species are down-concentrated along NB, however, the Mn-citrate fraction seems to be less controlled, which may be problematic under environmental load.
Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer
Authors: Cao Thanh-Luu , Le Tuan-Anh , Hadadian Yaser , Yoon Jungwon
Published: August 2021

In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier’s law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.
Contribution of the Commensal Microflora to the Immunological Homeostasis and the Importance of Immune-Related Drug Development for Clinical Applications
Authors: Beutgen Vanessa M. , Schmelter Carsten , Pfeiffer Norbert , Grus Franz H.
Published: August 2021

Not long ago, self-reactive immune activity was considered as pathological trait. A paradigm shift has now led to the recognition of autoimmune processes as part of natural maintenance of molecular homeostasis. The immune system is assigned further roles beneath the defense against pathogenic organisms. Regarding the humoral immune system, the investigation of natural autoantibodies that are frequently found in healthy individuals has led to further hypotheses involving natural autoimmunity in other processes as the clearing of cellular debris or decrease in inflammatory processes. However, their role and origin have not been entirely clarified, but accumulating evidence links their formation to immune reactions against the gut microbiome. Antibodies targeting highly conserved proteins of the commensal microflora are suggested to show self-reactive properties, following the paradigm of the molecular mimicry. Here, we discuss recent findings, which demonstrate potential links of the commensal microflora to the immunological homeostasis and highlight the possible implications for various diseases. Furthermore, specific components of the immune system, especially antibodies, have become a focus of attention for the medical management of various diseases and provide attractive treatment options in the future. Nevertheless, the development and optimization of such macromolecules still represents a very time-consuming task, shifting the need to more medical agents with simple structural properties and low manufacturing costs. Synthesizing only the biologically active sites of antibodies has become of great interest for the pharmaceutical industry and offers a wide range of therapeutic application areas as it will be discussed in the present review article.
Long-Term Consequences of Adolescent Exposure to THC-Rich/CBD-Poor and CBD-Rich/THC-Poor Combinations: A Comparison with Pure THC Treatment in Female Rats
Authors: Gabaglio Marina , Zamberletti Erica , Manenti Cristina , Parolaro Daniela , Rubino Tiziana
Published: August 2021

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.
Analysis of Several Pathways for Efficient Killing of Prostate Cancer Stem Cells: A Central Role of NF-κB RELA
Authors: Witte Kaya E. , Pfitzenmaier Jesco , Storm Jonathan , Lütkemeyer Melanie , Wimmer Clara , Schulten Wiebke , Czaniera Nele , Geisler Marvin , Förster Christine , Wilkens Ludwig , Knabbe Cornelius , Mertzlufft Fritz , Kaltschmidt Barbara , am Esch Jan Schulte , Kaltschmidt Christian
Published: August 2021

Prostate cancer is a common cause of death worldwide. Here, we isolated cancer stem cells (CSCs) from four adenocarcinomas of the prostate (Gleason scores from 3 + 3 up to 4 + 5). CSCs were characterized by the expression of the stem cell markers TWIST, the epithelial cell adhesion molecule (EPCAM), the transcription factors SNAI1 (SNAIL) and SNAI2 (SLUG) and cancer markers such as CD44 and prominin-1 (CD133). All investigated CSC populations contained a fraction highly positive for aldehyde dehydrogenase (ALDH) function and displayed robust expressions of programmed cell death 1 (PD-1) ligands. Furthermore, we investigated immunotherapeutic approaches but had no success even with the clinically used PD-1 inhibitor pembrolizumab. In addition, we studied another death-inducing pathway via interferon gamma signaling and detected high-level upregulations of human leukocyte antigen A (HLA-A) and beta 2-microglobulin (B2M) with only moderate killing efficacy. To examine further killing mechanisms in prostate cancer stem cells (PCSCs), we analyzed NF-κB signaling. Surprisingly, two patient-specific populations of PCSCs were found: one with canonical NF-κB signaling and another one with blunted NF-κB activation, which can be efficiently killed by tumor necrosis factor (TNF). Thus, culturing of PCSCs and analysis of respective NF-κB induction potency after surgery might be a powerful tool for optimizing patient-specific treatment options, such as the use of TNF-inducing chemotherapeutics and/or NF-κB inhibitors.
Contemporary Approach to the Porosity of Dental Materials and Methods of Its Measurement
Authors: Sarna-Boś Katarzyna , Skic Kamil , Sobieszczański Jarosław , Boguta Patrycja , Chałas Renata
Published: August 2021

