bluuebunny/crossref_metadata_2025 huggingface dataset:
Moving Together: Understanding Parent Perceptions Related to Physical Activity and Motor Skill Development in Preschool Children
Authors: Agard Becky , Zeng Nan , McCloskey Morgan L. , Johnson Susan L. , Bellows Laura L.
Published: September 2021

Background: Establishing physical activity (PA) and motor behaviors in early childhood are important for developing healthy activity behaviors. Parents play a central role in shaping young children’s PA and fundamental motor skills (FMS). This qualitative study explored parents’ attributes, values, perceptions, and practices related to PA and FMS. Methods: Thirty-one parents (26 mothers) of preschool-aged children participated in semi-structured in-person interviews. Interviews were audio-recorded, transcribed verbatim, coded and analyzed using an iterative approach. Results: Four themes related to PA and FMS emerged: (1) parent attributes; (2) parent–child interactions; (3) parent perception of children’s attributes; and (4) parenting practices. Although most parents enjoyed playing with their child, some did not realize the importance of engaging in PA with their child and even believed that FMS are naturally developed. Parents indicated that children’s temperament may influence their preference for practicing motor skills. Conclusions: Social support and positive parenting practices, including encouragement, monitoring, logistical support, co-participation, and facilitation, are important for the development of PA and FMS. The findings add emphasis to the importance of parents’ role in the development of young children’s PA and FMS, and they inform future strategies aiming to promote young children’s activity behaviors.
Association between Self-Reported Survey Measures and Biomarkers of Second-Hand Tobacco Smoke Exposure in Non-Smoking Pregnant Women
Authors: Chen Meiman Maggie , Guo Su-Er , Yuan Chi-Pin , Okoli Chizimuzo , Liao Yen-Chi
Published: September 2021

Second-hand tobacco smoke (SHS) causes adverse health outcomes in adults. Further studies are needed to evaluate psychosocial SHS exposure measures in comparison to SHS exposure biomarkers, particularly in pregnant women. This study aimed to compare self-reported SHS exposure to urinary cotinine levels in pregnant women. A cross-sectional correlation design was conducted using a convenience sample of 70 non-smoking pregnant women. Measures included self-reported questionnaires and laboratory confirmation of cotinine levels in the urinary samples. Multiple regression analysis was used to assess the correlation after controlling for potential confounding variables. The average level of urinary cotinine among non-smoking pregnant women was 6.77 ng/mL. Medium-strength correlations were found among psychosocial SHS exposure measures and urine cotinine levels. Questions regarding ‘instances of smoking in front of the individual’ and ‘subjective perceived frequency of SHS exposure in past 7 days’ are feasible items for pregnant women in clinics (particularly the first question). Hence, we suggest that these simple questions should be used to assist pregnant women in reducing the harm associated with SHS exposure.
Main Factors Determining the Economic Production Sustained by Public Long-Term Care Spending in Spain
Authors: Bermejo Fernando , del Pozo Raúl , Moya Pablo
Published: September 2021

Policy reforms of 2012 introduced in Spain a set of austerity measures to emerge from the 2008 global recession. However, attaining the sustainability of the long-term care (LTC) system by reducing public spending overlooks the drawbacks of a lower demand to meet dependency needs. In this context, this study is intended to provide a deeper insight into the economic factors affecting the shifts in the industrial output sustained by LTC spending before and after the austerity measures adopted in 2012. To accomplish this, we first apply a model based on the Input-Output methodology to quantify the output arisen from the consumption demand to meet the dependency needs covered by LTC spending in 2009, 2012 and 2015. Using the results of this model, we carry out a Structural Decomposition Analysis to explore the main drivers of change in the Spanish economic production for 2009–2012 and 2012–2015. The findings reveal that LTC demand factors have proven more relevant than technology factors in increasing production for the two periods considered. Such findings might guide political decision-making on the management of the LTC system in Spain, showing that public LTC spending does not merely contribute to the welfare of dependents, but also may boost economic production.
The Influence of Living Conditions on Self-Rated Health: Evidence from China
Authors: Gu Jiafeng , Ming Xing
Published: September 2021

Despite growing attention to living conditions as a social determinant of health, few studies have focused on its diverse impacts on self-rated health. Using data from the China Family Panel Study in 2018, this study used logistic regression analysis to examine how living conditions affect self-rated health in China, finding that people cooking with sanitary water and clean fuel were more likely to report good health, and that homeownership was associated with higher self-rated health. The self-rated health of people living in high-quality housing was lower than that of people living in ordinary housing, and people living in tidy homes were more likely to report good health. The findings suggest that the link between multiple living conditions and self-rated health is dynamic. Public health policies and housing subsidy programs should therefore be designed based on a comprehensive account of not only housing grade or income status, but also whole dwelling conditions.
Preliminary Research: Validation of the Method of Evaluating Resistance to Surface Wetting with Liquid of Protective Materials Intended for Polymer Protective Gloves
Authors: Irzmańska Emilia , Jastrzębska Aleksandra , Makowicz Magdalena
Published: September 2021

