bluuebunny/crossref_metadata_2025 huggingface dataset:
Lumbar Spinal Stenosis Treatment: Is Surgery Better than Non-Surgical Treatments in Afro-Descendant Populations?
Authors: Louis-Sidney Fabienne , Duby Jean-Florent , Signate Aïssatou , Arfi Serge , De Bandt Michel , Suzon Benoit , Cabre Philippe
Published: December 2022

(1) Background: Limited data are available on lumbar spine stenosis management in sub-Saharan African populations and Afro-descendant patients are underrepresented in European and US clinical trials. We aimed to compare the clinical response between decompressive surgery and conservative treatments in a population of self-reported Afro-Caribbean patients with lumbar spine stenosis over a 2-year follow-up period. (2) Methods: Prospective cohort of 137 self-reported Afro Caribbeans with lumbar spine stenosis based on clinical and radiological criteria. Patients were assigned to decompression surgery or to conservative treatments according to their outcome after a first course of steroid epidural injection and their preferences. The primary outcome was evolution of the Oswestry disability index at 3 months (3 M), 12 M, 18 M and 24 M follow-up. (3) Results: Decrease of ODI was significantly more important in the “decompression surgery” arm compared to “conservative treatment” arm at 3 M, 12 M and 18 M: −17.36 vs. 1.03 p < 10−4; −16.38 vs. −1.53 p = 0.0059 and −19.00 vs. −4.52 p = 0.021, respectively. No difference was reported at 24 M. (4) Conclusions: In this first comparative study between surgery and conservative treatments in an exclusively afro-descendant lumbar spine stenosis cohort, we report long term superiority of decompression surgery versus conservative treatments over an 18-month period.
Hyperbaric Oxygen Therapy and Tissue Regeneration: A Literature Survey
Authors: Lindenmann J. , Kamolz L. , Graier W. , Smolle J. , Smolle-Juettner F.-M.
Published: December 2022

By addressing the mechanisms involved in transcription, signaling, stress reaction, apoptosis and cell-death, cellular structure and cell-to-cell contacts, adhesion, migration as well as inflammation; HBO upregulates processes involved in repair while mechanisms perpetuating tissue damage are downregulated. Many experimental and clinical studies, respectively, cover wound healing, regeneration of neural tissue, of bone and cartilage, muscle, and cardiac tissue as well as intestinal barrier function. Following acute injury or in chronic healing problems HBO modulates proteins or molecules involved in inflammation, apoptosis, cell growth, neuro- and angiogenesis, scaffolding, perfusion, vascularization, and stem-cell mobilization, initiating repair by a variety of mechanisms, some of them based on the modulation of micro-RNAs. HBO affects the oxidative stress response via nuclear factor erythroid 2-related factor 2 (Nrf2) or c-Jun N-terminal peptide and downregulates inflammation by the modulation of high-mobility group protein B1 (HMGB-1), toll-like receptor 4 and 2 (TLR-4, TLR-2), nuclear factor kappa-B (NFκB), hypoxia-inducible factor (HIF-1α) and nitric oxide (NO•). HBO enhances stem-cell homeostasis via Wnt glycoproteins and mammalian target of rapamycin (mTOR) and improves cell repair, growth, and differentiation via the two latter but also by modulation of extracellular-signal regulated kinases (ERK) and the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway. The HBO-induced downregulation of matrix metalloproteinases-2 and 9 (MMP-2/-9), rho-associated protein kinase (ROCK) and integrins improve healing by tissue remodeling. Interestingly, the action of HBO on single effector proteins or molecules may involve both up- or downregulation, respectively, depending on their initial level. This probably mirrors a generally stabilizing potential of HBO that tends to restore the physiological balance rather than enhancing or counteracting single mechanisms.
Reliable and Fast Genotyping Protocol for Galactosylceramidase (Galc) in the Twitcher (Twi) Mouse
Authors: Carpi Sara , Del Grosso Ambra , De Sarlo Miriam , Colagiorgio Laura , Scaccini Luca , Tonazzini Ilaria , Parlanti Gabriele , Cecchini Marco
Published: December 2022

Twitcher (Twi) is a neurological Krabbe disease (KD, or globoid cell leukodystrophy) spontaneous mutant line in mice. The genome of the Twi mouse presents a single nucleotide polymorphism (SNP), leading to an enzymatically inactive galactosylceramidase (Galc) protein that causes KD. In this context, mouse Twi genotyping is an essential step in KD research. To date, the genotyping method used is labor-intensive and often has ambiguous results. Here, we evaluated a novel protocol for the genotype determination of Galc mutation status in Twi mice based on the allele-discrimination real-time polymerase chain reaction (PCR). Here, DNA is extracted from Twi mice (n = 20, pilot study; n = 120, verification study) and control group (n = 10, pilot study; n = 30 verification study) and assessed by allele-discrimination real-time PCR to detect SNP c.355G>A. Using the allele-discrimination PCR, all of the samples are identified correctly with the genotype GG (wild-type, WT), GA (heterozygote, HET), or AA (homozygote, HOM) using the first analysis and no animals are not genotyped. We demonstrated that this novel method can be used to distinguish KD timely, accurately, and without ambiguity in HOM, WT, and HET animals. This protocol represents a great opportunity to increase accuracy and speed in KD research.
Large-Scale Functional Assessment of Genes Involved in Rare Diseases with Intellectual Disabilities Unravels Unique Developmental and Behaviour Profiles in Mouse Models
Authors: Meziane Hamid , Birling Marie-Christine , Wendling Olivia , Leblanc Sophie , Dubos Aline , Selloum Mohammed , Pavlovic Guillaume , Sorg Tania , Kalscheuer Vera M. , Billuart Pierre , Laumonnier Frédéric , Chelly Jamel , van Bokhoven Hans , Herault Yann
Published: December 2022

