bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression of the D-Series Resolvin Pathway Predicts Activation of Anti-Tumor Immunity and Clinical Outcomes in Head and Neck Cancer
Authors: Mattoscio Domenico , Ferri Giulia , Miccolo Claudia , Chiocca Susanna , Romano Mario , Recchiuti Antonio
Published: June 2022

In human medicine, the progression from early neoplasia development to either complete resolution of tumorigenesis and associated inflammation or chronicity and fatal outcomes remain difficult to predict. Resolution of inflammation is an active process that stimulates the termination of the inflammatory response and promotes return to homeostasis, while failure in resolution contributes to the development of a number of diseases. To understand how resolution pathways contribute to tumorigenesis, we defined and employed a cumulative score based on the expression level of genes involved in synthesis, signaling, and metabolism of the D-series resolvin (RvD). This score was used for comparative analyses of clinical, cellular, and molecular features of tumors, based on RNA-sequencing (RNA-seq) datasets collected within The Cancer Genome Atlas (TCGA) program. Our results indicate that higher RvD scores are associated with better clinical outcome of patients with head and neck squamous cell carcinoma (HNSC), and with molecular and cellular signatures indicative of enhanced anti-tumor immunity and better response to immune-checkpoint inhibitors (ICI), also in human papilloma virus (HPV) negative HNSC subtypes. Thus, higher activity of the RvD pathway identifies patients with improved resolution and a more efficient immune reaction against cancer.
Brain Metastases Management in Oncogene-Addicted Non-Small Cell Lung Cancer in the Targeted Therapies Era
Authors: De Carlo Elisa , Bertoli Elisa , Del Conte Alessandro , Stanzione Brigida , Berto Eleonora , Revelant Alberto , Spina Michele , Bearz Alessandra
Published: June 2022

The therapeutic landscape in patients with advanced non-small-cell lung cancer harboring oncogenic biomarkers has radically changed with the development of targeted therapies. Although lung cancers are known to frequently metastasize to the brain, oncogene-driven non-small-cell lung cancer patients show a higher incidence of both brain metastases at baseline and a further risk of central nervous system progression/relapse. Recently, a new generation of targeted agents, highly active in the central nervous system, has improved the control of intracranial disease. The intracranial activity of these drugs poses a crucial issue in determining the optimal management sequence in oncogene-addicted non-small-cell lung cancer patients with brain metastases, with a potential change of paradigm from primary brain irradiation to central nervous system penetrating targeted inhibitors.
Reproductive Immunology and Pregnancy
Authors: Szukiewicz Dariusz
Published: June 2022

This Special Issue has been prepared to showcase the dynamic and comprehensive development of reproductive immunology, including the immunology of pregnancy [...]
Meta’omics: Challenges and Applications
Authors: Fulci Valerio
Published: June 2022

Metagenomics and metatranscriptomics are emerging as key disciplines towards a fully understanding the complex relationships between living organisms belonging to different kingdoms [...]
Integrative Proteome and Phosphoproteome Profiling of Early Cold Response in Maize Seedlings
Authors: Xing Jiayun , Tan Jinjuan , Feng Hanqian , Zhou Zhongjing , Deng Min , Luo Hongbing , Deng Zhiping
Published: June 2022

Cold limits the growth and yield of maize in temperate regions, but the molecular mechanism of cold adaptation remains largely unexplored in maize. To identify early molecular events during cold shock, maize seedlings were treated under 4 °C for 30 min and 2 h, and analyzed at both the proteome and phosphoproteome levels. Over 8500 proteins and 19,300 phosphopeptides were quantified. About 660 and 620 proteins were cold responsive at protein abundance or site-specific phosphorylation levels, but only 65 proteins were shared between them. Functional enrichment analysis of cold-responsive proteins and phosphoproteins revealed that early cold response in maize is associated with photosynthesis light reaction, spliceosome, endocytosis, and defense response, consistent with similar studies in Arabidopsis. Thirty-two photosynthesis proteins were down-regulated at protein levels, and 48 spliceosome proteins were altered at site-specific phosphorylation levels. Thirty-one kinases and 33 transcriptional factors were cold responsive at protein, phosphopeptide, or site-specific phosphorylation levels. Our results showed that maize seedlings respond to cold shock rapidly, at both the proteome and phosphoproteome levels. This study provides a comprehensive landscape at the cold-responsive proteome and phosphoproteome in maize seedlings that can be a significant resource to understand how C4 plants respond to a sudden temperature drop.
Hypertension and Type 2 Diabetes—The Novel Treatment Possibilities
Authors: Przezak Agnieszka , Bielka Weronika , Pawlik Andrzej
Published: June 2022

Elevated blood pressure and hyperglycaemia frequently coexist and are both components of metabolic syndrome. Enhanced cardiovascular risk is strongly associated with diabetes and the occurrence of hypertension. Both hypertension and type 2 diabetes, if treated inappropriately, lead to serious complications, increasing the mortality of patients and generating much higher costs of health systems. This is why it is of great importance to find the missing link between hypertension and diabetes development and to simultaneously search for drugs influencing these two disorders or even drugs aimed at their pathological bases. Standard antihypertensive therapy mainly focuses on blood pressure reduction, while novel drugs also possess a wide range of pleiotropic modes of actions, such as cardio- and nephroprotective properties or body weight reduction. These properties are especially desirable in a situation when type 2 diabetes coexists with hypertension. This review describes the connections between diabetes and hypertension development and briefly summarises the current knowledge regarding attempts to define targets for the treatment of high blood pressure in diabetic patients. It also describes the standard hypotensive drugs preferred in patients with type 2 diabetes, as well as novel drugs, such as finerenone, esaxerenone, sodium–glucose co-transporter-2 inhibitors, glucagon-like peptide-1 analogues and sacubitril/valsartan.
Suitability of Chitosan Scaffolds with Carbon Nanotubes for Bone Defects Treated with Photobiomodulation
Authors: Silva Samantha Ketelyn , Plepis Ana Maria Guzzi , Martins Virginia da Conceição Amaro , Horn Marilia Marta , Buchaim Daniela Vieira , Buchaim Rogerio Leone , Pelegrine André Antônio , Silva Vinícius Rodrigues , Kudo Mateus Hissashi Matsumoto , Fernandes José Francisco Rebello , Nazari Fabricio Montenegro , da Cunha Marcelo Rodrigues
Published: June 2022

