bluuebunny/crossref_metadata_2025 huggingface dataset:
Uptake of Nanotitania by Gingival Epithelial Cells Promotes Inflammatory Response and Is Accelerated by Porphyromonas gingivalis Lipopolysaccharide: An In Vitro Study
Authors: Sugawara Shiho , Ishikawa Taichi , Sato Shu , Kihara Hidemichi , Taira Masayuki , Sasaki Minoru , Kondo Hisatomo
Published: July 2021

Titanium is often used in the medical field and in dental implants due to its biocompatibility, but it has a high rate of leading to peri-implantitis, which progresses faster than periodontitis. Therefore, in the present study, the expression of cytokines from gingival epithelial cells by nanotitania was investigated, which is derived from titanium in the oral cavity, and the additional effect of Porphyromonasgingivalis (periodontopathic bacteria) lipopolysaccharide (PgLPS) was investigated. Ca9-22 cells were used as a gingival epithelial cell model and were cultured with nanotitania alone or with PgLPS. Cytokine expression was examined by reverse transcription-quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. In addition, cellular uptake of nanotitania was observed in scanning electron microscopy images. The expression of interleukin (IL)-6 and IL-8 significantly increased in Ca9-22 cells by nanotitania treatment alone, and the expression was further increased by the presence of PgLPS. Nanotitania was observed to phagocytose Ca9-22 cells in a dose- and time-dependent manner. Furthermore, when the expression of IL-11, related to bone resorption, was investigated, a significant increase was confirmed by stimulation with nanotitania alone. Therefore, nanotitania could be associated with the onset and exacerbation of peri-implantitis, and the presence of periodontal pathogens may worsen the condition. Further clinical reports are needed to confirm these preliminary results.
Lack of Glutamate Receptor Subunit Expression Changes in Hippocampal Dentate Gyrus after Experimental Traumatic Brain Injury in a Rodent Model of Depression
Authors: Knott Maxon V. , Ngwenya Laura B. , Correll Erika A. , Bohnert Judy , Ziemba Noah J. , Allgire Emily , Hopkins Tracy , McGuire Jennifer L.
Published: July 2021

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.
LncRNA AERRIE Is Required for Sulfatase 1 Expression, but Not for Endothelial-to-Mesenchymal Transition
Authors: Pham Tan Phát , van Bergen Anke S. , Kremer Veerle , Glaser Simone F. , Dimmeler Stefanie , Boon Reinier A.
Published: July 2021

Endothelial cells can acquire a mesenchymal phenotype through a process called Endothelial-to-Mesenchymal transition (EndMT). This event is found in embryonic development, but also in pathological conditions. Blood vessels lose their ability to maintain vascular homeostasis and ultimately develop atherosclerosis, pulmonary hypertension, or fibrosis. An increase in inflammatory signals causes an upregulation of EndMT transcription factors, mesenchymal markers, and a decrease in endothelial markers. In our study, we show that the induction of EndMT results in an increase in long non-coding RNA AERRIE expression. JMJD2B, a known EndMT regulator, induces AERRIE and subsequently SULF1. Silencing of AERRIE shows a partial regulation of SULF1 but showed no effect on the endothelial and mesenchymal markers. Additionally, the overexpression of AERRIE results in no significant changes in EndMT markers, suggesting that AERRIE is marginally regulating mesenchymal markers and transcription factors. This study identifies AERRIE as a novel factor in EndMT, but its mechanism of action still needs to be elucidated.
Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain
Authors: Tkachev Anna , Stekolshchikova Elena , Bobrovskiy Daniil M. , Anikanov Nickolay , Ogurtsova Polina , Park Dong Ik , Horn Anja K. E. , Petrova Daria , Khrameeva Ekaterina , Golub Mari S. , Turck Christoph W. , Khaitovich Philipp
Published: July 2021

Fluoxetine is an antidepressant commonly prescribed not only to adults but also to children for the treatment of depression, obsessive-compulsive disorder, and neurodevelopmental disorders. The adverse effects of the long-term treatment reported in some patients, especially in younger individuals, call for a detailed investigation of molecular alterations induced by fluoxetine treatment. Two-year fluoxetine administration to juvenile macaques revealed effects on impulsivity, sleep, social interaction, and peripheral metabolites. Here, we built upon this work by assessing residual effects of fluoxetine administration on the expression of genes and abundance of lipids and polar metabolites in the prelimbic cortex of 10 treated and 11 control macaques representing two monoamine oxidase A (MAOA) genotypes. Analysis of 8871 mRNA transcripts, 3608 lipids, and 1829 polar metabolites revealed substantial alterations of the brain lipid content, including significant abundance changes of 106 lipid features, accompanied by subtle changes in gene expression. Lipid alterations in the drug-treated animals were most evident for polyunsaturated fatty acids (PUFAs). A decrease in PUFAs levels was observed in all quantified lipid classes excluding sphingolipids, which do not usually contain PUFAs, suggesting systemic changes in fatty acid metabolism. Furthermore, the residual effect of the drug on lipid abundances was more pronounced in macaques carrying the MAOA-L genotype, mirroring reported behavioral effects of the treatment. We speculate that a decrease in PUFAs may be associated with adverse effects in depressive patients and could potentially account for the variation in individual response to fluoxetine in young people.
Preliminary Investigation on the Involvement of Cytoskeleton-Related Proteins, DAAM1 and PREP, in Human Testicular Disorders
Authors: Venditti Massimo , Arcaniolo Davide , De Sio Marco , Minucci Sergio
Published: July 2021