Major progress has been made over the last decade in identifying novel genes involved in neurodevelopmental disorders, although the task of elucidating their corresponding molecular and pathophysiological mechanisms, which are an essential prerequisite for developing therapies, has fallen far behind. We selected 45 genes for intellectual disabilities to generate and characterize mouse models. Thirty-nine of them were based on the frequency of pathogenic variants in patients and literature reports, with several corresponding to de novo variants, and six other candidate genes. We used an extensive screen covering the development and adult stages, focusing specifically on behaviour and cognition to assess a wide range of functions and their pathologies, ranging from basic neurological reflexes to cognitive abilities. A heatmap of behaviour phenotypes was established, together with the results of selected mutants. Overall, three main classes of mutant lines were identified based on activity phenotypes, with which other motor or cognitive deficits were associated. These data showed the heterogeneity of phenotypes between mutation types, recapitulating several human features, and emphasizing the importance of such systematic approaches for both deciphering genetic etiological causes of ID and autism spectrum disorders, and for building appropriate therapeutic strategies.
Key Challenges in Diamond Coating of Titanium Implants: Current Status and Future Prospects
Authors: Terranova Maria Letizia
Published: December 2022

Over past years, the fabrication of Ti-based permanent implants for fracture fixation, joint replacement and bone or tooth substitution, has become a routine task. However, it has been found that some degradation phenomena occurring on the Ti surface limits the life or the efficiency of the artificial constructs. The task of avoiding such adverse effects, to prevent microbial colonization and to accelerate osteointegration, is being faced by a variety of approaches in order to adapt Ti surfaces to the needs of osseous tissues. Among the large set of biocompatible materials proposed as an interface between Ti and the hosting tissue, diamond has been proven to offer bioactive and mechanical properties able to match the specific requirements of osteoblasts. Advances in material science and implant engineering are now enabling us to produce micro- or nano-crystalline diamond coatings on a variety of differently shaped Ti constructs. The aim of this paper is to provide an overview of the research currently ongoing in the field of diamond-coated orthopedic Ti implants and to examine the evolution of the concepts that are accelerating the full transition of such technology from the laboratory to clinical applications.
Endothelial Damage and the Microcirculation in Critical Illness
Authors: Cusack Rachael , Leone Marc , Rodriguez Alejandro H. , Martin-Loeches Ignacio
Published: December 2022

Endothelial integrity maintains microcirculatory flow and tissue oxygen delivery. The endothelial glycocalyx is involved in cell signalling, coagulation and inflammation. Our ability to treat critically ill and septic patients effectively is determined by understanding the underpinning biological mechanisms. Many mechanisms govern the development of sepsis and many large trials for new treatments have failed to show a benefit. Endothelial dysfunction is possibly one of these biological mechanisms. Glycocalyx damage is measured biochemically. Novel microscopy techniques now mean the glycocalyx can be indirectly visualised, using sidestream dark field imaging. How the clinical visualisation of microcirculation changes relate to biochemical laboratory measurements of glycocalyx damage is not clear. This article reviews the evidence for a relationship between clinically evaluable microcirculation and biological signal of glycocalyx disruption in various diseases in ICU. Microcirculation changes relate to biochemical evidence of glycocalyx damage in some disease states, but results are highly variable. Better understanding and larger studies of this relationship could improve phenotyping and personalised medicine in the future. Damage to the glycocalyx could underpin many critical illness pathologies and having real-time information on the glycocalyx and microcirculation in the future could improve patient stratification, diagnosis and treatment.
Associations of Betatrophin/ANGPTL8 with Septic Dyslipidemia in Human Peritonitis: An Explorative Analysis
Authors: Horn Paul , Radtke Sascha , Metzing Uta Barbara , Steidl Ricardo , Sponholz Christoph , Sommerfeld Oliver , Roth Johannes , Claus Ralf A. , Birkenfeld Andreas L. , Settmacher Utz , Rauchfuß Falk , von Loeffelholz Christian
Published: December 2022

Sepsis is defined by life-threatening organ dysfunction mediated by the host’s response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p < 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p < 0.05).
HCV Infection and Liver Cirrhosis Are Associated with a Less-Favorable Serum Cholesteryl Ester Profile Which Improves through the Successful Treatment of HCV
Authors: Weigand Kilian , Peschel Georg , Grimm Jonathan , Müller Martina , Höring Marcus , Krautbauer Sabrina , Liebisch Gerhard , Buechler Christa
Published: December 2022

