bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteins and Transcriptional Dysregulation of the Brain Extracellular Matrix in Parkinson’s Disease: A Systematic Review
Authors: Rike Wote Amelo , Stern Shani
Published: April 2023

The extracellular matrix (ECM) of the brain is a dynamic structure made up of a vast network of bioactive macromolecules that modulate cellular events. Structural, organizational, and functional changes in these macromolecules due to genetic variation or environmental stressors are thought to affect cellular functions and may result in disease. However, most mechanistic studies to date usually focus on the cellular aspects of diseases and pay less attention to the relevance of the processes governing the dynamic nature of the extracellular matrix in disease pathogenesis. Thus, due to the ECM’s diversified biological roles, increasing interest in its involvement in disease, and the lack of sufficient compiled evidence regarding its relationship with Parkinson’s disease (PD) pathology, we aimed to compile the existing evidence to boost the current knowledge on the area and provide refined guidance for the future research. Here, in this review, we gathered postmortem brain tissue and induced pluripotent stem cell (iPSC)-related studies from PubMed and Google Scholar to identify, summarize and describe common macromolecular alterations in the expression of brain ECM components in Parkinson’s disease (PD). A literature search was conducted up until 10 February 2023. The overall hits from the database and manual search for proteomic and transcriptome studies were 1243 and 1041 articles, respectively. Following a full-text review, 10 articles from proteomic and 24 from transcriptomic studies were found to be eligible for inclusion. According to proteomic studies, proteins such as collagens, fibronectin, annexins, and tenascins were recognized to be differentially expressed in Parkinson’s disease. Transcriptomic studies displayed dysregulated pathways including ECM–receptor interaction, focal adhesion, and cell adhesion molecules in Parkinson’s disease. A limited number of relevant studies were accessed from our search, indicating that much work remains to be carried out to better understand the roles of the ECM in neurodegeneration and Parkinson’s disease. However, we believe that our review will elicit focused primary studies and thus support the ongoing efforts of the discovery and development of diagnostic biomarkers as well as therapeutic agents for Parkinson’s disease.
Unravelling the Impact of Cyclic Mechanical Stretch in Keratoconus—A Transcriptomic Profiling Study
Authors: Akoto Theresa , Cai Jingwen , Nicholas Sarah , McCord Hayden , Estes Amy J. , Xu Hongyan , Karamichos Dimitrios , Liu Yutao
Published: April 2023

Biomechanical and molecular stresses may contribute to the pathogenesis of keratoconus (KC). We aimed to profile the transcriptomic changes in healthy primary human corneal (HCF) and KC-derived cells (HKC) combined with TGFβ1 treatment and cyclic mechanical stretch (CMS), mimicking the pathophysiological condition in KC. HCFs (n = 4) and HKCs (n = 4) were cultured in flexible-bottom collagen-coated 6-well plates treated with 0, 5, and 10 ng/mL of TGFβ1 with or without 15% CMS (1 cycle/s, 24 h) using a computer-controlled Flexcell FX-6000T Tension system. We used stranded total RNA-Seq to profile expression changes in 48 HCF/HKC samples (100 bp PE, 70–90 million reads per sample), followed by bioinformatics analysis using an established pipeline with Partek Flow software. A multi-factor ANOVA model, including KC, TGFβ1 treatment, and CMS, was used to identify differentially expressed genes (DEGs, |fold change| ≥ 1.5, FDR ≤ 0.1, CPM ≥ 10 in ≥1 sample) in HKCs (n = 24) vs. HCFs (n = 24) and those responsive to TGFβ1 and/or CMS. PANTHER classification system and the DAVID bioinformatics resources were used to identify significantly enriched pathways (FDR ≤ 0.05). Using multi-factorial ANOVA analyses, 479 DEGs were identified in HKCs vs. HCFs including TGFβ1 treatment and CMS as cofactors. Among these DEGs, 199 KC-altered genes were responsive to TGFβ1, thirteen were responsive to CMS, and six were responsive to TGFβ1 and CMS. Pathway analyses using PANTHER and DAVID indicated the enrichment of genes involved in numerous KC-relevant functions, including but not limited to degradation of extracellular matrix, inflammatory response, apoptotic processes, WNT signaling, collagen fibril organization, and cytoskeletal structure organization. TGFβ1-responsive KC DEGs were also enriched in these. CMS-responsive KC-altered genes such as OBSCN, CLU, HDAC5, AK4, ITGA10, and F2RL1 were identified. Some KC-altered genes, such as CLU and F2RL1, were identified to be responsive to both TGFβ1 and CMS. For the first time, our multi-factorial RNA-Seq study has identified many KC-relevant genes and pathways in HKCs with TGFβ1 treatment under CMS, suggesting a potential role of TGFβ1 and biomechanical stretch in KC development.
Extracellular Vesicles Secreted by Pre-Hatching Bovine Embryos Produced In Vitro and In Vivo Alter the Expression of IFNtau-Stimulated Genes in Bovine Endometrial Cells
Authors: Aguilera Constanza , Velásquez Alejandra Estela , Gutierrez-Reinoso Miguel Angel , Wong Yat Sen , Melo-Baez Barbara , Cabezas Joel , Caamaño Diego , Navarrete Felipe , Rojas Daniela , Riadi Gonzalo , Castro Fidel Ovidio , Rodriguez-Alvarez Llretny
Published: April 2023