Herein, for the first time, the potential relationships between the cytoskeleton-associated proteins DAAM1 and PREP with different testicular disorders, such as classic seminoma (CS), Leydig cell tumor (LCT), and Sertoli cell-only syndrome (SOS), were evaluated. Six CS, two LCT, and two SOS tissue samples were obtained during inguinal exploration in patients with a suspect testis tumor based on clinical examination and ultrasonography. DAAM1 and PREP protein levels and immunofluorescent localization were analyzed. An increased DAAM1 protein level in CS and SOS as compared to non-pathological (NP) tissue was observed, while LCT showed no significant differences. Conversely, PREP protein level increased in LCT, while it decreased in CS and SOS compared to NP tissue. These results were strongly supported by the immunofluorescence staining, revealing an altered localization and signal intensity of DAAM1 and PREP in the analyzed samples, highlighting a perturbed cytoarchitecture. Interestingly, in LCT spermatogonia, a specific DAAM1 nuclear localization was found, probably due to an enhanced testosterone production, as confirmed by the increased protein levels of steroidogenic enzymes. Finally, although further studies are needed to verify the involvement of other formins and microtubule-associated proteins, this report raised the opportunity to indicate DAAM1 and PREP as new potential markers, supporting the cytoskeleton dynamics changes occurring during normal and/or pathological cell differentiation.
Unique Aspects of Human Placentation
Authors: Carter Anthony M.
Published: July 2021

Human placentation differs from that of other mammals. A suite of characteristics is shared with haplorrhine primates, including early development of the embryonic membranes and placental hormones such as chorionic gonadotrophin and placental lactogen. A comparable architecture of the intervillous space is found only in Old World monkeys and apes. The routes of trophoblast invasion and the precise role of extravillous trophoblast in uterine artery transformation is similar in chimpanzee and gorilla. Extended parental care is shared with the great apes, and though human babies are rather helpless at birth, they are well developed (precocial) in other respects. Primates and rodents last shared a common ancestor in the Cretaceous period, and their placentation has evolved independently for some 80 million years. This is reflected in many aspects of their placentation. Some apparent resemblances such as interstitial implantation and placental lactogens are the result of convergent evolution. For rodent models such as the mouse, the differences are compounded by short gestations leading to the delivery of poorly developed (altricial) young.
The Genetic Landscape of Parkinsonism-Related Dystonias and Atypical Parkinsonism-Related Syndromes
Authors: Diez-Fairen Monica , Alvarez Jerez Pilar , Berghausen Joos , Bandres-Ciga Sara
Published: July 2021

In recent decades, genetic research has nominated promising pathways and biological insights contributing to the etiological landscape of parkinsonism-related dystonias and atypical parkinsonism-related syndromes. Several disease-causing mutations and genetic risk factors have been unraveled, providing a deeper molecular understanding of the complex genetic architecture underlying these conditions. These disorders are difficult to accurately diagnose and categorize, thus making genetics research challenging. On one hand, dystonia is an umbrella term linked to clinically heterogeneous forms of disease including dopa-responsive dystonia, myoclonus-dystonia, rapid-onset dystonia-parkinsonism and dystonia-parkinsonism, often viewed as a precursor to Parkinson’s disease. On the other hand, atypical parkinsonism disorders, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration, are rare in nature and represent a wide range of diverse and overlapping phenotypic variabilities, with genetic research limited by sample size availability. The current review summarizes the plethora of available genetic information for these diseases, outlining limits and future directions.
Delta: A Modular Ontology Evaluation System
Authors: Kondylakis Haridimos , Nikolaos Astyrakakis , Dimitra Papatsaroucha , Anastasios Koumarelis , Emmanouel Kritikakis , Kyriakos Kalkanis , Iraklis Skepasianos , Stylianos Klados , Papadakis Nikos
Published: July 2021

Ontologies are widely used nowadays. However, the plethora of ontologies currently available online, makes it really difficult to identify which ontologies are appropriate for a given task and to decide on their quality characteristics. This is further complicated by the fact that multiple quality criteria have been proposed for ontologies, making it even more difficult to decide which ontology to adopt. In this context, in this paper we present Delta, a modular online tool for analyzing and evaluating ontologies. The interested user can upload an ontology to the tool, which then automatically analyzes it and graphically visualizes numerous statistics, metrics, and pitfalls. Those visuals presented include a diverse set of quality dimensions, further guiding users to understand the benefits and the drawbacks of each individual ontology and how to properly develop and extend it.
Structural Features and Phylogenetic Implications of 11 New Mitogenomes of Typhlocybinae (Hemiptera: Cicadellidae)
Authors: Lin Shuanghu , Huang Min , Zhang Yalin
Published: July 2021

