bluuebunny/crossref_metadata_2025 huggingface dataset:
Tough Love Lessons: Lateral Violence among Hospital Nurses
Authors: Vidal-Alves María Joao , Pina David , Puente-López Esteban , Luna-Maldonado Aurelio , Luna Ruiz-Cabello Aurelio , Magalhães Teresa , Pina-López Yolanda , Ruiz-Hernández José Antonio , Jarreta Begoña Martínez
Published: August 2021

Background: Workplace violence is a growing social problem among many professions, but it particularly affects the health sector. Studies have mainly focused on evaluating user violence toward health professionals, with less attention being paid to other sources of conflict, such as co-workers themselves. There are different manifestations of this violence in what has been called a context of tolerated or normalized violence among co-workers. However, its effects are far from being tolerable, as they have an impact on general health and job satisfaction and contribute to burnout among professionals. Based on this idea, and following the line of the previous literature, nursing staff are a population at high risk of exposure to workplace violence. For this reason, the present study aims to evaluate exposure to lateral violence or violence among co-workers in nursing staff in public health services and the relationship of this exposure with some of the most studied consequences. (2) Methods: A cross-sectional associative study was carried out in which scales of workplace violence (HABS-CS), burnout (MBI-GS), job satisfaction (OJS), and general health (GHQ-28) were applied to a sample of 950 nursing staff from 13 public hospitals located in the southeast of Spain. (3) Results: The results show that nursing staff have a high exposure to violence from their co-workers, which is more common in male nurses. Greater exposure is observed in professionals with between 6 and 10 years of experience in the profession, and it is not characteristic of our sample to receive greater violence when they have less experience or are younger. A positive correlation is observed with high levels of burnout and a negative correlation with general health and job satisfaction. (4) Conclusions: The results of this work contribute to increasing the scientific evidence of the consequences of a type of workplace violence frequent among nursing staff and to which less attention has been paid in relative terms to other types of prevalent violence. Organizations should be aware of the importance of this type of workplace violence, its frequency and impact, and implement appropriate prevention policies that include the promotion of a culture that does not reward violence or minimize reporting. A change of mentality in the academic environment is also recommended in order to promote a more adequate training of nursing staff in this field.
Motivation Research on the Content Creation Behaviour of Young Adults in Anxiety Disorder Online Communities
Authors: Liu Jingfang , Liu Yafei
Published: August 2021

With the advancements in science and technology and the improvement of medical care, mental health problems are receiving increasing attention. Increasing numbers of children, adolescents, and young adults are susceptible to anxiety. This paper assesses young adults based on self-determination theory and the theory of planned behaviour to determine the intrinsic and extrinsic motivations and mediating variables behind young adults’ content creation behaviour within anxiety disorder online communities (ADOCs). In addition, the paper introduces empathy as a moderating variable, builds a model of the content creation behavioural motivation of young adults, studies the motivation behind young adults’ content creation behaviour in ADOCs, and determines the moderating effect of empathy on young adults’ content creation behaviour. The research data were obtained using a questionnaire survey, and the SmartPLS structural equation model was used for empirical analysis. The study found that expressing one’s anxiety was the most obvious motivation, the content creation intention of young adults significantly positively affected their content creation behaviour, perceived enjoyment motivation had a significant negative influence on young adults’ intention to create content, reward motivation had no significant influence on the content creation intention of young adults, other motivations had significant positive influences on young adults’ content creation intention, and empathy only had a significant negative moderating effect on the relationship between self-efficacy and young adults’ content creation intention. This study not only enriches and expands research on motivation theory but also has practical significance for the improvement and active development of ADOCs.
Diurnal Temperature Ranges in Relation to Lower Limb Amputation Rate of Diabetic Foot in South Korea: A Population Based Nationwide Study
Authors: Won Sung Hun , Chung Hyung-Jin , Lee Jinyoung , Jeon Ye Jin , Chun Dong-Il , Min Tae-Hong , Cho Jaeho , Won Sungho , Yi Young
Published: August 2021

The evidence for the association between diurnal temperature range (DTR) and diabetic foot amputations is limited. We aimed to investigate the region-specific association between DTR and the amputation rate of diabetic foot in Korean national-wide data. Daily data on DTR and the rate of diabetic foot amputations from 16 provincial capital cities in Korea were obtained (2011–2018). In this study, the latitude ranged from 33°11′ N to 38°61′ N, and we classified each region according to latitude. Region 1, which was located at a relatively high latitude, included Seoul, Incheon, Gyeonggi-do, and Gangwon-do. Region 2, which was located at a relatively low latitude, included Busan, Ulsan, Gyeonsannam-do, Gwangju, Jeollanam-do, Jeollabuk-do, and Jeju-do. The region-specific DTR effects on the amputation rate were estimated based on a quasi-Poisson generalized linear model, combined with a distributed lag non-linear model based on the self-controlled case series design. The DTR impacts were generally limited to a period of nine days, while significant effects during lag days 7–14 were only found in the cities of Seoul, Incheon, and Gyeonggi-do (10th lag day: RR [95% CI]; Seoul: 1.015, [1.001–1.029]; Incheon: 1.052 [1.006–1.101]; Gyeonggi-do: 1.018 [1.002–1.034]). In the subgroup analysis (according to the latitude), an increase of 1 °C in DTR was associated with the risk of diabetic foot in relatively high latitude regions. DTR has considerable effects on the risk of diabetic foot amputation in various provinces in Korea, and it was particularly affected by latitude. The results can inform the decisions on developing programs to protect vulnerable subpopulations from adverse impacts.
Chronic Pain and Associated Factors Related to Depression among Older Patients in Hanoi, Vietnam
Authors: Nguyen Anh Trung , Nguyen Trang Huyen Thi , Nguyen Thu Thi Hoai , Nguyen Huong Thi Thu , Nguyen Thanh Xuan , Nguyen Tam Ngoc , Nguyen Anh Lan , Vu Linh Gia , Do Hoa Thi , Doan Linh Phuong , Vu Giang Thu , Nguyen Huong Thi Thanh , Pham Thang , Vu Huyen Thi Thanh
Published: August 2021

