bluuebunny/crossref_metadata_2025 huggingface dataset:
Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: Review
Authors: Bhujel Basanta , Shin Hae-Eun , Choi Dong-Jun , Han Inbo
Published: July 2022

Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging, mechanical trauma, lifestyle factors, and certain genetic abnormalities, leads to loss of nucleus pulposus, alteration in the composition of the extracellular matrix, excessive oxidative stress, and inflammation in the intervertebral disc. Pharmacological and surgical interventions are considered a boon for the treatment of IVDD, but the effectiveness of those strategies is limited. Mesenchymal stem cells (MSCs) have recently emerged as a possible promising regenerative therapy for IVDD due to their paracrine effect, restoration of the degenerated cells, and capacity for differentiation into disc cells. Recent investigations have shown that the pleiotropic effect of MSCs is not related to differentiation capacity but is mediated by the secretion of soluble paracrine factors. Early studies have demonstrated that MSC-derived exosomes have therapeutic potential for treating IVDD by promoting cell proliferation, tissue regeneration, modulation of the inflammatory response, and reduced apoptosis. This paper highlights the current state of MSC-derived exosomes in the field of treatment of IVDD with further possible future developments, applications, and challenges.
Bagging Strategy and Identification of Coloring Mode of ‘Xinqihong’ Pear
Authors: Liu Jianlong , Sun Hongwei , Wang Xuening , Liu Xin , Xu Hongpeng , Liang Chenglin , Li Dingli , Yang Yingjie , Cui Zhenhua , Song Jiankun , Wang Ran
Published: July 2022

‘Xinqihong’ is a recently selected and well-colored red pear (Pyrus bretschneideri Rehd.) cultivar that is popular in the marketplace owing to the bright red color and high quality of the fruit. The red pigmentation is strongly associated with the light signal. However, its responses to bagging treatment and to light exposure after shading are unknown. In this study, the fruit were treated with three types of fruit bags. ’Xinqihong’ fruit colored rapidly in response to light stimulation. A white fruit bag was optimal for bagging of ‘Xinqihong’ fruit. To ensure satisfactory red pigmentation, the fruit required exposure to 30 days of light after bag removal. A transcriptome analysis was conducted to screen light-signal-related genes and identify their possible functions. PbCRY1 activated the promoter of PbHY5.2 and enhanced its expression. PbHY5.2 activated the promoter activity of PbUFGT and induced anthocyanin synthesis, and also showed self-activation characteristics. Both PbCRY2 and PbPHY1 induced anthocyanin accumulation. Thus, blue-light receptors played an important role in anthocyanin synthesis. This study provides a theoretical basis for the bagging cultivation of new varieties of ‘Xinqihong’, and lays a foundation for the study of the mechanisms of red pear fruit coloring in response to light signals.
Interleukin 15 in Cell-Based Cancer Immunotherapy
Authors: Zhou Yang , Husman Tiffany , Cen Xinjian , Tsao Tasha , Brown James , Bajpai Aarushi , Li Miao , Zhou Kuangyi , Yang Lili
Published: July 2022

Cell-based cancer immunotherapy, such as chimeric antigen receptor (CAR) engineered T and natural killer (NK) cell therapies, has become a revolutionary new pillar in cancer treatment. Interleukin 15 (IL-15), a potent immunostimulatory cytokine that potentiates T and NK cell immune responses, has demonstrated the reliability and potency to potentially improve the therapeutic efficacy of current cell therapy. Structurally similar to interleukin 2 (IL-2), IL-15 supports the persistence of CD8+ memory T cells while inhibiting IL-2-induced T cell death that better maintains long-term anti-tumor immunity. In this review, we describe the biology of IL-15, studies on administrating IL-15 and/or its derivatives as immunotherapeutic agents, and IL-15-armored immune cells in adoptive cell therapy. We also discuss the advantages and challenges of incorporating IL-15 in cell-based immunotherapy and provide directions for future investigation.
Omicron BA.2 Lineage, the “Stealth” Variant: Is It Truly a Silent Epidemic? A Literature Review
Authors: Tiecco Giorgio , Storti Samuele , Arsuffi Stefania , Degli Antoni Melania , Focà Emanuele , Castelli Francesco , Quiros-Roldan Eugenia
Published: July 2022

The epidemic curve of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is silently rising again. Worldwide, the dominant SARS-CoV-2 variant of concern (VOC) is Omicron, and its virological characteristics, such as transmissibility, pathogenicity, and resistance to both vaccine- and infection-induced immunity as well as antiviral drugs, are an urgent public health concern. The Omicron variant has five major sub-lineages; as of February 2022, the BA.2 lineage has been detected in several European and Asian countries, becoming the predominant variant and the real antagonist of the ongoing surge. Hence, although global attention is currently focused on dramatic, historically significant events and the multi-country monkeypox outbreak, this new epidemic is unlikely to fade away in silence. Many aspects of this lineage are still unclear and controversial, but its apparent replication advantage and higher transmissibility, as well as its ability to escape neutralizing antibodies induced by vaccination and previous infection, are rising global concerns. Herein, we review the latest publications and the most recent available literature on the BA.2 lineage of the Omicron variant.
Analysis of miRNA Expression Profiling of RIP2 Knockdown in Chicken HD11 Cells When Infected with Avian Pathogenic E. coli (APEC)
Authors: Sun Hongyan , Cao Yuxuan , Yang Yexin , Li Huan , Qu Lujiang
Published: July 2022

