bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulation/Non-Regulation/Dys-Regulation of Health Behavior, Psychological Reactance, and Health of University Undergraduate Students
Authors: Pachón-Basallo Mónica , de la Fuente Jesús , Gonzáles-Torres María Carmen
Published: April 2021

The Self-Regulation vs. External-Regulation Theory (2017) has postulated a continuum of regulation/non-regulation/dys-regulation that is present both in the individual and in the individual’s context. This gives rise to a behavioral heuristic that can predict and explain other health-related variables, such as psychological reactance and student health. On a voluntary basis, 269 university students completed validated questionnaires on variables of regulation, reactance and health. Using an ex post facto design, we performed correlational analysis and structural linear regression to build a structural equations model (SEM) with acceptable statistical values. The results showed various predicted relationships: self-regulation was associated with and positively predicted self-regulated health behavior; external health-regulating contexts were associated with and positively predicted self-regulated health behavior; non-regulatory and dysregulatory contexts negatively predicted self-regulated health behavior and students’ health itself, as well as positively predicting psychological reactance behavior. Implications are established for explaining variability in general and health-related self-regulation, as well as for intervening in these variables in health programs.
Detecting and Analyzing Urban Centers Based on the Localized Contour Tree Method Using Taxi Trajectory Data: A Case Study of Shanghai
Authors: Sun Mengqi , Fan Hongchao
Published: April 2021

Urban structure is of vital importance to urban planning, transportation, economics and other applications. Since detecting and analyzing urban centers is crucial for understanding urban structure, a large number of studies on urban center extraction have been performed. In this paper, we propose an analysis framework to identify urban centers by using taxi trajectory data. The proposed approach differs from previous methods by employing a novel way to simulate taxi trajectory data with the topographic surface. We extracted pick-up and drop-off spots from taxi trajectory data and employed the localized contour tree method to delineate the boundaries and hierarchies of urban centers. The experiments show that the proposed method can successfully detect urban centers and analyze their temporal patterns in different periods in Shanghai, China.
Effects of Lifestyle Intervention in Tissue-Specific Lipidomic Profile of Formerly Obese Mice
Authors: Dahdah Norma , Gonzalez-Franquesa Alba , Samino Sara , Gama-Perez Pau , Herrero Laura , Perales José Carlos , Yanes Oscar , Malagón Maria Del Mar , Garcia-Roves Pablo Miguel
Published: April 2021

Lipids are highly diverse in their composition, properties and distribution in different biological entities. We aim to establish the lipidomes of several insulin-sensitive tissues and to test their plasticity when divergent feeding regimens and lifestyles are imposed. Here, we report a proton nuclear magnetic resonance (1H-NMR) study of lipid abundance across 4 tissues of C57Bl6J male mice that includes the changes in the lipid profile after every lifestyle intervention. Every tissue analysed presented a specific lipid profile irrespective of interventions. Glycerolipids and fatty acids were most abundant in epididymal white adipose tissue (eWAT) followed by liver, whereas sterol lipids and phosphoglycerolipids were highly enriched in hypothalamus, and gastrocnemius had the lowest content in all lipid species compared to the other tissues. Both when subjected to a high-fat diet (HFD) and after a subsequent lifestyle intervention (INT), the lipidome of hypothalamus showed no changes. Gastrocnemius and liver revealed a pattern of increase in content in many lipid species after HFD followed by a regression to basal levels after INT, while eWAT lipidome was affected mainly by the fat composition of the administered diets and not their caloric density. Thus, the present study demonstrates a unique lipidome for each tissue modulated by caloric intake and dietary composition.
Brain Region-Dependent Effects of Neuropeptide Y on Conditioned Social Fear and Anxiety-Like Behavior in Male Mice
Authors: Kornhuber Johannes , Zoicas Iulia
Published: April 2021

Neuropeptide Y (NPY) has anxiolytic-like effects and facilitates the extinction of cued and contextual fear in rodents. We have previously shown that the intracerebroventricular administration of NPY reduces the expression of social fear in a mouse model of social fear conditioning (SFC). In the present study, we aimed to identify the brain regions that mediate these effects of NPY. We show that NPY (0.1 nmol/0.2 µL/side) reduces the expression of SFC-induced social fear in a brain-region-dependent manner. In more detail, NPY reduced the expression of social fear when administered into the dorsolateral septum (DLS) and central amygdala (CeA), but not when administered into the dorsal hippocampus (DH), medial amygdala (MeA) and basolateral amygdala (BLA). We also investigated whether the reduced expression of social fear might partly be due to a reduced anxiety-like behavior, and showed that NPY exerted anxiolytic-like effects when administered into the DH, DLS, CeA and BLA, but not when administered into the MeA. This study identifies the DLS and the CeA as brain regions mediating the effects of NPY on the expression of social fear and suggests that partly distinct neural circuitries mediate the effects of NPY on the expression of social fear and on anxiety-like behavior.
A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors
Authors: Angeloni Benedetta , Bigi Rachele , Bellucci Gianmarco , Mechelli Rosella , Ballerini Chiara , Romano Carmela , Morena Emanuele , Pellicciari Giulia , Reniè Roberta , Rinaldi Virginia , Buscarinu Maria Chiara , Romano Silvia , Ristori Giovanni , Salvetti Marco
Published: April 2021

