bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Ciliogenesis by 2-Isopropylmalic Acid Prevents PM2.5-Induced Inflammatory Response and MMP-1 Activation in Human Dermal Fibroblasts and a 3-D-Skin Model
Authors: Bae Ji-Eun , Min Daejin , Choi Ji Yeon , Choi Hyunjung , Kim Joon Bum , Park Na Yeon , Jo Doo Sin , Kim Yong Hwan , Na Hye-Won , Kim Yoon Jae , Kim Eun Sung , Kim Hyoung-June , Cho Dong-Hyung
Published: October 2021

Particulate matters (PMs) increase oxidative stress and inflammatory response in different tissues. PMs disrupt the formation of primary cilia in various skin cells, including keratinocytes and melanocytes. In this study, we found that 2-isopropylmalic acid (2-IPMA) promoted primary ciliogenesis and restored the PM2.5-induced dysgenesis of primary cilia in dermal fibroblasts. Moreover, 2-IPMA inhibited the generation of excessive reactive oxygen species and the activation of stress kinase in PM2.5-treated dermal fibroblasts. Further, 2-IPMA inhibited the production of pro-inflammatory cytokines, including IL-6 and TNF-α, which were upregulated by PM2.5. However, the inhibition of primary ciliogenesis by IFT88 depletion reversed the downregulated cytokines by 2-IPMA. Moreover, we found that PM2.5 treatment increased the MMP-1 expression in dermal fibroblasts and a human 3-D-skin model. The reduced MMP-1 expression by 2-IPMA was further reversed by IFT88 depletion in PM2.5-treated dermal fibroblasts. These findings suggest that 2-IPMA ameliorates PM2.5-induced inflammation by promoting primary ciliogenesis in dermal fibroblasts.
PACAP and VIP Modulate LPS-Induced Microglial Activation and Trigger Distinct Phenotypic Changes in Murine BV2 Microglial Cells
Authors: Karunia Jocelyn , Niaz Aram , Mandwie Mawj , Thomas Broome Sarah , Keay Kevin A. , Waschek James A. , Al-Badri Ghaith , Castorina Alessandro
Published: October 2021

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two structurally related immunosuppressive peptides. However, the underlying mechanisms through which these peptides regulate microglial activity are not fully understood. Using lipopolysaccharide (LPS) to induce an inflammatory challenge, we tested whether PACAP or VIP differentially affected microglial activation, morphology and cell migration. We found that both peptides attenuated LPS-induced expression of the microglial activation markers Iba1 and iNOS (### p < 0.001), as well as the pro-inflammatory mediators IL-1β, IL-6, Itgam and CD68 (### p < 0.001). In contrast, treatment with PACAP or VIP exerted distinct effects on microglial morphology and migration. PACAP reversed LPS-induced soma enlargement and increased the percentage of small-sized, rounded cells (54.09% vs. 12.05% in LPS-treated cells), whereas VIP promoted a phenotypic shift towards cell subpopulations with mid-sized, spindle-shaped somata (48.41% vs. 31.36% in LPS-treated cells). Additionally, PACAP was more efficient than VIP in restoring LPS-induced impairment of cell migration and the expression of urokinase plasminogen activator (uPA) in BV2 cells compared with VIP. These results suggest that whilst both PACAP and VIP exert similar immunosuppressive effects in activated BV2 microglia, each peptide triggers distinctive shifts towards phenotypes of differing morphologies and with differing migration capacities.
Decursinol Angelate Mitigates Sepsis Induced by Methicillin-Resistant Staphylococcus aureus Infection by Modulating the Inflammatory Responses of Macrophages
Authors: Pak Seongwon , Thapa Bikash , Lee Keunwook
Published: October 2021

The herbal plant Angelica gigas (A. gigas) has been used in traditional medicine in East Asian countries, and its chemical components are reported to have many pharmacological effects. In this study, we showed that a bioactive ingredient of A. gigas modulates the functional activity of macrophages and investigated its effect on inflammation using a sepsis model. Among 12 different compounds derived from A. gigas, decursinol angelate (DA) was identified as the most effective in suppressing the induction of TNF-α and IL-6 in murine macrophages. When mice were infected with a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA), DA treatment improved the mortality and bacteremia, and attenuated the cytokine storm, which was associated with decreased CD38+ macrophage populations in the blood and liver. In vitro studies revealed that DA inhibited the functional activation of macrophages in the expression of pro-inflammatory mediators in response to microbial infection, while promoting the bacterial killing ability with an increased production of reactive oxygen species. Mechanistically, DA treatment attenuated the NF-κB and Akt signaling pathways. Intriguingly, ectopic expression of an active mutant of IKK2 released the inhibition of TNF-α production by the DA treatment, whereas the inhibition of Akt resulted in enhanced ROS production. Taken together, our experimental evidence demonstrated that DA modulates the functional activities of pro-inflammatory macrophages and that DA could be a potential therapeutic agent in the management of sepsis.
L-Type Amino Acid Transporter 1 Regulates Cancer Stemness and the Expression of Programmed Cell Death 1 Ligand 1 in Lung Cancer Cells
Authors: Liu Yi-Heng , Li Yu-Ling , Shen Huan-Ting , Chien Peng-Ju , Sheu Gwo-Tarng , Wang Bing-Yen , Chang Wen-Wei
Published: October 2021