Background: Infection with hepatitis C virus (HCV) lowers serum cholesterol levels, which rapidly recover during therapy with direct-acting antivirals (DAAs). Serum cholesterol is also reduced in patients with liver cirrhosis. Studies investigating serum cholesterol in patients with chronic liver diseases are generally based on enzymatic assays providing total cholesterol levels. Hence, these studies do not account for the individual cholesteryl ester (CE) species, which have different properties according to acyl chain length and desaturation. Methods: Free cholesterol (FC) and 15 CE species were quantified by flow injection analysis high-resolution Fourier Transform mass spectrometry (FIA-FTMS) in the serum of 178 patients with chronic HCV before therapy and during treatment with DAAs. Results: Serum CEs were low in HCV patients with liver cirrhosis and, compared to patients without cirrhosis, proportions of CE 16:0 and 16:1 were higher whereas % CE 20:4 and 20:5 were reduced. FC levels were unchanged, and the CE/FC ratio was consequently low in cirrhosis. FC and CEs did not correlate with viral load. Four CE species were reduced in genotype 3 compared to genotype 1-infected patients. During DAA therapy, 9 of the 15 measured CE species, and the CE/FC ratio, increased. Relative to total CE levels, % CE 16:0 declined and % CE 18:3 was higher at therapy end. At this time, % CE 14:0, 16:0 and 16:1 were higher and % CE 20:4 and 22:6 were lower in the cirrhosis than the non-cirrhosis patients. Viral genotype associated changes of CEs disappeared at therapy end. Conclusions: The serum CE composition differs between patients with and without liver cirrhosis, and changes through the efficient elimination of HCV. Overall, HCV infection and cirrhosis are associated with a higher proportion of CE species with a lower number of carbon atoms and double bonds, reflecting a less-favorable CE profile.
Accuracy and Clinical Impact of Estimating Low-Density Lipoprotein-Cholesterol at High and Low Levels by Different Equations
Authors: Sampson Maureen , Wolska Anna , Cole Justine , Zubirán Rafael , Otvos James D. , Meeusen Jeff W. , Donato Leslie J. , Jaffe Allan S. , Remaley Alan T.
Published: December 2022

New more effective lipid-lowering therapies have made it important to accurately determine Low-density lipoprotein-cholesterol (LDL-C) at both high and low levels. LDL-C was measured by the β-quantification reference method (BQ) (N = 40,346) and compared to Friedewald (F-LDL-C), Martin (M-LDL-C), extended Martin (eM-LDL-C) and Sampson (S-LDL-C) equations by regression analysis, error-grid analysis, and concordance with the BQ method for classification into different LDL-C treatment intervals. For triglycerides (TG) < 175 mg/dL, the four LDL-C equations yielded similarly accurate results, but for TG between 175 and 800 mg/dL, the S-LDL-C equation when compared to the BQ method had a lower mean absolute difference (mg/dL) (MAD = 10.66) than F-LDL-C (MAD = 13.09), M-LDL-C (MAD = 13.16) or eM-LDL-C (MAD = 12.70) equations. By error-grid analysis, the S-LDL-C equation for TG > 400 mg/dL not only had the least analytical errors but also the lowest frequency of clinically relevant errors at the low (<70 mg/dL) and high (>190 mg/dL) LDL-C cut-points (S-LDL-C: 13.5%, F-LDL-C: 23.0%, M-LDL-C: 20.5%) and eM-LDL-C: 20.0%) equations. The S-LDL-C equation also had the best overall concordance to the BQ reference method for classifying patients into different LDL-C treatment intervals. The S-LDL-C equation is both more analytically accurate than alternative equations and results in less clinically relevant errors at high and low LDL-C levels.
A Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair
Authors: Dhasmana Archna , Malik Sumira , Ranjan Anuj , Chauhan Abhishek , Tashkandi Hanaa M. , Haque Shafiul , Al-Raddadi Rajaa , Harakeh Steve , Zengin Gökhan
Published: December 2022

Phytochemicals extracted from plant sources have potential remedial effects to cure a broad range of acute to severe illnesses and ailments. Quercetin is a flavonoid isolated from different dietary sources such as vegetables and fruits, exhibiting strong anti-inflammatory, anti-oxidative and non-toxic effects on the biological system. However, the direct uptake or administration of quercetin results in loss of functionality, poor activity, and reduced shelf-life of the bioactive component. In this regard, to improve the uptake, potential, and efficiency of natural components with prolonged storage in the host’s body after administration, numerous polymer drug delivery systems have been created. In the current study, three-dimensional (3D) porous (porosity: 92%; pore size: 81 µm) bio-polymeric foaming gelatin–alginate (GA) beads were fabricated for the entrapment of quercetin as therapeutic drug molecules—gelatin–alginate–quercetin (GAQ). The GAQ beads showed a significant uptake of quercetin molecules resulting in a reduction of reduced porosity up to 64% and pore size 63 µm with a controlled release profile in the PBS medium, showing ~80% release within 24 h. Subsequently, the GAQ beads showed remarkable antioxidant effects, and 95% anti-inflammatory activities along with remarkable in vitro cell culture growth and the observed proliferation of seeded fibroblast cells. Thus, we can conclude that the consistent release of quercetin showed non-toxic effects on normal cell lines and the bioactive surface of the GAQ beads enhances cell adhesion, proliferation, and differentiation more effectively than control GA polymeric beads and tissue culture plates (TCP). In summary, these findings show that these GAQ beads act as a biocompatible 3D construct with enormous potential in medicinal administration and tissue regeneration for accelerated healing.
Harnessing the Power of Mucosal-Associated Invariant T (MAIT) Cells in Cancer Cell Therapy
Authors: Sugimoto Chie , Fujita Hiroyoshi , Wakao Hiroshi
Published: December 2022