Porosity is an important parameter for characterizing the microstructure of solids that corresponds to the volume of the void space, which may contain fluid or air, over the total volume of the material. Many materials of natural and technically manufactured origin have a large number of voids in their internal structure, relatively small in size, compared to the characteristic dimensions of the body itself. Thus, porosity is an important feature of industrial materials, but also of biological ones. The porous structure affects a number of material properties, such as sorption capacity, as well as mechanical, thermal, and electrical properties. Porosity of materials is an important factor in research on biomaterials. The most popular materials used to rebuild damaged tooth tissues are composites and ceramics, whilst titanium alloys are used in the production of implants that replace the tooth root. Research indicates that the most comprehensive approach to examining such materials should involve an analysis using several complementary methods covering the widest possible range of pore sizes. In addition to the constantly observed increase in the resolution capabilities of devices, the development of computational models and algorithms improving the quality of the measurement signal remains a big challenge.
Eosinophil Count as Predictive Biomarker of Immune-Related Adverse Events (irAEs) in Immune Checkpoint Inhibitors (ICIs) Therapies in Oncological Patients
Authors: Giommoni Elisa , Giorgione Roberta , Paderi Agnese , Pellegrini Elisa , Gambale Elisabetta , Marini Andrea , Antonuzzo Andrea , Marconcini Riccardo , Roviello Giandomenico , Matucci-Cerinic Marco , Capaccioli David , Pillozzi Serena , Antonuzzo Lorenzo
Published: August 2021

Background: To date, no biomarkers are effective in predicting the risk of developing immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs). This study aims to evaluate the association between basal absolute eosinophil count (AEC) and irAEs during treatment with ICIs for solid tumors. Methods: We retrospectively evaluated 168 patients with metastatic melanoma (mM), renal cell carcinoma (mRCC), and non-small cell lung cancer (mNSCLC) receiving ICIs at our medical oncology unit. By combining baseline AEC with other clinical factors, we developed a mathematical model for predicting the risk of irAEs, which we validated in an external cohort of patients. Results: Median baseline AEC was 135/µL and patients were stratified into two groups accordingly; patients with high baseline AEC (>135/µL) were more likely to experience toxicity (p = 0.043) and have a better objective response rate (ORR) (p = 0.003). By constructing a covariance analysis model, it emerged that basal AEC correlated with the risk of irAEs (p < 0.01). Finally, we validated the proposed model in an independent cohort of 43 patients. Conclusions: Baseline AEC could be a predictive biomarker of ICI-related toxicity, as well as of response to treatment. The use of a mathematical model able to predict the risk of developing irAEs could be useful for clinicians for monitoring patients receiving ICIs.
Transcriptome Analysis of Hormone-and Cuticle-Related Genes in the Development Process of Deutonymph in Tetranychus urticae
Authors: Li Gang , Gu Xinyao , Gui Shunhua , Guo Jianjun , Yi Tianci , Jin Daochao
Published: August 2021

Tetranychus urticae is an important agricultural pest that feeds on more than 1100 plant species. To investigate gene expression network in development process of deutonymph, a comprehensive transcriptome analysis of different developmental time points of deutonymph in T. urticae was performed. Comparing with expression profile of 7 h, 309, 876, 2736, and 3432 differential expression genes were detected at time points 14 h, 21 h, 28 h, and 35 h, respectively. The expression dynamic analysis indicated that genes in hormone- (ecdysteroid and juvenile hormone) and cuticle- (chitin and cuticle proteins) related pathways were indispensable for development process in deutonymph. Among hormone related pathway genes, the ecdysteroid biosynthesis pathway genes were highly expressed at the growth period of development process, which is opposite to the expression patterns of juvenile hormone biosynthesis pathway genes. For cuticle related pathway genes, 13 chitinase genes were identified in the genome of T. urticae, and 8 chitinase genes were highly expressed in different time points of developmental process in the deutonymph of T. urticae. Additionally, 59 cuticle protein genes were identified from genome, and most of the cuticle protein genes were expressed in the molting period of developmental process in deutonymph. This study reveals critical genes involved in the development process of deutonymph and also provides comprehensive development transcriptome information for finding more molecular targets to control this pest.
Nutritional, Textural, and Sensory Quality of Aloe Vera Leaf Gel Powder Fortified Plain Cake
Authors: Singha Dhrubajyoti , Jubayer Md. Fahad , Devnath Kumkum , Akhter Delara , Ranganathan Thottiam Vasudevan , Rahman Md. Towhidur , Mazumder Md. Anisur Rahman
Published: August 2021