Colibacillosis is an acute and chronic avian disease caused by avian pathogenic E. coli (APEC). Previous studies have demonstrated that RIP2 plays a significant role in APEC infection. Moreover, increasing evidence indicates that microRNAs (miRNAs) are involved in host–pathogen interactions and the immune response. However, the role of miRNAs in the host against APEC infection remains unclear. Herein, we attempted to reveal new miRNAs potentially involved in the regulation of the immune and inflammatory response against APEC infection, with a particular focus on those possibly correlated with RIP2 expression, via miRNA-seq, RT-qPCR, Western blotting, dual-luciferase reporter assay, and CCK-8. The results showed that a total of 93 and 148 differentially expressed (DE) miRNAs were identified in the knockdown of RIP2 cells following APEC infection (shRIP2+APEC) vs. knockdown of RIP2 cells (shRIP2) and shRIP2 vs. wild-type cells (WT), respectively. Among those identified DE miRNAs, the biological function of gga-miR-455-5p was investigated. It was found that gga-miR-455-5p regulated by RIP2 was involved in the immune and inflammatory response against APEC infection via targeting of IRF2 to modulate the expression of type I interferons. Additionally, RIP2 could directly regulate the production of the type I interferons. Altogether, these findings highlighted the crucial role of miRNAs, especially gga-miR-455-5p, in host defense against APEC infection.
The Change in Paradigm for NSCLC Patients with EML4–ALK Translocation
Authors: Bearz Alessandra , De Carlo Elisa , Del Conte Alessandro , Spina Michele , Da Ros Valentina , Bertoli Elisa , Revelant Alberto , Stanzione Brigida , Tirelli Umberto
Published: July 2022

The severe prognosis linked with a lung cancer diagnosis has changed with the discovery of oncogenic molecularly driven subgroups and the use of tailored treatment. ALK-translocated advanced lung cancer is the most interesting model, having achieved the longest overall survival. Here, we report the most important paradigmatic shifts in the prognosis and treatment for this subgroup population occurred among lung cancer.
The Relationship between COVID-19 and Hypothalamic–Pituitary–Adrenal Axis: A Large Spectrum from Glucocorticoid Insufficiency to Excess—The CAPISCO International Expert Panel
Authors: Jensterle Mojca , Herman Rok , Janež Andrej , Mahmeed Wael Al , Al-Rasadi Khalid , Al-Alawi Kamila , Banach Maciej , Banerjee Yajnavalka , Ceriello Antonio , Cesur Mustafa , Cosentino Francesco , Galia Massimo , Goh Su-Yen , Kalra Sanjay , Kempler Peter , Lessan Nader , Lotufo Paulo , Papanas Nikolaos , Rizvi Ali A. , Santos Raul D. , Stoian Anca P. , Toth Peter P. , Viswanathan Vijay , Rizzo Manfredi
Published: July 2022

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.
Loxin Reduced the Inflammatory Response in the Liver and the Aortic Fatty Streak Formation in Mice Fed with a High-Fat Diet
Authors: Reyes Camila , Nova-Lamperti Estefanía , Duran-Sandoval Daniel , Rojas Daniela , Gajardo Jorge , Guzman-Gutierrez Enrique , Bustos-Ruiz Camila , Ormazábal Valeska , Zúñiga Felipe A. , Escudero Carlos , Aguayo Claudio
Published: July 2022

Oxidized low-density lipoprotein (ox-LDL) is the most harmful form of cholesterol associated with vascular atherosclerosis and hepatic injury, mainly due to inflammatory cell infiltration and subsequent severe tissue injury. Lox-1 is the central ox-LDL receptor expressed in endothelial and immune cells, its activation regulating inflammatory cytokines and chemotactic factor secretion. Recently, a Lox-1 truncated protein isoform lacking the ox-LDL binding domain named LOXIN has been described. We have previously shown that LOXIN overexpression blocked Lox-1-mediated ox-LDL internalization in human endothelial progenitor cells in vitro. However, the functional role of LOXIN in targeting inflammation or tissue injury in vivo remains unknown. In this study, we investigate whether LOXIN modulated the expression of Lox-1 and reduced the inflammatory response in a high-fat-diet mice model. Results indicate that human LOXIN blocks Lox-1 mediated uptake of ox-LDL in H4-II-E-C3 cells. Furthermore, in vivo experiments showed that overexpression of LOXIN reduced both fatty streak lesions in the aorta and inflammation and fibrosis in the liver. These findings were associated with the down-regulation of Lox-1 in endothelial cells. Then, LOXIN prevents hepatic and aortic tissue damage in vivo associated with reduced Lox-1 expression in endothelial cells. We encourage future research to understand better the underlying molecular mechanisms and potential therapeutic use of LOXIN.
Effect of the Size of Titanium Particles Released from Dental Implants on Immunological Response
Authors: Callejas Juan Antonio , Gil Javier , Brizuela Aritza , Pérez Román A. , Bosch Begoña M.
Published: July 2022

