bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers and Facilitators for Exclusive Breastfeeding within the Health System and Public Policies from In-Depth Interviews to Primary Care Midwives in Tenerife (Canary Islands, Spain)
Authors: Llorente-Pulido Seila , Custodio Estefanía , López-Giménez María Rosario , Otero-García Laura
Published: December 2021

The aim of this study is to describe the perspectives of Primary Care midwives regarding factors that benefit or are detrimental to exclusive breastfeeding (EBF) within the health system and public policies. The study was carried out in Tenerife (Canary Islands, Spain) and is based on qualitative methodology. Twenty in-depth interviews were carried out with midwives who work in Primary Care centres in Tenerife, using a content analysis approach. The transcript data were then encoded following an inductive approach. The factors, according to midwives, that affect EBF, with regard to the healthcare system, are related to training of healthcare professionals in breastfeeding and their support to women during pregnancy, childbirth and postnatal care. Regarding public policies, midwives believe the maternity leave periods in Spain, together with a lack of laws and social policies to protect EBF are detrimental. The findings from our study show that there is a need to boost training and the role of professionals in EBF and, at the same time, promote protective policies that foster equality, favouring, among other issues, the work-life balance.
Gambling in Spanish Adolescents: Prevalence and Association with Mental Health Indicators
Authors: Pérez-Albéniz Alicia , Gil Mario , Díez-Gómez Adriana , Martín-Seoane Gema , Lucas-Molina Beatriz
Published: December 2021

Concern about the development of behavioral addictions in adolescence, including gambling, has increased in recent years. Evidence shows that problem gambling can lead to personal, social, or health problems. However, even though gambling is an illegal activity, studies on this problem are quite limited in Spain. The main objective of this study was to analyze the prevalence of gambling in adolescents in Spain. Moreover, gambling behaviors were examined according to gender and age, and their possible relationship with several mental health indicators was analyzed. The results showed that 20.6% of the adolescents who participated in the study had gambled money in the past year. The highest gambling prevalence was found in boys and in adolescents from the age of 16 years old. Moreover, the results showed that gambling behavior was related to different mental health indicators.
Cultivated Land Fragmentation and Its Influencing Factors Detection: A Case Study in Huaihe River Basin, China
Authors: Liang Jiale , Pan Sipei , Chen Wanxu , Li Jiangfeng , Zhou Ting
Published: December 2021

The booming population and accelerating urbanization in the Huaihe River Basin have sped up the land use transformation and the cultivated land fragmentation (CLF), seriously impeded the advancement of agricultural modernization, and threatened regional stability and national food security as well. The analysis of CLF degree and its spatiotemporal distribution characteristics, along with the influencing factors in the Huaihe River Basin, is of great significance for promoting the intensive and efficient utilization of cultivated land resources and maintaining food security. Previous studies lack the measurement and cause analysis of CLF in Huaihe River Basin. To bridge the gap, this study introduces Fragstats4.2 and ArcGIS10.3 to analyze the spatiotemporal characteristics of CLF in county units in the Huaihe River Basin from 2000 to 2018 through the Lorentz curve, entropy method, and spatial auto-correlation method while the causes of the spatiotemporal differentiation of CLF in the basin were explored with the help of a geographic detector. The results show that the spatial distribution of cultivated land in the Huaihe River Basin is relatively balanced, and the Gini coefficients of cultivated land from 2000 to 2018 were 0.105, 0.108, and 0.113, respectively. More than 56% of the counties in the basin have a location entropy greater than 1. the percentage of landscape, area-weighted mean patch area, patch cohesion index, and aggregation index decrease year by year while the patch density and splitting index show an upward trend. The landscape pattern of cultivated land is highly complex, and the overall fragmentation degree is increasing. The county distribution pattern of the CLF degree with random and agglomeration is generally stable. The spatiotemporal differentiation of CLF in the Huaihe River Basin is affected by multiple factors, among which the influences of the normalized difference vegetation index, per capita cultivated land area, and intensity of human activity obviously stronger than other factors, and the contribution rate of the factors reached more than 0.4. The interaction effect among the factors is stronger than that of single factor, with dual-factor enhancement and nonlinear enhancement dominating. The results of this study have important implications for optimizing the agricultural structure in the Huaihe River Basin and alleviating the CLF in important grain production areas.
Time-Out with Young Children: A Parent-Child Interaction Therapy (PCIT) Practitioner Review
Authors: Woodfield Melanie J. , Brodd Irene , Hetrick Sarah E.
Published: December 2021