The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC) cells with high cancer stem cell (CSC) activity, and its mRNA expression level was associated with shorter overall survival in the lung adenocarcinoma dataset of the Cancer Genome Atlas database. The inhibition of LAT1 by a small molecule inhibitor, JPH203, or by RNA interference led to a significant reduction in tumorsphere formation and the downregulation of several cancer stemness genes in NSCLC cells through decreased AKT serine/threonine kinase (AKT)/mammalian target of rapamycin (mTOR) activation. The treatment of the cell-permeable leucine derivative promoted AKT/mTOR phosphorylation and reversed the inhibitory effect of JPH203 in the reduction of CSC activity in pemetrexed-resistant lung cancer cells. Furthermore, we observed that LAT1 silencing caused the downregulation of programmed cell death 1 ligand 1 (PD-L1) on lung cancer cells. The PD-L1+/LAT1+ subpopulation of NSCLC cells displayed great CSC activity with increased expression of several cancer stemness genes. These data suggest that LAT1 inhibitors can serve as anti-CSC agents and could be used in combination with immune checkpoint inhibitors in lung cancer therapy.
Elucidating Carfilzomib’s Induced Cardiotoxicity in an In Vivo Model of Aging: Prophylactic Potential of Metformin
Authors: Efentakis Panagiotis , Psarakou Garyfalia , Varela Aimilia , Papanagnou Eleni Dimitra , Chatzistefanou Michail , Nikolaou Panagiota-Efstathia , Davos Costantinos H. , Gavriatopoulou Maria , Trougakos Ioannis P. , Dimopoulos Meletios Athanasios , Andreadou Ioanna , Terpos Evangelos
Published: October 2021

Background: Carfilzomib is a first-line proteasome inhibitor indicated for relapsed/refractory multiple myeloma (MM), with its clinical use being hampered by cardiotoxic phenomena. We have previously established a translational model of carfilzomib cardiotoxicity in young adult mice, in which metformin emerged as a prophylactic therapy. Considering that MM is an elderly disease and that age is an independent risk factor for cardiotoxicity, herein, we sought to validate carfilzomib’s cardiotoxicity in an in vivo model of aging. Methods: Aged mice underwent the translational two- and four-dose protocols without and with metformin. Mice underwent echocardiography and were subsequently sacrificed for molecular analyses in the blood and cardiac tissue. Results: Carfilzomib decreased proteasomal activity both in PBMCs and myocardium in both protocols. Carfilzomib induced mild cardiotoxicity after two doses and more pronounced cardiomyopathy in the four-dose protocol, while metformin maintained cardiac function. Carfilzomib led to an increased Bip expression and decreased AMPKα phosphorylation, while metformin coadministration partially decreased Bip expression and induced AMPKα phosphorylation, leading to enhanced myocardial LC3B-dependent autophagy. Conclusion: Carfilzomib induced cardiotoxicity in aged mice, an effect significantly reversed by metformin. The latter possesses translational importance as it further supports the clinical use of metformin as a potent prophylactic therapy.
Receptor-Loaded Virion Endangers GPCR Signaling: Mechanistic Exploration of SARS-CoV-2 Infections and Pharmacological Implications
Authors: Zhang Qiangmin , Friedman Peter A.
Published: October 2021

SARS-CoV-2 exploits the respiratory tract epithelium including lungs as the primary entry point and reaches other organs through hematogenous expansion, consequently causing multiorgan injury. Viral E protein interacts with cell junction-associated proteins PALS1 or ZO-1 to gain massive penetration by disrupting the inter-epithelial barrier. Conversely, receptor-mediated viral invasion ensures limited but targeted infections in multiple organs. The ACE2 receptor represents the major virion loading site by virtue of its wide tissue distribution as demonstrated in highly susceptible lung, intestine, and kidney. In brain, NRP1 mediates viral endocytosis in a similar manner to ACE2. Prominently, PDZ interaction involves the entire viral loading process either outside or inside the host cells, whereas E, ACE2, and NRP1 provide the PDZ binding motif required for interacting with PDZ domain-containing proteins PALS1, ZO-1, and NHERF1, respectively. Hijacking NHERF1 and β-arrestin by virion loading may impair specific sensory GPCR signalosome assembling and cause disordered cellular responses such as loss of smell and taste. PDZ interaction enhances SARS-CoV-2 invasion by supporting viral receptor membrane residence, implying that the disruption of these interactions could diminish SARS-CoV-2 infections and be another therapeutic strategy against COVID-19 along with antibody therapy. GPCR-targeted drugs are likely to alleviate pathogenic symptoms-associated with SARS-CoV-2 infection.
Selected Applications of Chitosan Composites
Authors: Pal Kunal , Bharti Deepti , Sarkar Preetam , Anis Arfat , Kim Doman , Chałas Renata , Maksymiuk Paweł , Stachurski Piotr , Jarzębski Maciej
Published: October 2021