The techniques used in oral implantology to remove bacterial biofilm from the surface of implants by machining the titanium surface (implantoplasty) or by placing rough dental implants through friction with the cortical bone generate a large release of particles. In this work, we performed a simulation of particle generation following clinical protocols. The particles were characterized for commercially pure titanium with particle sizes of 5, 10, 15, and 30 μm. The aim was to determine the effect of particle size and chemical composition of the implant on the immune response. For this purpose, their morphology and possible contamination were characterized by scanning electron microscopy and X-ray microanalysis. In addition, the granulometry, specific surface area, release of metal ions into the medium, and studies of cytocompatibility, gene expression, and cytokine release linked to the inflammatory process were studied. The release of ions for titanium particles showed levels below 800 ppb for all sizes. Smaller particle sizes showed less cytotoxicity, although particles of 15 μm presented higher levels of cytocompatibility. In addition, inflammatory markers (TNFα and Il-1β) were higher compared to larger titanium. Specifically, particles of 15 μm presented a lower proinflammatory and higher anti-inflammatory response as characterized by gene expression and cytokine release, compared to control or smaller particles. Therefore, in general, there is a greater tendency for smaller particles to produce greater toxicity and a greater proinflammatory response.
11β-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation
Authors: Fenton Chloe G , Crastin Ana , Martin Claire S , Suresh Saicharan , Montagna Isabella , Hussain Bismah , Naylor Amy J , Jones Simon W , Hansen Morten S , Gorvin Caroline M , Price Maria , Filer Andrew , Cooper Mark S , Lavery Gareth G , Raza Karim , Hardy Rowan S
Published: July 2022

Therapeutic glucocorticoids (GCs) are powerful anti-inflammatory tools in the management of chronic inflammatory diseases such as rheumatoid arthritis (RA). However, their actions on bone in this context are complex. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a mediator of the anti-inflammatory actions of therapeutic glucocorticoids (GCs) in vivo. In this study we delineate the role of 11β-HSD1 in the effects of GC on bone during inflammatory polyarthritis. Its function was assessed in bone biopsies from patients with RA and osteoarthritis, and in primary osteoblasts and osteoclasts. Bone metabolism was assessed in the TNF-tg model of polyarthritis treated with oral GC (corticosterone), in animals with global (TNF-tg11βKO), mesenchymal (including osteoblast) (TNF-tg11βflx/tw2cre) and myeloid (including osteoclast) (TNF-tg11βflx/LysMcre) deletion. Bone parameters were assessed by micro-CT, static histomorphometry and serum metabolism markers. We observed a marked increase in 11β-HSD1 activity in bone in RA relative to osteoarthritis bone, whilst the pro-inflammatory cytokine TNFα upregulated 11β-HSD1 within osteoblasts and osteoclasts. In osteoclasts, 11β-HSD1 mediated the suppression of bone resorption by GCs. Whilst corticosterone prevented the inflammatory loss of trabecular bone in TNF-tg animals, counterparts with global deletion of 11β-HSD1 were resistant to these protective actions, characterised by increased osteoclastic bone resorption. Targeted deletion of 11β-HSD1 within osteoclasts and myeloid derived cells partially reproduced the GC resistant phenotype. These data reveal the critical role of 11β-HSD1 within bone and osteoclasts in mediating the suppression of inflammatory bone loss in response to therapeutic GCs in chronic inflammatory disease.
A Quantitative Assay for Ca2+ Uptake through Normal and Pathological Hemichannels
Authors: Nardin Chiara , Tettey-Matey Abraham , Donati Viola , Marazziti Daniela , Di Pietro Chiara , Peres Chiara , Raspa Marcello , Zonta Francesco , Yang Guang , Gorelik Maryna , Singh Serena , Cardarelli Lia , Sidhu Sachdev S. , Mammano Fabio
Published: July 2022

Connexin (Cx) hemichannels (HCs) are large pore hexameric structures that allow the exchange of ions, metabolites and a variety of other molecules between the cell cytoplasm and extracellular milieu. HC inhibitors are attracting growing interest as drug candidates because deregulated fluxes through HCs have been implicated in a plethora of genetic conditions and other diseases. HC activity has been mainly investigated by electrophysiological methods and/or using HC-permeable dye uptake measurements. Here, we present an all-optical assay based on fluorometric measurements of ionized calcium (Ca2+) uptake with a Ca2+-selective genetically encoded indicator (GCaMP6s) that permits the optical tracking of cytosolic Ca2+ concentration ([Ca2+]cyt) changes with high sensitivity. We exemplify use of the assay in stable pools of HaCaT cells overexpressing human Cx26, Cx46, or the pathological mutant Cx26G45E, under control of a tetracycline (Tet) responsive element (TRE) promoter (Tet-on). We demonstrate the usefulness of the assay for the characterization of new monoclonal antibodies (mAbs) targeting the extracellular domain of the HCs. Although we developed the assay on a spinning disk confocal fluorescence microscope, the same methodology can be extended seamlessly to high-throughput high-content platforms to screen other kinds of inhibitors and/or to probe HCs expressed in primary cells and microtissues.
Leafamine®, a Free Amino Acid-Rich Biostimulant, Promotes Growth Performance of Deficit-Irrigated Lettuce
Authors: Malécange Marthe , Pérez-Garcia Maria-Dolores , Citerne Sylvie , Sergheraert Renaud , Lalande Julie , Teulat Béatrice , Mounier Emmanuelle , Sakr Soulaiman , Lothier Jérémy
Published: July 2022