Biomaterials have been investigated as an alternative for the treatment of bone defects, such as chitosan/carbon nanotubes scaffolds, which allow cell proliferation. However, bone regeneration can be accelerated by electrotherapeutic resources that act on bone metabolism, such as low-level laser therapy (LLLT). Thus, this study evaluated the regeneration of bone lesions grafted with chitosan/carbon nanotubes scaffolds and associated with LLLT. For this, a defect (3 mm) was created in the femur of thirty rats, which were divided into 6 groups: Control (G1/Control), LLLT (G2/Laser), Chitosan/Carbon Nanotubes (G3/C+CNTs), Chitosan/Carbon Nanotubes with LLLT (G4/C+CNTs+L), Mineralized Chitosan/Carbon Nanotubes (G5/C+CNTsM) and Mineralized Chitosan/Carbon Nanotubes with LLLT (G6/C+CNTsM+L). After 5 weeks, the biocompatibility of the chitosan/carbon nanotubes scaffolds was observed, with the absence of inflammatory infiltrates and fibrotic tissue. Bone neoformation was denser, thicker and voluminous in G6/C+CNTsM+L. Histomorphometric analyses showed that the relative percentage and standard deviations (mean ± SD) of new bone formation in groups G1 to G6 were 59.93 ± 3.04a (G1/Control), 70.83 ± 1.21b (G2/Laser), 70.09 ± 4.31b (G3/C+CNTs), 81.6 ± 5.74c (G4/C+CNTs+L), 81.4 ± 4.57c (G5/C+CNTsM) and 91.3 ± 4.81d (G6/C+CNTsM+L), respectively, with G6 showing a significant difference in relation to the other groups (a ≠ b ≠ c ≠ d; p < 0.05). Immunohistochemistry also revealed good expression of osteocalcin (OC), osteopontin (OP) and vascular endothelial growth factor (VEGF). It was concluded that chitosan-based carbon nanotube materials combined with LLLT effectively stimulated the bone healing process.
Theory-Guided Design of a Method to Obtain Competitive Balance between U(VI) Adsorption and Swaying Zwitterion-Induced Fouling Resistance on Natural Hemp Fibers
Authors: Gu Huiquan , Yu Jing , Zhang Hongsen , Sun Gaohui , Li Rumin , Liu Peili , Li Ying , Wang Jun
Published: June 2022

The competitive balance between uranium (VI) (U(VI)) adsorption and fouling resistance is of great significance in guaranteeing the full potential of U(VI) adsorbents in seawater, and it is faced with insufficient research. To fill the gap in this field, a molecular dynamics (MD) simulation was employed to explore the influence and to guide the design of mass-produced natural hemp fibers (HFs). Sulfobetaine (SB)- and carboxybetaine (CB)-type zwitterions containing soft side chains were constructed beside amidoxime (AO) groups on HFs (HFAS and HFAC) to form a hydration layer based on the terminal hydrophilic groups. The soft side chains were swayed by waves to form a hydration-layer area with fouling resistance and to simultaneously expel water molecules surrounding the AO groups. HFAS exhibited greater antifouling properties than that of HFAO and HFAC. The U(VI) adsorption capacity of HFAS was almost 10 times higher than that of HFAO, and the max mass rate of U:V was 4.3 after 35 days of immersion in marine water. This paper offers a theory-guided design of a method to the competitive balance between zwitterion-induced fouling resistance and seawater U(VI) adsorption on natural materials.
Rare Monogenic Diseases: Molecular Pathophysiology and Novel Therapies
Authors: Condò Ivano
Published: June 2022

A rare disease is defined by its low prevalence in the general population [...]
Cytokines and Venous Leg Ulcer Healing—A Systematic Review
Authors: Burian Ewa A. , Sabah Lubna , Karlsmark Tonny , Kirketerp-Møller Klaus , Moffatt Christine J. , Thyssen Jacob P. , Ågren Magnus S.
Published: June 2022

Venous leg ulcers (VLUs) are the most common type of leg ulcers with a significant socioeconomic burden due to slow healing. Cytokines may be involved in the pathogenesis of VLUs. In this systematic review, our objective was to investigate the association between cytokine levels, including growth factors, with the healing of VLUs. PubMed, Embase, Web of Science and Cochrane Library were searched from their inception to August 2021. We retrieved 28 articles investigating 38 different cytokines in 790 patients. Cytokines were most commonly investigated in wound fluid and less frequently in biopsies and serum. The studies were judged as having a moderate to high risk of bias, and the results were often inconsistent and sometimes conflicting. A meta-analysis was not performed due to clinical and methodological heterogeneities. We found weak evidence for elevated IL-1α, IL-6, IL-8, TNF-α and VEGF levels in non-healing VLUs, an elevation that declined with healing. TGF-β1 levels tended to increase with VLU healing. Other cytokines warranting further investigations include EGF, FGF-2, GM-CSF, IL-1β, IL-1Ra and PDGF-AA/PDGF-BB. We conclude that non-healing VLUs may be associated with an elevation of a palette of pro-inflammatory cytokines, possibly reflecting activated innate immunity in these wounds. There is a paucity of reliable longitudinal studies monitoring the dynamic changes in cytokine levels during wound healing.
Selective Elimination of Senescent Fibroblasts by Targeting the Cell Surface Protein ACKR3
Authors: Takaya Kento , Asou Toru , Kishi Kazuo
Published: June 2022