Aloe Vera leaves have great potential as an economic supplement with an adequate nutritional profile. The current study aimed to fortify plain (loaf) cakes with Aloe Vera leaf gel (AVG) powder. AVG was freeze-dried to produce Aloe Vera powder (ALP), and four plain (loaf) cakes were prepared with different proportions of ALP (0, 4, 6, and 8%). ALP contained significantly (p < 0.05) more protein (22.23 vs. 12.24), ash (19.83 vs. 0.64), and iron (175 vs. 3.05) than refined wheat flour (RWF). Along with total polyphenols and total flavonoids, ALP demonstrated good antioxidant activity. ALP-cakes and RWF-cakes were also evaluated for their nutritional and functional properties. The addition of 6 and 8% ALP to the formulation increased total polyphenols, total flavonoids, and antioxidant activity in plain (loaf) cakes. Hardness and chewiness increased in ALP-cakes but decreased in RWF-cakes, while cohesiveness and springiness decreased in ALP-cakes. In conclusion, the best formulation was a 4% ALP incorporated cake, and ALP can be supplemented in plain cakes at a rate of up to 8% to improve nutrient value. This is the first study to evaluate the quality characteristics of fortified plain (loaf) cakes using ALP.
Functional Outcomes with Facial Artery Musculo-Mucosal (FAMM) Flap and Dental Implants for Reconstruction of Floor of the Mouth and Tongue Defects in Oncologic Patients
Authors: Navarro Cuéllar Carlos , Tousidonis Rial Manuel , Antúnez-Conde Raúl , Agea Martínez Marc , Navarro Cuéllar Ignacio , Salmerón Escobar José Ignacio , Navarro Vila Carlos
Published: August 2021

Optimal functional outcomes in oncologic patients with squamous cell carcinoma (SCCA) of the tongue and floor of the mouth require good lingual mobility, adequate facial competence, the cheek suction effect and dental rehabilitation with osseointegrated implants. In this study, twenty-two oncologic patients who had been diagnosed with intraoral SCCA affecting the tongue and the floor of the mouth and who had undergone wide resection of the tumor and immediate reconstruction with an inferiorly pedicled FAMM flap and immediate osseointegrated implants were assessed. Lingual mobility, speech articulation, deglutition, implant success rate, mouth opening, and aesthetic results were evaluated. All patients were staged as T2 and the defect size ranged from 3.7 × 2.1 cm to 6.3 × 4.2 cm. A selective neck dissection was performed in all patients as part of their oncologic treatment, either electively or for node positive disease. Thirteen patients (59%) were diagnosed with node positive disease and underwent adjuvant radiotherapy. A total of 101 osseointegrated implants were placed for prosthetic rehabilitation and 8 implants were lost (7.9%), of which 7 received radiotherapy (87.5%). The implant success rate was 92.1%. Mouth opening was reported as normal in 19 patients (86.3%). Tongue tip elevation was reported as excellent in 19 patients (86.3%) and good in 3 patients (13.6%). Lingual protrusion was referred to as excellent in 15 patients (68.2%) and good in 6 patients (27.2%). Lateral excursion was reported as excellent in 14 patients (63.6%) and good in 7 patients (31.8%). In terms of speech articulation, 20 patients reported normal speech (90.9%). Regarding deglutition, 19 patients (86.3%) reported a regular diet while a soft diet was reported by 3 patients (13.7%). Aesthetic results were referred to as excellent in 17 patients (77.3%). FAMM flaps, immediate implants and fixed prostheses enable the functional rehabilitation of oncologic patients, optimizing aesthetics and functional outcomes even in patients undergoing irradiation, thus returning oncologic patients to an excellent quality of life.
Age as a Prognostic Factor in Patients with Ewing Sarcoma—The Polish Sarcoma Group Experience
Authors: Jagodzińska-Mucha Paulina , Raciborska Anna , Koseła-Paterczyk Hanna , Kozak Katarzyna , Bilska Katarzyna , Świtaj Tomasz , Falkowski Sławomir , Dawidowska Anna , Rutkowski Piotr , Ługowska Iwona
Published: August 2021