Water deficit causes substantial yield losses that climate change is going to make even more problematic. Sustainable agricultural practices are increasingly developed to improve plant tolerance to abiotic stresses. One innovative solution amongst others is the integration of plant biostimulants in agriculture. In this work, we investigate for the first time the effects of the biostimulant –Leafamine®–a protein hydrolysate on greenhouse lettuce (Lactuca sativa L.) grown under well-watered and water-deficit conditions. We examined the physiological and metabolomic water deficit responses of lettuce treated with Leafamine® (0.585 g/pot) or not. Root application of Leafamine® increased the shoot fresh biomass of both well-watered (+40%) and deficit-irrigated (+20%) lettuce plants because the projected leaf area increased. Our results also indicate that Leafamine® application could adjust the nitrogen metabolism by enhancing the total nitrogen content, amino acid (proline) contents and the total protein level in lettuce leaves, irrespective of the water condition. Osmolytes such as soluble sugars and polyols, also increased in Leafamine®-treated lettuce. Our findings suggest that the protective effect of Leafamine is a widespread change in plant metabolism and could involve ABA, putrescine and raffinose.
Dually Responsive Nanoparticles for Drug Delivery Based on Quaternized Chitosan
Authors: Qiao Fenghui , Jiang Zhiqi , Fang Wen , Sun Jingzhi , Hu Qiaoling
Published: July 2022

In this work, we report the fabrication and functional demonstration of a kind of dually responsive nanoparticles (NPs) as a potential drug delivery vector. The pH value, corresponding to the acidic microenvironment at the tumor site, and mannitol, to the extracellular trigger agent, were employed as the dually responsive factors. The function of dual responses was achieved by breaking the dynamic covalent bonds between phenylboronic acid (PBA) groups and diols at low pH value (pH 5.0) and/or under the administration of mannitol, which triggered the decomposition of the complex NPs and the concomitant release of anticancer drug of doxorubicin (DOX) loaded inside the NPs. The NPs were composed of modified chitosan (PQCS) with quaternary ammonium and PBA groups on the side chains, heparin (Hep), and poly(vinyl alcohol) (PVA), in which quaternary ammonium groups offer the positive charge for the cell-internalization of NPs, PBA groups serve for the formation of dynamic bonds in responding to pH change and mannitol addition, PVA furnishes the NPs with diol groups for the interaction with PBA groups and the formation of dynamic NPS, and Hep plays the roles of reducing the cytotoxicity of highly positively-charged chitosan and forming of complex NPs for DOX up-loading. A three-step fabrication process of drug-loaded NPs was described, and the characterization results were comprehensively demonstrated. The sustained drug release from the drug-loaded NPs displayed obvious pH and mannitol dependence. More specifically, the cumulative DOX release was increased more than 1.5-fold at pH 5.0 with 20 mg mL−1 mannitol. Furthermore, the nanoparticles were manifested with effective antitumor efficient and apparently enhanced cytotoxicity in response to the acidic pH value and/or mannitol.
Diversity and Molecular Barcoding of Stink Bugs (Hemiptera: Pentatomidae) Associated with Macadamia in South Africa
Authors: Sonnekus Byron , Slippers Bernard , Hurley Brett P. , Joubert Elizabeth , Stiller Michael , Fourie Gerda
Published: July 2022

Stink bugs are major pests of macadamia in South Africa. Accurate identification and knowledge of species composition are important to inform management practices. The overall aims of this study were to identify stink bug species from macadamia orchards in South Africa using morphology, and to establish a DNA database based on the cytochrome c oxidase subunit 1 gene region. A total of 21 stink bug species were found in macadamia orchards in KwaZulu-Natal, Limpopo and Mpumalanga provinces. Bathycoelia distincta Distant, 1878, was the dominant species throughout all three growing regions. Two unidentified species of Boerias Kirkaldy, 1909, here designated as Boerias sp. 1 and Boerias sp. 2, were the second and third most abundant species found in KwaZulu-Natal. No species of Boerias has previously been reported in association with macadamia. Evidence of a cryptic third species of Boerias was also found. Species composition fluctuated over three growing seasons in Limpopo and differed between the three growing regions during the 2019–2020 season, highlighting the need for ongoing monitoring of these important pest species. The DNA barcode database developed in this study will be valuable for future monitoring and identifications, including cryptic or polymorphic stink bug species and different life stages.
Oxidative Stress and Antioxidant Therapy in Cardiovascular Diseases—Clinical Challenge
Authors: Pavlidis George
Published: July 2022

Oxidative stress reflects an imbalance between the production of reactive oxygen species (ROS) and the biological systems’ antioxidant mechanisms [...]
Reliable Prediction of Post-Operative Complications’ Rate Using the G8 Screening Tool: A Prospective Study on Elderly Patients Undergoing Surgery for Kidney Cancer
Authors: Traunero Fabio , Claps Francesco , Silvestri Tommaso , Mir Maria Carmen , Ongaro Luca , Rizzo Michele , Piasentin Andrea , Liguori Giovanni , Vedovo Francesca , Celia Antonio , Trombetta Carlo , Pavan Nicola
Published: July 2022