The article presents validation argumentation of the novel method of evaluating resistance to surface wetting with different liquids of protective materials intended for polymer protective gloves based on the three parameters: water permeability index, non-wettability index and absorption index. Using our own method of evaluating resistance to surface wetting, it was shown that the knurled structure of the palm part of polymer protective gloves may inhibit transport of harmful and hazardous liquids outside the area of the protective glove. Currently, there is lack of objectifying methods for evaluation of surface wettability focused on the mentioned aspects. In view of the above facts, an original method for evaluating the resistance of protective materials to surface wetting with mineral oils and water has been invented and validated. It was assumed that the non-wettability index will be subjected to metrological analysis. Consequently, the validation process refers to this index. A precise assessment of the uncertainty budget of the individual components was obtained. On the basis of the obtained results, the measurement errors that may affect the quality and reliability of the test result performed in the laboratory were identified.
Artificial Intelligence for Identifying the Prevention of Medication Incidents Causing Serious or Moderate Harm: An Analysis Using Incident Reporters’ Views
Authors: Härkänen Marja , Haatainen Kaisa , Vehviläinen-Julkunen Katri , Miettinen Merja
Published: September 2021

The purpose of this study was to describe incident reporters’ views identified by artificial intelligence concerning the prevention of medication incidents that were assessed, causing serious or moderate harm to patients. The information identified the most important risk management areas in these medication incidents. This was a retrospective record review using medication-related incident reports from one university hospital in Finland between January 2017 and December 2019 (n = 3496). Of these, incidents that caused serious or moderate harm to patients (n = 137) were analysed using artificial intelligence. Artificial intelligence classified reporters’ views on preventing incidents under the following main categories: (1) treatment, (2) working, (3) practices, and (4) setting and multiple sub-categories. The following risk management areas were identified: (1) verification, documentation and up-to-date drug doses, drug lists and other medication information, (2) carefulness and accuracy in managing medications, (3) ensuring the flow of information and communication regarding medication information and safeguarding continuity of patient care, (4) availability, update and compliance with instructions and guidelines, (5) multi-professional cooperation, and (6) adequate human resources, competence and suitable workload. Artificial intelligence was found to be useful and effective to classifying text-based data, such as the free text of incident reports.
Organophosphate Esters in Indoor Environment and Metabolites in Human Urine Collected from a Shanghai University
Authors: Wang Yujie , Yang Ming , Wang Fushun , Chen Xueping , Wu Minghong , Ma Jing
Published: September 2021

In China, organophosphate esters (OPEs) are widely used in indoor environments. However, there is little information regarding the internal and external exposure of university students to OPEs. Therefore, in this study, nine OPEs and eight OPE metabolites (mOPEs) were measured in indoor dust and atmospheric PM2.5 samples from a university campus in Shanghai, as well as in urine samples collected from the university students. The total concentration of OPEs in the indoor dust in female dormitories (1420 ng/g) was approximately twice that in male dormitories (645 ng/g). In terms of indoor PM2.5, the highest OPE concentration was found in meeting rooms (105 ng/m3, on average), followed by chemical laboratories (51.2 ng/m3), dormitories (44.9 ng/m3), and offices (34.9 ng/m3). The total concentrations of the eight mOPEs ranged from 279 pg/mL to 14,000 pg/mL, with a geometric mean value of 1590 pg/mL. The estimated daily intake values based on the indoor dust and PM2.5 OPE samples (external exposure) were 1–2 orders of magnitude lower than that deduced from the concentration of urinary mOPEs (internal exposure), indicating that dermal contact, dust ingestion, and inhalation do not contribute significantly to OPE exposure in the general population. Moreover, additional exposure routes lead to the accumulation of OPEs in the human body.
Examining the Role of Service Quality, Perceived Values, and Trust in Macau Food Festival
Authors: Pai Chen-Kuo , Lee Tingting , Kang Sangguk
Published: September 2021

An emerging paradigm for festival and event management reveals that hosting theme-based festivals can foster economic growth at the local and national levels. As a case of this research, the annual Macau Food Festival was selected to explore relationships among visitors’ perceptions of festival quality, festival value, trust in the festival, visitors’ satisfaction, and behavior intention. Out of 453 questionnaires distributed, 433 questionnaires were valid for data analysis using partial least squares-structural equation modeling. The results showed that festival quality consisting of the sub-dimensions of hospitality, venue, product, convenience, and program have a positive impact on festival value, trust in festival, and festival satisfaction, which in turn affect festival loyalty. Based on these empirical findings, the current study offers practical and theoretical implications for destination management organizations and festival hosts to sustain annual theme-based festivals held at a certain destination such as Macau Food Festival.
“I Have Nowhere to Go”: A Multiple-Case Study of Transgender and Gender Diverse Youth, Their Families, and Healthcare Experiences
Authors: Paceley Megan S. , Ananda Jennifer , Thomas Margaret M. C. , Sanders Isaac , Hiegert Delaney , Monley Taylor Davis
Published: September 2021