The interaction of chronic pain and depression among older people has been studied for many years. This study aimed to investigate the frequency of chronic pain and depression among older patients and correlated factors. A cross-sectional study was conducted in 921 older patients at the National Geriatric Hospital from November 2019 to March 2020. We used the Charlson Comorbidity Index (CCI) to assess the comorbid condition, a numerical rating scale (NRS) to examine pain severity, and Geriatric Depression Scale—15 items (GDS-15) to measure depression among participants. A chi-square test and Tobit regression were used to analyze the relationships. A total of 921 older patients participated in the study. The proportion of depression accounted for 55.8%. The mean Charlson score and number of diseases were 1.2 and 4.7, respectively. A positive correlation was found between comorbidity and chronic pain and depression. Moreover, socio-demographic variables such as occupation, education, and income were associated with pain and depressive symptoms. This study highlights the issue of mental health in older people with chronic pain. The results indicate the necessity of frequent depression screening, pain management, and social activity programs for older people to enhance their health.
Gravitational Force—Induced 3D Chromosomal Conformational Changes Are Associated with Rapid Transcriptional Response in Human T Cells
Authors: Vahlensieck Christian , Thiel Cora Sandra , Zhang Ye , Huge Andreas , Ullrich Oliver
Published: August 2021

The mechanisms underlying gravity perception in mammalian cells are unknown. We have recently discovered that the transcriptome of cells in the immune system, which is the most affected system during a spaceflight, responds rapidly and broadly to altered gravity. To pinpoint potential underlying mechanisms, we compared gene expression and three-dimensional (3D) chromosomal conformational changes in human Jurkat T cells during the short-term gravitational changes in parabolic flight and suborbital ballistic rocket flight experiments. We found that differential gene expression in gravity-responsive chromosomal regions, but not differentially regulated single genes, are highly conserved between different real altered gravity comparisons. These coupled gene expression effects in chromosomal regions could be explained by underlying chromatin structures. Based on a high-throughput chromatin conformation capture (Hi-C) analysis in altered gravity, we found that small chromosomes (chr16–22, with the exception of chr18) showed increased intra- and interchromosomal interactions in altered gravity, whereby large chromosomes showed decreased interactions. Finally, we detected a nonrandom overlap between Hi-C-identified chromosomal interacting regions and gravity-responsive chromosomal regions (GRCRs). We therefore demonstrate the first evidence that gravitational force-induced 3D chromosomal conformational changes are associated with rapid transcriptional response in human T cells. We propose a general model of cellular sensitivity to gravitational forces, where gravitational forces acting on the cellular membrane are rapidly and mechanically transduced through the cytoskeleton into the nucleus, moving chromosome territories to new conformation states and their genes into more expressive or repressive environments, finally resulting in region-specific differential gene expression.
Efficient Generation of Knock-In Zebrafish Models for Inherited Disorders Using CRISPR-Cas9 Ribonucleoprotein Complexes
Authors: de Vrieze Erik , de Bruijn Suzanne E. , Reurink Janine , Broekman Sanne , van de Riet Vince , Aben Marco , Kremer Hannie , van Wijk Erwin
Published: August 2021

CRISPR-Cas9-based genome-editing is a highly efficient and cost-effective method to generate zebrafish loss-of-function alleles. However, introducing patient-specific variants into the zebrafish genome with CRISPR-Cas9 remains challenging. Targeting options can be limited by the predetermined genetic context, and the efficiency of the homology-directed DNA repair pathway is relatively low. Here, we illustrate our efficient approach to develop knock-in zebrafish models using two previously variants associated with hereditary sensory deficits. We employ sgRNA-Cas9 ribonucleoprotein (RNP) complexes that are micro-injected into the first cell of fertilized zebrafish eggs together with an asymmetric, single-stranded DNA template containing the variant of interest. The introduction of knock-in events was confirmed by massive parallel sequencing of genomic DNA extracted from a pool of injected embryos. Simultaneous morpholino-induced blocking of a key component of the non-homologous end joining DNA repair pathway, Ku70, improved the knock-in efficiency for one of the targets. Our use of RNP complexes provides an improved knock-in efficiency as compared to previously published studies. Correct knock-in events were identified in 3–8% of alleles, and 30–45% of injected animals had the target variant in their germline. The detailed technical and procedural insights described here provide a valuable framework for the efficient development of knock-in zebrafish models.
Development of Effective Therapeutic Molecule from Natural Sources against Coronavirus Protease
Authors: Fadaka Adewale Oluwaseun , Sibuyi Nicole Remaliah Samantha , Martin Darius Riziki , Klein Ashwil , Madiehe Abram , Meyer Mervin
Published: August 2021