In the last years the incidence of renal neoplasms has been steadily increasing, along with the average age of patients at the time of diagnosis. Surgical management for localized disease is becoming more challenging because of patients’ frailty. We conducted a multi-center prospective study to evaluate the role of the G8 as a screening tool in the assessment of intra and post-operative complications of elderly patients (≥70 y.o.) undergoing surgery for kidney cancer. A total of 162 patients were prospectively enrolled between January 2015 to January 2019 and divided into two study groups (frail vs. not-frail) according to their geriatric risk profile based on G8 score. Several factors (i.e., age, CCI, ASA score, preoperative anemia, RENAL score, surgical procedures, and techniques) were analyzed to identify whether any of them would configure as a statistically significant predictor of surgical complications. According to the G8 Score, 90 patients were included in the frail group. A total of 52 frail patients vs. 4 non-frail patients developed a postoperative complication of any kind (p < 0.001). Of these, 11 were major complications and all occurred in the frail group. Our results suggest that the G8 screening tool is an effective and useful instrument to predict the risk of overall complications in elderly patients prior to renal surgery.
Special Issue “COVID-19: Diagnostic Imaging and Beyond—Part II”
Authors: Giraudo Chiara , Busch Isolde Martina
Published: July 2022

More than two years have passed since the onset of the COVID-19 pandemic [...]
Intrusion of Maxillary Posterior Teeth by Skeletal Anchorage: A Systematic Review and Case Report with Thin Alveolar Biotype
Authors: Manea Avram , Dinu Cristian , Băciuţ Mihaela , Buduru Smaranda , Almășan Oana
Published: July 2022

This study aimed to review the literature related to the intrusion of maxillary posterior teeth in subjects needing pre-prosthetic restoration or orthodontic treatment due to anterior open bite, and to report a thin alveolar biotype case needing a pre-prosthetic intrusion of maxillary teeth by introducing a novel, personalized method of intrusion measurement. An electronic search was conducted between February 2022 and March 2022 in the following databases: PubMed, Scopus, Embase, Web of Science, and Lilacs; the terms “tooth movement techniques”, “orthodontic anchorage procedures”, “tooth intrusion”, “intrusion”, “molar”, “premolar”, and “human” were surveyed. Eighteen articles were included in this review; the mean amount of intrusion ranged from between 2.1 ± 0.9 mm and 4.57 ± 0.98 mm (being mostly 2–3 mm). The intrusion force varied between 100 and 500 g; 10 articles reported miniscrews (MS), 7 reported zygomatic plates (ZP), and 1 publication reported both anchorage types. The average treatment time was 6.9 months for MS and 7.9 months for ZP. Levelling the occlusal plane by intrusion of the upper posterior teeth can be achieved by skeletal anchorage. The stability of the obtained results, shortening treatment time, and controlling treatment outcome are the main goals for a complex surgical and orthodontic treatment approach.
State-of-the-Art Research on Diabetic Retinopathy
Authors: Simó Rafael
Published: July 2022

The scientific community and health care providers should be seriously worried by the fact that diabetic retinopathy (DR) remains the main cause of preventable blindness in the working age population [...]
Special Issue: State of the Art of Cardiac Multimodality Imaging
Authors: Evangelista Arturo , Rodríguez-Palomares Jose
Published: July 2022

Imaging has progressed significantly in recent years and plays a pivotal role in the diagnosis, prognosis, and management of cardiac diseases [...]
High-Sensitivity Cardiac Troponin T and the Diagnosis of Cardiovascular Disease in the Emergency Room: The Importance of Combining Cardiovascular Biomarkers with Clinical Data
Authors: Golino Michele , Marazzato Jacopo , Blasi Federico , Morello Matteo , Chierchia Valentina , Cadonati Cristina , Matteo Federica , Licciardello Claudio , Zappa Martina , Ageno Walter , Passi Alberto , Angeli Fabio , De Ponti Roberto
Published: July 2022

Background. Nowadays, it is still not possible to clinically distinguish whether an increase in high-sensitivity cardiac troponin (hs-cTn) values is due to myocardial injury or an acute coronary syndrome (ACS). Moreover, predictive data regarding hs-cTnT in an emergency room (ER) setting are scarce. This monocentric retrospective study aimed to improve the knowledge and interpretation of this cardiac biomarker in daily clinical practice. Methods. Consecutive adult patients presenting at the ER and hospitalized with a first abnormal hs-cTnT value (≥14 ng/L) were enrolled for 6 months. The baseline hs-cTnT value and the ensuing changes and variations were correlated with the clinical presentation and the type of diagnosis. Subsequently, multivariable models were built to assess which clinical/laboratory variables most influenced hospital admissions in the investigated population analyzed according to the final reason for hospitalization: (1) cardiovascular vs. non-cardiovascular diagnosis, and (2) ACS vs. non-ACS one. Results. A total of 4660 patients were considered, and, after a first screening, 4149 patients were enrolled. Out of 4129 patients, 1555 (37.5%) had a first hs-cTnT ≥14 ng/L, and 1007 (65%) were hospitalized with the following types of diagnosis: ACS (182; 18%), non-ACS cardiovascular disease (337; 34%) and non-cardiovascular disease (487; 48%). Higher hs-cTnT values and significant hs-cTnT variations were found in the ACS group (p < 0.01). The mean percentage of variation was higher in patients with ACS, intermediate in those with non-ACS cardiovascular disease, and low in those with non-cardiovascular disease (407.5%, 270.6% and 12.4%, respectively). Only syncope and CRP (OR: 0.08, 95% CI: 0.02–0.39, p < 0.01 and OR: 0.9988, 95% CI: 0.9979–0.9998, p = 0.02, respectively) or CRP (OR: 0.9948, 95% CI: 0.9908–0.9989, p = 0.01) and NT-proBNP (OR: 1.0002, 95% CI: 1.0000–1.0004, p = 0.02) were independent predictors of a cardiovascular disease diagnosis. On the other hand, only chest pain (OR: 22.91, 95% CI: 3.97–132.32, p < 0.01) and eGFR (OR: 1.04, 95% CI: 1.004–1.083, p = 0.03) were associated with the ACS diagnosis. Conclusions. Differently from the investigated biomarkers, in this study, only clinical variables predicted hospitalizations in different patients’ subgroups.
The Effect of COVID-19 on the Menstrual Cycle: A Systematic Review
Authors: Lebar Vojka , Laganà Antonio Simone , Chiantera Vito , Kunič Tina , Lukanović David
Published: July 2022