Ewing sarcoma (ES) is a rare and aggressive disease that requires multidisciplinary treatment with the use of chemotherapy, radiotherapy, and surgery. Our retrospective study aimed to analyze the prognostic factors and treatment results in different age groups of patients. Between 1998 and 2018, 569 patients with ES were treated in two referral centers. The patients were divided into four age groups (≤10 years; 11–18 years; 19–25, and >25). The treatment results and prognostic factors were assessed for each group. For statistical analyses, we used the Chi2 test, the Kaplan–Meier estimator with a log-rank test, and the multivariate Cox model. Five-year overall survival (OS) rate was 56%. In the age subgroups: ≤10 years, 11–18 years, 19–25 years, and >25 years, the 5-year OS rates were 75%, 58%, 41%, and 52%, respectively. Favorable prognostic factors: female gender (p = 0.024), non-axial localization (p = 0.005), VIDE regimen (p < 0.001), and surgery as a local treatment (p < 0.001) dominated in the group ≤10 years. In multivariate analysis, male (HR = 1.53), axial localization (HR = 1.46), M1 status at presentation (HR = 2.64), and age > 10 years (HR = 2.29) were associated with shorter OS. The treatment results in ES are significantly better in children aged ≤10 years; the challenge is to provide therapy for adolescents and young adults. The diagnostics and treatment of ES patients must be provided in referral centers.
Living in the Southern Hemisphere: Metabolic Syndrome and Its Components in Amazonian Riverine Populations
Authors: Arrifano Gabriela P. , Alvarez-Leite Jacqueline I. , Macchi Barbarella M. , Campos Núbia F. S. S. , Augusto-Oliveira Marcus , Santos-Sacramento Letícia , Lopes-Araújo Amanda , Souza-Monteiro José Rogério , Alburquerque-Santos Raquel , do Nascimento José Luiz M. , Santos Sidney , Ribeiro-dos-Santos Ândrea , Oriá Reinaldo B. , Crespo-Lopez Maria Elena
Published: August 2021

The metabolic syndrome (MetS) epidemic is a global challenge. Although developing countries (including Brazil, India, and South Africa) present a higher proportion of deaths by cardiovascular diseases than developed countries, most of our knowledge is from these developed countries. Amazonian riverine populations (ARP), as well as other vulnerable populations of the Southern Hemisphere, share low-income and traditional practices, among other features. This large cross-sectional study of ARP (n = 818) shows high prevalence of hypertension (51%) and obesity (23%). MetS was diagnosed in 38% of participants (especially in women and 60–69 years-old individuals) without the influence of ancestry. Only 7–8% of adults had no cardio-metabolic abnormalities related to MetS. Atherogenic dyslipidemia (low HDL-cholesterol) was generally observed, including in individuals without MetS. Still, slight differences were detected between settings with a clear predominance of hypertension in Tucuruí. Hypotheses on possible genetic influence and factors (nutrition transition and environmental pollutants -mercury) are proposed for future studies. Moreover, a roadmap to MetS progression based on the most prevalent components is provided for the development of tailored interventions in the Amazon (initially, individuals would present low HDL-cholesterol levels, later progressing to increased blood pressure characterizing hypertension, and ultimately reaching MetS with obesity). Our alarming results support the need to improve our knowledge on these vulnerable populations.
Low-Intensity and Short-Duration Continuous Cervical Transcutaneous Spinal Cord Stimulation Intervention Does Not Prime the Corticospinal and Spinal Reflex Pathways in Able-Bodied Subjects
Authors: Sasaki Atsushi , de Freitas Roberto M. , Sayenko Dimitry G. , Masugi Yohei , Nomura Taishin , Nakazawa Kimitaka , Milosevic Matija
Published: August 2021