Transgender and gender diverse (TGD) youth experience health disparities due to stigma and victimization. Gender-affirming healthcare mitigates these challenges; yet, we have limited understanding of TGD youth’s healthcare experiences in the U.S. Midwest and South. Using a multiple case study design, we aimed to develop an in-depth and cross-contextual understanding of TGD youth healthcare experiences in one Midwestern state. Families with a TGD child under 18 were recruited with the goal of cross-case diversity by child age, gender, race, and/or region of the state; we obtained diversity in child age and region only. Four white families with TGD boys or non-binary youth (4–16) in rural, suburban, and small towns participated in interviews and observations for one year; public data were collected from each family’s community. Thematic analysis was used within and across cases to develop both family-level understanding and identify themes across families. Findings include a summary of each family as it relates to their child’s TGD healthcare experiences as well as the themes identified across cases: accessibility and affirming care. Although limited by a small sample with lack of gender and race diversity, this study contributes to our understanding of TGD youth healthcare in understudied regions.
Medical Health Records-Based Mild Cognitive Impairment (MCI) Prediction for Effective Dementia Care
Authors: Lim Soo-Jin , Lee Zoonky , Kwon Lee-Nam , Chun Hong-Woo
Published: September 2021

Dementia is a cognitive impairment that poses a global threat. Current dementia treatments slow the progression of the disease. The timing of starting such treatment markedly affects the effectiveness of the treatment. Some experts mentioned that the optimal timing for starting the currently available treatment in order to delay progression to dementia is the mild cognitive impairment stage, which is the prior stage of dementia. However, medical records are typically only available at a later stage, i.e., from the early or middle stage of dementia. In order to address this limitation, this study developed a model using national health information data from 5 years prior, to predict dementia development 5 years in the future. The Senior Cohort Database, comprising 550,000 samples, were used for model development. The F-measure of the model predicting dementia development after a 5-year incubation period was 77.38%. Models for a 1- and 3-year incubation period were also developed for comparative analysis of dementia risk factors. The three models had some risk factors in common, but also had unique risk factors, depending on the stage. For the common risk factors, a difference in disease severity was confirmed. These findings indicate that the diagnostic criteria and treatment strategy for dementia should differ depending on the timing. Furthermore, since the results of this study present new dementia risk factors that have not been reported previously, this study may also contribute to identification of new dementia risk factors.
Multivariate Analysis of Risk Factors of the COVID-19 Pandemic in the Community of Madrid, Spain
Authors: Pérez-Segura Víctor , Caro-Carretero Raquel , Rua Antonio
Published: September 2021

It has been more than one year since Chinese authorities identified a deadly new strain of coronavirus, SARS-CoV-2. Since then, the scientific work regarding the transmission risk factors of COVID-19 has been intense. The relationship between COVID-19 and environmental conditions is becoming an increasingly popular research topic. Based on the findings of the early research, we focused on the community of Madrid, Spain, which is one of the world’s most significant pandemic hotspots. We employed different multivariate statistical analyses, including principal component analysis, analysis of variance, clustering, and linear regression models. Principal component analysis was employed in order to reduce the number of risk factors down to three new components that explained 71% of the original variance. Cluster analysis was used to delimit the territory of Madrid according to these new risk components. An ANOVA test revealed different incidence rates between the territories delimited by the previously identified components. Finally, a set of linear models was applied to demonstrate how environmental factors present a greater influence on COVID-19 infections than socioeconomic dimensions. This type of local research provides valuable information that could help societies become more resilient in the face of future pandemics.
S1P Stimulates Erythropoietin Production in Mouse Renal Interstitial Fibroblasts by S1P1 and S1P3 Receptor Activation and HIF-2α Stabilization
Authors: Hafizi Redona , Imeri Faik , Wenger Roland H. , Huwiler Andrea
Published: September 2021

Erythropoietin (Epo) is the critical hormone for erythropoiesis. In adults, Epo is mainly produced by a subset of interstitial fibroblasts in the kidney, with minor amounts being produced in the liver and the brain. In this study, we used the immortalized renal interstitial fibroblast cell line FAIK F3-5 to investigate the ability of the bioactive sphingolipid sphingosine 1-phosphate (S1P) to stimulate Epo production and to reveal the mechanism involved. Stimulation of cells with exogenous S1P under normoxic conditions (21% O2) led to a dose-dependent increase in Epo mRNA and protein levels and subsequent release of Epo into the medium. S1P also enhanced the stabilization of HIF-2α, a key transcription factor for Epo expression. S1P-stimulated Epo mRNA and protein expression was abolished by HIF-2α mRNA knockdown or by the HIF-2 inhibitor compound 2. Furthermore, the approved S1P receptor modulator FTY720, and its active form FTY720-phosphate, both exerted a similar effect on Epo expression as S1P. The effect of S1P on Epo was antagonized by the selective S1P1 and S1P3 antagonists NIBR-0213 and TY-52156, but not by the S1P2 antagonist JTE-013. Moreover, inhibitors of the classical MAPK/ERK, the p38-MAPK, and inhibitors of protein kinase (PK) C and D all blocked the effect of S1P on Epo expression. Finally, the S1P and FTY720 effects were recapitulated in the Epo-producing human neuroblastoma cell line Kelly, suggesting that S1P receptor-dependent Epo synthesis is of general relevance and not species-specific. In summary, these data suggest that, in renal interstitial fibroblasts, which are the primary source of plasma Epo, S1P1 and 3 receptor activation upregulates Epo under normoxic conditions. This may have a therapeutic impact on disease situations such as chronic kidney disease, where Epo production is impaired, causing anemia, but it may also have therapeutic value as Epo can mediate additional tissue-protective effects in various organs.
Chemotherapy-Induced Intestinal Microbiota Dysbiosis Impairs Mucosal Homeostasis by Modulating Toll-like Receptor Signaling Pathways
Authors: Wei Ling , Wen Xue-Sen , Xian Cory J.
Published: September 2021