Researchers have been studying COVID-19 from day one, but not much is known about the impact of COVID-19 on the reproductive system, specifically the female reproductive system. There has been substantial anecdotal and media coverage on the effect of COVID-19 on the female reproductive system and changes in the menstrual cycle, but so far available data are not robust enough to draw firm conclusions about the topic. This article was carried out to present already published studies on the correlation between SARS-CoV-2 infection and menstrual cycle changes. A systematic literature search was conducted on the Medline, Scopus, and Cochrane Library databases in accordance with the PRISMA guidelines. Three studies were finally included in the review. The findings of the studies indicate changes in menstrual volume and changes in menstrual cycle length as consequences of SARS-CoV-2 infection; the latter was also the most common menstrual irregularity reported by the included studies. Women have mainly reported decreased menstrual volume and a prolonged cycle. The findings also indicate that the severity of COVID-19 does not play a role in menstrual cycle changes. However, the research on this topic is still too scarce to draw definitive conclusions, and there is a need for further research. The relevant conclusions, which could be drawn only from a well-constructed study, would have a major effect on defining the impact of SARS-CoV-2 infection on the menstrual cycle.
Outcomes of XEN 63 Device at 18-Month Follow-Up in Glaucoma Patients: A Two-Center Retrospective Study
Authors: Fea Antonio Maria , Menchini Martina , Rossi Alessandro , Posarelli Chiara , Malinverni Lorenza , Figus Michele
Published: July 2022

Background: Glaucoma surgery has significantly evolved over the last years. This paper aims to evaluate the midterm clinical outcomes of the XEN63 device in a real-world scenario. Methods: A retrospective clinical study was conducted on consecutive patients who underwent an XEN63 implant insertion, either alone or in combination with phacoemulsification. The primary endpoint was the mean intraocular pressure (IOP) at the month 18 visit. Results: Twenty-three eyes (23 patients) were included in the analysis. The preoperative IOP was significantly lowered from 27.0 ± 7.8 mmHg to 14.1 ± 3.4 mmHg at month 18 (p < 0.0001). At month 18, 14 (77.8%) and 11 (61.1%) eyes had an IOP ≤ 16 mmHg and ≤ 14 mmHg, respectively, without ocular hypotensive medication. The mean number of ocular hypotensive medication taken was significantly reduced from 2.3 ± 0.9 drugs at baseline to 1.0 ± 1.4 drugs at month 18 (p = 0.0020). Four (17.4%) eyes had hypotony at postoperative day 1, which was successfully resolved without sequelae. Four (17.4%) eyes underwent a needling procedure and four (17.4%) eyes underwent additional surgeries. Conclusions: The XEN63, either alone or in combination with cataract surgery, significantly lowered the IOP and reduced the need for ocular hypotensive drugs over a period of 18 months.
Aberrant Corneal Homeostasis in Neurosurgery-Induced Neurotrophic Keratopathy
Authors: Oba Shimpei , Araki-Sasaki Kaoru , Chihara Tomoyuki , Kojima Takashi , Murat Dogru , Takahashi Kanji
Published: July 2022

The characteristic features of neurotrophic keratopathy have been well documented by in vivo and in vitro studies using animal models. However, case reports of neurotrophic keratopathy induced by neurosurgery are limited. We describe the clinical characteristics, anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM) findings of neurotrophic keratopathy induced by surgery for intracranial lesions. This is a case series including 6 eyes of 3 patients (mean age, 69.67 ± 12.50 years) with unilateral neurotrophic keratopathy. The clinical findings of three patients were described and IVCM findings of three patients were analyzed. The duration of neuropathy ranged from 2 to 30 years (median, 22 years). Thickening of the epithelial layer and higher reflection density of the anterior stroma were observed during the healing process using AS-OCT. The mean nerve fiber density of the subepithelial plexus, as determined by IVCM, was 1943 ± 1000 μm/mm2 for neurotrophic eyes and 2242 ± 600.3 μm/mm2 for contralateral eyes (p = 0.0347). The mean respective dendritic cell densities were 30.8 ± 21.8 and 6.25 ± 5.59 cells/mm2 (p < 0.0001), while the mean basal cell sizes were 259 ± 86.5 and 185 ± 45.9 μm2 (p < 0.0001), respectively. These findings suggest that neurosurgery-induced neurotrophic keratopathy may be associated with alterations in the healing process and immune cell distribution in the cornea.
Potentially Inappropriate Medication and Polypharmacy in Nursing Home Residents: A Cross-Sectional Study
Authors: Díez Raquel , Cadenas Raquel , Susperregui Julen , Sahagún Ana M. , Fernández Nélida , García Juan J. , Sierra Matilde , López Cristina
Published: July 2022