The accumulation of senescent cells in aging tissues is associated with age-related diseases and functional decline. Thus, senolysis, a therapy aimed at rejuvenation by removing senescent cells from the body, is being developed. However, this therapy requires the identification of membrane surface antigens that are specifically expressed on senescent cells for their selective elimination. We showed that atypical chemokine receptor 3 (ACKR3), a receptor of the CXC motif chemokine 12 (CXCL12) implicated in cancer, inflammation, and cardiovascular disorders, is selectively expressed on the surface of senescent human fibroblasts but not on proliferating cells. Importantly, the differential presence of ACKR3 enabled the isolation of senescent cells by flow cytometry using anti-ACKR3 antibodies. Furthermore, antibody-dependent cellular cytotoxicity assays revealed that cell surface ACKR3 preferentially sensitizes senescent but not dividing fibroblasts to cell injury by natural killer cells. Conclusively, the selective expression of ACKR3 on the surface of senescent cells allows the preferential elimination of senescent cells. These results might contribute to the future development of novel senolysis approaches.
Risk Management Methodology for Transport Infrastructure Security
Authors: Makarova Irina , Yakupova Gulnara , Buyvol Polina , Abashev Albert , Mukhametdinov Eduard
Published: June 2022

The development of transport infrastructure is associated with risks, expressed in the likelihood of harm to the road users’ health during road accidents and their consequences. The risk management process is aimed at reducing the influence of factors that contribute to the occurrence of an accident and increase the consequences’ severity after it. This article proposes a risk management methodology within five stages: identification, analysis and evaluation, processing, development of recommendations, and monitoring. For each step, we describe the methods and models that allow us to effectively solve the problem of risk management. We proposed a risk management algorithm based on feedback. We tested the adequacy of the methodology on a specific example: we conducted an analysis, an assessment, and proposed risk management measures in the field of ensuring road safety in a small town.
Topical Fungal Infection Induces Shifts in the Gut Microbiota Structure of Brown Planthopper, Nilaparvata lugens (Homoptera: Delphacidae)
Authors: Wang Zhengliang , Cheng Yiqing , Wang Yandan , Yu Xiaoping
Published: June 2022

The brown planthopper (Nilaparvata lugens, BPH) is a destructive insect pest posing a serious threat to rice production. The fungal entomopathogen Metarhizium anisopliae is a promising alternative that can be used for BPH biocontrol. Recent studies have highlighted the significant involvement of gut microbiota in the insect–fungus interactions. In the presented study, we investigated the effects of topical fungal infection on the gut microbial community structure in BPH. Our results revealed that topical infection with M. anisopliae increased the bacterial load and altered the bacterial community structure in the gut of BPH. The relative abundances of the dominant gut bacteria at the order, family and genus level were significantly different between fungus-infected and uninfected groups. At the genus level, the uninfected BPH harbored high proportions of Pantoea and Enterobacter in the gut, whereas the fungus-infected BPH gut was absolutely dominated by Acinetobacter. Moreover, topical fungal infection significantly inhibited the expressions of immune-related genes encoding anti-microbial protein and dual oxidase that were involved in the maintenance of gut microbiota homeostasis, indicating that gut bacteria imbalance might be attributed in part to the suppression of gut immunity caused by fungal pathogen. Our results highlighted the importance of the gut microbial community during interactions between fungal pathogens and insect hosts.
Differential Hatching, Development, Oviposition, and Longevity Patterns among Colombian Aedes aegypti Populations
Authors: Arévalo-Cortés Andrea , Granada Yurany , Torres David , Triana-Chavez Omar
Published: June 2022

Dengue, Zika, and chikungunya are arboviral diseases for which there are no effective therapies or vaccines. The only way to avoid their transmission is by controlling the vector Aedes aegypti, but insecticide resistance limits this strategy. To generate relevant information for surveillance and control mechanisms, we determined life cycle parameters, including longevity, fecundity, and mortality, of Colombian Ae. aegypti populations from four different geographical regions: Neiva, Bello, Itagüí, and Riohacha. When reared at 28 °C, Bello had the shortest development time, and Riohacha had the longest. Each mosquito population had its own characteristic fecundity pattern during four gonotrophic cycles. The survival curves of each population were significantly different, with Riohacha having the longest survival in both males and females and Bello the shortest. High mortality was observed in mosquitoes from Neiva in the egg stage and for Bello in the pupae stage. Finally, when mosquitoes from Neiva and Bello were reared at 35 °C, development times and mortality were severely affected. In conclusion, each population has a unique development pattern with an innate trace in their biological characteristics that confers vulnerability in specific stages of development.
Resuscitated Sudden Cardiac Arrest of a Neonate with Congenital LQT Syndrome-Associated Torsades de Pointes: A Case Report and Literature Review
Authors: Hsu Yen-Teng , Lee Pi-Chang , Chen Yu-Hsuan , Yeh Shu-Jen , Chen Ming-Ren , Hsu Kung-Hong , Chang Chung-I , Lai Wei-Ting , Hung Wei-Li
Published: June 2022