Chitosan is one of the emerging materials for various applications. The most intensive studies have focused on its use as a biomaterial and for biomedical, cosmetic, and packaging systems. The research on biodegradable food packaging systems over conventional non-biodegradable packaging systems has gained much importance in the last decade. The deacetylation of chitin, a polysaccharide mainly obtained from crustaceans and shrimp shells, yields chitosan. The deacetylation process of chitin leads to the generation of primary amino groups. The functional activity of chitosan is generally owed to this amino group, which imparts inherent antioxidant and antimicrobial activity to the chitosan. Further, since chitosan is a naturally derived polymer, it is biodegradable and safe for human consumption. Food-focused researchers are exploiting the properties of chitosan to develop biodegradable food packaging systems. However, the properties of packaging systems using chitosan can be improved by adding different additives or blending chitosan with other polymers. In this review, we report on the different properties of chitosan that make it suitable for food packaging applications, various methods to develop chitosan-based packaging films, and finally, the applications of chitosan in developing multifunctional food packaging materials. Here we present a short overview of the chitosan-based nanocomposites, beginning with principal properties, selected preparation techniques, and finally, selected current research.
GPR Investigation at the Archaeological Site of Le Cesine, Lecce, Italy
Authors: Colica Emanuele , Antonazzo Antonella , Auriemma Rita , Coluccia Luigi , Catapano Ilaria , Ludeno Giovanni , D’Amico Sebastiano , Persico Raffaele
Published: October 2021

In this contribution, we present some results achieved in the archaeological site of Le Cesine, close to Lecce, in southern Italy. The investigations have been performed in a site close to the Adriatic Sea, only slightly explored up to now, and where the presence of an ancient Roman harbour is alleged on the basis of remains visible above all under the current sea level. This measurement campaign has been performed in the framework of a short-term scientific mission (STSM) performed in the framework of the European Cost Action 17131 (acronym SAGA), and has been aimed to identify possible points where future localized excavation might and hopefully will be performed in the next few years. Both a traditional elaboration and an innovative data processing based on a linear inverse scattering model have been performed on the data.
A Machine-Learning Approach for Extracting Modulus of Compacted Unbound Aggregate Base and Subgrade Materials Using Intelligent Compaction Technology
Authors: Fathi Aria , Tirado Cesar , Rocha Sergio , Mazari Mehran , Nazarian Soheil
Published: October 2021

This study presents a rigorous approach for the extraction of the modulus of soil and unbound aggregate base materials for quality management using intelligent compaction (IC) technology. The proposed approach makes use of machine-learning methods in tandem with IC technology and modulus-based spot testing as a local calibration process to estimate the mechanical properties of compacted geomaterials. A calibrated three-dimensional finite element (FE) model that simulates the proof-mapping process of compacted geomaterials was used to develop a comprehensive database of responses of a wide range of single and two-layered geosystems. The database was then used to develop different inverse solvers using artificial neural networks for the estimation of the modulus from the characteristics of the roller and information about the geomaterials. Several instrumented test sites were used for the evaluation and validation of the inverse solvers. The proposed approach was found promising for the extraction of the modulus of compacted geomaterials using IC. The accuracy of the inverse solvers is enhanced if a local calibration process is incorporated as part of a quality management program that includes the use of in situ measurements using modulus-based test devices and laboratory resilient modulus testing. Moreover, compaction uniformity plays a key role in the retrieval of the modulus of geomaterials with certainty. The proposed approach fuses artificial intelligence with mechanistic solutions to position IC as a technology that is well suited for the quality management of compacted materials.
Effect of Type of Curing and Metakaolin Replacement on Air Lime Mortars for the Durability of Masonries
Authors: Monteiro João , Silva Vitor , Faria Paulina
Published: October 2021

The interest in restoration and maintenance of old masonries towards their durability is nowadays combined with the concept of sustainability and the need to implement more suitable materials for building heritage interventions. This has led to the importance of having a better knowledge of air lime mortars, namely on the effect of pozzolanic additions, curing conditions and evolution at early stages. This study consisted in the characterization of mortars based on hydrated air lime and sand, with 1:2 (lime:sand) volumetric composition, with different weight percentages of substitution of lime by metakaolin (Mk): 0%, 10% and 20%. Mortar prisms were analyzed in three different curing environments: maritime (by the Atlantic Ocean), in laboratory humidity (95 ± 5% relative humidity, RH) and standard (65 ± 5% RH) conditioning. Tests were conducted to evaluate fresh and hardened properties of mortars, considering physical, chemical and mechanical performance at 28, 90 and 180 days. Results showed the viability of applying air lime-Mk mortars with curing conditions similar to the tested ones. In the standard curing, the mortar with 20% Mk revealed advantages in mechanical parameters. Concerning the behaviour towards water, improvements were shown at an early stage with the humid curing, while maritime curing benefited its behaviour for at least up to 6 months.
Understanding the Influence of Personality Traits on Risk of Suicidal Behaviour in Schizophrenia Spectrum Disorders: A Systematic Review
Authors: Canal-Rivero Manuel , Ayesa-Arriola Rosa , Setién-Suero Esther , Crespo-Facorro Benedicto , Arango Celso , Dutta Rina , Lopez-Morinigo Javier-David
Published: October 2021