The embryo-maternal interaction occurs during the early stages of embryo development and is essential for the implantation and full-term development of the embryo. In bovines, the secretion of interferon Tau (IFNT) during elongation is the main signal for pregnancy recognition, but its expression starts around the blastocyst stage. Embryos release extracellular vesicles (EVs) as an alternative mechanism of embryo-maternal communication. The aim of the study was to determine whether EVs secreted by bovine embryos during blastulation (D5-D7) could induce transcriptomic modifications, activating IFNT signaling in endometrial cells. Additionally, it aims to assess whether the EVs secreted by embryos produced in vivo (EVs-IVV) or in vitro (EVs-IVP) have different effects on the transcriptomic profiles of the endometrial cells. In vitro- and in vivo-produced bovine morulae were selected and individually cultured for 48 h to collect embryonic EVs (E-EVs) secreted during blastulation. E-EVs stained with PKH67 were added to in vitro-cultured bovine endometrial cells to assess EV internalization. The effect of EVs on the transcriptomic profile of endometrial cells was determined by RNA sequencing. EVs from both types of embryos induced several classical and non-classical IFNT-stimulated genes (ISGs) and other pathways related to endometrial function in epithelial endometrial cells. Higher numbers of differentially expressed genes (3552) were induced by EVs released by IVP embryos compared to EVs from IVV (1838). Gene ontology analysis showed that EVs-IVP/IVV induced the upregulation of the extracellular exosome pathway, the cellular response to stimulus, and the protein modification processes. This work provides evidence regarding the effect of embryo origin (in vivo or in vitro) on the early embryo-maternal interaction mediated by extracellular vesicles.
Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
Authors: Shurygina Anna-Polina , Zabolotnykh Natalia , Vinogradova Tatiana , Khairullin Berik , Kassenov Markhabat , Nurpeisova Ainur , Sarsenbayeva Gulbanu , Sansyzbay Abylai , Vasilyev Kirill , Buzitskaya Janna , Egorov Andrey , Stukova Marina
Published: April 2023

Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a “prime-boost” scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis.
Quantitative Risk Assessment Model and Optimization in Infrastructure Fast-Track Construction Projects
Authors: Garrido Martins Claudia , Bogus Susan M. , Valentin Vanessa
Published: April 2023

The construction industry has extensively applied the fast-tracking approach to the demanding need for the fast delivery of infrastructure projects. However, the fast-track strategy might be threatened by distinctive risks or changes in risk characteristics that emerge when activities are overlapped (overlapping risks). This article proposes a risk assessment simulation model to quantify the economic impact of overlapping risks on fast-track infrastructure projects. The model uses Monte Carlo simulation and a proprietary engine solution for the optimization procedure. It quantifies the overlapping risk impacts in the project duration and cost that could originate in three different overlapping degrees and evaluates the optimal overlapping degree to reduce the impact of the overlapping risks. The model demonstration used a commercial renovation project. The results suggest that overlapping risks have a high potential impact on the total cost, although with a high probability of attaining the target duration. Eight top risks affected the total duration, cost, or both. The optimum overlapping to reduce the economic impact and achieve the target project duration combines different overlapping degrees. This study contribution is a model for fast-track projects considering overlapping risks, their impact characteristic as a distribution, and the potential relationship between these risks.
Up and down from North to South: Latitudinal Distribution of Flea Beetle Genera in Continental Africa (Coleoptera, Chrysomelidae, Galerucinae, Alticini)
Authors: Biondi Maurizio , D’Alessandro Paola , Iannella Mattia
Published: April 2023