To explore the characteristics of mitogenomes and discuss the phylogenetic relationships and molecular evolution of the six tribes within Typhlocybinae, 11 complete mitogenomes are newly sequenced and comparatively analyzed. In all of these complete mitogenomes, the number and order of the genes are highly conserved in overall organization. The PCGs initiate with ATN/TTG/GTG and terminate with TAA/TAG/T. Almost all tRNAs are folded into the typical clover-leaf secondary structure. The control region is always variable in length and in numbers of multiple tandem repeat units. The atp8 and nad2 exhibits the highest evolution rate among all the PCGs. Phylogenetic analyses based on whole mitogenome sequences, with three different datasets, using both maximum likelihood and Bayesian methods, indicate the monophyly of Typhlocybinae and its inner tribes, respectively, except for Typhlocybini and Zyginellini that are paraphyletic. Finally, we confirm that Erythroneurini is a subtribe of Dikraneurini.
Using Matching Traits to Study the Impacts of Land-Use Intensification on Plant–Pollinator Interactions in European Grasslands: A Review
Authors: Goulnik Jérémie , Plantureux Sylvain , Dajoz Isabelle , Michelot-Antalik Alice
Published: July 2021

Permanent grasslands are suitable habitats for many plant and animal species, among which are pollinating insects that provide a wide range of ecosystem services. A global crisis in pollination ecosystem service has been highlighted in recent decades, partly the result of land-use intensification. At the grassland scale, however, the underlying mechanisms of land-use intensification that affect plant–pollinator interactions and pollination remain understudied. In this review, we first synthesise the literature to provide new insights into the relationships between land-use intensification and pollination by using matching community and interaction traits. We then identify knowledge gaps and summarise how land-use intensification of grassland influences floral traits that may in turn be associated with modifications to pollinator matching traits. Last, we summarise how these modifications may affect pollination function on permanent grasslands. Overall, land-use intensification may lead to a shift in flower colour, a decrease in mean nectar tube depth and a decrease in reward production and pollen quality at the community level. This, in turn, may generate a decrease in pollinator mouthparts length and body size, that may favour pollinators that require a low amount of floral reward. We found no study citing the effect of land-use intensification on volatile organic compounds emitted by flowers despite the importance of these molecules in pollinator community composition. Overall, our review highlighted major knowledge gaps about the effects of land-use intensification on plant–pollinator interactions, and suggests that land-use intensification could favour plants with generalised floral traits that adversely affect pollination.
Transgenerational Effects of a Neonicotinoid and a Novel Sulfoximine Insecticide on the Harlequin Ladybird
Authors: Dai Changchun , Ricupero Michele , Wang Zequn , Desneux Nicolas , Biondi Antonio , Lu Yanhui
Published: July 2021

The harlequin ladybird, Harmonia axyridis Pallas (Coleoptera: Coccinellidae), is a generalist predator and an effective biocontrol agent of various insect pests that has been exploited for the control of aphid pests in the greenhouse and field. However, insecticides are widely used to control aphid pests worldwide and the potential non-target effects of sulfoxaflor and imidacloprid for controlling aphid pests towards this biocontrol agent are little known. Although both sulfoxaflor and imidacloprid act on nicotinic acetylcholine receptors of insects, sulfoxaflor has a novel chemical structure compared with neonicotinoids. We assessed the lethal, sublethal and transgenerational effects of sulfoxaflor and imidacloprid on H. axyridis simultaneously exposed via ingestion of contaminated prey and via residual contact on the host plant at LC20 and LC50 doses estimated for the cotton aphid. Imidacloprid significantly reduced the survival of H. axyridis adults compared to sulfoxaflor at the same lethal concentration against cotton aphid. Both concentrations of imidacloprid and sulfoxaflor reduced the proportion of ovipositing females, and both concentrations of imidacloprid and sulfoxaflor, except LC20 dose of sulfoxaflor, reduced the fecundity and fertility of the parental generation. In the progeny of imidacloprid- and sulfoxaflor-exposed parents, both tested LC50 concentrations significantly decreased the juvenile survival rate, and both concentrations of imidacloprid and sulfoxaflor, except LC20 dose of sulfoxaflor, prolonged the development time. Our findings provide evidence of the negative influence of imidacloprid and sulfoxaflor at low lethal concentrations on the harlequin ladybird and on the progeny of exposed individuals, i.e., transgenerational effects. Hence, these findings stress the importance of optimizing the applications of imidacloprid and sulfoxaflor for the control of aphid pests, aiming at preserving the biocontrol services provided by H. axyridis throughout the integrated pest management approach.
The Association between IgG and Disease Severity Parameters in CF Patients
Authors: Gur Michal , Ben-David Yael , Hanna Moneera , Ilivitzki Anat , Weichhendler Adi , Bar-Yoseph Ronen , Toukan Yazeed , Masarweh Kamal , Bentur Lea
Published: July 2021