Sudden infant death syndrome (SIDS), the most common cause of infant death in developed countries, is attributed to diverse trigger factors. Malignant cardiac dysrhythmias are potentially treatable etiologies, and congenital long QT syndrome (LQTS) is the most common cardiac ionic channelopathy confronted. β-Blockers or class Ib agents are the drugs of choice for the control of arrhythmias, and an implantable cardioverter defibrillator (ICD) should be considered for secondary prevention in survivors of lethal cardiac death. We report the case of a 4-day old neonate, later genetically confirmed as LQT type 3 (LQT3), who survived a pulseless torsades de pointes (TdP) attack and was successfully treated with propranolol, mexiletine, and ICD implantation.
Nitrates vs. Other Types of Vasodilators and Clinical Outcomes in Patients with Vasospastic Angina: A Propensity Score-Matched Analysis
Authors: Kim Hyun-Jin , Jo Sang-Ho , Lee Min-Ho , Seo Won-Woo , Kim Hack-Lyoung , Lee Kwan Yong , Yang Tae-Hyun , Her Sung-Ho , Lee Byoung-Kwon , Park Keun-Ho , Ahn Youngkeun , Rha Seung-Woon , Gwon Hyeon-Cheol , Choi Dong-Ju , Baek Sang Hong
Published: June 2022

Although vasodilators are widely used in patients with vasospastic angina (VA), few studies have compared the long-term prognostic effects of different types of vasodilators. We investigated the long-term effects of vasodilators on clinical outcomes in VA patients according to the type of vasodilator used. Study data were obtained from a prospective multicenter registry that included patients who had symptoms suggestive of VA. Patients were classified into two groups according to use of nitrates (n = 239) or other vasodilators (n = 809) at discharge. The composite clinical events rate, including acute coronary syndrome (ACS), cardiac death, new-onset arrhythmia (including ventricular tachycardia and ventricular fibrillation), and atrioventricular block, was significantly higher in the nitrates group (5.3% vs. 2.2%, p = 0.026) during one year of follow-up. Specifically, the prevalence of ACS was significantly more frequent in the nitrates group (4.3% vs. 1.5%, p = 0.024). After propensity score matching, the adverse effects of nitrates remained. In addition, the use of nitrates at discharge was independently associated with a 2.69-fold increased risk of ACS in VA patients. In conclusion, using nitrates as a vasodilator at discharge can increase the adverse clinical outcomes in VA patients at one year of follow-up. Clinicians need to be aware of the prognostic value and consider prescribing other vasodilators.
The Value of Fetal Head Station as a Delivery Mode Predictor in Primiparous Women at Term before the Onset of Labor
Authors: Dîră Laurențiu Mihai , Cara Monica-Laura , Drăgușin Roxana Cristina , Nagy Rodica Daniela , Iliescu Dominic Gabriel
Published: June 2022

Objective: Our objective was to demonstrate the role of the clinical determination of fetal head station (FHS) at term to predict the delivery mode in primiparous women before the onset of labor. Methods: This prospective study included unselected primiparous women at term who presented at our tertiary maternity. We excluded multiparous patients, pregnancies with a planned Cesarean section, non-cephalic presentations, and multiple pregnancies. The protocol included weekly clinical examinations to assess the FHS. The results were used to describe the clinical fetal head descent at term. We correlated the fetal head station determinations at each week with labor outcome, including the evaluations performed within the week before delivery. Results: The data show no significant differences between vaginal (VD) and Cesarean section delivery (CS) cases regarding FHS determined at each week at term. The median determinations at the gestational ages (GW) from 37 to 41 were −2 and −3, similar between the two groups, with a more consistent difference at 41 GW: station -1 for VD compared to −3 for CS. There were significant differences between the “week before delivery” evaluations of the two groups. The determinations showed for both groups similar minimum (−5), maximum (+1), and median (−2) FHS values. Most vaginal deliveries cases presented at weekly examinations with increasing rates toward more advanced stations: from 10% at station −4 to 35% at station −1. Although we investigated a low-risk group, we found significant differences between the vaginal and Cesarean groups in terms of age, weight, and BMI. We provided a multiple logistic regression equation that considered the predictive clinical variables at term: the fetal head situation, age, weight, height, and BMI. Conclusion: The clinical evaluation of fetal head station in primiparous before labor onset has a limited value regarding the prediction of the delivery mode. There is a potential benefit for the determinations performed within the week before delivery, but such a policy would require weekly assessments of the FHS at term, which is unlikely to be implemented. Another potential benefit would involve estimating labor outcomes in late-term or prolonged pregnancy. The fine tuning of the logistic prediction should be achieved by increasing the studied population and the number of centers involved before counseling primiparous women at term based on the clinical fetal engagement data.
Comparison of Retention between Conventional and Nanofilled Resin Sealants in a Paediatric Population: A Randomized Clinical Trial
Authors: Kamath Vinayak , Hebbal Mamata , Ankola Anil , Sankeshwari Roopali , Jalihal Sagar , Choudhury Abhra , Soliman Mai , Eldwakhly Elzahraa
Published: June 2022