Multiple sclerosis is a complex, multifactorial, dysimmune disease prevalent in women. Its etiopathogenesis is extremely intricate, since each risk factor behaves as a variable that is interconnected with others. In order to understand these interactions, sex must be considered as a determining element, either in a protective or pathological sense, and not as one of many variables. In particular, sex seems to highly influence immune response at chromosomal, epigenetic, and hormonal levels. Environmental and genetic risk factors cannot be considered without sex, since sex-based immunological differences deeply affect disease onset, course, and prognosis. Understanding the mechanisms underlying sex-based differences is necessary in order to develop a more effective and personalized therapeutic approach.
Chronically Elevated Exogenous Glucose Elicits Antipodal Effects on the Proteome Signature of Differentiating Human iPSC-Derived Pancreatic Progenitors
Authors: Ghila Luiza , Legøy Thomas Aga , Mathisen Andreas Frøslev , Abadpour Shadab , Paulo Joao A. , Scholz Hanne , Ræder Helge , Chera Simona
Published: April 2021

The past decade revealed that cell identity changes, such as dedifferentiation or transdifferentiation, accompany the insulin-producing β-cell decay in most diabetes conditions. Mapping and controlling the mechanisms governing these processes is, thus, extremely valuable for managing the disease progression. Extracellular glucose is known to influence cell identity by impacting the redox balance. Here, we use global proteomics and pathway analysis to map the response of differentiating human pancreatic progenitors to chronically increased in vitro glucose levels. We show that exogenous high glucose levels impact different protein subsets in a concentration-dependent manner. In contrast, regardless of concentration, glucose elicits an antipodal effect on the proteome landscape, inducing both beneficial and detrimental changes in regard to achieving the desired islet cell fingerprint. Furthermore, we identified that only a subgroup of these effects and pathways are regulated by changes in redox balance. Our study highlights a complex effect of exogenous glucose on differentiating pancreas progenitors characterized by a distinct proteome signature.
Passive Immunoprophylaxis against Respiratory Syncytial Virus in Children: Where Are We Now?
Authors: Rocca Alessandro , Biagi Carlotta , Scarpini Sara , Dondi Arianna , Vandini Silvia , Pierantoni Luca , Lanari Marcello
Published: April 2021

Respiratory syncytial virus (RSV) represents the main cause of acute respiratory tract infections in children worldwide and is the leading cause of hospitalization in infants. RSV infection is a self-limiting condition and does not require antibiotics. However hospitalized infants with clinical bronchiolitis often receive antibiotics for fear of bacteria coinfection, especially when chest radiography is performed due to similar radiographic appearance of infiltrate and atelectasis. This may lead to unnecessary antibiotic prescription, additional cost, and increased risk of development of resistance. Despite the considerable burden of RSV bronchiolitis, to date, only symptomatic treatment is available, and there are no commercially available vaccines. The only licensed passive immunoprophylaxis is palivizumab. The high cost of this monoclonal antibody (mAb) has led to limiting its prescription only for high-risk children: infants with chronic lung disease, congenital heart disease, neuromuscular disorders, immunodeficiencies, and extreme preterm birth. Nevertheless, it has been shown that the majority of hospitalized RSV-infected children do not fully meet the criteria for immune prophylaxis. While waiting for an effective vaccine, passive immune prophylaxis in children is mandatory. There are a growing number of RSV passive immunization candidates under development intended for RSV prevention in all infants. In this review, we describe the state-of-the-art of palivizumab’s usage and summarize the clinical and preclinical trials regarding the development of mAbs with a better cost-effectiveness ratio.
Correction: Tyagi, C., et al. Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem. International Journal of Molecular Sciences, 2019, 20, 4268
Authors: Tyagi Chetna , Marik Tamás , Vágvölgyi Csaba , Kredics László , Ötvös Ferenc
Published: April 2021

The authors wish to make the following corrections to this paper [...]
Skin Pigmentation Abnormalities and Their Possible Relationship with Skin Aging
Authors: Lee Ai-Young
Published: April 2021

Skin disorders showing abnormal pigmentation are often difficult to manage because of their uncertain etiology or pathogenesis. Abnormal pigmentation is a common symptom accompanying aging skin. The association between skin aging and skin pigmentation abnormalities can be attributed to certain inherited disorders characterized by premature aging and abnormal pigmentation in the skin and some therapeutic modalities effective for both. Several molecular mechanisms, including oxidative stress, mitochondrial DNA mutations, DNA damage, telomere shortening, hormonal changes, and autophagy impairment, have been identified as involved in skin aging. Although each of these skin aging-related mechanisms are interconnected, this review examined the role of each mechanism in skin hyperpigmentation or hypopigmentation to propose the possible association between skin aging and pigmentation abnormalities.
Thyroid Cancer Stem-Like Cells: From Microenvironmental Niches to Therapeutic Strategies
Authors: Grassi Elisa Stellaria , Ghiandai Viola , Persani Luca
Published: April 2021