The SARS-CoV-2 main protease (Mpro) is one of the molecular targets for drug design. Effective vaccines have been identified as a long-term solution but the rate at which they are being administered is slow in several countries, and mutations of SARS-CoV-2 could render them less effective. Moreover, remdesivir seems to work only with some types of COVID-19 patients. Hence, the continuous investigation of new treatments for this disease is pivotal. This study investigated the inhibitory role of natural products against SARS-CoV-2 Mpro as repurposable agents in the treatment of coronavirus disease 2019 (COVID-19). Through in silico approach, selected flavonoids were docked into the active site of Mpro. The free energies of the ligands complexed with Mpro were computationally estimated using the molecular mechanics-generalized Born surface area (MM/GBSA) method. In addition, the inhibition process of SARS-CoV-2 Mpro with these ligands was simulated at 100 ns in order to uncover the dynamic behavior and complex stability. The docking results showed that the selected flavonoids exhibited good poses in the binding domain of Mpro. The amino acid residues involved in the binding of the selected ligands correlated well with the residues involved with the mechanism-based inhibitor (N3) and the docking score of Quercetin-3-O-Neohesperidoside (−16.8 Kcal/mol) ranked efficiently with this inhibitor (−16.5 Kcal/mol). In addition, single-structure MM/GBSA rescoring method showed that Quercetin-3-O-Neohesperidoside (−87.60 Kcal/mol) is more energetically favored than N3 (−80.88 Kcal/mol) and other ligands (Myricetin 3-Rutinoside (−87.50 Kcal/mol), Quercetin 3-Rhamnoside (−80.17 Kcal/mol), Rutin (−58.98 Kcal/mol), and Myricitrin (−49.22 Kcal/mol). The molecular dynamics simulation (MDs) pinpointed the stability of these complexes over the course of 100 ns with reduced RMSD and RMSF. Based on the docking results and energy calculation, together with the RMSD of 1.98 ± 0.19 Å and RMSF of 1.00 ± 0.51 Å, Quercetin-3-O-Neohesperidoside is a better inhibitor of Mpro compared to N3 and other selected ligands and can be repurposed as a drug candidate for the treatment of COVID-19. In addition, this study demonstrated that in silico docking, free energy calculations, and MDs, respectively, are applicable to estimating the interaction, energetics, and dynamic behavior of molecular targets by natural products and can be used to direct the development of novel target function modulators.
Enzymatic Pretreatment with Laccases from Lentinus sajor-caju Induces Structural Modification in Lignin and Enhances the Digestibility of Tropical Forage Grass (Panicum maximum) Grown under Future Climate Conditions
Authors: Freitas Emanuelle Neiverth de , Alnoch Robson Carlos , Contato Alex Graça , Nogueira Karoline Maria V. , Crevelin Eduardo José , Moraes Luiz Alberto Beraldo de , Silva Roberto Nascimento , Martínez Carlos Alberto , Polizeli Maria de Lourdes T. M.
Published: August 2021

Since laccase acts specifically in lignin, the major contributor to biomass recalcitrance, this biocatalyst represents an important alternative to the pretreatment of lignocellulosic biomass. Therefore, this study investigates the laccase pretreatment and climate change effects on the hydrolytic performance of Panicum maximum. Through a Trop-T-FACE system, P. maximum grew under current (Control (C)) and future climate conditions: elevated temperature (2 °C more than the ambient canopy temperature) combined with elevated atmospheric CO2 concentration(600 μmol mol−1), name as eT+eC. Pretreatment using a laccase-rich crude extract from Lentinus sajor caju was optimized through statistical strategies, resulting in an increase in the sugar yield of P. maximum biomass (up to 57%) comparing to non-treated biomass and enabling hydrolysis at higher solid loading, achieving up to 26 g L−1. These increments are related to lignin removal (up to 46%) and lignin hydrophilization catalyzed by laccase. Results from SEM, CLSM, FTIR, and GC-MS supported the laccase-catalyzed lignin removal. Moreover, laccase mitigates climate effects, and no significant differences in hydrolytic potential were found between C and eT+eC groups. This study shows that crude laccase pretreatment is a potential and sustainable method for biorefinery solutions and helped establish P. maximum as a promising energy crop.
Fibrotic Changes to Schlemm’s Canal Endothelial Cells in Glaucoma
Authors: Kelly Ruth A. , Perkumas Kristin M. , Campbell Matthew , Farrar G. Jane , Stamer W. Daniel , Humphries Pete , O’Callaghan Jeffrey , O’Brien Colm J.
Published: August 2021