Risk of suicidal behaviour (SB) in schizophrenia spectrum disorders (SSD) is a major concern, particularly in early stages of the illness, when suicide accounts for a high number of premature deaths. Although some risk factors for SB in SSD are well understood, the extent to which personality traits may affect this risk remains unclear, which may have implications for prevention. We conducted a systematic review of previous studies indexed in MEDLINE, PsycINFO and Embase examining the relationship between personality traits and SB in samples of patients with SSD. Seven studies fulfilled predetermined selection criteria. Harm avoidance, passive-dependent, schizoid and schizotypal personality traits increased the risk of SB, while self-directedness, cooperativeness, excluding persistence and self-transcendence acted as protective factors. Although only seven studies were retrieved from three major databases after applying predetermined selection criteria, we found some evidence to support that personality issues may contribute to SB in patients with SSD. Personality traits may therefore become part of routine suicide risk assessment and interventions targeting these personality-related factors may contribute to prevention of SB in SSD.
Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion
Authors: Cabrera-Borrego Eva , Montero-Vilchez Trinidad , Bermúdez-Jiménez Francisco José , Tercedor-Sánchez Jesús , Tercedor-Sánchez Luis , Sánchez-Díaz Manuel , Macías-Ruiz Rosa , Molina-Jiménez María , Cañizares-García Francisco Javier , Fernández-Segura Eduardo , Fernandez-Flores Angel , Arias-Santiago Salvador , Jiménez-Jáimez Juan
Published: October 2021

Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.
Involvement of Cutaneous Sensory Corpuscles in Non-Painful and Painful Diabetic Neuropathy
Authors: García-Mesa Yolanda , Feito Jorge , González-Gay Mario , Martínez Irene , García-Piqueras Jorge , Martín-Cruces José , Viña Eliseo , Cobo Teresa , García-Suárez Olivia
Published: October 2021

Distal diabetic sensorimotor polyneuropathy (DDSP) is the most prevalent form of diabetic neuropathy, and some of the patients develop gradual pain. Specialized sensory structures present in the skin encode different modalities of somatosensitivity such as temperature, touch, and pain. The cutaneous sensory structures responsible for the qualities of mechanosensitivity (fine touch, vibration) are collectively known as cutaneous mechanoreceptors (Meissner corpuscles, Pacinian corpuscles, and Merkel cell–axonal complexes), which results are altered during diabetes. Here, we used immunohistochemistry to analyze the density, localization within the dermis, arrangement of corpuscular components (axons and Schwann-like cells), and expression of putative mechanoproteins (PIEZO2, ASIC2, and TRPV4) in cutaneous mechanoreceptors of subjects suffering clinically diagnosed non-painful and painful distal diabetic sensorimotor polyneuropathy. The number of Meissner corpuscles, Pacinian corpuscles, and Merkel cells was found to be severely decreased in the non-painful presentation of the disease, and almost disappeared in the painful presentation. Furthermore, there was a marked reduction in the expression of axonal and Schwann-like cell markers (with are characteristics of corpuscular denervation) as well as of all investigated mechanoproteins in the non-painful distal diabetic sensorimotor polyneuropathy, and these were absent in the painful form. Taken together, these alterations might explain, at least partly, the impairment of mechanosensitivity system associated with distal diabetic sensorimotor polyneuropathy. Furthermore, our results support that an increasing severity of DDSP may increase the risk of developing painful neuropathic symptoms. However, why the absence of cutaneous mechanoreceptors is associated with pain remains to be elucidated.
The Impact of Infectious Complications after Esophagectomy for Esophageal Cancer on Cancer Prognosis and Treatment Strategy
Authors: Booka Eisuke , Kikuchi Hirotoshi , Hiramatsu Yoshihiro , Takeuchi Hiroya
Published: October 2021

Despite advances in the perioperative management of esophagectomy, it is still a highly invasive procedure for esophageal cancer and is associated with severe postoperative complications. The two major postoperative infectious complications after esophagectomy are pulmonary complications and anastomotic leakage. We previously reported that postoperative infectious complications after esophagectomy adversely affect long-term survival significantly in a single institution and meta-analysis. Additionally, we reviewed the mechanisms of proinflammatory cytokines, such as C-X-C motif ligand 8 (CXCL8) and its cognate receptor, C-X-C chemokine receptor 2 (CXCR2), in contributing to tumorigenesis and tumor progression. Moreover, we previously reported that introducing minimally invasive esophagectomy, including robot assistance, laparoscopic gastric mobilization, and multidisciplinary team management, significantly reduced postoperative infectious complications after esophagectomy. Further, this review also suggests future treatment strategies for esophageal cancer, considering the adverse effect of postoperative infectious complications after esophagectomy.
Bone Biopsy for Histomorphometry in Chronic Kidney Disease (CKD): State-of-the-Art and New Perspectives
Authors: Dalle Carbonare Luca , Valenti Maria Teresa , Giannini Sandro , Gallieni Maurizio , Stefani Francesca , Ciresa Roberto , Politi Cristina , Fusaro Maria
Published: October 2021

The use of bone biopsy for histomorphometric analysis is a quantitative histological examination aimed at obtaining quantitative information on bone remodeling, structure and microarchitecture. The labeling with tetracycline before the procedure also allows for a dynamic analysis of the osteoblastic activity and mineralization process. In the nephrological setting, bone biopsy is indicated to confirm the diagnosis of subclinical or focal osteomalacia and to characterize the different forms of renal osteodystrophy (ROD). Even if bone biopsy is the gold standard for the diagnosis and specific classification of ROD, the use of this approach is very limited. The main reasons for this are the lack of widespread expertise in performing or interpreting bone biopsy results and the cost, invasiveness and potential pain associated with the procedure. In this regard, the sedation, in addition to local anesthesia routinely applied in Italian protocol, significantly reduces pain and ameliorates the pain perception of patients. Concerning the lack of widespread expertise, in Italy a Hub/Spokes model is proposed to standardize the analyses, optimizing the approach to CKD patients and reducing the costs of the procedure. In addition, new tools offer the possibility to evaluate the osteogenic potential or the ability to form bone under normal and pathological conditions, analyzing mesenchymal stem cells and their ability to differentiate in the osteogenic lineage. In the same way, circulating microRNAs are suggested as a tool for exploring osteogenic potential. The combination of different diagnostic approaches and the optimization of the bioptic procedure represent a concrete solution to spread the use of bone biopsy and optimize CKD patient management.
Lack of Salivary Long Non-Coding RNA XIST Expression Is Associated with Increased Risk of Oral Squamous Cell Carcinoma: A Cross-Sectional Study
Authors: Shieh Tzong-Ming , Liu Chung-Ji , Hsia Shih-Min , Ningrum Valendriyani , Liao Chiu-Chu , Lan Wan-Chen , Shih Yin-Hwa
Published: October 2021