Time-out is a component of many evidence-based parent training programmes for the treatment of childhood conduct problems. Existing comprehensive reviews suggest that time-out is both safe and effective when used predictably, infrequently, calmly and as one component of a collection of parenting strategies—i.e., when utilised in the manner advocated by most parent training programmes. However, this research evidence has been largely oriented towards the academic community and is often in conflict with the widespread misinformation about time-out within communities of parents, and within groups of treatment practitioners. This dissonance has the potential to undermine the dissemination and implementation of an effective suite of treatments for common and disabling childhood conditions. The parent-practitioner relationship is integral to the success of Parent-Child Interaction Therapy (PCIT), an evidence-based treatment which involves live coaching of parent(s) with their young child(ren). Yet this relationship, and practitioner perspectives, attitudes and values as they relate to time-out, are often overlooked. This practitioner review explores the dynamics of the parent-practitioner relationship as they apply to the teaching and coaching of time-out to parents. It also acknowledges factors within the clinical setting that impact on time-out’s use, such as the views of administrators and professional colleagues. The paper is oriented toward practitioners of PCIT but is of relevance to all providers of parent training interventions for young children.
A Review of the Migration and Transformation of Microplastics in Inland Water Systems
Authors: Cai Yamei , Li Chen , Zhao Yaqian
Published: December 2021

Plastic productions continue to grow, and improper management of plastic wastes has raised increasing concerns. This reflects the need to explore the microplastics in water bodies. Microplastics have been regarded as emerging pollutants in water systems. In recent years, large numbers of studies across the world were conducted to investigate the distribution, behavior and the integrated impacts of microplastics in both the marine environment and the freshwater environment. Compared with the marine environment, the migration and transformation of microplastics in inland water systems seem more informative as they may reach the marine environment as one of their final destinations. Based on the updated literature, this review aims at overviewing the migration and transformation processes/behavior of microplastics in rivers, lakes and reservoirs. As for the migration, the microplastics’ fate is from manufacturing, consuming, discarding to migrating and returning to the human society which could form a closed though complicated circle. For transformation, microplastics experience five stages of their fate in inland water systems. These include changing into suspending pieces; ending up deposited as the sediment; resuspending under various changing conditions; ending up via burying into the soil as the part of the riverbed; reaching the marine environment; and being ingested by organisms and also becoming entangled with aquatic plants, etc. It is highly expected that this review can provide a valuable reference for better understanding microplastics’ migration and transformation mechanisms and a guide for the future study of microplastics in an inland water environment.
miR-205-5p Downregulation and ZEB1 Upregulation Characterize the Disseminated Tumor Cells in Patients with Invasive Ductal Breast Cancer
Authors: Kalinkova Lenka , Nikolaieva Nataliia , Smolkova Bozena , Ciernikova Sona , Kajo Karol , Bella Vladimir , Kajabova Viera Horvathova , Kosnacova Helena , Minarik Gabriel , Fridrichova Ivana
Published: December 2021

Background: Dissemination of breast cancer (BC) cells through the hematogenous or lymphogenous vessels leads to metastatic disease in one-third of BC patients. Therefore, we investigated the new prognostic features for invasion and metastasis. Methods: We evaluated the expression of miRNAs and epithelial-to-mesenchymal transition (EMT) genes in relation to CDH1/E-cadherin changes in samples from 31 patients with invasive ductal BC including tumor centrum (TU-C), tumor invasive front (TU-IF), lymph node metastasis (LNM), and CD45-depleted blood (CD45-DB). Expression of miRNA and mRNA was quantified by RT-PCR arrays and associations with clinico-pathological characteristics were statistically evaluated by univariate and multivariate analysis. Results: We did not verify CDH1 regulating associations previously described in cell lines. However, we did detect extremely high ZEB1 expression in LNMs from patients with distant metastasis, but without regulation by miR-205-5p. Considering the ZEB1 functions, this overexpression indicates enhancement of metastatic potential of lymphogenously disseminated BC cells. In CD45-DB samples, downregulated miR-205-5p was found in those expressing epithelial and/or mesenchymal markers (CTC+) that could contribute to insusceptibility and survival of hematogenously disseminated BC cells mediated by increased expression of several targets including ZEB1. Conclusions: miR-205-5p and potentially ZEB1 gene are promising candidates for markers of metastatic potential in ductal BC.
KIAA1217 Promotes Epithelial-Mesenchymal Transition and Hepatocellular Carcinoma Metastasis by Interacting with and Activating STAT3
Authors: Wang Yanhong , Li Na , Zheng Yanping , Wang Anqing , Yu Chunlei , Song Zhenbo , Wang Shuyue , Sun Ying , Zheng Lihua , Wang Guannan , Liu Lei , Yi Jingwen , Huang Yanxin , Zhang Muqing , Bao Yongli , Sun Luguo
Published: December 2021