Chemotherapy-induced intestinal mucositis, a painful debilitating condition affecting up to 40–100% of patients undergoing chemotherapy, can reduce the patients’ quality of life, add health care costs and even postpone cancer treatment. In recent years, the relationships between intestinal microbiota dysbiosis and mucositis have drawn much attention in mucositis research. Chemotherapy can shape intestinal microbiota, which, in turn, can aggravate the mucositis through toll-like receptor (TLR) signaling pathways, leading to an increased expression of inflammatory mediators and elevated epithelial cell apoptosis but decreased epithelial cell differentiation and mucosal regeneration. This review summarizes relevant studies related to the relationships of mucositis with chemotherapy regimens, microbiota, TLRs, inflammatory mediators, and intestinal homeostasis, aiming to explore how gut microbiota affects the pathogenesis of mucositis and provides potential new strategies for mucositis alleviation and treatment and development of new therapies.
Effects of β-Phenylethylamine on Psychomotor, Rewarding, and Reinforcing Behaviors and Affective State: The Role of Dopamine D1 Receptors
Authors: Ryu In Soo , Kim Oc-Hee , Kim Ji Sun , Sohn Sumin , Choe Eun Sang , Lim Ri-Na , Kim Tae Wan , Seo Joung-Wook , Jang Eun Young
Published: September 2021

Beta-phenylethylamine (β-PEA) is a well-known and widespread endogenous neuroactive trace amine found throughout the central nervous system in humans. In this study, we demonstrated the effects of β-PEA on psychomotor, rewarding, and reinforcing behaviors and affective state using the open-field test, conditioned place preference (CPP), self-administration, and ultrasonic vocalizations (USVs) paradigms. We also investigated the role of the dopamine (DA) D1 receptor in the behavioral effects of β-PEA in rodents. Using enzyme-linked immunosorbent assay (ELISA) and Western immunoblotting, we also determined the DA concentration and the DA-related protein levels in the dorsal striatum of mice administered with acute β-PEA. The results showed that acute β-PEA increased stereotypic behaviors such as circling and head-twitching responses in mice. In the CPP experiment, β-PEA increased place preference in mice. In the self-administration test, β-PEA significantly enhanced self-administration during a 2 h session under fixed ratio (FR) schedules (FR1 and FR3) and produced a higher breakpoint during a 6 h session under progressive ratio schedules of reinforcement in rats. In addition, acute β-PEA increased 50-kHz USV calls in rats. Furthermore, acute β-PEA administration increased DA concentration and p-DAT and TH expression in the dorsal striatum of mice. Finally, pretreatment with SCH23390, a DA D1 receptor antagonist, attenuated β-PEA-induced circling behavior and β-PEA-taking behavior in rodents. Taken together, these findings suggest that β-PEA has rewarding and reinforcing effects and psychoactive properties, which induce psychomotor behaviors and a positive affective state by activating the DA D1 receptor in the dorsal striatum.
Fc Receptor Variants and Disease: A Crucial Factor to Consider in the Antibody Therapeutics in Clinic
Authors: Kim Jin , Lee Ji Young , Kim Han Gil , Kwak Min Woo , Kang Tae Hyun
Published: September 2021

The fragment crystallizable (Fc) domain of antibodies is responsible for their protective function and long-lasting serum half-life via Fc-mediated effector function, transcytosis, and recycling through its interaction with Fc receptors (FcRs) expressed on various immune leukocytes, epithelial, and endothelial cells. Therefore, the Fc–FcRs interaction is a control point of both endogenous and therapeutic antibody function. There are a number of reported genetic variants of FcRs, which include polymorphisms in (i) extracellular domain of FcRs, which change their affinities to Fc domain of antibodies; (ii) both cytoplasmic and intracellular domain, which alters the extent of signal transduction; and (iii) the promoter region of the FcRs gene, which affects the expression level of FcRs, thus being associated with the pathogenesis of disease indications. In this review, we firstly describe the correlation between the genetic variants of FcRs and immunological disorders by individual differences in the extent of FcRs-mediated regulations. Secondly, we discuss the influence of the genetic variants of FcRs on the susceptibility to infectious diseases or cancer in the perspective of FcRs-induced effector functions. Overall, we concluded that the genetic variants of FcRs are one of the key elements in the design of antibody therapeutics due to their variety of clinical outcomes among individuals.
Non-Coding RNAs in Normal B-Cell Development and in Mantle Cell Lymphoma: From Molecular Mechanism to Biomarker and Therapeutic Agent Potential
Authors: Kersy Olga , Salmon-Divon Mali , Shpilberg Ofer , Hershkovitz-Rokah Oshrat
Published: September 2021