Thyroid cancer (TC) is the most common endocrine malignancy. Recent progress in thyroid cancer biology revealed a certain degree of intratumoral heterogeneity, highlighting the coexistence of cellular subpopulations with distinct proliferative capacities and differentiation abilities. Among those subpopulations, cancer stem-like cells (CSCs) are hypothesized to drive TC heterogeneity, contributing to its metastatic potential and therapy resistance. CSCs principally exist in tumor areas with specific microenvironmental conditions, the so-called stem cell niches. In particular, in thyroid cancer, CSCs’ survival is enhanced in the hypoxic niche, the immune niche, and some areas with specific extracellular matrix composition. In this review, we summarize the current knowledge about thyroid CSCs, the tumoral niches that allow their survival, and the implications for TC therapy.
Appendectomy and Non-Typhoidal Salmonella Infection: A Population-Based Matched Cohort Study
Authors: Wu Den-Ko , Yang Kai-Shan , Wei James Cheng-Chung , Yip Hei-Tung , Chang Renin , Hung Yao-Min , Hung Chih-Hsin
Published: April 2021

The potential association between appendectomy and non-typhoidal Salmonella (NTS) infection has not been elucidated. We hypothesized that appendectomy may be associated with gut vulnerability to NTS. The data were retrospectively collected from the Taiwan National Health Insurance Research Database to describe the incidence rates of NTS infection requiring hospital admission among patients with and without an appendectomy. A total of 208,585 individuals aged ≥18 years with an appendectomy were enrolled from January 2000 to December 2012, and compared with a control group of 208,585 individuals who had never received an appendectomy matched by propensity score (1:1) by index year, age, sex, occupation, and comorbidities. An appendectomy was defined by the International Classification of Diseases, Ninth Revision, Clinical Modification Procedure Codes. The main outcome was patients who were hospitalized for NTS. Cox proportional hazards models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Two sensitivity analyses were conducted for cross-validation. Of the 417,170 participants (215,221 (51.6%) male), 208,585 individuals (50.0%) had an appendectomy, and 112 individuals developed NTS infection requiring hospitalization. In the fully adjusted multivariable Cox proportional hazards regression model, the appendectomy group had an increased risk of NTS infection (adjusted HR (aHR), 1.61; 95% CI, 1.20–2.17). Females and individuals aged 18 to 30 years with a history of appendectomy had a statistically higher risk of NTS than the control group (aHR, 1.92; 95% CI, 1.26–2.93 and aHR, 2.67; 95% CI, 1.41–5.07). In this study, appendectomy was positively associated with subsequent hospitalization for NTS. The mechanism behind this association remains uncertain and needs further studies to clarify the interactions between appendectomy and NTS.
The Prognostic Value of Pain Phenotyping in Relation to Treatment Outcomes in Patients with Axial Spondyloarthritis Treated in Clinical Practice: A Prospective Cohort Study
Authors: Andreasen Rikke Asmussen , Kristensen Lars Erik , Egstrup Kenneth , Baraliakos Xenofon , Strand Vibeke , Horn Hans Christian , Wied Jimmi , Schiøttz-Christensen Berit , Aalykke Claus , Jensen Hansen Inger Marie , Ellingsen Torkell , Christensen Robin
Published: April 2021

Despite the control of inflammation, many patients with axial spondyloarthritis (axSpA) still report pain as a significant concern. Our objective was to explore the prognostic value of the painDETECT questionnaire (PDQ) in relation to treatment outcomes in axSpA patients treated in clinical practice. AxSpA patients with high disease activity initiating or switching a biological Disease-Modifying Antirheumatic Drug (bDMARD) were eligible. The PDQ score (range: −1 to 38) was used to distinguish participants with nociceptive pain (NcP) mechanisms from participants with a mixed pain mechanism (MP). The primary outcome was the proportion of individuals achieving a 50% improvement of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 12 weeks; logistic regression analysis models were used to determine the prognostic value of the nociceptive pain phenotype. Changes in continuous outcomes such as the Assessment of SpondyloArthritis International Society (ASAS) core outcome domains were analyzed using analysis of covariance (ANCOVA). Health-related quality of life (HR-QoL) was addressed using the Medical Outcomes Study SF-36. During a period of 22 months, 49 axSpA patients were included. Twenty (41%) had an NcP phenotype according to the PDQ score. BASDAI50 responses were reported by 40% (8/20) and 28% (8/29) NcP and MP groups, respectively. However, a prognostic value was not found in relation to the primary outcome (crude odds ratio [95% confidence interval]: 1.75 [0.52 to 5.87]). Across most of the secondary outcomes, axSpA NcP phenotype patients were reported having the most improvements in the HR-QoL measures. These data indicate the influence of personalized management strategies according to patients’ pain phenotypes for stratification of axSpA patients in randomized controlled trials.
Comparison of Three Different Internal Brace Augmentation Techniques for Scapholunate Dissociation: A Cadaveric Biomechanical Study
Authors: Park Il-Jung , Lim Dohyung , Maniglio Mauro , Shin Steven S. , Chae Seungbum , Truong Victor , McGarry Michelle H. , Lee Thay Q.
Published: April 2021