The survival and prognosis of hepatocellular carcinoma (HCC) are poor, mainly due to metastasis. Therefore, insights into the molecular mechanisms underlying HCC invasion and metastasis are urgently needed to develop a more effective antimetastatic therapy. Here, we report that KIAA1217, a functionally unknown macromolecular protein, plays a crucial role in HCC metastasis. KIAA1217 expression was frequently upregulated in HCC cell lines and tissues, and high KIAA1217 expression was closely associated with shorter survival of patients with HCC. Overexpression and knockdown experiments revealed that KIAA1217 significantly promoted cell migration and invasion by inducing epithelial-mesenchymal transition (EMT) in vitro. Consistently, HCC cells overexpressing KIAA1217 exhibited markedly enhanced lung metastasis in vivo. Mechanistically, KIAA1217 enhanced EMT and accordingly promoted HCC metastasis by interacting with and activating JAK1/2 and STAT3. Interestingly, KIAA1217-activated p-STAT3 was retained in the cytoplasm instead of translocating into the nucleus, where p-STAT3 subsequently activated the Notch and Wnt/β-catenin pathways to facilitate EMT induction and HCC metastasis. Collectively, KIAA1217 may function as an adaptor protein or scaffold protein in the cytoplasm and coordinate multiple pathways to promote EMT-induced HCC metastasis, indicating its potential as a therapeutic target for curbing HCC metastasis.
Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis
Authors: Bošnjak Matic , Večerić-Haler Željka , Boštjančič Emanuela , Kojc Nika
Published: December 2021

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.
TRPM3 Is Expressed in Afferent Bladder Neurons and Is Upregulated during Bladder Inflammation
Authors: Vanneste Matthias , Mulier Marie , Nogueira Freitas Ana , Van Ranst Nele , Kerstens Axelle , Voets Thomas , Everaerts Wouter
Published: December 2021

The cation channel TRPM3 is activated by heat and the neurosteroid pregnenolone sulfate. TRPM3 is expressed on sensory neurons innervating the skin, where together with TRPV1 and TRPA1, it functions as one of three redundant sensors of acute heat. Moreover, functional upregulation of TRPM3 during inflammation contributes to heat hyperalgesia. The role of TRPM3 in sensory neurons innervating internal organs such as the bladder is currently unclear. Here, using retrograde labeling and single-molecule fluorescent RNA in situ hybridization, we demonstrate expression of mRNA encoding TRPM3 in a large subset of dorsal root ganglion (DRG) neurons innervating the mouse bladder, and confirm TRPM3 channel functionality in these neurons using Fura-2-based calcium imaging. After induction of cystitis by injection of cyclophosphamide, we observed a robust increase of the functional responses to agonists of TRPM3, TRPV1, and TRPA1 in bladder-innervating DRG neurons. Cystometry and voided spot analysis in control and cyclophosphamide-treated animals did not reveal differences between wild type and TRPM3-deficient mice, indicating that TRPM3 is not critical for normal voiding. We conclude that TRPM3 is functionally expressed in a large proportion of sensory bladder afferent, but its role in bladder sensation remains to be established.
From Molecules to Behavior in Long-Term Inorganic Mercury Intoxication: Unraveling Proteomic Features in Cerebellar Neurodegeneration of Rats
Authors: Bittencourt Leonardo Oliveira , Chemelo Victória Santos , Aragão Walessa Alana Bragança , Puty Bruna , Dionizio Aline , Teixeira Francisco Bruno , Fernandes Mileni Silva , Silva Márcia Cristina Freitas , Fernandes Luanna Melo Pereira , de Oliveira Edivaldo Herculano Corrêa , Buzalaf Marilia Afonso Rabelo , Crespo-Lopez Maria Elena , Maia Cristiane do Socorro Ferraz , Lima Rafael Rodrigues
Published: December 2021

Mercury is a severe environmental pollutant with neurotoxic effects, especially when exposed for long periods. Although there are several evidences regarding mercury toxicity, little is known about inorganic mercury (IHg) species and cerebellum, one of the main targets of mercury associated with the neurological symptomatology of mercurial poisoning. Besides that, the global proteomic profile assessment is a valuable tool to screen possible biomarkers and elucidate molecular targets of mercury neurotoxicity; however, the literature is still scarce. Thus, this study aimed to investigate the effects of long-term exposure to IHg in adult rats’ cerebellum and explore the modulation of the cerebellar proteome associated with biochemical and functional outcomes, providing evidence, in a translational perspective, of new mercury toxicity targets and possible biomarkers. Fifty-four adult rats were exposed to 0.375 mg/kg of HgCl2 or distilled water for 45 days using intragastric gavage. Then, the motor functions were evaluated by rotarod and inclined plane. The cerebellum was collected to quantify mercury levels, to assess the antioxidant activity against peroxyl radicals (ACAPs), the lipid peroxidation (LPO), the proteomic profile, the cell death nature by cytotoxicity and apoptosis, and the Purkinje cells density. The IHg exposure increased mercury levels in the cerebellum, reducing ACAP and increasing LPO. The proteomic approach revealed a total 419 proteins with different statuses of regulation, associated with different biological processes, such as synaptic signaling, energy metabolism and nervous system development, e.g., all these molecular changes are associated with increased cytotoxicity and apoptosis, with a neurodegenerative pattern on Purkinje cells layer and poor motor coordination and balance. In conclusion, all these findings feature a neurodegenerative process triggered by IHg in the cerebellum that culminated into motor functions deficits, which are associated with several molecular features and may be related to the clinical outcomes of people exposed to the toxicant.
The Metabolism Reprogramming of microRNA Let-7-Mediated Glycolysis Contributes to Autophagy and Tumor Progression
Authors: Li Chien-Hsiu , Liao Chiao-Chun
Published: December 2021