Background: This study compared conventional-resin-sealant versus nanofilled-sealant retention at different intervals. Methods: A double-blinded split-mouth randomized control trial was performed on sixty-two children aged from six to nine years. Participants with one pair of contralateral permanent first molars with deep fissures or noncavitated carious lesions were randomly selected for sealant application. Conventional resin sealant was applied on one molar and nanofilled sealant on the contralateral molar. Evaluations were performed at one, three, six, twelve and eighteen months to check for retention. The chi-squared test, McNemar test, Wilcoxon signed-rank test and Friedman test were used for statistical analysis. Results: Conventional resin sealant showed complete retention in 91.4%, 86.2%, 74.1%, 62.1% and 55.2% of the teeth, and nanofilled sealant showed complete retention in 89.7%, 81%, 77.6%, 69% and 67.2% of the teeth, at the end of 1 month, 3 months, 6 months, 12 months and 18 months evaluation, respectively. Each sealant exhibited a statistically significant change (p < 0.05) in the retention rate during the evaluation period. However, when both the sealants were compared with each other, there was no statistically significant difference in any phase. At the end of 18 months, caries development was observed in 13.8% of the teeth sealed with conventional sealant, and in 10.3% of the teeth sealed with nanofilled sealant. Conclusion: At eighteen months, the nanofilled resin sealant exhibited complete retention in 12% more teeth than the conventional sealant. However, the difference was not statistically significant. The nanofilled resin sealant yielded an acceptable performance in sealing the occlusal pits and fissures of mandibular permanent first molars, compared to conventional pit-and-fissure sealants.
Evaluation of Radial Peripapillary Capillary Density in G6PD Deficiency: An OCT Angiography Pilot Study
Authors: Serra Rita , D’Amico Ricci Giuseppe , Dore Stefano , Coscas Florence , Pinna Antonio
Published: June 2022

Glucose-6-phosphate-dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder causing hemolytic anemia. The purpose of this pilot study was to compare vascular density (VD) values of the radial peripapillary capillary (RPC) plexus in G6PD-deficient and G6PD-normal men, using optical coherence tomography angiography (OCTA). Methods: 46 G6PD-deficient men and 23 age-matched male controls were included. A complete ophthalmological evaluation, consisting of slit-lamp biomicroscopy, best-corrected visual acuity, intra-ocular pressure measurement, structural optical coherence tomography, and OCTA scanning of the optic nerve head, was performed. The en-face angioflow images were carefully analyzed and the VD values of the RPC plexus were measured using the AngioAnalytics™ software embedded in the OCTA device. Medical conditions, including systemic hypertension, hypercholesterolemia, and diabetes mellitus, were also investigated. Results: G6PD-deficient eyes showed higher values of VD in all peripapillary sectors, but a statistical significance (p = 0.03) was reached only in the infero-temporal sector. There were no significant differences in terms of hypercholesterolemia, systemic arterial hypertension, and diabetes mellitus between the two study groups. Conclusion: Results show that VD values of the RPC plexus are higher in G6PD-deficient men than in G6PD-normal subjects, but a statistically significant difference was found only in the inferior temporal sector. Overall, our preliminary findings support the hypothesis that the RPC layer of G6PD-deficient men consists of a denser vascular network, which may contribute to offering protection against ocular atherosclerotic vasculopathies.
Soluble Urokinase Plasminogen Activator Receptor (suPAR) in the Emergency Department (Ed): A Tool for the Assessment of Elderly Patients
Authors: Holstein Ria M. , Seppälä Santeri , Kaartinen Johanna , Hongisto Mari , Hyppölä Harri , Castrén Maaret
Published: June 2022

Emergency department (ED) overcrowding is a global issue setting challenges to all care providers. Elderly patients are frequent visitors of the ED and their risk stratification is demanding due to insufficient assessment methods. A prospective cohort study was conducted to determine the risk-predicting value of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), in the ED, concentrating on elderly patients. SuPAR levels were determined as part of standard blood sampling of 1858 ED patients. The outcomes were assessed in the group of <75 years (=younger) and ≥75 years (=elderly). The elderly had higher median suPAR levels than the younger (5.4 ng/mL vs. 3.7 ng/mL, p < 0.001). Increasing suPAR levels were associated with higher probability for 30-day mortality and hospital admission in all age groups. SuPAR also predicted 30-day mortality when adjusted to other clinical factors. SuPAR acts successfully as a nonspecific risk predictor for 30-day mortality, independently and with other risk-assessment tools. Low suPAR levels predict positive outcomes and could be used in the discharging process. A cut-off value of 4 ng/mL could be used for all ED patients, 5 ng/mL being a potential alternative in elderly patients.
Age-Adjusted D-Dimer Levels May Improve Diagnostic Assessment for Pulmonary Embolism in COVID-19 Patients
Authors: Machowski Michał , Polańska Anna , Gałecka-Nowak Magdalena , Mamzer Aleksandra , Skowrońska Marta , Perzanowska-Brzeszkiewicz Katarzyna , Zając Barbara , Ou-Pokrzewińska Aisha , Pruszczyk Piotr , Kasprzak Jarosław D.
Published: June 2022