Mucosal-associated invariant T (MAIT) cells, a burgeoning type of the innate-like T cells, play a crucial role in maintaining immune homeostasis, particularly in host defense. Although many studies have implied the use of MAIT cells in tumor immunity, whether MAIT cells are pro-tumor or anti-tumor has remained elusive, as in the case for other innate-like T cells that possess dichotomous roles in tumor immunity. Although this difficulty persists where endogenous MAIT cells are the target for therapeutic intervention, the advent of induced pluripotent stem-cell-derived MAIT cells (reMAIT cells) will make it possible to harness these cells for immune cell therapy. In this review, we will discuss possible roles of MAIT cells in tumor immunity and the potential of reMAIT cells to treat tumors.
CpG Site-Based Signature Predicts Survival of Colorectal Cancer
Authors: Wu Jiande , Zhang Lu , Kuchi Aditi , Otohinoyi David , Hicks Chindo
Published: December 2022

Background: A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC. Methods: We analyzed DNA methylation patterns between tumor and control samples to discover signatures of CpG sites and genes associated with CRC and predictive of survival. We conducted functional analysis to identify molecular networks and signaling pathways driving clinical outcomes. Results: We discovered a signature of aberrantly methylated genes associated with CRC and a signature of thirteen (13) CpG sites predictive of survival. We discovered molecular networks and signaling pathways enriched for CpG sites likely to drive clinical outcomes. Conclusions: The investigation revealed that CpG sites can predict survival in CRC and that DNA methylation can capture the regulatory state of tumors through aberrantly methylated molecular networks and signaling pathways.
Acute Kidney Injury after Endoscopic Retrograde Cholangiopancreatography—A Hospital-Based Prospective Observational Study
Authors: Gadalean Florica , Parv Florina , Milas Oana , Petrica Ligia , Ratiu Iulia , Miutescu Bogdan , Goldis Adrian , Gluhovschi Cristina , Bob Flaviu , Simulescu Anca , Patruica Mihaela , Apostol Adrian , Ivan Viviana , Schiller Adalbert , Radu Daniela
Published: December 2022

Background: Endoscopic retrograde cholangiopancreatography (ERCP) represents a major pivotal point in gastrointestinal endoscopy. Little is known about acute kidney injury (AKI) post-ERCP. This study analyses the incidence, risk factors, and prognosis of post-ERCP AKI. Methods: A total of 396 patients were prospectively studied. AKI was defined by an increase in serum creatinine (SCr) ≥ 0.3 mg/dL or by an increase in SCr ≥ 50% in the first 48 h post-ERCP. Logistic regression analysis was used to identify the predictors of AKI and in-hospital mortality. A two-tailed p value < 0.05 was considered significant. Results: One hundred and three patients (26%) developed post-ERCP AKI. Estimated glomerular filtration rate (adjusted odds ratio (aOR) = 0.95, 95% confidence interval (CI): 0.94–0.96, p < 0.001), nonrenal Charlson Comorbidity Index (Aor = 1.19, 95% CI: 1.05–1.35, p = 0.006), choledocholithiasis (aOR = 4.05, 95% CI: 1.98–8.29, p < 0.001), and bilirubin (aOR = 1.1, 95% CI: 1.05–1.15, p < 0.001) were associated with post-ERCP AKI. Post-ERCP AKI was associated with longer hospital stay (p < 0.001) and with increased in-hospital mortality (7.76% versus 0.36%, p < 0.001). Moderate-to-severe (stage 2 and 3) AKI was independently associated with in-hospital mortality (aOR = 6.43, 95% CI: 1.48–27.88, p < 0.013). Conclusions: Post-ERCP AKI represented an important complication associated with longer hospital stay. Moderate-to-severe post-ERCP AKI was an independent risk factor for in-hospital mortality.
Biomimetic Approaches in Clinical Endodontics
Authors: Kumar Naresh , Maher Nazrah , Amin Faiza , Ghabbani Hani , Zafar Muhammad Sohail , Rodríguez-Lozano Francisco Javier , Oñate-Sánchez Ricardo E.
Published: December 2022