Cancer is usually a result of abnormal glucose uptake and imbalanced nutrient metabolization. The dysregulation of glucose metabolism, which controls the processes of glycolysis, gives rise to various physiological defects. Autophagy is one of the metabolic-related cellular functions and involves not only energy regeneration but also tumorigenesis. The dysregulation of autophagy impacts on the imbalance of metabolic homeostasis and leads to a variety of disorders. In particular, the microRNA (miRNA) Let-7 has been identified as related to glycolysis procedures such as tissue repair, stem cell-derived cardiomyocytes, and tumoral metastasis. In many cancers, the expression of glycolysis-related enzymes is correlated with Let-7, in which multiple enzymes are related to the regulation of the autophagy process. However, much recent research has not comprehensively investigated how Let-7 participates in glycolytic reprogramming or its links to autophagic regulations, mainly in tumor progression. Through an integrated literature review and omics-related profiling correlation, this review provides the possible linkage of the Let-7 network between glycolysis and autophagy, and its role in tumor progression.
The Study of Cerebrospinal Fluid microRNAs in Spinal Cord Injury and Neurodegenerative Diseases: Methodological Problems and Possible Solutions
Authors: Baichurina Irina , Valiullin Victor , James Victoria , Rizvanov Albert , Mukhamedshina Yana
Published: December 2021

Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.
EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production
Authors: Nowakowska-Gołacka Jowita , Czapiewska Justyna , Sominka Hanna , Sowa-Rogozińska Natalia , Słomińska-Wojewódzka Monika
Published: December 2021

Endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like protein 1 (EDEM1) is a quality control factor directly involved in the endoplasmic reticulum-associated degradation (ERAD) process. It recognizes terminally misfolded proteins and directs them to retrotranslocation which is followed by proteasomal degradation in the cytosol. The amyloid-β precursor protein (APP) is synthesized and N-glycosylated in the ER and transported to the Golgi for maturation before being delivered to the cell surface. The amyloidogenic cleavage pathway of APP leads to production of amyloid-β (Aβ), deposited in the brains of Alzheimer’s disease (AD) patients. Here, using biochemical methods applied to human embryonic kidney, HEK293, and SH-SY5Y neuroblastoma cells, we show that EDEM1 is an important regulatory factor involved in APP metabolism. We find that APP cellular levels are significantly reduced after EDEM1 overproduction and are increased in cells with downregulated EDEM1. We also report on EDEM1-dependent transport of APP from the ER to the cytosol that leads to proteasomal degradation of APP. EDEM1 directly interacts with APP. Furthermore, overproduction of EDEM1 results in decreased Aβ40 and Aβ42 secretion. These findings indicate that EDEM1 is a novel regulator of APP metabolism through ERAD.
Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform
Authors: Wu Dongwei , Berg Johanna , Arlt Birte , Röhrs Viola , Al-Zeer Munir A. , Deubzer Hedwig E. , Kurreck Jens
Published: December 2021

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.
14-3-3η Promotes Invadosome Formation via the FOXO3–Snail Axis in Rheumatoid Arthritis Fibroblast-like Synoviocytes
Authors: Kadiri Maleck , Charbonneau Martine , Lalanne Catherine , Harper Kelly , Balg Frédéric , Marotta Anthony , Dubois Claire M.
Published: December 2021