Inappropriate prescribing in the elderly is a risk factor for higher adverse drugs reactions, hospitalisation, and mortality rates. Therefore, it is necessary to identify irrational prescriptions and implement interventions to improve geriatric clinical practices in nursing homes. This study aimed to examine and compare the prevalence of potentially inappropriate medications in nursing home residents using three different updated criteria: 2019 Beers criteria, PRISCUS list, and v2 STOPP criteria, and to determine the prevalence of potential prescribing omissions according to v2 START criteria. A descriptive, observational, and cross-sectional study design was used. A total of 218 residents were involved in this study. Data on drug use were collected from medical charts. Information was screened with the software CheckTheMeds. Potentially inappropriate medications were present in 96.3%, 90.8%, and 35.3% of residents, according to the STOPP, Beers, and PRISCUS criteria or list, respectively. Inappropriate medication was found to be significantly associated with polypharmacy and severe or moderate drug–drug interactions with the three tools and with pathologies and unnecessary drugs only for STOPP criteria. The most frequent inappropriate medications were benzodiazepines and proton pump inhibitors. A regular use of software to review medications in nursing home residents would help to reduce the risk of these drug-related problems.
Neuromodulation Using Transcranial Focused Ultrasound on the Bilateral Medial Prefrontal Cortex
Authors: Kim Young Goo , Kim Song E. , Lee Jihye , Hwang Sungeun , Yoo Seung-Schik , Lee Hyang Woon
Published: July 2022

Transcranial focused ultrasound (tFUS) is a promising technique of non-invasive brain stimulation for modulating neuronal activity with high spatial specificity. The medial prefrontal cortex (mPFC) has been proposed as a potential target for neuromodulation to prove emotional and sleep qualities. We aim to set up an appropriate clinical protocol for investigating the effects of tFUS stimulation of the bilateral mPFC for modulating the function of the brain-wide network using different sonication parameters. Seven participants received 20 min of 250 kHz tFUS to the bilateral mPFC with excitatory (70% duty cycle with sonication interval at 5 s) or suppressive (5% duty cycle with no interval) sonication protocols, which were compared to a sham condition. By placing the cigar-shaped sonication focus on the falx between both mPFCs, it was possible to simultaneously stimulate the bilateral mPFCs. Brain activity was analyzed using continuous electroencephalographic (EEG) recording during, before, and after tFUS. We investigated whether tFUS stimulation under the different conditions could lead to distinctive changes in brain activity in local brain regions where tFUS was directly delivered, and also in adjacent or remote brain areas that were not directly stimulated. This kind of study setting suggests that dynamic changes in brain cortical responses can occur within short periods of time, and that the distribution of these responses may differ depending on local brain states and functional brain architecture at the time of tFUS administration, or perhaps, at least temporarily, beyond the stimulation time. If so, tFUS could be useful for temporarily modifying regional brain activity, modulating functional connectivity, or reorganizing brain functions associated with various neuropsychiatric diseases, such as insomnia and depression.
Hypercholesterolemia Diagnosis, Treatment Patterns, and 12-Month Target Achievement in Clinical Practice in Germany in Patients with Familial Hypercholesterolemia
Authors: Gitt Anselm K. , Laufs Ulrich , März Winfried , Paar W. Dieter , Bramlage Peter , Marx Nikolaus , Parhofer Klaus G.
Published: July 2022

Background: Familial hypercholesterolemia (FH) is a highly prevalent disorder and a risk factor for early coronary artery disease. The objective of this registry was to document the clinical characteristics of patients with definite FH in Germany and to document lipid profiles, lipid-lowering therapy, and lipid target achievement during longitudinal follow-up. Methods: HYDRA-FH was a national, prospective, multicenter, non-interventional registry conducted in 35 centers in Germany. Consecutive adult patients with definite FH were included (n = 241). Results: In the cross-sectional analysis (n = 233), lipid-lowering therapy involved statins (82.0%), ezetimibe (31.8%), and PCSK9 antibodies (18.5%); 11.2% of patients were receiving no lipid-lowering drugs. Median lipid levels were: low-density lipoprotein cholesterol (LDL-C) 134 mg/dL (3.5 mmol/L), high-density lipoprotein cholesterol (HDL-C) 48 mg/dL (1.2 mmol/L), triglycerides 160 mg/dL (1.9 mmol/L), total cholesterol 211 mg/dL (5.5 mmol/L). Values were above the normal threshold (150 mg/dL) for LDL-C in 72.9%, total cholesterol in 29.7%, and triglycerides in 45.0% of patients. After the 12-month follow-up (n = 145), only 17.2% had LDL-C < 70 mg/dL, and 20.7% had either LDL-C < 70 mg/dL or a reduction of ≥50% versus baseline. Conclusion: This study provides insight into the clinical characteristics and current treatment status of patients with FH in Germany. Many patients with FH do not achieve recommended lipid levels.
Cutaneous Reactions to COVID-19 Vaccines in a Monocentric Study: A Case Series
Authors: Cantisani Carmen , Chello Camilla , Grieco Teresa , Ambrosio Luca , Kiss Norbert , Tammaro Antonella , Tosti Giulio , Paolino Giovanni , Pellacani Giovanni
Published: July 2022