In the last few decades, biomimetic concepts have been widely adopted in various biomedical fields, including clinical dentistry. Endodontics is an important sub-branch of dentistry which deals with the different conditions of pulp to prevent tooth loss. Traditionally, common procedures, namely pulp capping, root canal treatment, apexification, and apexigonesis, have been considered for the treatment of different pulp conditions using selected materials. However, clinically to regenerate dental pulp, tissue engineering has been advocated as a feasible approach. Currently, new trends are emerging in terms of regenerative endodontics which have led to the replacement of diseased and non-vital teeth into the functional and healthy dentine-pulp complex. Root- canal therapy is the standard management option when dental pulp is damaged irreversibly. This treatment modality involves soft-tissue removal and then filling that gap through the obturation technique with a synthetic material. The formation of tubular dentine and pulp-like tissue formation occurs when stem cells are transplanted into the root canal with an appropriate scaffold material. To sum up tissue engineering approach includes three components: (1) scaffold, (2) differentiation, growth, and factors, and (3) the recruitment of stem cells within the pulp or from the periapical region. The aim of this paper is to thoroughly review and discuss various pulp-regenerative approaches and materials used in regenerative endodontics which may highlight the current trends and future research prospects in this particular area.
A Systematic Review of Virtual Reality and Robot Therapy as Recent Rehabilitation Technologies Using EEG-Brain–Computer Interface Based on Movement-Related Cortical Potentials
Authors: Said Ramadhan Rashid , Heyat Md Belal Bin , Song Keer , Tian Chao , Wu Zhe
Published: December 2022

To enhance the treatment of motor function impairment, patients’ brain signals for self-control as an external tool may be an extraordinarily hopeful option. For the past 10 years, researchers and clinicians in the brain–computer interface (BCI) field have been using movement-related cortical potential (MRCP) as a control signal in neurorehabilitation applications to induce plasticity by monitoring the intention of action and feedback. Here, we reviewed the research on robot therapy (RT) and virtual reality (VR)-MRCP-based BCI rehabilitation technologies as recent advancements in human healthcare. A list of 18 full-text studies suitable for qualitative review out of 322 articles published between 2000 and 2022 was identified based on inclusion and exclusion criteria. We used PRISMA guidelines for the systematic review, while the PEDro scale was used for quality evaluation. Bibliometric analysis was conducted using the VOSviewer software to identify the relationship and trends of key items. In this review, 4 studies used VR-MRCP, while 14 used RT-MRCP-based BCI neurorehabilitation approaches. The total number of subjects in all identified studies was 107, whereby 4.375 ± 6.3627 were patient subjects and 6.5455 ± 3.0855 were healthy subjects. The type of electrodes, the epoch, classifiers, and the performance information that are being used in the RT- and VR-MRCP-based BCI rehabilitation application are provided in this review. Furthermore, this review also describes the challenges facing this field, solutions, and future directions of these smart human health rehabilitation technologies. By key items relationship and trends analysis, we found that motor control, rehabilitation, and upper limb are important key items in the MRCP-based BCI field. Despite the potential of these rehabilitation technologies, there is a great scarcity of literature related to RT and VR-MRCP-based BCI. However, the information on these rehabilitation methods can be beneficial in developing RT and VR-MRCP-based BCI rehabilitation devices to induce brain plasticity and restore motor impairment. Therefore, this review will provide the basis and references of the MRCP-based BCI used in rehabilitation applications for further clinical and research development.
Bioprinting on Organ-on-Chip: Development and Applications
Authors: Chliara Maria Anna , Elezoglou Stavroula , Zergioti Ioanna
Published: December 2022

Organs-on-chips (OoCs) are microfluidic devices that contain bioengineered tissues or parts of natural tissues or organs and can mimic the crucial structures and functions of living organisms. They are designed to control and maintain the cell- and tissue-specific microenvironment while also providing detailed feedback about the activities that are taking place. Bioprinting is an emerging technology for constructing artificial tissues or organ constructs by combining state-of-the-art 3D printing methods with biomaterials. The utilization of 3D bioprinting and cells patterning in OoC technologies reinforces the creation of more complex structures that can imitate the functions of a living organism in a more precise way. Here, we summarize the current 3D bioprinting techniques and we focus on the advantages of 3D bioprinting compared to traditional cell seeding in addition to the methods, materials, and applications of 3D bioprinting in the development of OoC microsystems.
Application of Au@Pt Nanozyme as Enhancing Label for the Sensitive Lateral Flow Immunoassay of Okadaic Acid
Authors: Hendrickson Olga D. , Zvereva Elena A. , Panferov Vasily G. , Solopova Olga N. , Zherdev Anatoly V. , Sveshnikov Peter G. , Dzantiev Boris B.
Published: December 2022

In this study, a lateral flow immunoassay (LFIA) was developed to detect okadaic acid (OA) belonging to the diarrheic shellfish poisoning group of aquatic toxins. Newly obtained anti-OA monoclonal antibodies and bimetallic core@shell Au@Pt nanoparticles were used in the indirect format of the LFIA. Peroxidase-mimicking nanozyme properties of Au@Pt enabled using them to enhance band coloration on the test strips and, consequently, for increasing the LFIA sensitivity. The instrumental limit of detection (LOD), the working range of detectable concentrations, and the visual cutoff of the assay were 0.5, 0.8–6.8, and 10 ng/mL, respectively. The assay duration was 20 min. The rapid and simple sample preparation procedure was applied for seawater, river water, and fish samples. The total duration of the sample pretreatment and LFIA was 25/40 min for water/fish samples, ensuring testing rapidity. The developed test system provides sensitive control of raw materials and food products and can be used to detect OA at all stages of the food industry «from sea to fork» chains.
Innovative Technologies in the Neurorehabilitation of Traumatic Brain Injury: A Systematic Review
Authors: Bonanno Mirjam , De Luca Rosaria , De Nunzio Alessandro Marco , Quartarone Angelo , Calabrò Rocco Salvatore
Published: December 2022