Introduction: SARS-CoV-2 infection leads to a hypercoagulable state. The prevalence of pulmonary embolism (PE) seems to be higher in this subgroup of patients. Patients and methods: We combined data from two tertiary referral centers specialized in the management of PE. The aims of this study were as follows: (1) to evaluate the prevalence of PE among a large population of consecutive patients admitted for COVID-19 pneumonia in two centers, (2) to identify a plasma D-dimer threshold that may be useful in PE diagnostic assessment, (3) to characterize the abnormalities associated with PE and mortality in COVID-19 patients. Results: The incidence of symptomatic acute PE was 19.3%. For diagnosing PE in COVID-19 patients, based on ROC curve analysis, we identified a D-dimer concentration/patient’s age ratio of 70, which improved D-dimer diagnostic capacity for PE and led to a reclassification improvement of 14% (NRI 0.14, p = 0.03) when compared to a cut-off level of 1000 ng/mL. Especially in severe COVID-19 lung involvement, D-dimer/age ratio cut-off equal to 70 was characterized by high diagnostic feasibility (sensitivity, specificity, negative predictive value, positive predictive value of 83%, 94%, 96%, and 73%, respectively). Apart from PE status, lung involvement and troponin T concentration were also independent predictors of in-hospital mortality. In the subgroup of PE patients, mortality was comparable with non-PE patients (19/88 (21.5%) vs. 101/368 (27.4%) for non-PE, p = 0.26) and was associated with older age, higher Bova scores, and higher troponin T concentrations. Age was the sole independent predictor for mortality in this subgroup. Conclusions: PE in COVID-19 patients is common, but it may not influence mortality when managed at a specialized center. In suspected PE, age-adjusted D-dimer levels (upper limit of normal obtained from the formula patient’s age × 70) may still be a useful tool to start the diagnostic workup. In COVID-19 patients without PE, older age, more extensive parenchymal involvement, or higher D-dimer levels are factors predicting mortality.
Association between Occupation and Cervical Disc Degeneration in 1211 Asymptomatic Subjects
Authors: Machino Masaaki , Nakashima Hiroaki , Ito Keigo , Ando Kei , Ito Sadayuki , Kato Fumihiko , Imagama Shiro
Published: June 2022

Magnetic resonance imaging (MRI) system has frequently observed degenerative changes in the cervical discs of healthy subjects. Although there are concerns regarding the link between an individual’s occupation and intervertebral disc degeneration (IDD) in the cervical spine, whether the occupation affects IDD is still not clear. This study aimed to evaluate the occupation and IDD interplay using cervical spine MRI among a cohort of healthy individuals, and to evaluate any association between the type of labor and IDD. Using MRI, we prospectively measured at every level, the anteroposterior (AP) intervertebral disc diameter and disc height, in a cohort of 1211 healthy volunteers (606 (50%) male; mean age, 49.5 years). Using a minimum of 100 male and female each from the third to eighth decades of age (20–79 years), IDD was evaluated based on the modified Pfirrmann classification system to derive a disc degeneration score (DDS). We also measured the AP diameters of disc protrusion and of the dural sac as well as the spinal cord. The overall DDS and number of disc protrusions increased with age. Among 11 occupations, there were no significant differences in AP diameter of the dural sac as well as the spinal cord. For the four labor types (heavy object handling, same position maintenance, cervical extension position, and cervical flexion position), there were no significant differences in overall DDS and number of disc protrusions, with or without work. Also, among the four labor types, there were no significant differences in the AP diameter of the dural sac as well as the spinal cord. In this cross-sectional survey of cervical spine MRI data among healthy adult volunteers, occupation and type of labor might have no effect on IDD in the cervical spine.
The Role of Wilms’ Tumor Gene (WT1) Expression as a Marker of Minimal Residual Disease in Acute Myeloid Leukemia
Authors: Lazzarotto Davide , Candoni Anna
Published: June 2022

The Minimal Residual Disease(MRD) monitoring in acute myeloid leukemia (AML) is crucial to guide treatment after morphologic complete remission, to define the need for consolidation with allogeneic stem cell transplantation (Allo-SCT), and to detect impending relapse allowing early intervention. However, more than 50% of patients with AML lack a specific or measurable molecular marker to monitor MRD. We reviewed the key studies on WT1 overexpression as a marker of MRD in AML patients undergoing an intensive chemotherapy program, including Allo-SCT. In addition, we provided some practical considerations on how to properly use WT1 expression as an MRD marker, considering its strengths and weaknesses. In order to achieve the best sensitivity and specificity, it is recommended to refer to the standardized method of European LeukemiaNet and its defined threshold (250 WT1 copies/104 Abelson (ABL) on Bone Marrow-BM and 50 WT1 copies/104 ABL on Peripheral Blood-PB), which has been validated in a large and multicenter cohort of patients and normal controls.
Mechanical Fatigue Performance of Patient-Specific Polymer Plates in Oncologic Mandible Reconstruction
Authors: Lommen Julian , Schorn Lara , Sproll Christoph , Kübler Norbert R. , Nicolini Luis Fernando , Merfort Ricarda , Dilimulati Ayimire , Hildebrand Frank , Rana Majeed , Greven Johannes
Published: June 2022

Mandible defects are conventionally reconstructed using titanium plates. However, titanium causes metallic artifacts which impair radiological imaging. This study aims at evaluating mechanical fatigue of radiolucent fiber-reinforced polyetheretherketone (f-PEEK), polyetheretherketone (PEEK), polyetherketoneketone (PEKK), and polyphenylsulfone (PPSU) polymer plates for mandible reconstruction. A total of 30 plates (titanium [n = 6], f-PEEK [n = 6], PEEK [n = 6], PEKK [n = 6], PPSU [n = 6]) were implanted in synthetic mandibulectomized polyurethane mandibles. Servo-pneumatic mechanical testing with cyclic application of 30–300 N at 3 Hz was conducted. Bite forces were 70% on the unresected and 30% on the resected side. Total number of cycles was set to 250,000. Testing was aborted in case of plate or screw failure. Axial load to failure was tested with a speed of 1 mm/s. Kruskal–Wallis and Dunn’s post hoc tests were used. Titanium, f-PEEK, and PEEK showed no failure in fatigue testing and PPSU (p < 0.001) failed against titanium, f-PEEK, PEEK, and PEKK. Titanium allowed the highest load to failure compared to f-PEEK (p = 0.049), PEEK (p = 0.008), PEKK (p < 0.001), and PPSU (p = 0.007). f-PEEK, PEEK, and PEKK withstood expected physiological bite force. Although titanium plates provided the highest fatigue strength, f-PEEK and PEEK plates showed no failure over 250,000 chewing cycles indicating sufficient mechanical strength for mandible reconstruction.
Effect of Intragastric Botulinum Type A Injection Combined with a Low-Calorie High-Protein Diet in Adults with Overweight or Obesity
Authors: Hsu Po-Ke , Wu Chia-Lin , Yang Yu-Hsuan , Wei James Cheng-Chung
Published: June 2022