Assessing disease severity in patients with cystic fibrosis (CF) is essential when directing therapies. Serum immunoglobulin G (IgG) levels increase with disease severity. Lung clearance index (LCI) is recognized as an outcome measure for CF clinical trials. Our aim was to evaluate the correlations between IgG and disease severity markers. This was a single-center retrospective study, evaluating association between IgG and markers of severity in CF patients (including clinical characteristics, lung spirometry, LCI, clinical scores and computed tomography (CT) scores) during stable conditions. There were 69 patients, age 20.5 ± 11.6 years. Nineteen (27.5%) patients had elevated IgG. IgG correlated positively with LCI (r = 0.342, p = 0.005). IgG was higher in pancreatic insufficient (PI) and patients with liver disease (1504.3 ± 625.5 vs. 1229 ± 276.1 mg/dL in PI vs. PS, p = 0.023, and 1702.6 ± 720.3 vs. 1256.2 ± 345.5 mg/dL with vs. without liver disease, p = 0.001, respectively). IgG also correlated positively with CRP, CT score, and days with antibiotics in the previous year (r = 0.38, p = 0.003; r = 0.435, p = 0.001; and r = 0.361, p = 0.002, respectively), and negatively with FEV1% and SK score (r = −0.527, p < 0.001 and r = −0.613, p < 0.001, respectively). IgG correlated with clinical parameters, pulmonary functions, and imaging. However, this is still an auxiliary test, complementing other tests, including lung function and imaging tests. Larger multi-center longitudinal studies are warranted.
Association between Subclinical Hypothyroidism and Incident Hypertension in Women: A Systematic Review and Meta-Analysis
Authors: Kim Jean , Prasitlumkum Narut , Randhawa Sandeep , Banerjee Dipanjan
Published: July 2021

Subclinical hypothyroidism (SCH) has been found to be associated with an increased risk of cardiovascular diseases. However, there is no clear consensus on the relationship between SCH and hypertension (HTN). We sought to investigate the association between SCH and incident HTN in women. MEDLINE and EMBASE databases were searched for studies that reported the incidence of HTN in females with SCH versus without SCH. Pooled odds ratio (OR) and 95% confidence interval (CI) of the outcome were obtained using a random-effects model. Studies were also divided into the middle-aged (mean age < 65) and the older (mean age ≥ 65) subgroups, and a subgroup analysis was performed to examine the potential age-effect on the association between SCH and HTN. Nine studies with a total of 21,972 subjects met the inclusion criteria. SCH was found to be positively associated with HTN (OR = 1.32, 95% CI = 1.02–1.71). Such association varied depending on the age of women. In the middle-aged subgroup, SCH was more positively associated with HTN (OR = 1.64, 95% CI = 1.18–2.27), while there was no significant association in the older subgroup (OR = 0.97, 95% CI = 0.80–1.16). Our study showed that the middle-aged females with SCH had an increased risk of HTN, while there was no significant association in the older females with SCH.
Cerebellar Dysfunction in Adults with Prader Willi Syndrome
Authors: Blanco-Hinojo Laura , Casamitjana Laia , Pujol Jesus , Martínez-Vilavella Gerard , Esteba-Castillo Susanna , Giménez-Palop Olga , Freijo Valentín , Deus Joan , Caixàs Assumpta
Published: July 2021

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.
Influence of an Implant Fixture including a Freely Removable Micro-Locking Implant Prosthesis on Peri-Implant Tissues and Implant Prostheses: A Prospective Clinical Study
Authors: Shin Young-Gun , Cho Won-Tak , Lim Ho-Kyung , Hwang Su-Hyun , Bae Ji-Hyeon , Bae Gang-Ho , Lee Jeong-Yol , Huh Jung-Bo
Published: July 2021

This prospective study was undertaken to evaluate the clinical usefulness of a newly developed one-piece, screw-free, and micro-locking implant system, which was designed to overcome the shortcomings of the existing implant systems. Thirty-eight patients were recruited and randomly and equally assigned to an experimental group (micro-locking one-piece fixture, MLF; n = 19) or a control group (micro-locking abutment, MLA). Cumulative implant survival rates, marginal bone resorptions, probing depths, plaque indices, bleeding indices, and complications were obtained by using clinical and radiographic findings at 6 months and 12 months after prosthesis placement. Complications that occurred multiple times for single implants were counted. During the 12 month observation period, survival rates were 100% in both groups. No significant intergroup differences were observed for marginal bone resorption, probe depth, or bleeding index. However, mean plaque index was significantly lower in the MLF group at 12 months (p < 0.05). During the 12-month observation period, food impaction (26.3%) was the main complication in the MLF group and screw loosening (5.3%), prosthesis detachment (5.3%), and food impaction (5.3%) were observed in the MLA group. The results of this study suggest that the one-piece micro-locking implant system offers a predictable treatment method.
Unexpected Outcomes of Renal Function after Radical Nephrectomy: Histology Relevance along with Clinical Aspects
Authors: Di Marco Federico , Pani Antonello , Floris Matteo , Martini Alberto , Dell’Antonio Giacomo , Capitanio Umberto , Bettiga Arianna , Larcher Alessandro , Cinque Alessandra , Bertini Roberto , Briganti Alberto , Salonia Andrea , Montorsi Francesco , Trevisani Francesco
Published: July 2021