Previous studies have shown that glaucomatous Schlemm’s canal endothelial cells (gSCECs) are stiffer and associated with reduced porosity and increased extracellular matrix (ECM) material compared to SCECs from healthy individuals. We hypothesised that Schlemm’s canal (SC) cell stiffening was a function of fibrotic changes occurring at the inner wall of SC in glaucoma. This study was performed in primary cell cultures isolated from the SC lumen of human donor eyes. RNA and protein quantification of both fibrotic and endothelial cell markers was carried out on both healthy and gSCECs. Functional assays to assess cell density, size, migration, proliferation, and mitochondrial function of these cells were also carried out. Indeed, we found that gSCECs deviate from typical endothelial cell characteristics and exhibit a more fibrotic phenotype. For example, gSCECs expressed significantly higher protein levels of the fibrotic markers α-SMA, collagen I-α1, and fibronectin, as well as significantly increased protein expression of TGFβ-2, the main driver of fibrosis, compared to healthy SCECs. Interestingly, we observed a significant increase in protein expression of endothelial marker VE-cadherin in gSCECs, compared to healthy SCECs. gSCECs also appeared to be significantly larger, and surprisingly proliferate and migrate at a significantly higher rate, as well as showing significantly reduced mitochondrial activity, compared to healthy SCECs.
Novel Sulfonamide-Based Carbamates as Selective Inhibitors of BChE
Authors: Magar Pratibha , Parravicini Oscar , Štěpánková Šárka , Svrčková Katarina , Garro Adriana D. , Jendrzejewska Izabela , Pauk Karel , Hošek Jan , Jampílek Josef , Enriz Ricardo D. , Imramovský Aleš
Published: August 2021

A series of 14 target benzyl [2-(arylsulfamoyl)-1-substituted-ethyl]carbamates was prepared by multi-step synthesis and characterized. All the final compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and the selectivity index (SI) was determined. Except for three compounds, all compounds showed strong preferential inhibition of BChE, and nine compounds were even more active than the clinically used rivastigmine. Benzyl {(2S)-1-[(2-methoxybenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5k), benzyl {(2S)-1-[(4-chlorobenzyl)sulfamoyl]-4-methylpentan-2-yl}carbamate (5j), and benzyl [(2S)-1-(benzylsulfamoyl)-4-methylpentan-2-yl]carbamate (5c) showed the highest BChE inhibition (IC50 = 4.33, 6.57, and 8.52 µM, respectively), indicating that derivatives 5c and 5j had approximately 5-fold higher inhibitory activity against BChE than rivastigmine, and 5k was even 9-fold more effective than rivastigmine. In addition, the selectivity index of 5c and 5j was approx. 10 and that of 5k was even 34. The process of carbamylation and reactivation of BChE was studied for the most active derivatives 5k, 5j. The detailed information about the mode of binding of these compounds to the active site of both BChE and AChE was obtained in a molecular modeling study. In this study, combined techniques (docking, molecular dynamic simulations, and QTAIM (quantum theory of atoms in molecules) calculations) were employed.
Mechanisms of Systolic Cardiac Dysfunction in PP2A, PP5 and PP2AxPP5 Double Transgenic Mice
Authors: Dörner Mara-Francine , Boknik Peter , Köpp Friedrich , Buchwalow Igor B. , Neumann Joachim , Gergs Ulrich
Published: August 2021

As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated transgenic mice with cardiac muscle cell-specific overexpression of PP2Acα (PP2A) and PP5 (PP5). For further studies we crossbred PP2A and PP5 mice to obtain PP2AxPP5 double transgenic mice (PP2AxPP5, DT) and compared them with littermate wild-type mice (WT) serving as a control. The mortality of DT mice was greatly enhanced vs. other genotypes. Cardiac fibrosis was noted histologically and mRNA levels of collagen 1α, collagen 3α and fibronectin 1 were augmented in DT. DT and PP2A mice exhibited an increase in relative heart weight. The ejection fraction (EF) was reduced in PP2A and DT but while the EF of PP2A was nearly normalized after β-adrenergic stimulation by isoproterenol, it was almost unchanged in DT. Moreover, left atrial preparations from DT were less sensitive to isoproterenol treatment both under normoxic conditions and after hypoxia. In addition, levels of the hypertrophy markers atrial natriuretic peptide and B-type natriuretic peptide as well as the inflammation markers interleukin 6 and nuclear factor kappa B were increased in DT. PP2A enzyme activity was enhanced in PP2A vs. WT but similar to DT. This was accompanied by a reduced phosphorylation state of phospholamban at serine-16. Fittingly, the relaxation times in left atria from DT were prolonged. In summary, cardiac co-overexpression of PP2A and PP5 were detrimental to animal survival and cardiac function, and the mechanism may involve dephosphorylation of important regulatory proteins but also fibrosis and inflammation.
The Human Gut Microbiota: A Key Mediator of Osteoporosis and Osteogenesis
Authors: Seely Kevin D. , Kotelko Cody A. , Douglas Hannah , Bealer Brandon , Brooks Amanda E.
Published: August 2021

An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.
New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway
Authors: Hsu Sheng-Kai , Cheng Kai-Chun , Mgbeahuruike Miracle Oluebube , Lin Yi-Hsiung , Wu Chang-Yi , Wang Hui-Min David , Yen Chia-Hung , Chiu Chien-Chih , Sheu Shwu-Jiuan
Published: August 2021

Under metabolic stress conditions such as hypoxia and glucose deprivation, an increase in the AMP:ATP ratio activates the AMP-activated protein kinase (AMPK) pathway, resulting in the modulation of cellular metabolism. Metformin, which is widely prescribed for type 2 diabetes mellitus (T2DM) patients, regulates blood sugar by inhibiting hepatic gluconeogenesis and promoting insulin sensitivity to facilitate glucose uptake by cells. At the molecular level, the most well-known mechanism of metformin-mediated cytoprotection is AMPK pathway activation, which modulates metabolism and protects cells from degradation or pathogenic changes, such as those related to aging and diabetic retinopathy (DR). Recently, it has been revealed that metformin acts via AMPK- and non-AMPK-mediated pathways to exert effects beyond those related to diabetes treatment that might prevent aging and ameliorate DR. This review focuses on new insights into the anticancer effects of metformin and its potential modulation of several novel types of nonapoptotic cell death, including ferroptosis, pyroptosis, and necroptosis. In addition, the antimetastatic and immunosuppressive effects of metformin and its hypothesized mechanism are also discussed, highlighting promising cancer prevention strategies for the future.
Molecular Characterization of Wheat Stripe Rust Pathogen (Puccinia striiformis f. sp. tritici) Collections from Nine Countries
Authors: Bai Qing , Wan Anmin , Wang Meinan , See Deven R. , Chen Xianming
Published: August 2021

Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most important diseases of wheat worldwide. To understand the worldwide distribution of its molecular groups, as well as the diversity, differentiation, and migration of the Pst populations, 567 isolates collected from nine countries (China, Pakistan, Italy, Egypt, Ethiopia, Canada, Mexico, Ecuador, and the U.S.) in 2010–2018 were genotyped using 14 codominant simple sequence repeat markers. A total of 433, including 333 new multi-locus genotypes (MLGs), were identified, which were clustered into ten molecular groups (MGs). The MGs and country-wise populations differed in genetic diversity, heterozygosity, and correlation coefficient between the marker and virulence data. Many isolates from different countries, especially the isolates from Mexico, Ecuador, and the U.S., were found to be identical or closely related MLGs, and some of the MGs were present in all countries, indicating Pst migrations among different countries. The analysis of molecular variance revealed 78% variation among isolates, 12% variation among countries, and 10% variation within countries. Only low levels of differentiation were found by the pairwise comparisons of country populations. Of the 10 MGs, 5 were found to be involved in sexual and/or somatic recombination. Identical and closely related MLGs identified from different countries indicated international migrations. The study provides information on the distributions of various Pst genetic groups in different countries and evidence for the global migrations, which should be useful in understanding the pathogen evolution and in stressing the need for continual monitoring of the disease and pathogen populations at the global scale.
Epigenetic Alterations Related to Gestational Diabetes Mellitus
Authors: Valencia-Ortega Jorge , Saucedo Renata , Sánchez-Rodríguez Martha A. , Cruz-Durán José G. , Martínez Edgar G. Ramos
Published: August 2021

Gestational diabetes mellitus (GDM) is the most common metabolic complication in pregnancy, which affects the future health of both the mother and the newborn. Its pathophysiology involves nutritional, hormonal, immunological, genetic and epigenetic factors. Among the latter, it has been observed that alterations in DNA (deoxyribonucleic acid) methylation patterns and in the levels of certain micro RNAs, whether in placenta or adipose tissue, are related to well-known characteristics of the disease, such as hyperglycemia, insulin resistance, inflammation and excessive placental growth. Furthermore, epigenetic alterations of gestational diabetes mellitus are observable in maternal blood, although their pathophysiological roles are completely unknown. Despite this, it has not been possible to determine the causes of the epigenetic characteristics of GDM, highlighting the need for integral and longitudinal studies. Based on this, this article summarizes the most relevant and recent studies on epigenetic alterations in placenta, adipose tissue and maternal blood associated with GDM in order to provide the reader with a general overview of the subject and indicate future research topics.
Beyond Single-Cell Analysis of Metallodrugs by ICP-MS: Targeting Cellular Substructures
Authors: Galé Audrey , Hofmann Lukas , Lüdi Nicola , Hungerbühler Martin Nils , Kempf Christoph , Heverhagen Johannes Thomas , von Tengg-Kobligk Hendrik , Broekmann Peter , Ruprecht Nico
Published: August 2021

Platinum compounds such as cisplatin (cisPt) embody the backbone of combination chemotherapy protocols against advanced lung cancer. However, their efficacy is primarily limited by inherent or acquired platinum resistance, the origin of which has not been fully elucidated yet, although of paramount interest. Using single cell inductively coupled plasma mass spectrometry (SC-ICP-MS), this study quantifies cisPt in single cancer cells and for the first time in isolated nuclei. A comparison of cisPt uptake was performed between a wild type (wt) cancer cell line and related resistant sublines. In both, resistant cells, wt cells, and their nuclei, cisPt uptake was measured at different incubation times. A lower amount of cisPt was found in resistant cell lines and their nuclei compared to wt cells. Moreover, the abundance of internalized cisPt decreased with increasing resistance. Interestingly, concentrations of cisPt found within the nuclei were higher than compared to cellular concentrations. Here, we show, that SC-ICP-MS allows precise and accurate quantification of metallodrugs in both single cells and cell organelles such as nuclei. These findings pave the way for future applications investigating the potency and efficacy of novel metallodrugs developed for cancer treatment.
Mammalian and Invertebrate Models as Complementary Tools for Gaining Mechanistic Insight on Muscle Responses to Spaceflight
Authors: Cahill Thomas , Cope Henry , Bass Joseph J. , Overbey Eliah G. , Gilbert Rachel , da Silveira Willian Abraham , Paul Amber M. , Mishra Tejaswini , Herranz Raúl , Reinsch Sigrid S. , Costes Sylvain V. , Hardiman Gary , Szewczyk Nathaniel J. , Tahimic Candice G. T.
Published: August 2021