Internal bracing (IB) is an augmentation method using high-strength nonabsorbable tape. However, there is no detailed information about the direction, location, or number of IBs required for scapholunate interosseous ligament (SLIL) injury repair. Thus, this study compared the biomechanical characteristics of short-transverse IB, long-oblique IB, and the combination of short-transverse and long-oblique (Combo) IB for SLIL injury in a biomechanical cadaveric model. We prepared nine fresh-frozen full upper extremity cadaveric specimens for this study. The scapholunate distance, scapholunate angle, and radioscaphoid angle were measured using the MicroScribe digitizing system with the SLIL intact, after scapholunate dissociation and the three different reconstructions. Three-dimensional digital records were obtained in six wrist positions in each experimental condition. Short-transverse IB had a similar effect compared with long-oblique IB in addressing the widening of the scapholunate distance. However, both were less effective than Combo IB. For scaphoid flexion deformity, short-transverse IB had minimal effect, while long-oblique IB had a similar effect compared to Combo IB. Combo IB was the most effective for improving distraction intensity and rotational strength. This study provides important information about the biomechanical characteristics of three different IB methods for SLIL injury and may be useful to clinicians in treating scapholunate dissociation.
A New Toolbox in Experimental Embryology—Alternative Model Organisms for Studying Preimplantation Development
Authors: Springer Claudia , Wolf Eckhard , Simmet Kilian
Published: April 2021

Preimplantation development is well conserved across mammalian species, but major differences in developmental kinetics, regulation of early lineage differentiation and implantation require studies in different model organisms, especially to better understand human development. Large domestic species, such as cattle and pig, resemble human development in many different aspects, i.e., the timing of zygotic genome activation, mechanisms of early lineage differentiations and the period until blastocyst formation. In this article, we give an overview of different assisted reproductive technologies, which are well established in cattle and pig and make them easily accessible to study early embryonic development. We outline the available technologies to create genetically modified models and to modulate lineage differentiation as well as recent methodological developments in genome sequencing and imaging, which form an immense toolbox for research. Finally, we compare the most recent findings in regulation of the first lineage differentiations across species and show how alternative models enhance our understanding of preimplantation development.
A Novel Low-Risk Germline Variant in the SH2 Domain of the SRC Gene Affects Multiple Pathways in Familial Colorectal Cancer
Authors: Skopelitou Diamanto , Miao Beiping , Srivastava Aayushi , Kumar Abhishek , Kuświk Magdalena , Dymerska Dagmara , Paramasivam Nagarajan , Schlesner Matthias , Lubiński Jan , Hemminki Kari , Försti Asta , Bandapalli Obul Reddy
Published: April 2021

Colorectal cancer (CRC) shows one of the largest proportions of familial cases among different malignancies, but only 5–10% of all CRC cases are linked to mutations in established predisposition genes. Thus, familial CRC constitutes a promising target for the identification of novel, high- to moderate-penetrance germline variants underlying cancer susceptibility by next generation sequencing. In this study, we performed whole genome sequencing on three members of a family with CRC aggregation. Subsequent integrative in silico analysis using our in-house developed variant prioritization pipeline resulted in the identification of a novel germline missense variant in the SRC gene (V177M), a proto-oncogene highly upregulated in CRC. Functional validation experiments in HT-29 cells showed that introduction of SRCV177M resulted in increased cell proliferation and enhanced protein expression of phospho-SRC (Y419), a potential marker for SRC activity. Upregulation of paxillin, β-Catenin, and STAT3 mRNA levels, increased levels of phospho-ERK, CREB, and CCND1 proteins and downregulation of the tumor suppressor p53 further proposed the activation of several pathways due to the SRCV177M variant. The findings of our pedigree-based study contribute to the exploration of the genetic background of familial CRC and bring insights into the molecular basis of upregulated SRC activity and downstream pathways in colorectal carcinogenesis.
MicroRNA Expression Profile Distinguishes Glioblastoma Stem Cells from Differentiated Tumor Cells
Authors: Tomei Sara , Volontè Andrea , Ravindran Shilpa , Mazzoleni Stefania , Wang Ena , Galli Rossella , Maccalli Cristina
Published: April 2021