Motor and cognitive rehabilitation in individuals with traumatic brain injury (TBI) is a growing field of clinical and research interest. In fact, novel rehabilitative approaches allow a very early verticalization and gait training through robotic devices and other innovative tools boosting neuroplasticity, thanks to the high-intensity, repetitive and task-oriented training. In the same way, cognitive rehabilitation is also evolving towards advanced interventions using virtual reality (VR), computer-based approaches, telerehabilitation and neuromodulation devices. This review aimed to systematically investigate the existing evidence concerning the role of innovative technologies in the motor and cognitive neurorehabilitation of TBI patients. We searched and reviewed the studies published in the Cochrane Library, PEDro, PubMed and Scopus between January 2012 and September 2022. After an accurate screening, only 29 papers were included in this review. This systematic review has demonstrated the beneficial role of innovative technologies when applied to cognitive rehabilitation in patients with TBI, while evidence of their effect on motor rehabilitation in this patient population is poor and still controversial.
Impact of In-Home Repair Services on Physical and Mental Harm among Essential Workers: The Mediating Effect of Fear and Moderating Effect of Types of Employment
Authors: Hwang Jee-Hyun , Jung Hye-Sun
Published: December 2022

This study attempted to establish a hypothetical model describing the severity of physical and mental harm among essential workers during the COVID-19 pandemic. To this end, the mediating effect of fear on the relationship between in-home services and the severity of physical and mental harm was analyzed. Moreover, this study utilized multigroup path analysis to examine differences according to the type of employment. Thus, data from all 502 participants were included in the final analysis. The study found that in-home service did not have a direct effect on fear in the path model for the permanent employment group, but did have a direct effect on fear in the path model for the non-permanent employment group. The implications for the field are that the following is required: an anti-infection system should be incorporated at workplaces; employment stability should be provided for essential workers; providing systematic support, such as professional counseling to alleviate negative emotional responses, should be considered.
Design of Structural Steel Components According to Manufacturing Possibilities of the Robot-Guided DED-Arc Process
Authors: Müller Christoph , Müller Johanna , Kloft Harald , Hensel Jonas
Published: December 2022

Additive manufacturing with the DED-arc process offers limited freedom in terms of the geometric shape of work pieces. The process and fabrication systems restrict the part geometry producible, which must be taken into account during design already. For this reason, a design process was investigated in which geometry generation is based on a self-organizing system. The aim of using a self-organizing system is the possibility to directly control the geometry-defining points. Next to load cases, the design method considers geometric boundary conditions from the production process when generating the geometry. In order to identify these geometrical constraints from production experimentally, a concept of Case Study Demonstrators was applied. This was used to investigate how path planning and production can be carried out for specific geometrical features and to identify restraints of the process and the manufacturing system, e.g., smallest producible wall thickness and overhangs. Subsequently, the obtained restraints were considered as boundary conditions for the design process and were included in the modification of an example geometry. By applying the presented design method, it was possible to maintain a minimum wall thickness throughout the structure while generating a topologically optimized geometry. In contrast to compliance with the minimum wall thickness, no satisfactory behavioral rule could be found for limiting the overhang.
Smart Textiles in Building and Living Applications: WG4 CONTEXT Insight on Elderly and Healthcare Environments
Authors: Venturini Degli Esposti Enrico , Bedon Chiara , Jonaitiene Vaida , Kazak Jan K. , Liotta Leonarda Francesca , Priniotakis Georgios , Stachewicz Urszula
Published: December 2022

Over the past 30 years, the development of new technologies and especially of smart textiles has unavoidably led to new applications of traditional textiles in the built environment. Depending on special constructional needs (i.e., acoustic insulation, thermal insulation, shading system, etc.) or health monitoring and supporting needs (i.e., for patients with chronical disease, etc.), an increasing number of possible applications has been proposed to improve human well-being. This is especially the case for healthcare environments (like elderly or nursing homes, etc.), but also educational environments (like schools, etc.) where young or old customers can benefit from technological innovation in several ways. As an ongoing activity of WG4 members for the CA17107 “CONTEXT” European research network, this study presents a review on selected applications for building and living solutions, with special attention to healthcare environments, giving evidence of major outcomes and potentials for smart textiles-based products.
Testing of Diamond Electrodes as Biosensor for Antibody-Based Detection of Immunoglobulin Protein with Electrochemical Impedance Spectroscopy
Authors: Menzler Martin , Ganskow Charity S. G. , Ruschig Maximilian , Moustafa Essam , Sittinger Volker , Lachmann Kristina , Wenzel Esther Veronika , Russo Giulio , Klahn Philipp , Gäbler Jan
Published: December 2022