Cervical transcutaneous spinal cord stimulation (tSCS) has been utilized in applications for improving upper-limb sensory and motor function in patients with spinal cord injury. Although therapeutic effects of continuous cervical tSCS interventions have been reported, neurophysiological mechanisms remain largely unexplored. Specifically, it is not clear whether sub-threshold intensity and 10-min duration continuous cervical tSCS intervention can affect the central nervous system excitability. Therefore, the purpose of this study was to investigate effects of sub-motor-threshold 10-min continuous cervical tSCS applied at rest on the corticospinal and spinal reflex circuit in ten able-bodied individuals. Neurophysiological assessments were conducted to investigate (1) corticospinal excitability via transcranial magnetic stimulation applied on the primary motor cortex to evoke motor-evoked potentials (MEPs) and (2) spinal reflex excitability via single-pulse tSCS applied at the cervical level to evoke posterior root muscle (PRM) reflexes. Measurements were recorded from multiple upper-limb muscles before, during, and after the intervention. Our results showed that low-intensity and short-duration continuous cervical tSCS intervention applied at rest did not significantly affect corticospinal and spinal reflex excitability. The stimulation duration and/or intensity, as well as other stimulating parameters selection, may therefore be critical for inducing neuromodulatory effects during cervical tSCS.
Prognostic Value of Cardiac Troponin and Risk Assessment in Pediatric Supraventricular Tachycardia
Authors: Yen Chieh-Ching , Chen Shou-Yen , Chaou Chung-Hsien , Wang Chih-Kai , Yeh Hsin-Tzu , Ng Chip-Jin
Published: August 2021

Cardiac troponin I (cTnI) elevation is common in an acute episode of supraventricular tachycardia (SVT). However, there is limited evidence regarding the prognostic value of cTnI and the predictors of SVT recurrence in pediatric patients. We screened the electronic medical records of all pediatric patients presenting to the emergency departments at five Taiwanese hospitals from 1 January 2010 to 31 May 2021. Our primary outcomes were the occurrence of major adverse cardiac events (MACEs) during the follow-up period and 30-day SVT recurrence. A total of 112 patients were included in our study. Of these, 29 (25.9%) patients had positive cTnI values. Patients with cTnI elevation had significantly more complaints of dyspnea (27.6% vs. 7.2%, p = 0.008) and gastrointestinal discomfort (24.1% vs. 4.8%, p = 0.006). There were significantly more intensive care unit admissions (41.4% vs. 16.9%, p = 0.007) among the cTnI-positive group. One MACE was found in the cTnI-negative group. For 30-day SVT recurrence, the cTnI-positive group had a higher recurrence rate, without a statistically significant difference (20.7% vs. 7.2%, p = 0.075). Multivariable logistic regression analysis showed hypotension as an independent predictor of 30-day SVT recurrence (OR = 4.98; Cl 1.02–24.22; p = 0.047). Troponin had low value for predicting the outcomes of pediatric patients with SVT. The only significant predictor for recurrent SVT was initial hypotension.
Factors Associated with Increased Neuroretinal Rim Thickness Measured Based on Bruch’s Membrane Opening-Minimum Rim Width after Trabeculectomy
Authors: Park Do-Young , Cha Soon-Cheol
Published: August 2021

Purpose: To investigate the factors associated with an increase in the neuroretinal rim (NRR) thickness measured based on Bruch’s membrane opening-minimum rim width (BMO-MRW) after trabeculectomy in patients with primary open-angle glaucoma (POAG). Methods: We analyzed the BMO-MRW using spectral-domain optical coherence tomography (SD-OCT) of patients with POAG who underwent a trabeculectomy for uncontrolled intraocular pressure (IOP) despite maximal IOP reduction treatment. The BMO-MRW was measured before and after trabeculectomy in patients with POAG. Demographic and systemic factors, ocular factors, pre- and post-operative IOP, and visual field parameters were collected, together with SD-OCT measurements. A regression analysis was performed to investigate the factors that affected the change in the BMO-MRW after the trabeculectomy. Results: Forty-four eyes of 44 patients were included in the analysis. The IOP significantly decreased from a preoperative 27.0 mmHg to a postoperative 10.5 mmHg. The mean interval between the trabeculectomy and the date of post-operative SD-OCT measurement was 3.3 months. The global and sectoral BMO-MRW significantly increased after trabeculectomy, whereas the peripapillary retinal nerve fiber layer thickness did not show a difference between before and after the trabeculectomy. Younger age and a greater reduction in the IOP after the trabeculectomy were significantly associated with the increase in the BMO-MRW after trabeculectomy. Conclusions: The NRR thickness measured based on the BMO-MRW increased with decreasing IOP after trabeculectomy, and the increase in the BMO-MRW was associated with the young age of the patients and greater reduction in the IOP after trabeculectomy. Biomechanically, these suggest that the NRR comprises cells and substances that sensitively respond to changes in the IOP and age.
Improved Visibility of Early Gastric Cancer after Successful Helicobacter pylori Eradication with Image-Enhanced Endoscopy: A Multi-Institutional Study Using Video Clips
Authors: Matsumura Shinya , Dohi Osamu , Yamada Nobuhisa , Harusato Akihito , Yasuda Takeshi , Yoshida Takuma , Ishida Tsugitaka , Azuma Yuka , Kitae Hiroaki , Doi Toshifumi , Hirose Ryohei , Inoue Ken , Yoshida Naohisa , Kamada Kazuhiro , Uchiyama Kazuhiko , Takagi Tomohisa , Ishikawa Takeshi , Konishi Hideyuki , Morinaga Yukiko , Kishimoto Mitsuo , Yagi Nobuaki , Naito Yuji , Itoh Yoshito
Published: August 2021