Glioblastoma (GBM) represents the most common and aggressive tumor of the brain. Despite the fact that several studies have recently addressed the molecular mechanisms underlying the disease, its etiology and pathogenesis are still poorly understood. GBM displays poor prognosis and its resistance to common therapeutic approaches makes it a highly recurrent tumor. Several studies have identified a subpopulation of tumor cells, known as GBM cancer stem cells (CSCs) characterized by the ability of self-renewal, tumor initiation and propagation. GBM CSCs have been shown to survive GBM chemotherapy and radiotherapy. Thus, targeting CSCs represents a promising approach to treat GBM. Recent evidence has shown that GBM is characterized by a dysregulated expression of microRNA (miRNAs). In this study we have investigated the difference between human GBM CSCs and their paired autologous differentiated tumor cells. Array-based profiling and quantitative Real-Time PCR (qRT-PCR) were performed to identify miRNAs differentially expressed in CSCs. The Cancer Genome Atlas (TCGA) data were also interrogated, and functional interpretation analysis was performed. We have identified 14 miRNAs significantly differentially expressed in GBM CSCs (p < 0.005). MiR-21 and miR-95 were among the most significantly deregulated miRNAs, and their expression was also associated to patient survival. We believe that the data provided here carry important implications for future studies aiming at elucidating the molecular mechanisms underlying GBM.
Personalized Clinical Phenotyping through Systems Medicine and Artificial Intelligence
Authors: Cesario Alfredo , D’Oria Marika , Bove Francesco , Privitera Giuseppe , Boškoski Ivo , Pedicino Daniela , Boldrini Luca , Erra Carmen , Loreti Claudia , Liuzzo Giovanna , Crea Filippo , Armuzzi Alessandro , Gasbarrini Antonio , Calabresi Paolo , Padua Luca , Costamagna Guido , Antonelli Massimo , Valentini Vincenzo , Auffray Charles , Scambia Giovanni
Published: April 2021

Personalized Medicine (PM) has shifted the traditional top-down approach to medicine based on the identification of single etiological factors to explain diseases, which was not suitable for explaining complex conditions. The concept of PM assumes several interpretations in the literature, with particular regards to Genetic and Genomic Medicine. Despite the fact that some disease-modifying genes affect disease expression and progression, many complex conditions cannot be understood through only this lens, especially when other lifestyle factors can play a crucial role (such as the environment, emotions, nutrition, etc.). Personalizing clinical phenotyping becomes a challenge when different pathophysiological mechanisms underlie the same manifestation. Brain disorders, cardiovascular and gastroenterological diseases can be paradigmatic examples. Experiences on the field of Fondazione Policlinico Gemelli in Rome (a research hospital recognized by the Italian Ministry of Health as national leader in “Personalized Medicine” and “Innovative Biomedical Technologies”) could help understanding which techniques and tools are the most performing to develop potential clinical phenotypes personalization. The connection between practical experiences and scientific literature highlights how this potential can be reached towards Systems Medicine using Artificial Intelligence tools.
Laparoscopic Liver Resection Should Be a Standard Procedure for Hepatocellular Carcinoma with Low or Intermediate Difficulty
Authors: Gau Ruoh-Yun , Yu Ming-Chin , Tsai Hsin-I , Lee Cheng-Han , Kuo Tony , Lee Kuan-Chieh , Lee Wei-Chen , Chan Kun-Ming , Chiu Chien-Chih , Lee Chao-Wei
Published: April 2021

Background: To investigate the feasibility of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC), we compared the outcome between LLR and conventional open liver resection (OLR) in patient groups with different IWATE criteria difficulty scores (DS). Methods: We retrospectively reviewed 607 primary HCC patients (LLR: 81, OLR: 526) who underwent liver resection in Linkou Chang Gung Memorial hospital from 2012 to 2019. By using 1:1 propensity score-matched (PSM) analysis, their baseline characteristics and the DS stratified by the IWATE criteria were matched between the LLR and OLR. Their perioperative and oncologic outcomes were compared. Results: After 1:1 PSM, 146 patients (73 in LLR, 73 in OLR) were analyzed. Among them, 13, 41, 13 and 6 patients were classified as low, intermediate, advanced and expert DS group, respectively. Compared to OLR, the LLR had shorter hospital stay (9.4 vs. 11.5 days, p = 0.071), less occurrence of surgical complications (16.4% vs. 30.1%, p = 0.049), lower rate of hepatic inflow control (42.5% vs. 65.8%, p = 0.005), and longer time of inflow control (70 vs. 51 min, p = 0.022). The disease-free survival (DFS) and overall survivals were comparable between the two groups. While stratified by the DS groups, the LLR tended to have lower complication rate and shorter hospital stay than OLR. The DFS of LLR in the intermediate DS group was superior to that of the OLR (p = 0.020). In the advanced and expert DS groups, there were no significant differences regarding outcomes between the two groups. Conclusion: We have demonstrated that with sufficient experience and technique, LLR for HCC is feasible and the perioperative outcome is favorable. Based on the current study, we suggest LLR should be a standard procedure for HCC with low or intermediate difficulty. It can provide satisfactory postoperative recovery and comparable oncological outcomes. Further larger scale prospective studies are warranted to validate our findings.
Management of Hepatitis B Virus Reactivation in Malignant Lymphoma Prior to Immunosuppressive Treatment
Authors: Tsai Yu-Fen , Hsu Chin-Mu , Hsiao Hui-Hua
Published: April 2021