Studies have shown that there is a disparity between males and females in south-east Asia with regard to oral cancer morbidity. A previous study found that oral cancer tissue showed loss of heterozygosity of the X-linked lncRNA XIST gene. We suggest that XIST may play an important role in oral cancer morbidity when associated with sex. Saliva contains proteins and RNAs that are potential biomarkers for the diagnosis of diseases. This study investigated salivary XIST expression and the correlation to clinical–pathological data among oral squamous cell carcinoma patients. Salivary XIST expression was only observed in females, and a high proportion of females with OSCC lack salivary lncRNA XIST expression (88%). The expression showed no correlation with alcohol consumption, betel quid chewing, or cigarette smoking habits. People lacking salivary lncRNA XIST expression had a significantly increased odds ratio of suffering from OSCC (OR = 19.556, p < 0.001), particularly females (OR = 33.733, p < 0.001). The ROC curve showed that salivary lncRNA XIST expression has acceptable discrimination accuracy to predict the risk of OSCC (AUC = 0.73, p < 0.01). Lack of salivary lncRNA XIST expression was associated with an increased risk of OSCC. We provided an insight into the role of salivary lncRNA XIST as a biomarker to predict the morbidity of OSCC.
Emerging Comorbidities in Inflammatory Bowel Disease: Eating Disorders, Alcohol and Narcotics Misuse
Authors: Kuźnicki Paweł , Neubauer Katarzyna
Published: October 2021

Inflammatory bowel disease (IBD) is a chronic and potentially devastating condition of the digestive tract which is exemplified by increasing prevalence worldwide, byzantine pathogenesis with a poorly defined role of the environmental factors, and complex clinical demonstration. As a systemic disease, IBD may progress with a wide spectrum of extraintestinal manifestations (EMs) and comorbidities affecting different organs and systems, from anaemia, undernutrition, and cancer to those which are often neglected like anxiety and depression. Evolving IBD epidemiology and changing environment are reflected by an expanding list of IBD-related comorbidities. In contrast to the well-established role of smoking the connection between alcohol and IBD is still debatable on many levels, from pathogenesis to complications. Furthermore, little is known about narcotics use in IBD patients, even if there are obvious factors that may predispose them to narcotics as well as alcohol misuse. Last but not least, the question arises what is the prevalence of eating disorders in IBD. In our paper, we aimed to discuss the current knowledge on alcohol and drugs misuse and eating disorders as emerging extraintestinal comorbidities in IBD.
Paravalvular Aortic Regurgitation Severity Assessed by Quantitative Aortography: ACURATE neo2 versus ACURATE neo Transcatheter Aortic Valve Implantation
Authors: Rück Andreas , Kim Won-Keun , Kawashima Hideyuki , Abdelshafy Mahmoud , Elkoumy Ahmed , Elzomor Hesham , Wang Rutao , Meduri Christopher U. , Verouhis Dinos , Saleh Nawzad , Onuma Yoshinobu , Mylotte Darren , Serruys Patrick W. , Soliman Osama
Published: October 2021

The new-generation ACURATE neo2 system was commercially released in September 2020. In this study, we sought to compare the aortic regurgitation (AR) severity of the ACURATE neo2 versus the ACURATE neo transcatheter heart valve, using quantitative videodensitometric angiography (qAR). This is a retrospective, Corelab analysis of final post-transcatheter aortic valve implantation (TAVI) aortograms of patients treated with the ACURATE neo2 and ACURATE neo systems. The ACURATE neo2 cohort comprised consecutive patients treated between September 2020 and January 2021 at two centers. The ACURATE neo cohort included consecutive patients treated before September 2020. Our primary objective was to compare AR severity on qAR following TAVI with ACURATE neo2 and ACURATE neo. Out of 401 aortograms, 228 (56.9%) were analyzable, with 120 in the ACURATE neo2 cohort, and 108 in the ACURATE neo cohort. The mean AR fraction was 4.4 ± 4.8% in the neo2 cohort, and 9.9 ± 8.2% in the neo cohort (p < 0.001). Furthermore, moderate or severe AR (qAR > 17%) was detected in 2 aortograms (1.7%) in the neo2 cohort and 15 aortograms (13.9%) in the neo cohort (p < 0.001). Quantitative aortography shows a lower rate of moderate or severe paravalvular AR in what is the first European experience of the new-generation, self-expanding ACURATE neo2 when compared to the first-generation ACURATE neo. Moreover, aortographic data need to be correlated and compared to Core Laboratory-adjudicated 30-day echocardiographic data.
Outcomes of Different Reperfusion Strategies of Multivessel Disease Undergoing Newer-Generation Drug-Eluting Stent Implantation in Patients with Non-ST-Elevation Myocardial Infarction and Chronic Kidney Disease
Authors: Kim Yong Hoon , Her Ae-Young , Jeong Myung Ho , Kim Byeong-Keuk , Hong Sung-Jin , Lee Seung-Jun , Ahn Chul-Min , Kim Jung-Sun , Ko Young-Guk , Choi Donghoon , Hong Myeong-Ki , Jang Yangsoo
Published: October 2021