B-lymphocytes are essential for an efficient immune response against a variety of pathogens. A large fraction of hematologic malignancies are of B-cell origin, suggesting that the development and activation of B cells must be tightly regulated. In recent years, differentially expressed non-coding RNAs have been identified in mantle cell lymphoma (MCL) tumor samples as opposed to their naive, normal B-cell compartment. These aberrantly expressed molecules, specifically microRNAs (miRNAs), circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), have a role in cellular growth and survival pathways in various biological models. Here, we provide an overview of current knowledge on the role of non-coding RNAs and their relevant targets in B-cell development, activation and malignant transformation, summarizing the current understanding of the role of aberrant expression of non-coding RNAs in MCL pathobiology with perspectives for clinical use.
MicroRNAs as Biomarkers for Predicting Complications following Aneurysmal Subarachnoid Hemorrhage
Authors: Wang Wang-Xia , Springer Joe E. , Hatton Kevin W.
Published: September 2021

Aneurysmal subarachnoid hemorrhage (aSAH) is a high mortality hemorrhagic stroke that affects nearly 30,000 patients annually in the United States. Approximately 30% of aSAH patients die during initial hospitalization and those who survive often carry poor prognosis with one in five having permanent physical and/or cognitive disabilities. The poor outcome of aSAH can be the result of the initial catastrophic event or due to the many acute or delayed neurological complications, such as cerebral ischemia, hydrocephalus, and re-bleeding. Unfortunately, no effective biomarker exists to predict or diagnose these complications at a clinically relevant time point when neurologic injury can be effectively treated and managed. Recently, a number of studies have demonstrated that microRNAs (miRNAs) in extracellular biofluids are highly associated with aSAH and complications. Here we provide an overview of the current research on relevant human studies examining the correlation between miRNAs and aSAH complications and discuss the potential application of using miRNAs as biomarkers in aSAH management.
Protective and Anti-Inflammatory Effects of Protegrin-1 on Citrobacter rodentium Intestinal Infection in Mice
Authors: Osakowicz Celina , Fletcher Lauren , Caswell Jeff L. , Li Julang
Published: September 2021

Infectious intestinal colitis, manifesting as intestinal inflammation, diarrhea, and epithelial barrier disruption, affects millions of humans worldwide and, without effective treatment, can result in death. In addition to this, the significant rise in antibiotic-resistant bacteria poses an urgent need for alternative anti-infection therapies for the treatment of intestinal disorders. Antimicrobial peptides (AMPs) are potential therapies that have broad-spectrum antimicrobial activity due to their (1) unique mode of action, (2) broad-spectrum antimicrobial activity, and (3) protective role in GI tract maintenance. Protegrin-1 (PG-1) is an AMP of pig origin that was previously shown to reduce the pathological effects of chemically induced digestive tract inflammation (colitis) and to modulate immune responses and tissue repair. This study aimed to extend these findings by investigating the protective effects of PG-1 on pathogen-induced colitis in an infection study over a 10-day experimental period. The oral administration of PG-1 reduced Citrobacter rodentium intestinal infection in mice as evidenced by reduced histopathologic change in the colon, prevention of body weight loss, milder clinical signs of disease, and more effective clearance of bacterial infection relative to challenged phosphate-buffered saline (PBS)-treated mice. Additionally, PG-1 treatment altered the expression of various inflammatory mediators during infection, which may act to resolve inflammation and re-establish intestinal homeostasis. PG-1 administered in its mature form was more effective relative to the pro-form (ProPG-1). To our knowledge, this is the first study demonstrating the protective effects of PG-1 on infectious colitis.
Genome-Wide Identification and Characterization of Short-Chain Dehydrogenase/Reductase (SDR) Gene Family in Medicago truncatula
Authors: Yu Shuhan , Sun Qiguo , Wu Jiaxuan , Zhao Pengcheng , Sun Yanmei , Guo Zhenfei
Published: September 2021

Short-chain dehydrogenase/reductase (SDR) belongs to the NAD(P)(H)-dependent oxidoreductase superfamily. Limited investigations reveal that SDRs participate in diverse metabolisms. A genome-wide identification of the SDR gene family in M. truncatula was conducted. A total of 213 MtSDR genes were identified, and they were distributed on all chromosomes unevenly. MtSDR proteins were categorized into seven subgroups based on phylogenetic analysis and three types including ‘classic’, ‘extended’, and ‘atypical’, depending on the cofactor-binding site and active site. Analysis of the data from M. truncatula Gene Expression Atlas (MtGEA) showed that above half of MtSDRs were expressed in at least one organ, and lots of MtSDRs had a preference in a tissue-specific expression. The cis-acting element responsive to plant hormones (salicylic acid, ABA, auxin, MeJA, and gibberellin) and stresses were found in the promoter of some MtSDRs. Many genes of MtSDR7C,MtSDR65C, MtSDR110C, MtSDR114C, and MtSDR108E families were responsive to drought, salt, and cold. The study provides useful information for further investigation on biological functions of MtSDRs, especially in abiotic stress adaptation, in the future.
Impaired Differentiation of Highly Proliferative ICOS+-Tregs Is Involved in the Transition from Low to High Disease Activity in Systemic Lupus Erythematosus (SLE) Patients
Authors: Kälble Florian , Wu Lisa , Lorenz Hanns-Martin , Zeier Martin , Schaier Matthias , Steinborn Andrea
Published: September 2021