Hepatitis B reactivation is a common complication in lymphoma patients under immunosuppressive treatment with potentially serious and life-threating consequences. In this review, we discuss the basis of chronic Hepatitis B virus (HBV) infection, the definition and risk factors for HBV reactivation. We overview the management of HBV reactivation based on virological status and immunosuppressive regimen risk stratification. We also highlight and update information about the HBV reactivation in lymphoma patients under novel agent treatment, including newer monoclonal antibodies, small molecule inhibitors, and even chimeric antigen receptor T-cell immunotherapy.
Multifaceted Sexual Dysfunction in Dialyzing Men and Women: Pathophysiology, Diagnostics, and Therapeutics
Authors: Chou Jadzia , Kiebalo Thomas , Jagiello Piotr , Pawlaczyk Krzysztof
Published: April 2021

Patient survival continues to increase with the growing quality of dialysis and management of chronic kidney disease (CKD). As such, chronic therapy must include considerations of quality of life (QOL), and this includes the disproportionate prevalence of sexual dysfunction (SD) in this patient population. This review aims to describe the pathophysiological and the psychosocial causes of SD with regard to renal replacement therapy, particularly hemo- and peritoneal dialysis. The differences in its manifestation in men and women are compared, including hormonal imbalances—and therefore fertility, libido, and sexual satisfaction—the experience of depression and anxiety, and QOL. The impact of comorbidities and the iatrogenic causes of SD are described. This review also presents validated scales for screening and diagnosis of SD in CKD patients and outlines novel therapies and strategies for the effective management of SD. Increased prevalence of CKD invariably increases the number of patients with SD, and it is crucial for health care professional teams to become familiar with the clinical tools used to manage this sensitive and under-quantified field. As a known predictor of QOL, sexual function should become a point of focus in the pursuit of patient-centered care, particularly as we seek to achieve as “normal” a life as possible for individuals who receive dialysis.
Design and Additive Manufacturing of Porous Sound Absorbers—A Machine-Learning Approach
Authors: Kuschmitz Sebastian , Ring Tobias P. , Watschke Hagen , Langer Sabine C. , Vietor Thomas
Published: April 2021

Additive manufacturing (AM), widely known as 3D-printing, builds parts by adding material in a layer-by-layer process. This tool-less procedure enables the manufacturing of porous sound absorbers with defined geometric features, however, the connection of the acoustic behavior and the material’s micro-scale structure is only known for special cases. To bridge this gap, the work presented here employs machine-learning techniques that compute acoustic material parameters (Biot parameters) from the material’s micro-scale geometry. For this purpose, a set of test specimens is used that have been developed in earlier studies. The test specimens resemble generic absorbers by a regular lattice structure based on a bar design and allow a variety of parameter variations, such as bar width, or bar height. A set of 50 test specimens is manufactured by material extrusion (MEX) with a nozzle diameter of 0.2 mm and a targeted under extrusion to represent finer structures. For the training of the machine learning models, the Biot parameters are inversely identified from the manufactured specimen. Therefore, laboratory measurements of the flow resistivity and absorption coefficient are used. The resulting data is used for training two different machine learning models, an artificial neural network and a k-nearest neighbor approach. It can be shown that both models are able to predict the Biot parameters from the specimen’s micro-scale with reasonable accuracy. Moreover, the detour via the Biot parameters allows the application of the process for application cases that lie beyond the scope of the initial database, for example, the material behavior for other sound fields or frequency ranges can be predicted. This makes the process particularly useful for material design and takes a step forward in the direction of tailoring materials specific to their application.
The Effect of Increasing the Amount of Indium Alloying Material on the Efficiency of Sacrificial Aluminium Anodes
Authors: Zakowski Krzysztof , Orlikowski Juliusz , Darowicki Kazimierz , Czekajlo Marcin , Iglinski Piotr , Domanska Kinga
Published: April 2021

Al-Zn-In alloys having 4.2% zinc content and various indium content in the range of 0.02–0.2% were tested with respect to the most important electrochemical properties of sacrificial anodes in a cathodic protection, i.e., the current capacity and potential of the operating anode. The distribution of In and Zn in the tested alloys was mapped by means of the EDX technique, which demonstrated that these elements dissolve well in the alloy matrix and are evenly distributed within it. The current capacity of such alloys was determined by means of the method of determining the mass loss during the dissolution by a current of known charge. The results obtained demonstrate that the current capacity of Al-Zn-In alloy decreases with the increase in the In content, which results in an increased consumption of anode material and shorter lifetime of anodes. With 0.02% In content, the capacity amounted to approx. 2500 Ah/kg, whereas the alloy with 0.2% In had as much as 30% lower capacity amounting to approx. 1750 Ah/kg. Microscopic examination for the morphology and surface profile of the samples after their exposure demonstrated that a higher indium content in the alloy results in a more uneven general corrosion pattern during the dissolution of such alloy, and the cavities (pits) appearing on the alloy surface are larger and deeper. As the indium content is increased from 0.02% to 0.05%, the Al-Zn-In alloy potential decreases by about 50 mV to −1100 mV vs. Ag/AgCl electrode, which is advantageous in terms of using this alloy as a sacrificial anode. When the indium content is further increased from 0.05% to 0.2%, the potential of the alloy is no longer changed to a more negative one. The results obtained from all these tests demonstrate that alloys containing up to 0.05% of In additive are practically applicable for cathodic protection.
Hierarchical Microtextures Embossed on PET from Laser-Patterned Stamps
Authors: Bouchard Felix , Soldera Marcos , Baumann Robert , Lasagni Andrés Fabián
Published: April 2021