Bioinformatics approaches have proven useful in understanding biological responses to spaceflight. Spaceflight experiments remain resource intensive and rare. One outstanding issue is how to maximize scientific output from a limited number of omics datasets from traditional animal models including nematodes, fruitfly, and rodents. The utility of omics data from invertebrate models in anticipating mammalian responses to spaceflight has not been fully explored. Hence, we performed comparative analyses of transcriptomes of soleus and extensor digitorum longus (EDL) in mice that underwent 37 days of spaceflight. Results indicate shared stress responses and altered circadian rhythm. EDL showed more robust growth signals and Pde2a downregulation, possibly underlying its resistance to atrophy versus soleus. Spaceflight and hindlimb unloading mice shared differential regulation of proliferation, circadian, and neuronal signaling. Shared gene regulation in muscles of humans on bedrest and space flown rodents suggest targets for mitigating muscle atrophy in space and on Earth. Spaceflight responses of C. elegans were more similar to EDL. Discrete life stages of D. melanogaster have distinct utility in anticipating EDL and soleus responses. In summary, spaceflight leads to shared and discrete molecular responses between muscle types and invertebrate models may augment mechanistic knowledge gained from rodent spaceflight and ground-based studies.
Betraying Blockchain: Accountability, Transparency and Document Standards for Non-Fungible Tokens (NFTs)
Authors: Cornelius Kristin
Published: August 2021

Transparency and accountability are important aspects to any technological endeavor and are popular topics of research as many everyday items have become ‘smart’ and interact with user data on a regular basis. Recent technologies such as blockchain tout these traits through the design of their infrastructure and their ability as recordkeeping mechanisms. This project analyzes and compares records produced by non-fungible tokens (NFTs), an increasingly popular blockchain application for recording and trading digital assets, and compares them to ‘document standards,’ an interdisciplinary method of contract law, diplomatics, document/interface theory, and evidentiary proof, to see if they live up to the bar that has been set by a body of literature concerned with authentic documents. Through a close reading of the current policies on transparency (i.e., CCPA, GDPR), compliance and recordkeeping (i.e., FCPA, SOX, UETA), and the consideration of blockchain records as user-facing interfaces, this study draws the conclusion that without an effort to design these records with these various concerns in mind and from the perspectives of all three stakeholders (Users, Firms, and Regulators), any transparency will only be illusory and could serve the opposite purpose for bad actors if not resolved.
Insect Epigenetic Mechanisms Facing Anthropogenic-Derived Contamination, an Overview
Authors: Olivares-Castro Gabriela , Cáceres-Jensen Lizethly , Guerrero-Bosagna Carlos , Villagra Cristian
Published: August 2021

Currently, the human species has been recognized as the primary species responsible for Earth’s biodiversity decline. Contamination by different chemical compounds, such as pesticides, is among the main causes of population decreases and species extinction. Insects are key for ecosystem maintenance; unfortunately, their populations are being drastically affected by human-derived disturbances. Pesticides, applied in agricultural and urban environments, are capable of polluting soil and water sources, reaching non-target organisms (native and introduced). Pesticides alter insect’s development, physiology, and inheritance. Recently, a link between pesticide effects on insects and their epigenetic molecular mechanisms (EMMs) has been demonstrated. EMMs are capable of regulating gene expression without modifying genetic sequences, resulting in the expression of different stress responses as well as compensatory mechanisms. In this work, we review the main anthropogenic contaminants capable of affecting insect biology and of triggering EMMs. EMMs are involved in the development of several diseases in native insects affected by pesticides (e.g., anomalous teratogenic reactions). Additionally, EMMs also may allow for the survival of some species (mainly pests) under contamination-derived habitats; this may lead to biodiversity decline and further biotic homogenization. We illustrate these patterns by reviewing the effect of neonicotinoid insecticides, insect EMMs, and their ecological consequences.
Subjective and Electroencephalographic Sleep Parameters in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review
Authors: Petruzzelli Maria Giuseppina , Matera Emilia , Giambersio Donatella , Marzulli Lucia , Gabellone Alessandra , Legrottaglie Anna Rosi , Margari Anna , Margari Lucia
Published: August 2021

Background: Sleep problems have commonly manifested in children and adolescents with autism spectrum disorder (ASD) with a complex and multifactorial interaction between clinical and etiological components. These disorders are associated with functional impairment, and provoke significant physical and mental affliction. The purpose of this study is to update the existing literature about objective and subjective sleep parameters in children and adolescents with ASD, extrapolating information from polysomnography or sleep electroencephalography, and sleep related questionnaires. Methods: We have conducted a systematic review of case-control studies on this topic, performing a web-based search on PubMed, Scopus and the Web of Science databases according to the Preferred Reporting items for Systematic Review and Meta-analyses (PRISMA) guidelines. Results: Data collected from 20 survey result reports showed that children and adolescents with ASD experienced a higher rate of sleep abnormalities than in typically developing children. The macrostructural sleep parameters that were consistent with subjective parent reported measures unveil a greater percentage of nighttime signs of insomnia. Sleep microstructure patterns, in addition, pointed towards the bidirectional relationship between brain dysfunctions and sleep problems in children with ASD. Conclusions: Today’s literature acknowledges that objective and subjective sleep difficulties are more often recognized in individuals with ASD, so clinicians should assess sleep quality in the ASD clinical population, taking into consideration the potential implications on treatment strategies. It would be worthwhile in future studies to examine how factors, such as age, cognitive level or ASD severity could be related to ASD sleep abnormalities. Future research should directly assess whether sleep alterations could represent a specific marker for atypical brain development in ASD.
Cardiac Remodeling and Diastolic Dysfunction in Paroxysmal Atrial Fibrillation
Authors: Noirclerc Nathalie , Huttin Olivier , de Chillou Christian , Selton-Suty Christine , Fillipetti Laura , Sellal Jean Marc , Bozec Erwan , Donal Erwan , Lamiral Zohra , Kobayashi Masatake , Ferreira João Pedro , Rossignol Patrick , Girerd Nicolas
Published: August 2021