After coronavirus disease 2019 (COVID-19) caused a global pandemic, vaccines were rapidly developed to control the spread of the virus. Although they were effective in most of the cases at protecting people from becoming seriously ill and being hospitalized, they showed side effects, too. Among other adverse vaccine reactions, cutaneous eruptions following SARS-CoV-2 have been described in the literature, but they are not well-characterized yet. We described the morphology and timing of the spectrum of cutaneous reactions following most of the COVID-19 vaccines available in Italy, which were observed in outpatients referred to our non-invasive diagnostic clinic. Most of these reactions appeared after the second or third COVID-19 vaccine dose (most of them after mRNA COVID-19 vaccines). Our data support that cutaneous reactions to COVID-19 vaccination are generally self-limited; in addition, history of allergic reaction to a specific food, medicine or vaccine should not discourage vaccination in the general population, although patients with immune dysregulation should be accurately selected and monitored. Further research is necessary to better assess the true prevalence and preventive measures of skin reactions to COVID-19 vaccination.
Segmentation and Recognition of the Pathological Features of Squamous Cell Carcinoma of the Skin Based on Multispectral Imaging
Authors: Wang Cheng , Chen Qi , Gao Tijie , Guo Shijun , Xiang Huazhong , Zheng Gang , Zhang Dawei , Wang Xiuli
Published: July 2022

Cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers, a definitive diagnosis of cSCC is crucial to prevent patients from missing out on treatment. The gold standard for the diagnosis of cSCC is still pathological biopsy. Currently, its diagnostic efficiency and accuracy largely depend on the experience of pathologists. Here, we present a simple, fast, and robust technique, a microscopic multispectral imaging system based on LED illumination, to diagnose cSCC qualitatively and quantitatively. The adaptive threshold segmentation method was used to segment the multispectral images into characteristic structures. There was a statistically significant difference between the average nucleocytoplasmic ratio of normal skin (4.239%) and cSCC tissues (15.607%) (p < 0.01), and the keratin pearls cSCC have well-defined qualitative features. These results show that the qualitative and quantitative features obtained from multispectral imaging can be used to comprehensively determine whether or not the tissue is cancerous. This work has significant implications for the development of a low-cost and easy-to-use device, which can not only reduce the complexity of pathological diagnosis but can also achieve the goal of convenient digital staining and access to critical histological information.
Postoperative Pain Following Root Canal Instrumentation Using ProTaper Next or Reciproc in Asymptomatic Molars: A Randomized Controlled Single-Blind Clinical Trial
Authors: Oliveira Patrícia Santos , Ferreira Meire Coelho , Paula Natália Gomes Nascimento , Loguercio Alessandro Dourado , Grazziotin-Soares Renata , da Silva Gisele Rodrigues , da Mata Helena Cristina Santos , Bauer José , Carvalho Ceci Nunes
Published: July 2022

Aim: The development of postoperative pain following root canal instrumentation may impair patient’s comfort and undermine their trust in the dentist. This study assessed the effect of root canal instrumentation techniques (rotary (PTN; ProTaper Next®) and reciprocating (R; Reciproc®)) on the postoperative pain intensity (primary outcome) and tenderness on biting (secondary outcome) of patients’ asymptomatic molars. Methodology: This study protocol was registered with ReBec-WHO (U1111-1182-2800). From a pool of 112 patients evaluated for eligibility (healthy adults (≤18 years old)), with a single asymptomatic molar (maxillary or mandibular) indicated for root canal treatment, diagnosed with asymptomatic irreversible pulpitis (including chronic hyperplastic pulpitis), 75 were randomly allocated in similar proportions to receive the intervention (two-appointment root canal therapy) in either the PTN or R group. The allocated procedures were performed using standardized protocols. Participants (blinded to the instrumentation technique) rated their pain intensity at 6, 12 and 24 h and from day 2 to day 7 following the root canal instrumentation appointment using a VAS and an NRS; the ibuprofen tablets taken and the presence of tenderness on biting were recorded. The instrumentation time was registered. Univariate and multivariate statistics measured the effect of independent variables on the outcomes. Results: From the 75 patients allocated, 8 patients (4 from each group) were lost; in total, 33 patients were analyzed in the PTN group and 34 in the R group. The frequencies of postoperative pain (p > 0.05) and tenderness on biting (p > 0.05) were similar between groups. The medication intake (mean of 1.31 tablets) and the time of instrumentation (approximately 11 min) were similar between groups. Conclusion: ProTaper Next and Reciproc® caused a slight risk of tenderness on biting and contributed to similar self-reported postoperative pain (low intensity) up to 7 days following root canal shaping.
Traits of Complex Thinking: A Bibliometric Review of a Disruptive Construct in Education
Authors: Baena-Rojas Jose Jaime , Ramírez-Montoya María Soledad , Mazo-Cuervo Diego Mauricio , López-Caudana Edgar Omar
Published: July 2022

The purpose of this research is to contextualize the behavior of publications on complex thinking in education. A total of 428 documents compiled in Scopus from 1937 to 2022 were analyzed with a bibliometric study considering criteria such as “complex thinking”, “complex thought”, and “reasoning for complexity”, all combined with education. The results show 153, 47, and 5 publications for each criterion with their related disciplines, citations, types of documents, universities, prominent authors, researching countries, and the general diachronic evolution of the subject, this allows to establish an idea about the implications of the present study according to one of the most important databases in the world. It is concluded that complex thinking and its relationship with education awakens a greater interest in the academy, not only because of its incidence in diverse fields that are nourished by it for the generation of new multidisciplinary knowledge but also because of the published research that demonstrates its transcendence.