Because available data are limited, we compared the 2-year clinical outcomes among different reperfusion strategies (culprit-only percutaneous coronary intervention (C-PCI), multivessel PCI (M-PCI), complete revascularization (CR) and incomplete revascularization (IR)) of multivessel disease (MVD) undergoing newer-generation drug-eluting stent implantation in patients with non-ST-elevation myocardial infarction (NSTEMI) and chronic kidney disease (CKD). In this nonrandomized, multicenter, retrospective cohort study, a total of 1042 patients (C-PCI, n = 470; M-PCI, n = 572; CR, n = 432; IR, n = 140) were recruited from the Korea Acute Myocardial Infarction Registry (KAMIR) and evaluated. The primary outcome was the occurrence of major adverse cardiac events, defined as all-cause death, recurrent myocardial infarction and any repeat coronary revascularization. The secondary outcome was probable or definite stent thrombosis. During the 2-year follow-up period, the cumulative incidences of the primary (C-PCI vs. M-PCI, adjusted hazard ratio (aHR), 1.020; p = 0.924; CR vs. IR, aHR, 1.012; p = 0.967; C-PCI vs. CR, aHR, 1.042; p = 0.863; or C-PCI vs. IR, aHR, 1.060; p = 0.844) and secondary outcomes were statistically insignificant in the four comparison groups. In the contemporary newer-generation DES era, C-PCI may be a better reperfusion option for patients with NSTEMI with MVD and CKD rather than M-PCI, including CR and IR, with regard to the procedure time and the risk of contrast-induced nephropathy. However, further well-designed, large-scale randomized studies are warranted to confirm these results.
Nationwide Data on the Characteristics of Linked-to-Care Chronic Hepatitis B in Korea
Authors: Ju Young Cheol , Jun Dae Won , Yoon Eileen L. , Ahn Sang Bong , Kim Yun Jin , Nguyen Mindie H.
Published: October 2021

Linkage-to-care rate of chronic hepatitis B (CHB) is less well characterized. We aimed to evaluate the proportion, characteristics of CHB patients who are linked to care. We retrospectively analyzed insurance reimbursement claims data provided by the Korean National Health Insurance Service. CHB patients who had at least two clinic or hospital visits that were associated with a CHB diagnostic code during 2002–2006 were included. Those without a history of malignancy at baseline were followed up until 2018. Mean follow-up period was 14.5 ± 2.9 years. Among the participants, 553,085 patients (35.8%) were found to be linked to care. The rates were lower in men than women (35.7% vs. 36.0%, p = 0.006). By age, it was highest for the 40′s age group at 44.8% and lowest at 29.4% for the 20′s age group (All p < 0.0001). The linkage-to-care rate was higher in rural area than metropolitan area (p < 0.0001). The 15-year cumulative incidence of hepatocellular carcinoma and overall survival rates among linked-to-care CHB patients were 18.2% and 93.8%, respectively. Two thirds of CHB patients were not linked to care. Those who are male, dwelling in metropolitan areas, and not in life transition periods need to be targeted to improve the linkage-to-care rate in Korea.
Prevalence of the Absence of Cirrhosis in Subjects with NAFLD-Associated Hepatocellular Carcinoma
Authors: Castellana Marco , Donghia Rossella , Lampignano Luisa , Castellana Fabio , Zupo Roberta , Sardone Rodolfo , Pergola Giovanni De , Giannelli Gianluigi
Published: October 2021

Background. Hepatocellular carcinoma (HCC) is most commonly considered as a complication of cirrhosis. However, an increasing number of HCC in subjects with non-alcoholic fatty liver disease (NAFLD) without cirrhosis is being reported. We conducted a meta-analysis to assess the prevalence of the absence of cirrhosis in NAFLD-associated HCC. Methods. Four databases were searched until March 2021 (CRD42021242969). The original articles included were those reporting data on the presence or absence of cirrhosis among at least 50 subjects with NAFLD-associated HCC. The number of subjects with absent cirrhosis in each study was extracted. For statistical pooling of data, a random-effects model was used. Subgroup analyses according to the continent, target condition and reference standard for the diagnosis of cirrhosis were conducted. Results. Thirty studies were included, evaluating 13,371 subjects with NAFLD-associated HCC. The overall prevalence of cases without cirrhosis was 37% (95%CI 28 to 46). A higher prevalence was reported in Asia versus Europe, North America and South America (45, 36, 37 and 22%, respectively) as well as in studies adopting histology only as the reference standard for the diagnosis of cirrhosis versus histology and other modalities (e.g., radiology, endoscopy, biochemistry or overt clinical findings) (53 and 27%, respectively). No difference was found between studies including subjects with non-alcoholic steatohepatitis (NASH) only, versus NAFLD with or without NASH (p = 0.385). One in three subjects with NAFLD-associated HCC presented without cirrhosis. This should be reflected in future guidelines and surveillance programs adapted to allow for the early detection of these cancers too.
Alzheimer’s Disease, Mild Cognitive Impairment and Mediterranean Diet. A Systematic Review and Dose-Response Meta-Analysis
Authors: García-Casares Natalia , Gallego Fuentes Paloma , Barbancho Miguel Ángel , López-Gigosos Rosa , García-Rodríguez Antonio , Gutiérrez-Bedmar Mario
Published: October 2021