To control the increasing virus pandemics, virus detection methods are essential. Today’s standard virus detections methods are fast (immune assays) or precise (PCR). A method that is both fast and precise would enable more efficient mitigation measures and better life comfort. According to recent papers, electrochemical impedance spectroscopy (EIS) has proven to detect viruses fast and precise. Boron-doped diamond (BDD) was used as a high-performance electrode material in these works. The aim of this work was to perform an initial test of BDD-based EIS for biosensing. As an easily available standard biomaterial, human immunoglobulin G (IgG) was used as analyte. Niobium plates were coated via hot-filament activated chemical vapor deposition with polycrystalline diamond, and doped with boron for electrical conductivity. An anti-human IgG antibody was immobilised on the BDD electrodes as a biosensing component. Four different analyte concentrations up to 1.1 µg per litre were tested. During EIS measurements, both impedance over frequency curves and Nyquist plot demonstrated no clear sign of a change of the charge transfer resistance. Thus, no positive statement about a successful biosensing could be made so far. It is assumed that these issues need to be investigated and improved, including the relation of BDD electrode size to electrolyte volume, termination of the BDD electrodes (H, O) for a successful functionalisation and EIS frequency range. The work will be continued concerning these improvement issues in order to finally use virus materials as analyte.
The Reporting, Use, and Validity of Patient-Reported Outcomes in Multiple Myeloma in Clinical Trials: A Systematic Literature Review
Authors: Salek Sam , Ionova Tatiana , Oliva Esther Natalie , Andreas Marike , Skoetz Nicole , Kreuzberger Nina , Laane Edward
Published: December 2022

Background: Patient-reported outcomes (PROs) are becoming increasingly important in supporting clinical outcomes in clinical trials. In multiple myeloma (MM), PRO measurement is useful to reveal how treatment affects physical, psychosocial, and functional behaviour as well as symptoms and treatment-related adverse events to evaluate the benefit-risk ratio of a particular drug or drug combination. We report the types of PRO instruments used in MM, the frequency in which they are utilised in randomised controlled trials (RCTs), and the consistency of their reporting. Methods: The European Hematology Association (EHA) supports the development of guidelines for the use of PROs in adult patients with haematological malignancies. The first step is the present systematic review of the literature. MEDLINE and CENTRAL were searched for RCTs in MM between 2015 and 2020. Study design, characteristics of MM and its treatment, the primary outcomes, and the types of PRO instrument(s) were extracted using a predefined template. Additionally, in a stepwise approach, it was assessed whether the identified instruments had been validated for multiple myeloma patients, patients with haematological malignancies, or cancer patients. Results: Following screening for RCTs, 283 studies were included for review from 10,707 records retrieved, and 118 of these planned the use of PRO measures. Thirty-eight PRO instruments were reported. The most frequently used instrument (92 studies) was the EORTC QLQ-30. The EORTC-MY20 MM-specific questionnaire was the second most frequently used (50 studies), together with the EQ-5D (50 studies). Only 19 PRO instruments reported were consistent with the trial registry. Furthermore, in 58 publications, the information on PRO instruments differed between the publication and the trial registry. Further, information on PRO in HTA reports was available for 26 studies, of which 18 reports were consistent with the trial registries. Out of the 38 instruments used, six had been validated for patients with multiple myeloma (the most frequently used), six for patients with haematological malignancies, and 10 for cancer patients in general. Conclusions: The findings indicate that the measurement of PROs in RCTs for MM is underutilised, underreported, and often inconsistent. Guidelines for the appropriate use of PROs in MM are needed to ensure standardisation in selection and reporting. Furthermore, not all PRO instruments identified have been validated for myeloma patients or patients with haematological malignancies. Thus, guidelines for the appropriate use and reporting of PROs are needed in MM to ensure standardisation in the selection and reporting of PROs.
Small Gastric Stromal Tumors: An Underestimated Risk
Authors: Guo Jintao , Ge Qichao , Yang Fan , Wang Sheng , Ge Nan , Liu Xiang , Shi Jing , Fusaroli Pietro , Liu Yang , Sun Siyu
Published: December 2022

Background and Objectives: Small gastrointestinal stromal tumors (GISTs) are defined as tumors less than 2 cm in diameter, which are often found incidentally during gastroscopy. There is controversy regarding the management of small GISTs, and a certain percentage of small GISTs become malignant during follow-up. Previous studies which used Sanger targeted sequencing have shown that the mutation rate of small GISTs is significantly lower than that of large tumors. The aim of this study was to investigate the overall mutational profile of small GISTs, including those of wild-type tumors, using whole-exome sequencing (WES) and Sanger sequencing. Methods: Thirty-six paired small GIST specimens, which were resected by endoscopy, were analyzed by WES. Somatic mutations identified by WES were confirmed by Sanger sequencing. Sanger sequencing was performed in an additional 38 small gastric stromal tumor samples for examining hotspot mutations in KIT, PDGFRA, and BRAF. Results: Somatic C-KIT/PDGFRA mutations accounted for 81% of the mutations, including three novel mutation sites in C-KIT at exon 11, across the entire small gastric stromal tumor cohort (n = 74). In addition, 15% of small GISTs harbored previously undescribed BRAF-V600E hotspot mutations. No significant correlation was observed among the genotype, pathological features, and clinical classification. Conclusions: Our data revealed a high overall mutation rate (~96%) in small GISTs, indicating that genetic alterations are common events in early GIST generation. We also identified a high frequency of oncogenic BRAF-V600E mutations (15%) in small GISTs, which has not been previously reported.
Integrating Pharmacogenomics Data-Driven Computational Drug Prediction with Single-Cell RNAseq to Demonstrate the Efficacy of a NAMPT Inhibitor against Aggressive, Taxane-Resistant, and Stem-like Cells in Lethal Prostate Cancer
Authors: Mazumder Suman , Mitra Ghosh Taraswi , Mukherjee Ujjal K. , Chakravarti Sayak , Amiri Farshad , Waliagha Razan S. , Hemmati Farnaz , Mistriotis Panagiotis , Ahmed Salsabil , Elhussin Isra , Salam Ahmad-Bin , Dean-Colomb Windy , Yates Clayton , Arnold Robert D. , Mitra Amit K.
Published: December 2022