The visibility and diagnostic accuracy of early gastric cancer (EGC) after Helicobacter pylori (HP) eradication have been reported to improve using image-enhanced endoscopy (IEE) compared with white light imaging (WLI). The present study clarified the appropriate IEE for the detection and diagnosis of EGC in clinical settings. This prospective and cross-sectional study evaluated the visibility of EGC and endoscopic findings of gastric mucosa after successful HP eradication (n = 31) using videos with WLI and IEE. Three endoscopists evaluated high-definition videos in a randomized order. The mean visibility scores (MVSs) on linked color imaging (LCI) for atrophic border, intestinal metaplasia, map-like redness, and EGC were the highest among each modality (3.87 ± 0.34, 3.82 ± 0.49, 3.87 ± 0.50, and 3.35 ± 0.92, respectively). The MVSs with blue laser imaging (BLI) were highest for magnifying view of the demarcation line (DL), microsurface pattern (MSP), and microvascular pattern (MVP) for EGC (3.77 ± 0.49, 3.94 ± 0.25, and 3.92 ± 0.34, respectively). LCI had the highest visibility among findings of gastric mucosa and EGC after HP eradication, and BLI had the highest visibility of MVP, MSP, and DL in magnifying observation. These results suggest that LCI observation in the entire stomach and further magnifying BLI are the best methods for detecting and diagnosing EGCs after HP eradication, respectively.
Post-Stroke Psychiatric and Cognitive Symptoms in West Asia, South Asia and Africa: A Systematic Review and Meta-Analysis
Authors: Mahadevan Sangeetha , Chan Moon Fai , Moghadas Marzieh , Shetty Maithili , Burke David T. , Al-Rasadi Khalid , Al-Adawi Samir
Published: August 2021

Recent research has shown that the prevalence of stroke incidents and the number of survivors in developing countries surpass those from developed countries. This study aimed to enumerate the prevalence of post-stroke psychiatric and cognitive symptoms among stroke survivors from West and South Asia and Africa through a systematic review and meta-analysis. Data from each country was systematically acquired from five major databases (PsycINFO, Web of Science, Scopus, PubMed/Medline, and Google Scholar (for any missing articles and grey literature)). Meta-analytic techniques were then used to estimate the prevalence of various post-stoke psychiatric and cognitive symptoms. A total of 36 articles were accrued from 11 countries, of which 25 were evaluated as part of the meta-analysis. The pooled prevalence of post-stroke depression as per the Hospital Anxiety and Depression Scale (HADS), Hamilton Depression Rating Scale, Patient Health Questionnaire, Schedules for Clinical Assessment in Neuropsychiatry (SCAN), Geriatric Depression Scale, and the Montgomery–Asberg Depression Rating Scale ranged from 28.00 to 50.24%. Pooled prevalence of post-stroke anxiety based on the HADS and SCAN was 44.19% and 10.96%, respectively. The pooled prevalence of post-stroke cognitive impairment as per the Mini-Mental Status Examination was 16.76%. This present review has suggested that both psychiatric and cognitive symptoms are common among stroke survivors. Concerted efforts are needed to institute robust studies using culturally sensitive measures to contemplate mechanisms that address the unmet needs of this vulnerable population.
Clinical Relevance of Immersive Virtual Reality in the Assessment and Treatment of Addictive Disorders: A Systematic Review and Future Perspective
Authors: Langener Simon , Van Der Nagel Joanne , van Manen Jeannette , Markus Wiebren , Dijkstra Boukje , De Fuentes-Merillas Laura , Klaassen Randy , Heitmann Janika , Heylen Dirk , Schellekens Arnt
Published: August 2021