The distribution of global biodiversity can be investigated based on comprehensive datasets and many methods to process them. The taxonomic diversity of phytophagous insects is typically linked to plant diversity, which increases from temperate to tropical latitudes. In this paper, we explored the latitudinal distribution of the flea beetle genera (Coleoptera, Chrysomelidae, Galerucinae, Alticini) on the African continent. We divided the area into latitudinal belts and looked for possible correlations with the number and types of vegetational divisions, the area of each belt, and the bioclimatic variables. The number of flea beetle genera is related to the number and types of vegetation divisions rather than the area of each belt. Some bioclimatic variables are highly related to the number of genera, which is higher within those belts where climate factors limit the oscillation of temperature over the year and favor high precipitations, especially in the warmest months. These biotic and abiotic factors lead to a two-peak trend in the taxonomic richness of flea beetle genera from north to south. Genera endemic to restricted areas are linked to the presence of high mountain systems and increase the taxonomic richness of the belt they belong to.
Clinical Impact of ACE-I/ARB for Conservatively Treated Patients with Moderate to Severe Mitral Regurgitation: A Single Center Observational Study
Authors: Uzel Robert , Bruno Raphael R. , Jung Christian , Lang Christian , Hoi Hannes , Grünbart Martin , Datz Christian , Hoppichler Friedrich , Wernly Bernhard
Published: April 2023

(1) Background: Mitral regurgitation (MR) is associated with increased mortality and frequent hospital admissions. Although mitral valve intervention offers improved clinical outcomes for MR, it is not feasible in many cases. Moreover, conservative therapeutic opportunities remain limited. The aim of this study was to evaluate the impact of ACE inhibitors and angiotensin receptor blockers (ACE-I/ARB) on elderly patients with moderate-to-severe MR and mildly reduced to preserved ejection fraction. (2) Methods: In total, 176 patients were included in our hypothesis-generating, single-center observational study. Hospitalization for heart failure and all-cause death have been defined as the combined 1-year primary endpoint. (3) Results: Patients treated with ACE-I/ARB showed a lower risk for the combined endpoint of death and heart failure-related readmission (HR 0.52 95%CI 0.27–0.99; p = 0.046), even after adjustment for EUROScoreII and frailty (HR 0.52 95%CI 0.27–0.99; p = 0.049) (4) Conclusions: The use of an ACE-I/ARB in patients with moderate-to-severe MR and preserved to mildly reduced left-ventricular ejection fraction (LVEF) significantly associates with improved clinical outcome and might be indicated as a valuable therapeutic option in conservatively treated patients.
Performance of [18F]FDG-PET/CT Imaging in First Recurrence of Invasive Lobular Carcinoma
Authors: Bonnin David , Ladoire Sylvain , Briot Nathalie , Bertaut Aurélie , Drouet Clément , Cochet Alexandre , Alberini Jean-Louis
Published: April 2023

Background: Invasive lobular carcinoma accounts for 10 to 15% of all breast cancers. The first objective of this retrospective study was to assess the diagnostic performance of FDG-PET/CT scanning in women previously treated for invasive lobular carcinoma with suspected first recurrence. The secondary objectives were to evaluate the impact of PET/CT in a change in treatment and its prognostic value on specific survival. Methods: Patients in whom a PET/CT scan was performed from January 2011 to July 2019 in our Cancer Research Center were enrolled. Recurrence was suspected based on clinical symptoms, abnormal findings on conventional imaging, and/or elevated tumor markers. The diagnosis of recurrence was established by the oncologist after integration of all clinical, biological, histological, imaging, and follow-up data. Prognostic factors of recurrence as predicted by PET were determined using univariate logistic regression. KI67, mitotic index, or grade of mitosis were tested. Survival curves were compared using the log-rank test. Sixty-four patients (mean age: 60.3; SD = 12.4 years) were enrolled. The average time from initial diagnosis of the primary tumor to suspicion of recurrence was 5.2 ± 4.1 years. Forty-eight patients (75%) were judged to have recurrence by the oncologist: 7 local and 41 metastatic, with mainly bone (n = 24), lymph node (n = 14) and liver (n = 10) metastases. Results: Sensitivity, specificity, and positive and negative predictive values of PET/CT to predict recurrence were, respectively: 87%, 87%, 95%, and 70%. SUVmax at recurrence sites was generally high (mean: 6.4; SD = 2.9). False negative PET/CT results occurred with local (n = 2), peritoneal (n = 2), meningeal (n = 1), or bladder (n = 1) recurrences. In 40 patients with available histopathological data from suspected sites of recurrence, 30 PET/CT were true positive. In four patients, primary lung (n = 1) or gastric (n = 1) tumors or lymphomas (n = 2) were found. The detection of a recurrence resulted in a change in treatment in 44/48 patients (92%). No association between recurrence predicted by PET and biological biomarkers was found. Median specific survival appears shorter in patients with metastatic recurrence versus patients with local or no recurrence on PET/CT (p = 0.067). Conclusions: FDG-PET/CT is an effective and reliable tool for the detection of invasive lobular carcinoma recurrence, although certain recurrence sites specific to this histological type can impair its diagnostic performance.
Guide Wire Selection (Straight vs. Angled) in Endoscopic Retrograde Cholangiopancreatography Using a Normal Contrast Catheter Performed by a Trainee: A Single-Center Prospective Randomized Controlled Cross-Over Study
Authors: Maki Takumi , Irisawa Atsushi , Yamamiya Akira , Tominaga Keiichi , Abe Yoko , Imbe Koh , Hoshi Koki , Yamabe Akane , Igarashi Ryo , Nakajima Yuki , Sato Kentaro , Shibukawa Goro
Published: April 2023