Erosive destruction of joint structures is a critical event in the progression of rheumatoid arthritis (RA), in which fibroblast-like synoviocytes (FLS) are the primary effectors. We previously reported that the ability of RA FLS to degrade extracellular matrix (ECM) components depends on the formation of actin-rich membrane protrusions, called invadosomes, through processes that remain elusive. 14-3-3η belongs to a family of scaffolding proteins involved in a wide range of cellular functions, and its expression is closely related to joint damage and disease activity in RA patients. In this study, we sought to assess the role of 14-3-3η in joint damage by examining its contribution to the invadosome formation phenotype of FLS. Using human primary FLS, we show that 14-3-3η expression is closely associated with their ability to form invadosomes. Furthermore, knockdown of 14-3-3η using shRNAs decreases the level of invadosome formation in RA FLS, whereas addition of the recombinant protein to FLS from healthy individuals promotes their formation. Mechanistic studies suggest that 14-3-3η regulates invadosome formation by increasing Snail expression, a mechanism that involves nuclear exclusion of the transcription repressor FOXO3. Our results implicate the 14-3-3η–FOXO3–Snail axis in promoting the aggressive ECM-degrading phenotype of RA FLS, and suggest a role for this scaffolding protein in cartilage degradation.
The Roles of Coenzyme Q in Disease: Direct and Indirect Involvement in Cellular Functions
Authors: Pallotti Francesco , Bergamini Christian , Lamperti Costanza , Fato Romana
Published: December 2021

Coenzyme Q (CoQ) is a key component of the respiratory chain of all eukaryotic cells. Its function is closely related to mitochondrial respiration, where it acts as an electron transporter. However, the cellular functions of coenzyme Q are multiple: it is present in all cell membranes, limiting the toxic effect of free radicals, it is a component of LDL, it is involved in the aging process, and its deficiency is linked to several diseases. Recently, it has been proposed that coenzyme Q contributes to suppressing ferroptosis, a type of iron-dependent programmed cell death characterized by lipid peroxidation. In this review, we report the latest hypotheses and theories analyzing the multiple functions of coenzyme Q. The complete knowledge of the various cellular CoQ functions is essential to provide a rational basis for its possible therapeutic use, not only in diseases characterized by primary CoQ deficiency, but also in large number of diseases in which its secondary deficiency has been found.
CLDN6 Suppresses c–MYC–Mediated Aerobic Glycolysis to Inhibit Proliferation by TAZ in Breast Cancer
Authors: Qu Huinan , Qi Da , Wang Xinqi , Dong Yuan , Jin Qiu , Wei Junyuan , Quan Chengshi
Published: December 2021

Claudin 6 (CLDN6) was found to be a breast cancer suppressor gene, which is lowly expressed in breast cancer and inhibits breast cancer cell proliferation upon overexpression. However, the mechanism by which CLDN6 inhibits breast cancer proliferation is unclear. Here, we investigated this issue and elucidated the molecular mechanisms by which CLDN6 inhibits breast cancer proliferation. First, we verified that CLDN6 was lowly expressed in breast cancer tissues and that patients with lower CLDN6 expression had a worse prognosis. Next, we confirmed that CLDN6 inhibited breast cancer proliferation through in vitro and in vivo experiments. As for the mechanism, we found that CLDN6 inhibited c–MYC–mediated aerobic glycolysis based on a metabolomic analysis of CLDN6 affecting cellular lactate levels. CLDN6 interacted with a transcriptional co–activator with PDZ-binding motif (TAZ) and reduced the level of TAZ, thereby suppressing c–MYC transcription, which led to a reduction in glucose uptake and lactate production. Considered together, our results suggested that CLDN6 suppressed c–MYC–mediated aerobic glycolysis to inhibit the proliferation of breast cancer by TAZ, which indicated that CLDN6 acted as a novel regulator of aerobic glycolysis and provided a theoretical basis for CLDN6 as a biomarker of progression in breast cancer.
The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases
Authors: Paluszkiewicz Patrycja , Martuszewski Adrian , Zaręba Natalia , Wala Kamila , Banasik Mirosław , Kepinska Marta
Published: December 2021

Nanomedicine is currently showing great promise for new methods of diagnosing and treating many diseases, particularly in kidney disease and transplantation. The unique properties of nanoparticles arise from the diversity of size effects, used to design targeted nanoparticles for specific cells or tissues, taking renal clearance and tubular secretion mechanisms into account. The design of surface particles on nanoparticles offers a wide range of possibilities, among which antibodies play an important role. Nanoparticles find applications in encapsulated drug delivery systems containing immunosuppressants and other drugs, in imaging, gene therapies and many other branches of medicine. They have the potential to revolutionize kidney transplantation by reducing and preventing ischemia–reperfusion injury, more efficiently delivering drugs to the graft site while avoiding systemic effects, accurately localizing and visualising the diseased site and enabling continuous monitoring of graft function. So far, there are known nanoparticles with no toxic effects on human tissue, although further studies are still needed to confirm their safety.
Transcriptome Analysis of Salt Stress in Hibiscus hamabo Sieb. et Zucc Based on Pacbio Full-Length Transcriptome Sequencing
Authors: Ni Longjie , Wang Zhiquan , Liu Xiangdong , Wu Shuting , Hua Jianfeng , Yin Yunlong , Li Huogen , Gu Chunsun
Published: December 2021