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common events after radical nephrectomy (RN). In this study we aimed to predict AKI and CKD after RN relying on specific histological aspects. We collected data from a cohort of 144 patients who underwent radical nephrectomy. A histopathological review of the healthy part of the removed kidney was performed using an established chronicity score (CS). Logistic regression analyses were performed to predict AKI after RN, while linear regression analysis was adopted for estimated glomerular filtration rate (eGFR) variation at 1 year. The outcomes of the study were to determine variables correlated with AKI onset, and with eGFR decay at 1 year. The proportion of AKI was 64%. Logistic analyses showed that baseline eGFR independently predicted AKI (odds ratio 1.04, 95%CI 1.02:1.06). Moreover, AKI (Beta −16, 95%CI −21:−11), baseline eGFR (Beta −0.42, 95%CI −0.52:−0.33), and the presence of arterial narrowing (Beta 10, 95%CI 4:15) were independently associated with eGFR decline. Our findings showed that AKI onset and eGFR decline were more likely to occur with higher baseline eGFR and lower CS, highlighting that RN in normal renal function patients represents a more traumatic event than its CKD counterpart.
Endocrine Follow-Up of Men with Non-Obstructive Azoospermia Following Testicular Sperm Extraction
Authors: Billa Evangelia , Kanakis George A. , Goulis Dimitrios G.
Published: July 2021

Testicular sperm extraction (TESE) is a surgical procedure which, combined with intracytoplasmic sperm injection, constitutes the main treatment for achieving biological parenthood for patients with infertility due to non-obstructive azoospermia (NOA). Although it is effective, TESE procedures might cause structural testicular damage leading to Leydig cell dysfunction and, consequently, temporary or even permanent hypogonadism with long-term health consequences. To a lesser extent, the same complications have been reported for microdissection TESE, which is considered less invasive. The resulting hypogonadism is more profound and of longer duration in patients with Klinefelter syndrome compared with other NOA causes. Most studies on serum follicle-stimulating hormone and luteinizing hormone concentrations negatively correlate with total testosterone concentrations, which depends on the underlying histology. As hypogonadism is usually temporary, and a watchful waiting approach for about 12 months postoperative is suggested. In cases where replacement therapy with testosterone is indicated, temporary discontinuation of treatment may promote the expected recovery of testosterone secretion and revise the decision for long-term treatment.
Prognostic Significance of the Extranodal Extension of Regional Lymph Nodes in Stage III-N2 Non-Small-Cell Lung Cancer after Curative Resection
Authors: Shih Beatrice Chia-Hui , Jeon Jae Hyun , Chung Jin-Haeng , Kwon Hyun Jung , Lee Jeong Hoon , Jung Woohyun , Hwang Yoohwa , Cho Sukki , Kim Kwhanmien , Jheon Sanghoon
Published: July 2021

The present study investigated the prognostic role of extranodal extension (ENE) in stage III-N2 non-small-cell lung cancer (NSCLC) following curative surgery. From January 2005 to December 2018, pathologic stage III-N2 disease was diagnosed in 371 patients, all of whom underwent anatomic pulmonary resection accompanied by mediastinal lymph node dissection. This study included 282 patients, after excluding 89 patients who received preoperative chemotherapy or incomplete surgical resection. Their lymph nodes were processed; after hematoxylin and eosin staining, histopathologic slides of the metastatic nodes were reviewed by a designated pathologist. Predictors of disease free survival (DFS), including age, sex, operation type, pathologic T stage, nodal status, visceral pleural invasion, perioperative treatment, and the presence of ENE, were investigated. Among the 282 patients, ENE was detected in 85 patients (30.1%). ENE presence was associated with advanced T stage (p = 0.034), N2 subgroups (p < 0.001), lymphatic invasion (p = 0.001), and pneumonectomy (p = 0.002). The multivariable analysis demonstrated that old age (p < 0.001), advanced T stage (p = 0.012), N2 subgroups (p = 0.005), and ENE presence (p = 0.005) were significant independent predictors of DFS. The DFS rate at five years was 21.4% in patients who had ENE and 43.4% in patients who did not have ENE (p < 0.001). The presence of ENE, coupled with tumor-node-metastasis staging, should be recognized as a meaningful prognostic factor in stage III-N2 NSCLC patients.
Preoperative Doppler Ultrasonography Allen Test for Radial Forearm Free Flap in Oral Cancer Reconstruction: Implications in Clinical Practice
Authors: Tousidonis Manuel , Escobar José Ignacio Salmerón , Caicoya Santiago Ochandiano , Vila Carlos Navarro , Cuéllar Ignacio Navarro , Montiel Alberto Díez , López Ana María López , Cuéllar Carlos Navarro
Published: July 2021

The Radial Forearm Free Flap (RFFF) is one of the most widely used microsurgical flaps for intraoral reconstruction. Although the Clinical Allen Test (CAT) is the most widely used preoperative diagnostic method with which to study the distal patency of the hand prior to the use of RFFF, several authors have reported potentially preventable serious vascular complications. This study included 87 consecutive patients with cancer of the oral cavity and RFFF as the flap of choice who were treated between 2010 and 2020, and compares the results of the Clinical Allen Test (CAT), the Doppler Allen Test (DAT) and the Surgical Allen Test (SAT). The preoperative vascular study found vascular abnormalities severe enough for the surgical team to change the preoperative flap of choice in 39% of patients. The Kappa index showed a weak concordance between the CAT and DAT. The study reflected a total concordance in the preoperative results of the Doppler study and the intraoperative results of the SAT. Due to its excellent agreement with SAT, the DAT would be the preoperative test of choice in patients who are candidates for RFFF. This study of vascular mapping tests with Doppler is intended to inform therapeutic decisions and present methods to gain information that cannot be obtained by physical examination alone.
Surgical Site Infection Following Intramedullary Nailing of Subtrochanteric Femoral Fractures
Authors: Panteli Michalis , Vun James S. H. , West Robert M. , Howard Anthony , Pountos Ippokratis , Giannoudis Peter V.
Published: July 2021