Introduction: Wire-guided cannulation (WGC) during endoscopic retrograde cholangiopancreatography (ERCP) is a selective biliary cannulation technique aimed at improving the successful selective biliary cannulation rate and reducing the rate of post-ERCP pancreatitis (PEP) incidence. This study aimed to evaluate the effectiveness of angled-tip guidewires (AGW) vs. straight-tip guidewires (SGW) for biliary cannulation via WGC by a trainee. Methods: We conducted a prospective, single-center, open-labeled, randomized, and controlled trial. Fifty-seven patients were enrolled in this study and assigned randomly to two groups (Group A to S and Group S to A). In this study, we started selective biliary cannulation via WGC with an AGW or an SGW for 7 min. If cannulation was unsuccessful, the other guidewire was used, and cannulation was continued for another 7 min (cross-over method). Results: The selective biliary cannulation success rate over 14 min was significantly higher with an AGW compared with an SGW over 14 min (57.8% vs. 34.3%, p = 0.04) and for the second 7-min segment (36.4% vs. 0%, p = 0.04). No significant difference was found for adverse events such as pancreatitis between the two guidewires. Conclusions: Our results suggest that an AGW is recommended for WGC performed by a trainee.
Differences in Cerebral Oxygenation in Cardiogenic and Respiratory Cardiac Arrest Before, During, and After Cardiopulmonary Resuscitation
Authors: Koyama Yasuaki , Ouchi Akira , Shimojo Nobutake , Inoue Yoshiaki
Published: April 2023

We compared the changes in cerebral oxygen saturation (ScO2) levels during cardiac arrest (CA) events using porcine models of ventricular fibrillation CA (VF-CA) and asphyxial CA (A-CA). Twenty female pigs were randomly divided into VF-CA and A-CA groups. We initiated cardiopulmonary resuscitation (CPR) 4 min after CA and measured the cerebral tissue oxygenation index (TOI) using near-infrared spectroscopy (NIRS) before, during, and after CPR. In both groups, the TOI was the lowest at 3–4 min after pre-CPR phase initiation (VF-CA group: 3.4 min [2.8–3.9]; A-CA group: 3.2 min [2.9–4.6]; p = 0.386). The increase in TOI differed between the groups in the CPR phase (p < 0.001); it increased more rapidly in the VF-CA group (16.6 [5.5–32.6] vs. 1.1 [0.6–3.3] %/min; p < 0.001). Seven pigs surviving for 60 min after the return of spontaneous circulation in the VF-CA group recovered limb movement, whereas only one in the A-CA group (p = 0.023) achieved movement recovery. The increase in the TOI did not differ significantly between the groups in the post-CPR phase (p = 0.341). Therefore, it is better to monitor ScO2 concomitantly with CPR initiation using NIRS to assess the responsiveness to CPR in clinical settings.
Impact of Age and Sex Interaction on Post-Acute Sequelae of COVID-19: An Italian Cohort Study on Adults and Children
Authors: Puntoni Matteo , Esposito Susanna , Patrizi Laura , Palo Chiara Maria , Deolmi Michela , Autore Giovanni , Fainardi Valentina , Caminiti Caterina ,   on behalf of the University Hospital of Parma LONG-COVID Research Team
Published: April 2023