Alzheimer’s Disease (AD) is a pathology with increasing prevalence in the context of a more long-lived society and it is the first cause of dementia in western countries. It is important to investigate factors that can be protective and may influence its development, in order to act on them trying to reduce AD incidence and its progression. The aim of this study was to conduct a systematic review and meta-analysis to determine the effects of a higher adherence to Mediterranean diet (MD) on Mild Cognitive Impairment (MCI) and AD. A literature search in PubMed, The Cochrane Library Plus and Scopus was conducted, selecting articles that analyzed associations between MD adherence and AD biomarkers (Volumetry assessed by MRI and betamiloide and Tau deposits by PET); cognitive performance in patients at risk or presenting MCI and AD; and incidence or progression from MCI to AD. Out of the 589 studies screened, 22 studies met eligibility criteria for the systematic review and qualitative synthesis. Finally, 11 studies were included in the meta-analysis (12,458 participants). Higher adherence to MD was associated with a significantly lower risk of MCI (RR = 0.91, 95%CI = 0.85–0.97) and lower risk of AD (RR = 0.89, 95% CI = 0.84–0.93). Our results enhance the importance of taking health-promoting lifestyle measures like following Mediterranean dietary patterns in order to reduce AD risk.
Osteoblastoma: When the Treatment Is Not Minimally Invasive, an Overview
Authors: Zoccali Carmine , Novello Mariangela , Arrigoni Francesco , Scotto di Uccio Alessandra , Attala Dario , Ferraresi Virginia
Published: October 2021

Background: osteoblastoma is a bone-forming tumor accounting for about 1% of all primary bone tumors and 3% of benign bone tumors. The gold-standard treatment is surgical excision; nevertheless, minimally invasive radiological techniques such as thermoablation and, more recently, high intensity focused ultrasound are gaining more importance. The aim of the present paper is to analyze surgical indications based on our experience and on the evidences in the literature. Methods: all patients affected by osteoblastoma who underwent surgical excision in January 2009 and December 2018 were reviewed; eleven patients were enrolled in the study. The epidemiological aspects, size of the disease and site of onset, symptoms, surgery type, indications, and results are reported for every case. Results: all treatments were based on a preoperative diagnosis; pain was constant in all cases. Intralesional surgeries were performed in 9 out of 11 cases; the remaining 2 cases underwent wide resection. No early or late complications occurred after the surgical procedure. The indications for surgery were lesions very close to nerves or joints, unclear diagnosis, risk of fracture, lesion too large for radiofrequency thermoablation, or failure of minimally invasive treatments. At a medium follow-up of 88 months, no local recurrences were verified. Conclusions: osteoblastoma is a rare tumor with difficult diagnosis. Identification is based on symptoms, imaging, and histology. When possible, minimally invasive techniques is preferred for treatment but surgery is still considered the gold standard.
Lymphedema in Endometrial Cancer Survivor: A Nationwide Cohort Study
Authors: Lee Su-Jeong , Myong Jun-Pyo , Lee Yun-Hee , Cho Eui-Jin , Lee Sung-Jong , Kim Chan-Joo , Kim Jin-Hwi
Published: October 2021

Background: Endometrial cancer is the most common gynecological cancer in developed countries. Treatment-related lymphedema negatively affects the quality of life and function of patients. This study investigated the cumulative incidence and risk factors of, and utilization of health care resources for, lymphedema in patients with endometrial cancer. Methods: We conducted a nationwide, retrospective cohort study of women with endometrial cancer who underwent cancer-direct treatment using the Korean National Health Insurance Service (NHIS) database. Patients were categorized by age, region, income, and treatment modality. Cox proportional hazards regression models were used to analyze the incidence and risk factors of lymphedema. We also analyzed utilization of health care resources for lymphedema using diagnostic and treatment claim codes. Results: A total of 19,027 patients with endometrial cancer were evaluated between January 2004 and December 2017. Among them, 2493 (13.1%) developed lymphedema. Age (<40 years, adjusted odds ratio [aOR] = 1 vs. 40–59 years, aOR = 1.413; 95% confidence interval (CI) 1.203–1.66 vs. 60+ years, aOR = 1.472; 95% CI 1.239–1.748) and multimodal treatment (surgery only, aOR = 1 vs. surgery + radiation + chemotherapy, aOR = 2.571; 95% CI 2.27–2.912) are considered to be possible risk factors for lymphedema in patients with endometrial cancer (p < 0.001). The utilization of health care resources for the treatment of lymphedema has increased over the years. Conclusions: Lymphedema is a common complication affecting women with endometrial cancer and leads to an increase in national healthcare costs. Post-treatment surveillance of lymphedema, especially in high-risk groups, is needed.
Direct Oral Anticoagulant Therapy for Isolated Distal Deep Vein Thrombosis Associated with Cancer in Routine Clinical Practice
Authors: Ogino Yutaka , Ishigami Tomoaki , Sato Ryosuke , Nakahashi Hidefumi , Minamimoto Yugo , Kimura Yuichiro , Okada Kozo , Matsuzawa Yasushi , Iwahashi Noriaki , Hibi Kiyoshi , Kosuge Masami , Ebina Toshiaki , Ishikawa Toshiyuki , Tamura Kouichi , Kimura Kazuo
Published: October 2021