(1) Background: Virtual reality (VR) has been investigated in a variety of psychiatric disorders, including addictive disorders (ADs); (2) Objective: This systematic review evaluates the current evidence of immersive VR (using head-mounted displays) in the clinical assessment and treatment of ADs; (3) Method: PubMed and PsycINFO were queried for publications up to November 2020; (4) Results: We screened 4519 titles, 114 abstracts and 85 full-texts, and analyzed 36 articles regarding the clinical assessment (i.e., diagnostic and prognostic value; n = 19) and treatment (i.e., interventions; n = 17) of ADs. Though most VR assessment studies (n = 15/19) showed associations between VR-induced cue-reactivity and clinical parameters, only two studies specified diagnostic value. VR treatment studies based on exposure therapy showed no or negative effects. However, other VR interventions like embodied and aversive learning paradigms demonstrated positive findings. The overall study quality was rather poor; (5) Conclusion: Though VR in ADs provides ecologically valid environments to induce cue-reactivity and provide new treatment paradigms, the added clinical value in assessment and therapy remains to be elucidated before VR can be applied in clinical care. Therefore, future work should investigate VR efficacy in randomized clinical trials using well-defined clinical endpoints.
Changes in the Proteome Profile of People Achieving Remission of Type 2 Diabetes after Bariatric Surgery
Authors: Iqbal Zohaib , Fachim Helene A. , Gibson J. Martin , Baricevic-Jones Ivona , Campbell Amy E. , Geary Bethany , Donn Rachelle P. , Hamarashid Dashne , Syed Akheel , Whetton Anthony D. , Soran Handrean , Heald Adrian H.
Published: August 2021

Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass (n = 7) or sleeve gastrectomy (n = 3). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was done on samples taken at 4 months before (baseline) and 6 and 12 months after BS. Four hundred sixty-seven proteins were quantified by SWATH-MS. Principal component analysis resolved samples from distinct time points after selection of key discriminatory proteins: 25 proteins were differentially expressed between baseline and 6 months post-surgery; 39 proteins between baseline and 12 months. Eight proteins (SHBG, TF, PRG4, APOA4, LRG1, HSPA4, EPHX2 and PGLYRP) were significantly different to baseline at both 6 and 12 months post-surgery. The panel of proteins identified as consistently different included peptides related to insulin sensitivity (SHBG increase), systemic inflammation (TF and HSPA4—both decreased) and lipid metabolism (APOA4 decreased). We found significant changes in the proteome for eight proteins at 6- and 12-months post-BS, and several of these are key components in metabolic and inflammatory pathways. These may represent potential biomarkers of remission of T2DM.
GDF-15 Predicts In-Hospital Mortality of Critically Ill Patients with Acute Kidney Injury Requiring Continuous Renal Replacement Therapy: A Multicenter Prospective Study
Authors: Lim Jeong-Hoon , Jeon Yena , Ahn Ji-Sun , Kim Sejoong , Kim Dong Ki , Lee Jung Pyo , Ryu Dong-Ryeol , Seong Eun Young , Ahn Shin Young , Baek Seon Ha , Jung Hee-Yeon , Choi Ji-Young , Park Sun-Hee , Kim Chan-Duck , Kim Yong-Lim , Cho Jang-Hee
Published: August 2021