Hibiscus hamabo Sieb. et Zucc is an important semi-mangrove plant with great morphological features and strong salt resistance. In this study, by combining single molecule real time and next-generation sequencing technologies, we explored the transcriptomic changes in the roots of salt stressed H. hamabo. A total of 94,562 unigenes were obtained by clustering the same isoforms using the PacBio RSII platform, and 2269 differentially expressed genes were obtained under salt stress using the Illumina platform. There were 519 differentially expressed genes co-expressed at each treatment time point under salt stress, and these genes were found to be enriched in ion signal transduction and plant hormone signal transduction. We used Arabidopsis thaliana (L.) Heynh. transformation to confirm the function of the HhWRKY79 gene and discovered that overexpression enhanced salt tolerance. The full-length transcripts generated in this study provide a full characterization of the transcriptome of H. hamabo and may be useful in mining new salt stress-related genes specific to this species, while facilitating the understanding of the salt tolerance mechanisms.
Macrophage Polarity and Disease Control
Authors: Kadomoto Suguru , Izumi Kouji , Mizokami Atsushi
Published: December 2021

Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.
Abnormal Ca2+ Signals in Reactive Astrocytes as a Common Cause of Brain Diseases
Authors: Koizumi Schuichi , Shigetomi Eiji , Sano Fumikazu , Saito Kozo , Kim Sun Kwang , Nabekura Junichi
Published: December 2021

In pathological brain conditions, glial cells become reactive and show a variety of responses. We examined Ca2+ signals in pathological brains and found that reactive astrocytes share abnormal Ca2+ signals, even in different types of diseases. In a neuropathic pain model, astrocytes in the primary sensory cortex became reactive and showed frequent Ca2+ signals, resulting in the production of synaptogenic molecules, which led to misconnections of tactile and pain networks in the sensory cortex, thus causing neuropathic pain. In an epileptogenic model, hippocampal astrocytes also became reactive and showed frequent Ca2+ signals. In an Alexander disease (AxD) model, hGFAP-R239H knock-in mice showed accumulation of Rosenthal fibers, a typical pathological marker of AxD, and excessively large Ca2+ signals. Because the abnormal astrocytic Ca2+ signals observed in the above three disease models are dependent on type II inositol 1,4,5-trisphosphate receptors (IP3RII), we reanalyzed these pathological events using IP3RII-deficient mice and found that all abnormal Ca2+ signals and pathologies were markedly reduced. These findings indicate that abnormal Ca2+ signaling is not only a consequence but may also be greatly involved in the cause of these diseases. Abnormal Ca2+ signals in reactive astrocytes may represent an underlying pathology common to multiple diseases.
Supercritical Carbon Dioxide Impregnation of Gold Nanoparticles Demonstrates a New Route for the Fabrication of Hybrid Silk Materials
Authors: Singh Manish , Dey Estera S. , Bhand Sunil , Dicko Cedric
Published: December 2021

How many nanoparticles can we load in a fiber? How much will leak? Underlying is the relatively new question of the “space available” in fibers for nanoparticle loading. Here, using supercritical carbon dioxide (scCO2) as a carrier fluid, we explored the impregnation in four Indian silks (Mulberry, Eri, Muga, and Tasar) with five standard sizes of gold nanoparticles (5, 20, 50, 100 and 150 nm in diameter). All silks could be permanently impregnated with nanoparticles up to 150 nm in size under scCO2 impregnation. Accompanying structural changes indicated that the amorphous silk domains reorganized to accommodate the gold NPs. The mechanism was studied in detail in degummed Mulberry silk fibers (i.e., without the sericin coating) with the 5 nm nanoparticle. The combined effects of concentration, time of impregnation, scCO2 pressure, and temperature showed that only a narrow set of conditions allowed for permanent impregnation without deterioration of the properties of the silk fibers.
The Impact of Deforestation, Urbanization, and Changing Land Use Patterns on the Ecology of Mosquito and Tick-Borne Diseases in Central America
Authors: Ortiz Diana I. , Piche-Ovares Marta , Romero-Vega Luis M. , Wagman Joseph , Troyo Adriana
Published: December 2021