Aim: To investigate the incidence, risk factors and pathogenic micro-organisms causing superficial and deep infection in subtrochanteric femoral fractures managed with an intramedullary nail. Materials and Methods: Following institutional board approval, all consecutive patients presenting with a subtrochanteric fracture were retrospectively identified, over an 8-year period. Basic demographics, fracture characteristics, fracture union, revision operation, mortality and other complications were reported and analysed. Variables deemed statistically significant (p-value < 0.05) were then included into a revised adjusted model of logistic regression analysis, where we reported on the odds ratio (OR). Results: The overall incidence of infection was 6.4% (n = 36/561; superficial: 3.7%; deep: 2.7%). Associations with deep infection included: non-union (OR 9.29 (2.56–3.38)), the presence of an open fracture (OR 4.23 (3.18–5.61)), the need for massive transfusion (OR 1.42 (2.39–8.39)), post-operative transfusion (OR 1.40 (1.10–1.79)) and prolonged length of stay (OR 1.04 (1.02–1.06)). The Commonest causes of superficial infection were Staphylococcus aureus (28.5%), enteric flora (23.8%) and mixed flora (23.8%); whereas coliforms (60%) and Staphylococcus aureus (26.7%) were the commonest micro-organisms isolated in deep infection. Polymicrobial infection was identified in 38.5% and 80% of superficial and deep infections, respectively. Conclusion: Causative micro-organisms identified in both superficial and deep infection were similar to those reported in post-traumatic osteomyelitis. In an attempt to minimise infection, the treating clinician should focus on modifiable risk factors with adequate patient optimisation, prompt surgical treatment, adequate antibiotic coverage and wound care when treating patients with subtrochanteric femur fracture.
Effects of Transcatheter Mitral Valve Repair Using MitraClip® Device on Sleep Disordered Breathing in Patients with Mitral Valve Regurgitation
Authors: Daher Ayham , Müller Tobias , Marx Nikolaus , Schröder Jörg , Almalla Mohammad , Keszei András P. , Reith Sebastian , Dreher Michael
Published: July 2021

Sleep disordered breathing (SDB) is common among patients with valvular heart disease, and successful valve surgery could reduce SDB severity. However, data about the effects of transcatheter mitral valve repair on SDB are scarce. Therefore, mitral regurgitation (MR) patients undergoing MitraClip-placement were prospectively enrolled. Before MitraClip-placement, daytime sleepiness and sleep quality were assessed using the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), respectively; and all patients underwent SDB screening using five-channel respiratory polygraphy. After 3–6 months, patients had a similar reassessment including: ESS, PSQI, and respiratory polygraphy. 67 patients were included (77 ± 8years). Despite normal sleepiness scores, 41 patients (61%) had SDB with apnea-hypopnea-index (AHI) ≥ 15 h before MitraClip-placement, of whom only three patients had known SDB previously. Compared to patients without SDB, patients with SDB had similar sleepiness scores but higher NT-proBNP values at baseline (4325 vs. 1520 pg/mL, p < 0.001). At follow-up, there were significant AHI improvements among patients with SDB (p = 0.013). However, there were no significant sleepiness score changes. In conclusion, the prevalence of SDB among MitraClip candidates is very high even in those without daytime sleepiness. MR patients with SDB have higher NT-proBNP values, which may reflect a worse prognosis. MitraClip-placement may improve the underlying SDB, which could be an additional benefit of the procedure.
Calculated Plasma Volume Status Is Associated with Adverse Outcomes in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Seoudy Hatim , Saad Mohammed , Salem Mostafa , Allouch Kassem , Frank Johanne , Puehler Thomas , Salem Mohamed , Lutter Georg , Kuhn Christian , Frank Derk
Published: July 2021

Background: Calculated plasma volume status (PVS) reflects volume overload based on the deviation of the estimated plasma volume (ePV) from the ideal plasma volume (iPV). Calculated PVS is associated with prognosis in the context of heart failure. This single-center study investigated the prognostic impact of PVS in patients undergoing transcatheter aortic valve implantation (TAVI). Methods: A total of 859 TAVI patients had been prospectively enrolled in an observational study and were included in the analysis. An optimal cutoff for PVS of −5.4% was determined by receiver operating characteristic curve analysis. The primary endpoint was a composite of all-cause mortality or heart failure hospitalization within 1 year after TAVI. Results: A total of 324 patients had a PVS < −5.4% (no congestion), while 535 patients showed a PVS ≥ −5.4% (congestion). The primary endpoint occurred more frequently in patients with a PVS ≥ −5.4% compared to patients with PVS < −5.4% (22.6% vs. 13.0%, p < 0.001). After multivariable adjustment, PVS was confirmed as a significant predictor of the primary endpoint (HR 1.53, 95% CI 1.05–2.22, p = 0.026). Conclusions: Elevated PVS, as a marker of subclinical congestion, is significantly associated with all-cause mortality and heart failure hospitalization within 1 year after TAVI.
Predisposing Factors for Severe Complications after Cataract Surgery: A Nationwide Population-Based Study
Authors: Lin I-Hung , Lee Chia-Yi , Chen Jiann-Torng , Chen Yi-Hao , Chung Chi-Hsiang , Sun Chien-An , Chien Wu-Chien , Chen Hung-Chi , Chen Ching-Long
Published: July 2021