Metastatic prostate cancer/PCa is the second leading cause of cancer deaths in US men. Most early-stage PCa are dependent on overexpression of the androgen receptor (AR) and, therefore, androgen deprivation therapies/ADT-sensitive. However, eventual resistance to standard medical castration (AR-inhibitors) and secondary chemotherapies (taxanes) is nearly universal. Further, the presence of cancer stem-like cells (EMT/epithelial-to-mesenchymal transdifferentiation) and neuroendocrine PCa (NEPC) subtypes significantly contribute to aggressive/lethal/advanced variants of PCa (AVPC). In this study, we introduced a pharmacogenomics data-driven optimization-regularization-based computational prediction algorithm (“secDrugs”) to predict novel drugs against lethal PCa. Integrating secDrug with single-cell RNA-sequencing/scRNAseq as a ‘Double-Hit’ drug screening tool, we demonstrated that single-cells representing drug-resistant and stem-cell-like cells showed high expression of the NAMPT pathway genes, indicating potential efficacy of the secDrug FK866 which targets NAMPT. Next, using several cell-based assays, we showed substantial impact of FK866 on clinically advanced PCa as a single agent and in combination with taxanes or AR-inhibitors. Bulk-RNAseq and scRNAseq revealed that, in addition to NAMPT inhibition, FK866 regulates tumor metastasis, cell migration, invasion, DNA repair machinery, redox homeostasis, autophagy, as well as cancer stemness–related genes, HES1 and CD44. Further, we combined a microfluidic chip-based cell migration assay with a traditional cell migration/‘scratch’ assay and demonstrated that FK866 reduces cancer cell invasion and motility, indicating abrogation of metastasis. Finally, using PCa patient datasets, we showed that FK866 is potentially capable of reversing the expression of several genes associated with biochemical recurrence, including IFITM3 and LTB4R. Thus, using FK866 as a proof-of-concept candidate for drug repurposing, we introduced a novel, universally applicable preclinical drug development pipeline to circumvent subclonal aggressiveness, drug resistance, and stemness in lethal PCa.
Clinical Potential of Circulating Cell-Free DNA (cfDNA) for Longitudinally Monitoring Clinical Outcomes in the First-Line Setting of Non-Small-Cell Lung Cancer (NSCLC): A Real-World Prospective Study
Authors: Gristina Valerio , Barraco Nadia , La Mantia Maria , Castellana Luisa , Insalaco Lavinia , Bono Marco , Perez Alessandro , Sardo Delia , Inguglia Sara , Iacono Federica , Cutaia Sofia , Bazan Russo Tancredi Didier , Francini Edoardo , Incorvaia Lorena , Badalamenti Giuseppe , Russo Antonio , Galvano Antonio , Bazan Viviana
Published: December 2022

Background: Despite the increasing implementation of targeted and immunotherapy-based treatments, the prognosis of patients with advanced NSCLC remains dismal. We prospectively evaluated longitudinal plasma cfDNA kinetics as an early marker of therapeutic efficacy in patients with advanced NSCLC undergoing standard first-line treatments. Methods: From February 2020 to May 2022, treatment-naïve patients with advanced NSCLC were consecutively enrolled at the Medical Oncology Unit of the Paolo Giaccone University Hospital, Palermo (Italy). We quantified cfDNA in terms of ng/μL using a QubitTM dsDNA HS Assay Kit. The agreement between the cfDNA and radiologic response was evaluated from baseline (T0) to the radiologic evaluation (T1). Results: A total of 315 liquid biopsy samples were collected from 63 patients at baseline, with a total of 235 paired plasma samples from 47 patients at disease re-evaluation. A fair concordance was observed between early and durable radiographic and cfDNA response (Cohen’s kappa coefficient = 0.001); 11 and 18 patients receiving TKI (Pearson’s chi-squared test = 4.278; Cohen’s kappa coefficient = 0.039) and IO treatments (Pearson’s chi-squared test = 7.481; Cohen’s kappa coefficient = 0.006) showed a significant and durable association between cfDNA dynamics and the first radiologic evaluation, whereas among the 18 patients undergoing CT, no significant correlation was observed (Pearson’s chi-squared test = 0.720; Cohen’s kappa coefficient = 0.396). The ECOG-PS 2 patients presented with the mean baseline cfDNA levels 2.6-fold higher than those with ECOG-PS 0–1 (1.71 vs. 0.65 ng/µL; p = 0.105). Conclusions: Our real-world study demonstrates that quantitative changes in cfDNA values correlated with responses to therapy and relapse of disease in treatment-naïve patients with advanced NSCLC undergoing TKI- and IO-based treatments.