Dysregulations in the differentiation of CD4+-regulatory-T-cells (Tregs) and CD4+-responder-T-cells (Tresps) are involved in the development of active systemic lupus erythematosus (SLE). Three differentiation pathways of highly proliferative inducible costimulatory molecule (ICOS)+- and less proliferative ICOS−-CD45RA+CD31+-recent-thymic-emigrant (RTE)-Tregs/Tresps via CD45RA−CD31+-memory-Tregs/Tresps (CD31+-memory-Tregs/Tresps), their direct proliferation via CD45RA+CD31−-mature naïve (MN)-Tregs/Tresps, and the production and differentiation of resting MN-Tregs/Tresp into CD45RA−CD31−-memory-Tregs/Tresps (CD31−-memory-Tregs/Tresps) were examined in 115 healthy controls, 96 SLE remission patients, and 20 active disease patients using six color flow cytometric analysis. In healthy controls an appropriate sequence of these pathways ensured regular age-dependent differentiation. In SLE patients, an age-independently exaggerated differentiation was observed for all Treg/Tresp subsets, where the increased conversion of resting MN-Tregs/Tresps particularly guaranteed the significantly increased ratios of ICOS+-Tregs/ICOS+-Tresps and ICOS−-Tregs/ICOS−-Tresps during remission. Changes in the differentiation of resting ICOS+-MN-Tresps and ICOS−-MN-Tregs from conversion to proliferation caused a significant shift in the ratio of ICOS+-Tregs/ICOS+-Tresps in favor of ICOS+-Tresps and a further increase in the ratio of ICOS−-Tregs/ICOS−-Tresps with active disease. The differentiation of ICOS+-RTE-Tregs/Tresps seems to be crucial for keeping patients in remission, where their limited production of proliferating resting MN-Tregs may be responsible for the occurrence of active disease flares.
The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
Authors: Martínez María Sofía , Manzano Alexander , Olivar Luis Carlos , Nava Manuel , Salazar Juan , D’Marco Luis , Ortiz Rina , Chacín Maricarmen , Guerrero-Wyss Marion , Cabrera de Bravo Mayela , Cano Clímaco , Bermúdez Valmore , Angarita Lisse
Published: September 2021

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.
Follistatin-Like-1 (FSTL1) Is a Fibroblast-Derived Growth Factor That Contributes to Progression of Chronic Kidney Disease
Authors: Maksimowski Nicholas A. , Song Xuewen , Bae Eun Hui , Reich Heather , John Rohan , Pei York , Scholey James W. ,   Nephrotic Syndrome Study Network (NEPTUNE)
Published: September 2021

Our understanding of the mechanisms responsible for the progression of chronic kidney disease (CKD) is incomplete. Microarray analysis of kidneys at 4 and 7 weeks of age in Col4a3-/- mice, a model of progressive nephropathy characterized by proteinuria, interstitial fibrosis, and inflammation, revealed that Follistatin-like-1 (Fstl1) was one of only four genes significantly overexpressed at 4 weeks of age. mRNA levels for the Fstl1 receptors, Tlr4 and Dip2a, increased in both Col4a-/- mice and mice subjected to unilateral ureteral obstruction (UUO). RNAscope® (Advanced Cell Diagnostics, Newark CA, USA) localized Fstl1 to interstitial cells, and in silico analysis of single cell transcriptomic data from human kidneys showed Fstl1 confined to interstitial fibroblasts/myofibroblasts. In vitro, FSTL1 activated AP1 and NFκB, increased collagen I (COL1A1) and interleukin-6 (IL6) expression, and induced apoptosis in cultured kidney cells. FSTL1 expression in the NEPTUNE cohort of humans with focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and IgA nephropathy (IgAN) was positively associated with age, eGFR, and proteinuria by multiple linear regression, as well as with interstitial fibrosis and tubular atrophy. Clinical disease progression, defined as dialysis or a 40 percent reduction in eGFR, was greater in patients with high baseline FSTL1 mRNA levels. FSTL1 is a fibroblast-derived cytokine linked to the progression of experimental and clinical CKD.
Docking to a Basic Helix Promotes Specific Phosphorylation by G1-Cdk1
Authors: Faustova Ilona , Möll Kaidi , Valk Ervin , Loog Mart , Örd Mihkel
Published: September 2021

Cyclins are the activators of cyclin-dependent kinase (CDK) complex, but they also act as docking scaffolds for different short linear motifs (SLiMs) in CDK substrates and inhibitors. According to the unified model of CDK function, the cell cycle is coordinated by CDK both via general CDK activity thresholds and cyclin-specific substrate docking. Recently, it was found that the G1-cyclins of S. cerevisiae have a specific function in promoting polarization and growth of the buds, making the G1 cyclins essential for cell survival. Thus, while a uniform CDK specificity of a single cyclin can be sufficient to drive the cell cycle in some cells, such as in fission yeast, cyclin specificity can be essential in other organisms. However, the known G1-CDK specific LP docking motif, was not responsible for this essential function, indicating that G1-CDKs use yet other unknown docking mechanisms. Here we report a discovery of a G1 cyclin-specific (Cln1,2) lysine-arginine-rich helical docking motif (the K/R motif) in G1-CDK targets involved in the mating pathway (Ste7), transcription (Xbp1), bud morphogenesis (Bud2) and spindle pole body (Spc29, Spc42, Spc110, Sli15) function of S. cerevisiae. We also show that the docking efficiency of K/R motif can be regulated by basophilic kinases such as protein kinase A. Our results further widen the list of cyclin specificity mechanisms and may explain the recently demonstrated unique essential function of G1 cyclins in budding yeast.
Limits of Compartmental Models and New Opportunities for Machine Learning: A Case Study to Forecast the Second Wave of COVID-19 Hospitalizations in Lombardy, Italy
Authors: Gatto Andrea , Accarino Gabriele , Aloisi Valeria , Immorlano Francesco , Donato Francesco , Aloisio Giovanni
Published: September 2021