We conducted a retrospective group study to evaluate the potential systemic risk factors for major postoperative complications of cataract surgery. Individuals diagnosed with (n = 2046) and without (n = 8184) serious complications after cataract surgery were matched 1:4 for age, sex, and index date obtained using Taiwan’s National Health Insurance Research Database. The outcome was defined as at least one new inpatient or outpatient diagnosis of systemic disease one year before the index date. The effect of demographic data on postoperative complications was also analyzed in the multivariable model. Data were analyzed using univariate and multivariate conditional logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals of the risk of developing serious complications. After the entire study interval, the major postoperative complications of cataract surgery were associated with the following systemic diseases: hypertension (adjusted OR (aOR) = 2.329, p < 0.001), diabetes mellitus (aOR = 2.818, p < 0.001), hyperlipidemia (aOR = 1.702, p < 0.001), congestive heart failure (aOR = 2.891, p < 0.001), rheumatic disease (aOR = 1.965, p < 0.001), and kidney disease needing hemodialysis (aOR = 2.942, p < 0.001). Additionally, demographic data including old age, higher urbanization level, higher level of care, and more frequent inpatient department visits were associated with a higher rate of postoperative complications. In conclusion, metabolic syndrome, chronic heart failure, end-stage renal disease, rheumatic disease, older age, and frequent inpatient department visits are correlated with the development of severe postoperative complications of cataract surgery. Therefore, cataract surgery patients should be informed about a higher possibility of postoperative complications.
Serum Biomarkers of Liver Fibrosis Staging in the Era of the Concept “Compensated Advanced Chronic Liver Disease”
Authors: Fujita Koji , Masaki Tsutomu
Published: July 2021

Non-invasive indexes of liver fibrosis based on blood examinations have been developed for decades, partially replacing liver biopsy examinations. Recently, the concept of liver cirrhosis was revised and converted to “compensated advanced chronic liver diseases” since the Baveno VI consensus statement in 2015. The term “compensated advanced chronic liver diseases” was established based on the premise that serum biomarkers were not able to differentiate cirrhosis from severe fibrosis. The difficulty to histologically distinguish cirrhosis from severe fibrosis had been pointed out in 1977, when the definition and nomenclatures of cirrhosis had been determined by the World Health Organization. That was decades before serum biomarkers available at present were investigated. Though we are accustomed to differentiating the fibrosis stage as stage 1, 2, 3 (severe fibrosis), and 4 (cirrhosis), differentiation of cirrhosis from severe fibrosis is difficult even by histopathological examination. The current review will provide readers a framework to revise how to apply serum biomarkers on liver fibrosis staging in an era of the concept of “compensated advanced chronic liver disease”.
Correlation of Process Conditions, Porosity Levels and Crystallinity in Atmospherically Plasma Sprayed Yb2Si2O7 Environmental Barrier Coatings
Authors: Vaßen Robert , Bakan Emine , Sebold Doris , Sohn Yoo Jung
Published: July 2021

Environmental barrier coatings are necessary to protect fibre reinforced ceramics from high recession rates in fast and hot water vapor-containing gases as they typically are found in the hot gas sections of gas turbines. A standard material to protect SiC/SiC composites is atmospherically plasma sprayed (APS) Yb2Si2O7. For this material, it is difficult to obtain at reasonable substrate temperatures both low porosity and high crystallinity levels during APS. In this paper results of coatings prepared by a so-called high velocity APS process and also more conventional processes are presented. All coatings have been prepared by a single layer deposition method which avoids inter passage porosity bands. Furthermore, the samples were heat-treated in air at 1300 °C for 100 h and the influence of the topcoat density on the growth of the silica scale on the used silicon bond coat was studied.
The Effect of Low Temperature on the Early Life Stages of the Walleye Pollock, Gadus chalcogrammus—A Laboratory Study
Authors: Yoo Hae-Kyun , Kim Woo-Jin , Lim Hyung-Jun , Byun Soon-Gyu , Yamamoto Jun , Sakurai Yasunori
Published: July 2021