Background: Atrial fibrillation (AF) leads to the development of cardiac remodeling/diastolic dysfunction and vice versa. We intended to determine whether cardiac remodeling/diastolic dysfunction is present at early stages of AF. Methods: We studied 175 patients with paroxysmal AF, compared with 175 matched control subjects, who had available echocardiography data to investigate the association between echocardiographic variables and AF from the STANISLAS cohort. Results: In this study (mean age 55 years; 70.3% male), patients with paroxysmal AF had greater left ventricular mass compared to matched controls (p < 0.05). Patients with paroxysmal AF were also likely to have larger left atrial volume and a higher peak tricuspid regurgitation velocity, leading to higher prevalence (though <10% in the AF group) of diastolic dysfunction (all-p < 0.05). Multivariable conditional logistic regression models showed that paroxysmal AF was significantly associated with increased left ventricular mass and left atrial enlargement (all-p < 0.001), but not with e’ and deceleration time of E wave (all-p > 0.1). Conclusions: Left ventricular mass and left atrial enlargement rather than diastolic dysfunction (as evaluated by echocardiography) were associated with paroxysmal AF irrespective of body mass index, blood pressure and renal function. These findings suggest that cardiac remodeling may occur very early in the natural history of AF.
Erythema Increase Predicts Psoriasis Improvement after Phototherapy
Authors: Montero-Vilchez Trinidad , Martinez-Lopez Antonio , Sierra-Sanchez Alvaro , Soler-Gongora Miguel , Jimenez-Mejias Eladio , Molina-Leyva Alejandro , Buendia-Eisman Agustin , Arias-Santiago Salvador
Published: August 2021

Psoriasis is a major global health problem. There is a need to develop techniques to help physicians select the most appropriate cost-effective therapy for each patient. The main objectives of this study are (1) to evaluate changes in epidermal barrier function and skin homeostasis after phototherapy and (2) to explore potentially predictive values in epidermal barrier function and skin homeostasis to assess clinical improvement after fifteen sessions of phototherapy. A total of 76 subjects, 38 patients with plaque-type psoriasis and 38 gender- and age-matched healthy volunteers, were included in the study. Erythema, transepidermal water loss (TEWL), temperature, stratum corneum hydration (SCH), pH, sebum, and antioxidant capacity were measured before and after the first and fifteenth phototherapy session. Erythema (401.09 vs. 291.12 vs. 284.52 AU, p < 0.001) and TEWL (18.23 vs. 11.44 vs. 11.41 g·m−2·h−1, p < 0.001) were significantly higher at psoriatic plaques than in uninvolved psoriatic skin and healthy volunteers, respectively, while SCH was lower (9.71 vs. 44.64 vs. 40.00 AU, p < 0.001). After fifteen phototherapy sessions, TEWL (–5.19 g·m−2·h−1, p = 0.016) decreased while SCH (+7.01 AU, p = 0.013) and erythema (+30.82 AU, p = 0.083) increased at psoriatic plaques. An erythema increase exceeding 53.23 AU after the first phototherapy session, with a sensitivity of 71.4% and specificity of 84.2%, indicates that a patient may improve Psoriasis Area and Severity Index (PASI) by ≥3 points after fifteen phototherapy sessions. In conclusion, phototherapy improves epidermal barrier function in psoriatic patients and the erythema increase after one phototherapy session could help doctors select psoriasis patients who are more likely to respond to phototherapy.
Long-Term Outcome of Patients with TPO Mutations
Authors: Tobias Leraz , Elias-Assad Ghadir , Khayat Morad , Admoni Osnat , Almashanu Shlomo , Tenenbaum-Rakover Yardena
Published: August 2021

Introduction: Thyroid peroxidase (TPO) deficiency is the most common enzymatic defect causing congenital hypothyroidism (CH). We aimed to characterize the long-term outcome of patients with TPO deficiency. Methods: Clinical and genetic data were collected retrospectively. Results: Thirty-three patients with primary CH caused by TPO deficiency were enrolled. The follow-up period was up to 43 years. Over time, 20 patients (61%) developed MNG. Eight patients (24%) underwent thyroidectomy: one of them had minimal invasive follicular thyroid carcinoma. No association was found between elevated lifetime TSH levels and the development of goiter over the years. Conclusions: This cohort represents the largest long-term follow up of patients with TPO deficiency. Our results indicate that elevated TSH alone cannot explain the high rate of goiter occurrence in patients with TPO deficiency, suggesting additional factors in goiter development. The high rate of MNG development and the risk for thyroid carcinoma indicate a need for long-term follow up with annual ultrasound scans.
Pili Torti: A Feature of Numerous Congenital and Acquired Conditions
Authors: Hoffmann Aleksandra , Waśkiel-Burnat Anna , Żółkiewicz Jakub , Blicharz Leszek , Rakowska Adriana , Goldust Mohamad , Olszewska Małgorzata , Rudnicka Lidia
Published: August 2021