Compartmental models have long been used in epidemiological studies for predicting disease spread. However, a major issue when using compartmental mathematical models concerns the time-invariant formulation of hyper-parameters that prevent the model from following the evolution over time of the epidemiological phenomenon under investigation. In order to cope with this problem, the present work suggests an alternative hybrid approach based on Machine Learning that avoids recalculation of hyper-parameters and only uses an initial set. This study shows that the proposed hybrid approach makes it possible to correct the expected loss of accuracy observed in the compartmental model when the considered time horizon increases. As a case study, a basic compartmental model has been designed and tested to forecast COVID-19 hospitalizations during the first and the second pandemic waves in Lombardy, Italy. The model is based on an extended formulation of the contact function that allows modelling of the trend of personal contacts throughout the reference period. Moreover, the scenario analysis proposed in this work can help policy-makers select the most appropriate containment measures to reduce hospitalizations and relieve pressure on the health system, but also to limit any negative impact on the economic and social systems.
Diversity Patterns of Dung Beetles along a Mediterranean Elevational Gradient
Authors: Mantoni Cristina , Tsafack Noelline , Palusci Ettore , Di Pietro Stefano , Fattorini Simone
Published: September 2021

Most studies of biodiversity–elevational patterns do not take species abundance into consideration. Hill numbers are a unified family of indices that use species abundance and allow a complete characterization of species assemblages through diversity profiles. Studies on dung beetle responses to elevation were essentially based on species richness and produced inconsistent results because of the non-distinction between different habitats and the use of gradients dispersed over wide areas. We analyzed dung beetle diversity in a Mediterranean mountain (central Italy) for different habitats (woodlands vs. grasslands) and taxonomic groups (scarabaeids and aphodiids). Scarabaeids were the most abundant. Since scarabaeids are able to construct subterranean nests, this indicates that the warm and dry summer climatic conditions of high elevations favor species capable of protecting their larvae from desiccation. Dung beetles were more abundant and diversified in grasslands than in woodlands, which is consistent with their preference for open habitats. In the woodlands, diversity increased with increasing elevation because of increasing tree thinning, whereas, in the grasslands, diversity decreased with elevation because of increasingly harsher environmental conditions. These results indicate a trade-off in the beetle response to elevation between the positive effects of increasing the availability of more suitable habitats and the decrease of optimal environmental conditions.
Smart Cane Developed with DFSS, QFD, and SDE for the Visually Impaired
Authors: Frizziero Leonardo , Liverani Alfredo , Donnici Giampiero , Papaleo Paola , Leon-Cardenas Christian
Published: September 2021

This study shows an application of the Design for Six Sigma (DFSS) Methodology in the field of medical engineering. This research aims to demonstrate the application of a systematic design approach in the development of the “Ocane”, an innovative concept of smart cane for visually impaired patients which was thought of in answer to the end user’s needs, deploying an easy to transport, locate, and adjust element with ultrasonic sensors and tactile feedback. DFSS is an analytical design methodology meant to organize project workflow in a sequence of specific steps. Other standardized design procedures such as Quality Function Deployment (QFD) and Stylistic Design Engineering (SDE) have been used to support DFSS in terms of targeting customer requirements and focusing on aesthetics for ergonomics analysis, respectively. First, the QFD process is introduced and applied to gather the final customer needs, completing the analysis with benchmarking and similar-thought products on the market. Afterwards, a description of the DFSS methodology and application to the case study was deployed. Thereafter, the SDE procedure is exposed by identifying the “Ocane” concept and development, and moving towards the completion of an inventive product with a creative design and careful attention to visually impaired clients’ requirements.
Shaping the Future of Smart Dentistry: From Artificial Intelligence (AI) to Intelligence Augmentation (IA)
Authors: Hassani Hossein , Amiri Andi Pedram , Ghodsi Alireza , Norouzi Kimia , Komendantova Nadejda , Unger Stephan
Published: September 2021