(1) Background/aims: Intragastric botulinum toxin A injection (IGBI) combined with diet control is a new and effective weight loss method for grade 2 obese patients. However, the application of IGIB on overweight or obese adults still needs further research to confirm its efficacy. (2) Methods: We retrospectively collected medical data from 1 July 2021 to 1 January 2022 from a total of 71 patients without diabetes who participated in the bariatric clinic with a body mass index (BMI) > 25 kg/m2. Forty-nine participants opted for intragastric botulinum injection (IGBI) using 300 units of botulinum injected into the antrum, body, and fundus, followed with a low-calorie high-protein diet course. Another 22 people participated only in the low-calorie high-protein diet course as a placebo group. This study analyzes the weight loss percentage of the two groups. Adverse events after IGBI are also reported in a safety assessment. (3) Results: In terms of the characteristics of the two groups, the mean BMI was 29.3 kg/m2 in the IGBI group and 28.0 kg/m in the placebo group (p = 0.63 without significant difference). Comparing the percent weight loss from baseline in the two groups after 12 weeks, the IGBI group lost 11.5% of their body weight and the placebo group lost 1.8%. In terms of group analysis, the percentages of participants with a weight reduction of at least 5% for the IGBI and placebo groups were 95% and 4%, respectively. For weight reduction of at least 10%, these values for the IGBI and placebo groups were 63% and 4%, respectively. In terms of adverse events after IGBI for 12 weeks, 12 participants (24.4%) had constipation, which was the main side effect. No serious adverse events were observed during the study period. (4) Conclusion: The combination of a low-calorie high-protein diet and IGBI is an effective and safe procedure in overweight or obese adults for weight reduction, but further larger studies are needed.
Longwise Cluster Analysis for the Prediction of COVID-19 Severity within 72 h of Admission: COVID-DATA-SAVE-LIFES Cohort
Authors: San-Cristobal Rodrigo , Martín-Hernández Roberto , Ramos-Lopez Omar , Martinez-Urbistondo Diego , Micó Víctor , Colmenarejo Gonzalo , Villares Fernandez Paula , Daimiel Lidia , Martínez Jose Alfredo
Published: June 2022

The use of routine laboratory biomarkers plays a key role in decision making in the clinical practice of COVID-19, allowing the development of clinical screening tools for personalized treatments. This study performed a short-term longitudinal cluster from patients with COVID-19 based on biochemical measurements for the first 72 h after hospitalization. Clinical and biochemical variables from 1039 confirmed COVID-19 patients framed on the “COVID Data Save Lives” were grouped in 24-h blocks to perform a longitudinal k-means clustering algorithm to the trajectories. The final solution of the three clusters showed a strong association with different clinical severity outcomes (OR for death: Cluster A reference, Cluster B 12.83 CI: 6.11–30.54, and Cluster C 14.29 CI: 6.66–34.43; OR for ventilation: Cluster-B 2.22 CI: 1.64–3.01, and Cluster-C 1.71 CI: 1.08–2.76), improving the AUC of the models in terms of age, sex, oxygen concentration, and the Charlson Comorbidities Index (0.810 vs. 0.871 with p < 0.001 and 0.749 vs. 0.807 with p < 0.001, respectively). Patient diagnoses and prognoses remarkably diverged between the three clusters obtained, evidencing that data-driven technologies devised for the screening, analysis, prediction, and tracking of patients play a key role in the application of individualized management of the COVID-19 pandemics.
Current Advances in Breast Reconstruction
Authors: Cevik Jevan , Hunter-Smith David J. , Rozen Warren M.
Published: June 2022

Breast cancer management is multidisciplinary, and while oncologic surgery, adjuvant therapy, and psychological therapies are central to this, breast reconstruction also forms an integral part of management [...]
Calcification in Salivary Gland Cancer Mimicking Sialolithiasis—A Diagnostic Pitfall on Imaging: Report of Two Cases and Brief Review of the Literature
Authors: Thimsen Vivian , Fauck Vanessa , Wiesmüller Marco , Agaimy Abbas , Schapher Mirco , Iro Heinrich , Koch Michael , Mantsopoulos Konstantinos
Published: June 2022

Objectives: Sialolithiasis is the most common cause of calcifications detected with ultrasound in patients with chronic inflammatory symptoms and swellings of the salivary glands. Other differential diagnoses of calcifications are extremely rare and mostly benign. Methods: Case report and literature review. Results: Two rare cases of malignant parotid gland tumors with calcifications in a localization typical for sialolithiasis, which were mistaken for salivary calculi based on image findings, are presented. Conclusions: This report intends to highlight the pitfalls in the imaging of parotid gland diseases. Even if malignant tumors of the parotid gland with calcifications are extremely rare, in ambiguous cases, differential diagnoses should be considered carefully. A high suspicion index of the need for further diagnostics in cases with calcifications is practical and could include missing periprandial symptoms, no obstruction signs in the proximal duct, and missing evidence of sialolithiasis in sialendoscopy.
Conventional Laparoscopy versus Robotic-Assisted Aortic Lymph-Nodal Staging for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis
Authors: Di Donna Mariano Catello , Giallombardo Vincenzo , Lo Balbo Giuseppina , Cucinella Giuseppe , Sozzi Giulio , Capozzi Vito Andrea , Abbate Antonino , Laganà Antonio Simone , Garzon Simone , Chiantera Vito
Published: June 2022