Central America is a unique geographical region that connects North and South America, enclosed by the Caribbean Sea to the East, and the Pacific Ocean to the West. This region, encompassing Belize, Costa Rica, Guatemala, El Salvador, Honduras, Panama, and Nicaragua, is highly vulnerable to the emergence or resurgence of mosquito-borne and tick-borne diseases due to a combination of key ecological and socioeconomic determinants acting together, often in a synergistic fashion. Of particular interest are the effects of land use changes, such as deforestation-driven urbanization and forest degradation, on the incidence and prevalence of these diseases, which are not well understood. In recent years, parts of Central America have experienced social and economic improvements; however, the region still faces major challenges in developing effective strategies and significant investments in public health infrastructure to prevent and control these diseases. In this article, we review the current knowledge and potential impacts of deforestation, urbanization, and other land use changes on mosquito-borne and tick-borne disease transmission in Central America and how these anthropogenic drivers could affect the risk for disease emergence and resurgence in the region. These issues are addressed in the context of other interconnected environmental and social challenges.
Extended Trochanteric Osteotomy with Intermediate Resection Arthroplasty Is Safe for Use in Two-Stage Revision Total Hip Arthroplasty for Infection
Authors: Hardt Sebastian , Leopold Vincent , Khakzad Thilo , Pumberger Matthias , Perka Carsten , Hipfl Christian
Published: December 2021

Background: This study sought to compare the results of two-stage revision total hip arthroplasty (THA) for periprosthetic infection (PJI) in patients with and without the use of an extended trochanteric osteotomy (ETO) for removal of a well-fixed femoral stem or cement. Methods: Thirty-two patients who had undergone an ETO as part of a two-stage revision without spacer placement were matched 1:2 with a cohort of sixty-four patients of the same sex and age who had stem removal without any osteotomy. Clinical outcomes including interim revision, reinfection and aseptic failure rates were evaluated. Modified Harris hip scores (mHHS) were calculated. Minimum follow-up was two years. Results: Patients undergoing ETO had a significantly lower rate of interim re-debridement compared to non-ETO patients (0% vs. 14.1%, p = 0.026). Reinfection following reimplantation was similar in both groups (12.5% in ETO patients vs. 9.4% in non-ETO patients, p = 0.365). Revision for aseptic reason was necessary in 12.5% in the ETO group and 14.1% in the non-ETO group (p = 0.833). Periprosthetic femoral fractures were seen in three patients (3.1%), of which all occurred in non-ETO patients. Dislocation was the most common complication, which was equally distributed in both groups (12.5%). The mean mHHS was 37.7 in the ETO group and 37.3 in the non-ETO group, and these scores improved significantly in both groups following reimplantation (p < 0.01). Conclusion: ETO without the use of spacer is a safe and effective method to manage patients with well-fixed femoral stems and for thorough cement removal in two-stage revision THA for PJI. While it might reduce the rate of repeated debridement in the interim period, the use of ETO appears to lead to similar reinfection rates following reimplantation.
Evaluating the 0–10 Point Pain Scale on Adolescent Opioid Use in US Emergency Departments
Authors: Phan Michael T. , Tomaszewski Daniel M. , Arbuckle Cody , Yang Sun , Jenkins Brooke , Fortier Michelle A. , Heyming Theodore , Linstead Erik , Donaldson Candice , Kain Zeev
Published: December 2021

Objective: To evaluate trends in national emergency department (ED) adolescent opioid use in relation to reported pain scores. Methods: A retrospective, cross-sectional analysis on National Hospital Ambulatory Medical Care Survey (NHAMCS) data was conducted on ED visits involving patients aged 11–21 from 2008–2017. Crude observational counts were extrapolated to weighted estimates matching total population counts. Multivariate models were used to evaluate the role of a pain score in the reported use of opioids. Anchors for pain scores were 0 (no pain) and 10 (worst pain imaginable). Results: 31,355 observations were captured, which were extrapolated by the NHAMCS to represent 162,515,943 visits nationwide. Overall, patients with a score of 10 were 1.35 times more likely to receive an opioid than patients scoring a 9, 41.7% (CI95 39.7–43.8%) and 31.0% (CI95 28.8–33.3%), respectively. Opioid use was significantly different between traditional pain score cutoffs of mild (1–3) and moderate pain (4–6), where scores of 4 were 1.76 times more likely to receive an opioid than scores of 3, 15.5% (CI95 13.7–17.3%) and 8.8% (CI95 7.1–10.6%), respectively. Scores of 7 were 1.33 times more likely to receive opioids than scores of 6, 24.7% (CI95 23.0–26.3%) and 18.5% (CI95 16.9–20.0%), respectively. Fractures had the highest likelihood of receiving an opioid, as 49.2% of adolescents with a fracture received an opioid (CI95 46.4–51.9%). Within this subgroup, only adolescents reporting a fracture pain score of 10 had significantly higher opioid use than adjacent pain scores, where fracture patients scoring a 10 were 1.4 times more likely to use opioids than those scoring 9, 82.2% (CI95 76.1–88.4%) and 59.8% (CI95 49.0–70.5%), respectively. Conclusions: While some guidelines in the adult population have revised cut-offs and groupings of the traditional tiers on a 0–10 point pain scale, the adolescent population may also require further examination to potentially warrant a similar adjustment.
Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review
Authors: Blay Martin , Adam Ondine , Bation Rémy , Galvao Filipe , Brunelin Jérôme , Mondino Marine
Published: December 2021