Digitization is the emerging process in the current transformation of industry. Understanding the role and socio-economic consequences of digitalization is crucial for the way technology is being deployed in each sector. One of the affected sectors is dentistry. This study highlights the current advances and challenges in integrating and merging artificial intelligence (AI), intelligence augmentation (IA), and machine learning (ML) in dentistry. We conduct a comparative analysis to give an overview of which technology is being currently deployed and what role IA and AI will play in dentistry, as AI plays an assistive role in advancing human capabilities. We find that challenges range from AI finding its way into routine medical practice to qualitative challenges of retrieving adequate data input. Other challenges lie in the yet unanswered questions of liability in how to reduce deployment costs of new technology. Given these challenges, we provide an outlook of how future technology can be deployed in daily-life dentistry and how robots and humans will interact, given the current technology developments. The aim of this paper is to discuss the future of dentistry and whether it is AI or IA conquering the modern dentistry era.
The Comparison of Clinical Result between Primary Repair of the Anterior Cruciate Ligament with Additional Internal Bracing and Anatomic Single Bundle Reconstruction—A Retrospective Study
Authors: Szwedowski Dawid , Paczesny Łukasz , Zabrzyński Jan , Gagat Maciej , Domżalski Marcin , Huri Gazi , Widuchowski Wojciech
Published: September 2021

Background: The current standard of treatment of anterior cruciate ligament (ACL) is reconstruction (ACLR). This technique has some disadvantages: poor proprioception, donor site morbidity and the inability to restore joint kinematics. ACL repair could be an alternative treatment. The purpose of the study was to compare the stability and the function after ACL primary repair versus single-bundle ACLR. Methods: In a retrospective study, 12 patients underwent primary ACL repair with internal bracing, 15 patients underwent standard ACLR. Follow-up examinations were evaluated at up to 2 years postoperatively. One patient in the ACL repair group was lost to follow-up due to re-rupture. The absolute value of anterior tibial translation (ATT) and the side-to-side difference in the same patient (ΔATT) were evaluated using the GNRB arthrometer. The Lysholm knee scoring was obtained. Re-ruptures and other complications were recorded. Results: Anterior tibial translation (ATT) was significantly decreased in the ACL repair group compared with the ACLR group (5.31 mm vs. 7.18 mm, respectively; p = 0.0137). Arthrometric measurements demonstrated a mean side-to-side difference (ΔATT) 1.87 (range 0.2 to 4.9) mm significantly decreased compared to ACLR 3.36 (range 1.2–5.6 mm; p = 0.0107). The mean Lysholm score was 85.3 points in the ACL repair group and 89.9 in ACLR group. No significant differences between ACL repair and ACLR were found for the Lysholm score. There was no association between AP laxity and clinical outcomes. There were two complications in the internal bracing group: one patient had re-rupture and was treated by ACLR, another had limited extension and had arthroscopic debridement. Conclusions: Anterior tibial translation was significantly decreased after ACL repair. Additionally, the functional results after ACL repair with internal bracing were comparable with those after ACLR. It should be noted that the two complications occurred. The current study supports further development of ACL repair techniques.
Guided Bone Regeneration with Concentrated Growth Factor Enriched Bone Graft Matrix (Sticky Bone) vs. Bone-Shell Technique in Horizontal Ridge Augmentation: A Retrospective Study
Authors: Barbu Horia Mihail , Iancu Stefania Andrada , Rapani Antonio , Stacchi Claudio
Published: September 2021

Background: The purpose of this study was to compare clinical results of two different horizontal ridge augmentation techniques: guided bone regeneration with sticky bone (SB) and the bone-shell technique (BS). Methods: Records of patients who underwent horizontal ridge augmentation with SB (test) and BS (control) were screened for inclusion. Pre-operative and 6-month post-operative ridge widths were measured on cone beam computer tomography (CBCT) and compared. Post-operative complications and implant survival rate were recorded. Results: Eighty consecutive patients were included in the present study. Post-operative complications (flap dehiscence, and graft infection) occurred in ten patients, who dropped out from the study (12.5% complication rate). Stepwise multivariate logistic regression analysis showed a significant inverse correlation between the occurrence of post-operative complications and ridge width (p = 0.025). Seventy patients (35 test; 35 control) with a total of 127 implants were included in the final analysis. Mean ridge width gain was 3.7 ± 1.2 mm in the test and 3.7 ± 1.1 mm in the control group, with no significant difference between the two groups. No implant failure was recorded, with a mean follow-up of 42.7 ± 16.0 months after functional loading. Conclusions: SB and BS showed comparable clinical outcomes in horizontal ridge augmentation, resulting in sufficient crestal width increase to allow implant placement in an adequate bone envelope.
GLP-1 Receptor Agonists in Diabetic Kidney Disease: From Physiology to Clinical Outcomes
Authors: Rojano Toimil Alba , Ciudin Andreea
Published: September 2021

Diabetic kidney disease (DKD) is one of the most common complications in type 2 diabetes mellitus (T2D) and a major cause of morbidity and mortality in diabetes. Despite the widespread use of nephroprotective treatment of T2D, the incidence of DKD is increasing, and it is expected to become the fifth cause of death worldwide within 20 years. Previous studies have demonstrated that GLP-1 receptor agonists (GLP-1 RA) have improved macrovascular and microvascular outcomes independent of glycemic differences, including DKD. GLP-1Ras’ improvement on kidney physiology is mediated by natriuresis, reduction in hyperfiltration and renin-angiotensin-aldosterone system (RAAS) activity and anti-inflammatory properties. These findings translate into improved clinical outcomes such as an enhanced urine albumin-to-creatinine ratio (UACR) and a reduction in renal impairment and the need for renal replacement therapies (RRT). In this article, we review the role of GLP-1RAs on the mechanisms and effect in DKD and their clinical efficacy.