Nowadays, the demand for surface functionalized plastics is constantly rising. To address this demand with an industry compatible solution, here a strategy is developed for producing hierarchical microstructures on polyethylene terephthalate (PET) by hot embossing using a stainless steel stamp. The master was structured using three laser-based processing steps. First, a nanosecond-Direct Laser Writing (DLW) system was used to pattern dimples with a depth of up to 8 µm. Next, the surface was smoothed by a remelting process with a high-speed laser scanning at low laser fluence. In the third step, Direct Laser Interference Patterning (DLIP) was utilized using four interfering sub-beams to texture a hole-like substructure with a spatial period of 3.1 µm and a depth up to 2 µm. The produced stamp was used to imprint PET foils under controlled temperature and pressure. Optical confocal microscopy and scanning electron microscopy imaging showed that the hierarchical textures could be accurately transferred to the polymer. Finally, the wettability of the single- and multi-scaled textured PET surfaces was characterized with a drop shape analyzer, revealing that the highest water contact angles were reached for the hierarchical patterns. Particularly, this angle was increased from 77° on the untreated PET up to 105° for a hierarchical structure processed with a DLW spot distance of 60 µm and with 10 pulses for the DLIP treatment.
Fabry-Perot Pressure Sensors Based on Polycrystalline Diamond Membranes
Authors: Pettinato Sara , Barettin Daniele , Sedov Vadim , Ralchenko Victor , Salvatori Stefano
Published: April 2021

Pressure sensors based on diamond membranes were designed and tested for gas pressure measurement up to 6.8 MPa. The diamond film (2” diameter, 6 μm thickness)—grown by microwave plasma chemical vapor deposition on a silicon substrate—was a starting material to produce an array of membranes with different diameters in the 130–400 μm range, in order to optimize the sensor performance. Each 5 mm × 5 mm sensing element was obtained by subsequent silicon slicing. The fixed film thickness, full-scale pressure range, and sensor sensitivity were established by a proper design of the diameter of diamond membrane which represents the sensing element for differential pressure measurement. The pressure-induced deflection of the membrane was optically measured using a Fabry-Pérot interferometer formed by a single mode optical fiber front surface and the deflecting diamond film surface. The optical response of the system was numerically simulated using geometry and the elastic properties of the diamond diaphragm, and was compared with the experiments. Depending on the diamond membrane’s diameter, the fabricated sensors displayed a good modulation depth of response over different full-scale ranges, from 3 to 300 bar. In view of the excellent mechanical, thermal, and chemical properties of diamond, such pressure sensors could be useful for performance in a harsh environment.
Effect of D-Mannitol on the Microstructure and Rheology of Non-Aqueous Carbopol Microgels
Authors: Migliozzi Simona , Angeli Panagiota , Mazzei Luca
Published: April 2021

D-mannitol is a common polyol that is used as additive in pharmaceutical and personal care product formulations. We investigated its effect on the microstructure and rheology of novel non-aqueous Carbopol dispersions employing traditional and time-resolved rheological analysis. We considered two types of sample, (i) fresh (i.e., mannitol completely dissolved in solution) and aged (i.e., visible in crystalline form). The analysis of the intracycle rheological transitions that were observed for different samples revealed that, when completely dissolved in solution, mannitol does not alter the rheological behaviour of the Carbopol dispersions. This highlights that the chemical similarity of the additive with the molecules of the surrounding solvent allows preserving the swollen dimension and interparticle interactions of the Carbopol molecules. Conversely, when crystals are present, a hierarchical structure forms, consisting of a small dispersed phase (Carbopol) agglomerated around a big dispersed phase (crystals). In keeping with this microstructural picture, as the concentration of Carbopol reduces, the local dynamics of the crystals gradually start to control the integrity of the microstructure. Rheologically, this results in a higher elasticity of the suspensions at infinitesimal deformations, but a fragile yielding process at intermediate strains.
Phase-Field Modeling of Chemoelastic Binodal/Spinodal Relations and Solute Segregation to Defects in Binary Alloys
Authors: Mianroodi Jaber Rezaei , Shanthraj Pratheek , Svendsen Bob , Raabe Dierk
Published: April 2021