Pili torti is a rare condition characterized by the presence of the hair shaft, which is flattened at irregular intervals and twisted 180° along its long axis. It is a form of hair shaft disorder with increased fragility. The condition is classified into inherited and acquired. Inherited forms may be either isolated or associated with numerous genetic diseases or syndromes (e.g., Menkes disease, Björnstad syndrome, Netherton syndrome, and Bazex-Dupré-Christol syndrome). Moreover, pili torti may be a feature of various ectodermal dysplasias (such as Rapp-Hodgkin syndrome and Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome). Acquired pili torti was described in numerous forms of alopecia (e.g., lichen planopilaris, discoid lupus erythematosus, dissecting cellulitis, folliculitis decalvans, alopecia areata) as well as neoplastic and systemic diseases (such as cutaneous T-cell lymphoma, scalp metastasis of breast cancer, anorexia nervosa, malnutrition, cataracts, and chronic graft-vs.-host disease). The condition may also be induced by several drugs (epidermal growth factor receptor inhibitors, oral retinoids, sodium valproate, and carbamide perhydrate). The diagnosis of pili torti is based on trichoscopic or microscopic examination. As pili torti is a marker of numerous congenital and acquired disorders, in every case, the search for the signs of underlying conditions is recommended.
Prognosis Associated with Sub-Types of Hyperglycaemia in Pregnancy
Authors: Cosson Emmanuel , Bentounes Sid Ahmed , Nachtergaele Charlotte , Berkane Narimane , Pinto Sara , Sal Meriem , Bihan Hélène , Tatulashvili Sopio , Portal Jean-Jacques , Carbillon Lionel , Vicaut Eric
Published: August 2021

We aimed to compare pregnancy outcomes in 4665 women according to the following types of hyperglycaemia in pregnancy sub-types: (i) normoglycaemia, (ii) gestational diabetes mellitus (GDM), (iii) diabetes in pregnancy (DIP), (iv) early-diagnosed (i.e., <22 weeks of gestation) GDM (eGDM), and (v) early-diagnosed DIP (eDIP). The prevalence of normoglycaemia, eGDM, eDIP, GDM, and DIP was 76.4%, 10.8%, 0.6%, 11.7%, and 0.6%, respectively. With regard to pregnancy outcomes, gestational weight gain (11.5 ± 5.5, 9.0 ± 5.4, 8.3 ± 4.7, 10.4 ± 5.3, and 10.1 ± 5.0 kg, p < 0.0001) and insulin requirement (none, 46.0%, 88.5%, 25.5%, and 51.7%; p < 0.001) differed according to the glycaemic sub-types. eGDM and eDIP were associated with higher rates of infant malformation. After adjustment for confounders, with normoglycaemia as the reference, only GDM was associated with large-for-gestational-age infant (odds ratio 1.34 (95% interval confidence 1.01–1.78) and only DIP was associated with hypertensive disorders (OR 3.48 (1.26–9.57)). To conclude, early-diagnosed hyperglycaemia was associated with an increased risk of malformation, suggesting that it was sometimes present at conception. Women with GDM, but not those with eGDM, had an increased risk of having a large-for-gestational-age infant, possibly because those with eGDM were treated early and therefore had less gestational weight gain. Women with DIP might benefit from specific surveillance for hypertensive disorders.
Fecal Zonulin as a Noninvasive Biomarker of Intestinal Permeability in Pediatric Patients with Inflammatory Bowel Diseases—Correlation with Disease Activity and Fecal Calprotectin
Authors: Szymanska Edyta , Wierzbicka Aldona , Dadalski Maciej , Kierkus Jaroslaw
Published: August 2021

Background: Recent data indicate that increased intestinal permeability plays a key role in the pathogenesis of inflammatory bowel diseases (IBD) and correlates with disease flare. Since zonulin related proteins (ZRP) are the proteins that increase permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions, they may serve as a new, noninvasive biomarker of disease activity. The aim of this study was to investigate fecal ZRP in pediatric IBD patients as well as its correlation with disease activity and fecal calprotectin (FCP). Methods: Ninety-four individuals: 47 Crohn’s disease (CD) patients, 41 ulcerative colitis (UC) patients, and 6 healthy controls were examined for fecal ZRP. Values were correlated to IBD type, disease activity for IBD patients, and FCP for all children included in the study. A stool specimen was collected the day before the visit to the hospital, then fecal ZRP and FCP were tested using the ELISA test. Non-parametric statistical tests were used for data analysis. Results: The level of fecal ZRP was higher among IBD patients compared to the control group (CG): medians for CD—113.3 (53.6–593.6) ng/mL; UC—103.6 (50.7–418.3) ng/mL; and CG—46.9 (31.8–123.0) ng/mL (p < 0.05). No difference in fecal ZRP concentration was observed between children with CD and those with UC (p = 0.55). A slight correlation between disease activity (PCDAI for CD and PUCAI for UC) and the fecal ZRP level was found for CD (p = 0.03/R = 0.33), but not UC (p = 0.62/R = 0.08), patients. A correlation between fecal ZRP and FCP was observed (R = 0.73, p = 0.00). Conclusions: Fecal ZRP levels are increased among those with IBD, are associated with CD activity, and strongly correlate with FCP. Further research into the role of intestinal permeability in IBD and the clinical usefulness of ZRP in IBD is warranted.