Background: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for isolated distal deep vein thrombosis (IDDVT) associated with cancer in routine clinical practice remain unclear. Moreover, prior studies on prolonged therapy for IDDVT are limited. Methods: This retrospective study enrolled 1641 consecutive patients with acute venous thromboembolism (VTE) who had received oral anticoagulant therapy, including warfarin or DOAC, between April 2014 and September 2018 in our institutions. In these patients, 200 patients with cancer-associated IDDVT were evaluated. Results: Mean follow-up period was 780 ± 593 days. Major bleeding and VTE recurrence were observed in 22 (11.0%) and 11 (5.5%) patients, respectively. In multivariate analysis, statistically significant factors correlated with major bleeding were advanced cancer stage, high performance status, stomach cancer, and gallbladder cancer; those correlated with all-cause death were advanced cancer stage, high performance status, liver dysfunction, pancreatic cancer, and major bleeding. Cumulative events of major bleeding and recurrence between patients with prolonged DOAC therapy (≥90 days) and those with nonprolonged therapy were not significantly different. Conclusions: Preventing major bleeding is important because it is a significant risk factor for all-cause death. Major bleeding and recurrent events were comparable between prolonged and nonprolonged therapy.
Immunotherapy for Peritoneal Metastases from Gastric Cancer: Rationale, Current Practice and Ongoing Trials
Authors: Ruiz Hispán Eva , Pedregal Manuel , Cristobal Ion , García-Foncillas Jesús , Caramés Cristina
Published: October 2021

Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy treatment of peritoneal dissemination. The immunogenicity of the peritoneum has been described to be particularly active at omentum and peritoneal lymph nodes. Also, both innate and acquired immunity seems to be involved at different molecular levels. Recent works show PDL1 expression being less present at the peritoneal level; however, some clinical trials have begun to yield results. For example, the ATTRACTION-2 trial has demonstrated the activity of Nivolumab in heavily pretreated patients even though peritoneal metastases were diagnosed in a 30% of them. Despite positive results in the metastatic setting, peritoneal responses to systemic checkpoint inhibitors remains unclear, therefore, new strategies for intraperitoneal immunotherapy are being proposed for different ongoing clinical trials.
Cataract Surgery in Very Old Patients: A Case-Control Study
Authors: Nussinovitch Hanan , Tsumi Erez , Tuuminen Raimo , Malyugin Boris , Lior Yotam , Naidorf Rosenblatt Hadar , Boyko Matthew , Achiron Asaf , Knyazer Boris
Published: October 2021

Advancements in surgical techniques and increased life expectancy have made cataract surgery more common among very old patients. However, surgical outcomes seem impaired in patients older than 90 years, especially with ocular comorbidities. A retrospective case-control study of 53 eyes of 53 very old patients (mean 92.6 ± 3.0) and 140 eyes of 140 matched patients (mean 75.2 ± 7.6) was undertaken. Groups were matched in terms of gender and systemic and ocular comorbidities. In very old patients, higher phacoemulsification energy (cumulative dissipated energy [CDE], 25.0 ± 22.4 vs. 16.1 ± 10.7, p = 0.01) and rate of intraoperative floppy iris syndrome (IFIS, 9.4% vs. 1.4%, p = 0.02) were observed compared to controls. Uncorrected (UCVA) and best-corrected distance visual acuity (BCVA) gains were significantly poorer among the very old patients than among the control at postoperative day 30 (0.20 ± 0.70 vs. 0.56 ± 0.61 logMAR, p < 0.001 and 0.27 ± 0.64 vs. 0.55 ± 0.62 logMAR, p = 0.006, respectively). Even after including CDE and IFIS as covariates, age remained an independent factor for poor visual gain at 30 days (p < 0.001). Cataract surgery in very old patients may demand more experienced surgeons due to higher nuclear density and the rates of IFIS. Expectations in visual acuity gains should be aligned with the patient’s age.
Mitigation of Risks Associated with Gas Pipeline Failure by Using Quantitative Risk Management Approach: A Descriptive Study on Gas Industry
Authors: Abdoul Nasser Avoce Honga , Ndalila Petro Dickson , Mawugbe Edem A. , Emmanuel Kouame Melaine , Arthur Paterne Mioumnde , Li Yuxing
Published: October 2021

Risk assessment is one of the main tools that oil and gas industries use to assess the hazards and risks in their facilities worldwide. Qualitative and quantitative risk assessments are carried out at various phases of the process industry: conceptual stage, design stage, construction stage, operational stage, decommissioning stage, etc. The quantitative risk assessment is directed during the detailed design stage to decide the spacing and layout out of equipment for safe operation and maintenance of oil and gas industries. The equipment layout and spacing are based on the safe distances are to be carried out on various design safety studies. In this work, a study was carried out on upstream onshore natural gas gathering stations and associated equipment and pipeline networks. The fire, explosion assessment, and toxic gas dispersion are conducted to evaluate how it affects people, assets, and the environment. Whether the design protection systems are adequate to mitigate the consequences or any additional measures to reduce risk to an acceptable level is analyzed.