Patients with schizophrenia are often unaware of their condition and the consequences of their illness. This lack of insight results in impaired functioning, treatment non-adherence and poor prognosis. Here, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on two forms of insight, clinical and cognitive, in patients with schizophrenia. We conducted a systematic review of the literature registered in the PROSPERO database (CRD42020220323) according to PRISMA guidelines. The literature search was conducted in Medline and Web of Science databases based on studies published up until October 2020 that included pre-NIBS and post-NIBS measurements of clinical and/or cognitive insight in adults with schizophrenia. A total of 14 studies were finally included, and their methodological quality was assessed by using the QualSyst tool. Despite the lack of well-conducted large randomized-controlled studies using insight as the primary outcome, the available findings provide preliminary evidence that NIBS can improve clinical insight in patients with schizophrenia, with a majority of studies using transcranial direct current stimulation with a left frontotemporal montage. Further studies should investigate the effect of NIBS on insight as a primary outcome and how these effects on insight could translate into clinical and functional benefits in patients with schizophrenia.
Triglyceride Glucose-Waist Circumference Is Superior to the Homeostasis Model Assessment of Insulin Resistance in Identifying Nonalcoholic Fatty Liver Disease in Healthy Subjects
Authors: Kim Hwi Seung , Cho Yun Kyung , Kim Eun Hee , Lee Min Jung , Jung Chang Hee , Park Joong-Yeol , Kim Hong-Kyu , Lee Woo Je
Published: December 2021

The triglyceride glucose (TyG) index has been suggested as a marker for insulin resistance; however, few studies have investigated the clinical implications of markers that combine obesity markers with the TyG index. This study aimed to investigate the associations between non-alcoholic fatty liver disease (NAFLD) and TyG-related markers in healthy subjects in Korea. We enrolled 21,001 asymptomatic participants who underwent hepatic ultrasonography. The homeostasis model assessment of insulin resistance (HOMA-IR), TyG index, TyG-body mass index, and TyG-waist circumference (WC) were subsequently analyzed. NAFLD was diagnosed using hepatic ultrasonography. A multiple logistic regression analysis was performed to evaluate the associations between the quartiles of each parameter and the risk of NAFLD. The increase in the NAFLD risk was most evident when the TyG-WC quartiles were applied; the multivariate-adjusted odds ratios for NAFLD were 4.72 (3.65–6.10), 13.28 (10.23–17.24), and 41.57 (31.66–54.59) in the 2nd, 3rd, and 4th TyG-WC quartiles, respectively, when compared with the lowest quartile. The predictability of the TyG-WC for NAFLD was better than that of the HOMA-IR using the area under the curve. The TyG-WC index was superior to the HOMA-IR for identifying NAFLD in healthy Korean adults, especially in the non-obese population.
Acute and Long-Term Effects of an Internet-Based, Self-Help Comprehensive Behavioral Intervention for Children and Teens with Tic Disorders with Comorbid Attention Deficit Hyperactivity Disorder, or Obsessive Compulsive Disorder: A Reanalysis of Data from a Randomized Controlled Trial
Authors: Rachamim Lilach , Mualem-Taylor Hila , Rachamim Osnat , Rotstein Michael , Zimmerman-Brenner Sharon
Published: December 2021

Attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and tic disorders (TD) commonly co-occur. In addition, specific inattention difficulties and poor impulse control are related to TD in the absence of comorbid ADHD. In this study we reanalyzed data from a recently completed study comparing internet-delivered, self-help comprehensive behavioral intervention for tics (ICBIT) with a waiting-list control group. The current study describes the effects of an (ICBIT) in children and adolescents with TD with and without comorbid diagnoses of ADHD or OCD at post intervention and over three- and six-month follow-up periods. Thirty-eight 7 to 18-year-olds completed the ICBIT. Of these, 16 were diagnosed with comorbid ADHD and 11 were diagnosed with OCD. A significant improvement in tic measures was found in all groups. Both the TD + ADHD and the TD − ADHD groups were similar in the magnitude of tic reduction from baseline to post-treatment, and at the three and six-month follow-up assessments. However, the TD + OCD group benefitted less from intervention than the TD—OCD group. There were meaningful reductions in parental reports of inattention, as well as hyperactive and impulsive symptoms at post intervention and over the 6-month follow-up period. Thus, ICBIT can be effectively delivered in the presence of comorbid ADHD or OCD symptomatology and may reduce symptoms of inattention and impulsivity. Larger studies of ICBIT in children and teens with TD and comorbid ADHD and OCD are needed to optimize responses to ICBIT.