Microscopic phase-field chemomechanics (MPFCM) is employed in the current work to model solute segregation, dislocation-solute interaction, spinodal decomposition, and precipitate formation, at straight dislocations and configurations of these in a model binary solid alloy. In particular, (i) a single static edge dipole, (ii) arrays of static dipoles forming low-angle tilt (edge) and twist (screw) grain boundaries, as well as at (iii) a moving (gliding) edge dipole, are considered. In the first part of the work, MPFCM is formulated for such an alloy. Central here is the MPFCM model for the alloy free energy, which includes chemical, dislocation, and lattice (elastic), contributions. The solute concentration-dependence of the latter due to solute lattice misfit results in a strong elastic influence on the binodal (i.e., coexistence) and spinodal behavior of the alloy. In addition, MPFCM-based modeling of energy storage couples the thermodynamic forces driving (Cottrell and Suzuki) solute segregation, precipitate formation and dislocation glide. As implied by the simulation results for edge dislocation dipoles and their configurations, there is a competition between (i) Cottrell segregation to dislocations resulting in a uniform solute distribution along the line, and (ii) destabilization of this distribution due to low-dimensional spinodal decomposition when the segregated solute content at the line exceeds the spinodal value locally, i.e., at and along the dislocation line. Due to the completely different stress field of the screw dislocation configuration in the twist boundary, the segregated solute distribution is immediately unstable and decomposes into precipitates from the start.
Temperature Compensation of the MEMS-Based Electrochemical Seismic Sensors
Authors: Xu Chao , Wang Junbo , Chen Deyong , Chen Jian , Qi Wenjie , Liu Bowen , Liang Tian , She Xu
Published: April 2021

Electrochemical seismic sensors that employ liquid as their inertial masses have the advantages of high performances in the low-frequency domain and a large working inclination. However, the surrounding temperature changes have serious impacts on the sensitivities of the sensors, which makes them unable to work as expected. This paper studied the temperature characteristics of electrochemical seismic sensors based on MEMS (micro–electro–mechanical systems), and analyzed the influences of the temperature effects on the open-loop and closed-loop amplitude-frequency curves. Most importantly, the temperature compensation circuits based on thermistors were developed, which effectively adjusted pole frequencies and sensitivity coefficients, and finally realized the real-time temperature compensation for both open-loop and closed-loop measurements for the first time. The results showed that in the temperature range of −10 °C ~ +40 °C, and with the 3 dB bandwidth range of 0.01 Hz ~ 40 Hz, the change of the maximum sensitivity was reduced from about 25 dB before temperature compensation to less than 2 dB after temperature compensation.
Protonation Equilibrium in the Active Site of the Photoactive Yellow Protein
Authors: Campomanes Pablo , Vanni Stefano
Published: April 2021

The role and existence of low-barrier hydrogen bonds (LBHBs) in enzymatic and protein activity has been largely debated. An interesting case is that of the photoactive yellow protein (PYP). In this protein, two short HBs adjacent to the chromophore, p-coumaric acid (pCA), have been identified by X-ray and neutron diffraction experiments. However, there is a lack of agreement on the chemical nature of these H-bond interactions. Additionally, no consensus has been reached on the presence of LBHBs in the active site of the protein, despite various experimental and theoretical studies having been carried out to investigate this issue. In this work, we perform a computational study that combines classical and density functional theory (DFT)-based quantum mechanical/molecular mechanical (QM/MM) simulations to shed light onto this controversy. Furthermore, we aim to deepen our understanding of the chemical nature and dynamics of the protons involved in the two short hydrogen bonds that, in the dark state of PYP, connect pCA with the two binding pocket residues (E46 and Y42). Our results support the existence of a strong LBHB between pCA and E46, with the H fully delocalized and shared between both the carboxylic oxygen of E46 and the phenolic oxygen of pCA. Additionally, our findings suggest that the pCA interaction with Y42 can be suitably described as a typical short ionic H-bond of moderate strength that is fully localized on the phenolic oxygen of Y42.
Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review
Authors: Brito Vanessa , Alves Gilberto , Almeida Paulo , Silvestre Samuel
Published: April 2021

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.
Milk Consumption and Respiratory Function in Asthma Patients: NHANES Analysis 2007–2012
Authors: Sveiven Stefanie N. , Bookman Rachel , Ma Jihyun , Lyden Elizabeth , Hanson Corrine , Nordgren Tara M.
Published: April 2021

Per the Centers for Disease Control and Prevention, asthma prevalence has steadily risen since the 1980s. Using data from the National Health and Nutrition Examination Survey (NHANES), we investigated associations between milk consumption and pulmonary function (PF). Multivariable analyses were performed, adjusted for a priori potential confounders for lung function, within the eligible total adult population (n = 11,131) and those self-reporting asthma (n = 1,542), included the following variables: milk-consumption, asthma diagnosis, forced vital capacity (FVC), FVC%-predicted (%), forced expiratory volume in one-second (FEV1), FEV1% and FEV1/FVC. Within the total population, FEV1% and FVC% were significantly associated with regular (5+ days weekly) consumption of exclusively 1% milk in the prior 30-days (β:1.81; 95% CI: [0.297, 3.325]; p = 0.020 and β:1.27; [0.16, 3.22]; p = 0.046). Among participants with asthma, varied-regular milk consumption in a lifetime was significantly associated with FVC (β:127.3; 95% CI: [13.1, 241.4]; p = 0.002) and FVC% (β:2.62; 95% CI: [0.44, 4.80]; p = 0.006). No association between milk consumption and FEV1/FVC was found, while milk-type had variable influence and significance. Taken together, we found certain milk consumption tendencies were associated with pulmonary function values among normal and asthmatic populations. These findings propound future investigations into the potential role of dairy consumption in altering lung function and asthma outcomes, with potential impact on the protection and maintenance of pulmonary health.