The walleye pollock Gadus chalcogrammus is an important commercial species in Japan whose larvae and eggs may be negatively affected by the cold water mass from the coastal Oyashio current that is present in the spawning ground of the Japanese Pacific stock of this species. Therefore, we investigated egg and larval specific density, larval mortality, and behavioral response to temperature change during the ontogenetic development of the walleye pollock to understand the effect of this cold surface water mass (<1.5 °C). Egg and larval specific density varied during development but were lower than the corresponding values from the coastal Oyashio waters. Within our study temperature range (0.3–10.0 °C), the number of days to 50% mortality (D50) was high at 3.1 °C. Below and above this temperature, the D50 showed a decreasing trend. Regarding larval response, at 1.5°C and 5.0°C, newly hatched larvae occurred abundantly in the surface layer, irrespective of the surface and rearing temperatures. When these larvae were released into a thermally stratified water column (surface: 1.5 °C, bottom: 5.0 °C), larvae reared at 5.0 °C with the mouth open and yolk sac completely absorbed moved to the lower layers. However, larvae reared at 1.5 °C remained in the surface layer. These results suggest that the cold water mass could negatively affect larval survival and may limit the escape ability of larvae from unfavorable cold conditions.
The Optimization and Biological Significance of a 29-Host-Immune-mRNA Panel for the Diagnosis of Acute Infections and Sepsis
Authors: He Yudong D. , Wohlford Eric M. , Uhle Florian , Buturovic Ljubomir , Liesenfeld Oliver , Sweeney Timothy E.
Published: July 2021

In response to the unmet need for timely accurate diagnosis and prognosis of acute infections and sepsis, host-immune-response-based tests are being developed to help clinicians make more informed decisions including prescribing antimicrobials, ordering additional diagnostics, and assigning level of care. One such test (InSep™, Inflammatix, Inc.) uses a 29-mRNA panel to determine the likelihood of bacterial infection, the separate likelihood of viral infection, and the risk of physiologic decompensation (severity of illness). The test, being implemented in a rapid point-of-care platform with a turnaround time of 30 min, enables accurate and rapid diagnostic use at the point of impact. In this report, we provide details on how the 29-biomarker signature was chosen and optimized, together with its molecular, immunological, and medical significance to better understand the pathophysiological relevance of altered gene expression in disease. We synthesize key results obtained from gene-level functional annotations, geneset-level enrichment analysis, pathway-level analysis, and gene-network-level upstream regulator analysis. Emerging findings are summarized as hallmarks on immune cell interaction, inflammatory mediators, cellular metabolism and homeostasis, immune receptors, intracellular signaling and antiviral response; and converging themes on neutrophil degranulation and activation involved in immune response, interferon, and other signaling pathways.
Of Screening, Stratification, and Scores
Authors: Knoppers Bartha M. , Bernier Alexander , Granados Moreno Palmira , Pashayan Nora
Published: July 2021

Technological innovations including risk-stratification algorithms and large databases of longitudinal population health data and genetic data are allowing us to develop a deeper understanding how individual behaviors, characteristics, and genetics are related to health risk. The clinical implementation of risk-stratified screening programmes that utilise risk scores to allocate patients into tiers of health risk is foreseeable in the future. Legal and ethical challenges associated with risk-stratified cancer care must, however, be addressed. Obtaining access to the rich health data that are required to perform risk-stratification, ensuring equitable access to risk-stratified care, ensuring that algorithms that perform risk-scoring are representative of human genetic diversity, and determining the appropriate follow-up to be provided to stratification participants to alert them to changes in their risk score are among the principal ethical and legal challenges. Accounting for the great burden that regulatory requirements could impose on access to risk-scoring technologies is another critical consideration.
The Impact of Brand Equity on Conversion Behavior in the Use of Personal Banking Services: Case Study of Commercial Banks in Vietnam
Authors: Nguyen Thi Thu Cuc
Published: July 2021

The brand equity of banks plays a crucial role in determining customer behavior of using their services. The study aims to examine the impact of brand equity on conversion behavior in the use of personal banking services at commercial banks in Vietnam. The paper uses quantitative research methods, through linear SEM (Structural Equation Modelling) analysis, with survey data including 554 samples of individual customers of commercial banks. The study’s findings show that the bank’s brand equity has a negative impact on the behavior of individual customers. In the relationship between these two factors, competitive advertising effectiveness and loyalty of customers act as intermediary factors. On that basis, the study makes a number of recommendations to preclude customers leaving and minimize business losses caused by the conversion of customers’ banks. The findings of this study have shown the importance and impact of brand equity on conversion behavior in the use of personal customer services. These are meaningful contributions both theoretically and practically to help banks get a deeper insight into brand equity and the need to pay attention to building and developing sustainable brand equity for the bank, as well as an important basis for further research.
Income Diversification Strategies of Italian Peri-Urban Farms: A Structural Equation Modeling Approach
Authors: Cimino Orlando , Vassallo Marco , Henke Roberto , Vanni Francesco
Published: July 2021

On-farm diversification in non-agricultural activities has been increasingly recognized as a rewarding farm strategy through which farmers produce on-farm non-agricultural goods and services. The main objective of this paper is to explore to what extent the condition of peri-urbanity affects farm income diversification in Italy by looking at the push and pull factors that allow peri-urban farmers to re-organize their business by developing diversification strategies that are tightly connected to the demand of goods and services coming from the urban society. A structural equation modeling (SEM) statistical technique has been applied to estimate direct and indirect causal relationships among the multiple variables involved. The SEM analytical approach allowed us to untie the complexity of the push and pull factors connections and to highlight the most significant ones. The strengths of the structural paths provide evidence on the key diversification strategies adopted by peri-urban farms.