Aortic lymph node metastases are a relative common finding in locally advanced cervical cancer. Minimally invasive surgery is the preferred approach to perform para-aortic lymph nodal staging to reduce complications, hospital stay, and the time to primary treatment. This meta-analysis (CRD42022335095) aimed to compare the surgical outcomes of the two most advanced approaches for the aortic staging procedure: conventional laparoscopy (CL) versus robotic-assisted laparoscopy (RAL). The meta-analysis was conducted according to the PRISMA guideline. The search string included the following keywords: “Laparoscopy” (MeSH Unique ID: D010535), “Robotic Surgical Procedures” (MeSH Unique ID: D065287), “Lymph Node Excision” (MeSH Unique ID: D008197) and “Aorta” (MeSH Unique ID: D001011), and “Uterine Cervical Neoplasms” (MeSH Unique ID: D002583). A total of 1324 patients were included in the analysis. Overall, 1200 patients were included in the CL group and 124 patients in the RAL group. Estimated blood loss was significantly higher in CL compared with RAL (p = 0.02), whereas hospital stay was longer in RAL compared with CL (p = 0.02). We did not find significant difference for all the other parameters, including operative time, intra- and postoperative complication rate, and number of lymph nodes excised. Based on our data analysis, both CL and RAL are valid options for para-aortic staging lymphadenectomy in locally advanced cervical cancer.
Surgical Management after Chiari Decompression Failure: Craniovertebral Junction Revision versus Shunting Strategies
Authors: Knafo Steven , Malcoci Mihai , Morar Silvia , Parker Fabrice , Aghakhani Nozar
Published: June 2022

Revision surgery after posterior fossa decompression for Chiari malformation is not uncommon and poses both strategic and technical challenges. We conducted a single-center retrospective cohort study including all adult patients who underwent revision surgery after posterior fossa decompression for Chiari type I malformation between 2010 and 2019. Among 311 consecutive patients operated on for Chiari malformation at our institution, 35 patients had a least one revision surgery with a mean follow-up of 70.2 months. Mean delay for revision was 28.8 months. First revision surgery was performed at the level of the foramen magnum in 25/35 cases and consisted in duraplasty revision in all cases, arachnolysis (51.4%), additional bone decompression (37.1%), tonsillar coagulation or resection (25.7%), 4th ventricle to cervical subarachnoid spaces shunt (5.7%). Most repeat revisions consisted in CSF diversion procedures, with either ventriculo-peritoneal or syringo-peritoneal shunts. Mean number of interventions per patient was 3.2, with 22.9% of patients undergoing 4 or more surgeries. Based on our experience, we propose that revision at the level of the foramen magnum should be considered as a first-line strategy for Chiari decompression failure. Shunting procedures can be performed in case of extensive arachnoiditis or repeated failures.
The Need for a Specialized Neurocognitive Screen and Consistent Cognitive Impairment Criteria in Spinal Cord Injury: Analysis of the Suitability of the Neuropsychiatry Unit Cognitive Assessment Tool
Authors: Sandalic Danielle , Tran Yvonne , Craig Ashley , Arora Mohit , Pozzato Ilaria , Simpson Grahame , Gopinath Bamini , Kaur Jasbeer , Shetty Sachin , Weber Gerard , Benad Lisa , Middleton James
Published: June 2022

The assessment of mild cognitive impairment (MCI) following spinal cord injury (SCI) is vital. However, there are no neurocognitive screens which have been developed specifically to meet the unique requirements for SCI, nor are there consistent MCI criteria applied to determine the rates of MCI. The aim of this study was to determine the suitability of a neurocognitive screen for assessing MCI in adults with SCI. A total of 127 participants were recruited. Socio-demographic and injury related variables were assessed. All participants completed the screen. Descriptive statistics are provided for total/domain screen scores and all items, and the screen’s ability to distinguish MCI was examined. Congeneric confirmatory factor analyses (CFA) were employed to investigate structural validity. The screen total score was sensitive to differences in neurocognitive capacity, as well as for time since the injury occurred (p < 0.01). The MCI rate ranged between 17–36%. CFA revealed attention and visuoconstruction domains had an adequate model fit and executive function had poor fit, while CFA models for memory and language did not fit the data (did not converge), hence could not be determined. While the screen differentiated between those with MCI and those without, and MCI as a function of time since injury, limitations of its suitability for assessing MCI after SCI exist, demonstrating the need for a specialized neurocognitive screen for adults with SCI.
Proton Generation Using Chitin–Chitinase and Collagen–Collagenase Composites
Authors: Semizo Hitoki , Yabu Ryusei , Matsuo Yasumitsu
Published: June 2022

Hydrogen energy is focused on as next-generation energy without environmental load. Therefore, hydrogen production without using fossil fuels is a key factor in the progress of hydrogen energy. In the present work, it was found that chitin–chitinase and collagen–collagenase composites can generate protons by the hydrolysis of the enzyme. The concentration of the generated proton in the chitin–chitinase and collagen–collagenase composites are 1.68 × 1017 cm−3 and 1.02 × 1017 cm−3, respectively. Accompanying these results, proton diffusion constants in the chitin and collagen membranes are also estimated to be 8.59 × 10−8 cm2/s and 8.69 × 10−8 cm2/s, respectively. Furthermore, we have fabricated the bio-fuel cell using these composites as hydrogen fuel and demonstrated that these composites become a fuel of the fuel cell.