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine. This study evaluated the association between GDF-15 and in-hospital mortality among patients with severe acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). Among the multicenter prospective CRRT cohort between 2017 and 2019, 66 patients whose blood sample was available were analyzed. Patients were divided into three groups according to the GDF-15 concentrations. The median GDF-15 level was 7865.5 pg/mL (496.9 pg/mL in the healthy control patients). Baseline characteristics were not different among tertile groups except the severity scores and serum lactate level, which were higher in the third tertile. After adjusting for confounding factors, the patients with higher GDF-15 had significantly increased risk of mortality (second tertile: adjusted hazards ratio [aHR], 3.67; 95% confidence interval [CI], 1.05–12.76; p = 0.041; third tertile: aHR, 6.81; 95% CI, 1.98–23.44; p = 0.002). Furthermore, GDF-15 predicted in-hospital mortality (area under the curve, 0.710; 95% CI, 0.585–0.815) better than APACHE II and SOFA scores. Serum GDF-15 concentration was elevated in AKI patients requiring CRRT, higher in more severe patients. GDF-15 is a better independent predictor for in-hospital mortality of critically ill AKI patients than the traditional risk scoring system such as APACHE II and SOFA scores.
An Iterative Algorithm for Semisupervised Classification of Hotspots on Bone Scintigraphies of Patients with Prostate Cancer
Authors: Providência Laura , Domingues Inês , Santos João
Published: August 2021

Prostate cancer (PCa) is the second most diagnosed cancer in men. Patients with PCa often develop metastases, with more than 80% of this metastases occurring in bone. The most common imaging technique used for screening, diagnosis and follow-up of disease evolution is bone scintigraphy, due to its high sensitivity and widespread availability at nuclear medicine facilities. To date, the assessment of bone scans relies solely on the interpretation of an expert physician who visually assesses the scan. Besides this being a time consuming task, it is also subjective, as there is no absolute criteria neither to identify bone metastases neither to quantify them by a straightforward and universally accepted procedure. In this paper, a new algorithm for the false positives reduction of automatically detected hotspots in bone scintigraphy images is proposed. The motivation relies in the difficulty of building a fully annotated database. In this way, our algorithm is a semisupervised method that works in an iterative way. The ultimate goal is to provide the physician with a fast, precise and reliable tool to quantify bone scans and evaluate disease progression and response to treatment. The algorithm is tested in a set of bone scans manually labeled according to the patient’s medical record. The achieved classification sensitivity, specificity and false negative rate were 63%, 58% and 37%, respectively. Comparison with other state-of-the-art classification algorithms shows superiority of the proposed method.
Classification of Geometric Forms in Mosaics Using Deep Neural Network
Authors: Ghosh Mridul , Obaidullah Sk Md , Gherardini Francesco , Zdimalova Maria
Published: August 2021

The paper addresses an image processing problem in the field of fine arts. In particular, a deep learning-based technique to classify geometric forms of artworks, such as paintings and mosaics, is presented. We proposed and tested a convolutional neural network (CNN)-based framework that autonomously quantifies the feature map and classifies it. Convolution, pooling and dense layers are three distinct categories of levels that generate attributes from the dataset images by introducing certain specified filters. As a case study, a Roman mosaic is considered, which is digitally reconstructed by close-range photogrammetry based on standard photos. During the digital transformation from a 2D perspective view of the mosaic into an orthophoto, each photo is rectified (i.e., it is an orthogonal projection of the real photo on the plane of the mosaic). Image samples of the geometric forms, e.g., triangles, squares, circles, octagons and leaves, even if they are partially deformed, were extracted from both the original and the rectified photos and originated the dataset for testing the CNN-based approach. The proposed method has proved to be robust enough to analyze the mosaic geometric forms, with an accuracy higher than 97%. Furthermore, the performance of the proposed method was compared with standard deep learning frameworks. Due to the promising results, this method can be applied to many other pattern identification problems related to artworks.
Hue-Preserving Saturation Improvement in RGB Color Cube
Authors: Inoue Kohei , Jiang Minyao , Hara Kenji
Published: August 2021

This paper proposes a method for improving saturation in the context of hue-preserving color image enhancement. The proposed method handles colors in an RGB color space, which has the form of a cube, and enhances the contrast of a given image by histogram manipulation, such as histogram equalization and histogram specification, of the intensity image. Then, the color corresponding to a target intensity is determined in a hue-preserving manner, where a gamut problem should be taken into account. We first project any color onto a surface in the RGB color space, which bisects the RGB color cube, to increase the saturation without a gamut problem. Then, we adjust the intensity of the saturation-enhanced color to the target intensity given by the histogram manipulation. The experimental results demonstrate that the proposed method achieves higher saturation than that given by related methods for hue-preserving color image enhancement.