Identifying factors predisposing individuals to post-acute sequelae of COVID-19 (PASC) would allow for the timely treatment of those vulnerable. Attention on the role of sex and age is growing, but published studies have shown mixed results. Our objective was to estimate the effect modification of age on sex as a risk factor for PASC. We analyzed data from two longitudinal prospective cohort studies on adult and pediatric subjects positive to SARS-CoV-2 infection that were enrolled between May 2021 and September 2022. Age classes (≤5, 6–11, 12–50, >50 years) were based on the potential role of sex hormones on inflammatory/immune and autoimmune processes. A total of 452 adults and 925 children were analyzed: 46% were female and 42% were adults. After a median follow-up of 7.8 months (IQR: 5.0 to 9.0), 62% of children and 85% of adults reported at least one symptom. Sex and age alone were not significantly associated to PASC, but their interaction was statistically significant (p-value = 0.024): the risk was higher for males aged 0–5 (females vs. males HR: 0.64, 95% CI: 0.45–0.91, p = 0.012) and for females aged 12–50 (HR: 1.39, 95% CI: 1.04–1.86, p = 0.025), especially those in the cardiovascular, neurological, gastrointestinal and sleep categories. Further research on PASC with regard to sex and age is warranted.
Long-Term Mortality after New-Onset Atrial Fibrillation in COVID-19
Authors: Jurisic Stjepan , Komminoth Mathis , Todorov Atanas , Bertschi Daniela A. , Jurisic Martin , Vranjic Ivica , Wiggli Benedikt , Schmid Hansruedi , Gebhard Catherine , Gebhard Caroline E. , Heidecker Bettina , Beer Jürg-Hans , Patriki Dimitri
Published: April 2023

Background: Atrial fibrillation (AF) has been described as a common cardiovascular manifestation in patients suffering from coronavirus disease 2019 (COVID-19) and has been suggested to be a potential risk factor for a poor clinical outcome. Methods: In this observational study, all patients hospitalized due to COVID-19 in 2020 in the Cantonal Hospital of Baden were included. We assessed clinical characteristics, in-hospital outcomes as well as long-term outcomes with a mean follow-up time of 278 (±90) days. Results: Amongst 646 patients diagnosed with COVID-19 (59% male, median age: 70 (IQR: 59–80)) in 2020, a total of 177 (27.4%) patients were transferred to the intermediate/intensive care unit (IMC/ICU), and 76 (11.8%) were invasively ventilated during their hospitalization. Ninety patients (13.9%) died. A total of 116 patients (18%) showed AF on admission of which 34 (29%) had new-onset AF. Patients with COVID-19 and newly diagnosed AF were more likely to require invasive ventilation (OR: 3.5; p = 0.01) but did not encounter an increased in-hospital mortality. Moreover, AF neither increased long-term mortality nor the number of rehospitalizations during follow-up after adjusting for confounders. Conclusions: In patients suffering from COVID-19, the new-onset of AF on admission was associated with an increased risk of invasive ventilation and transfer to the IMC/ICU but did not affect in-hospital or long-term mortality.
Minimal Invasive Abdominal Sacral Colpopexy and Abdominal Lateral Suspension: A Prospective, Open-Label, Multicenter, Non-Inferiority Trial
Authors: Russo Eleonora , Montt Guevara Maria Magdalena , Sacinti Koray Gorkem , Misasi Giulia , Falcone Maria , Morganti Riccardo , Mereu Liliana , Dalprà Francesca , Tateo Saverio , Simoncini Tommaso
Published: April 2023

Background: Abdominal minimally invasive surgery has become increasingly prominent for the treatment of prolapse. Abdominal sacral colpopexy (ASC) is the gold standard for the treatment of advanced apical prolapse; however, alternative surgical approaches such as the abdominal lateral suspension (ALS) have been developed to improve patient outcomes. This study aims to determine whether ALS improves outcomes compared to ASC in multicompartmental prolapse patients. Methods: A prospective, open-label, multicenter, non-inferiority trial was conducted in 360 patients who underwent ASC or ALS for the treatment of apical prolapse. The primary outcome was anatomical and symptomatic cure of the apical compartment at 1-year follow-up; secondary outcomes included prolapse recurrence, re-operation rate, and post-operative complications. A 300-patient cohort was subdivided into 200-patients who underwent ALS and 100-patients who underwent ASC. The confidence interval method was used to calculate the p-value of non-inferiority. Results: At the 12-months follow-up, the objective cure rate of the apical defect was 92% for ALS and 94% for ASC (recurrence rates were 8% and 6%, respectively, and the p-value for non-inferiority was <0.01). The mMesh complication rates were 1% and 2% for ALS and ASC, respectively. Conclusions: This study demonstrated that the ALS technique is not inferior to the gold standard ASC for the surgical treatment of apical prolapse.
Evolution of Quality of Life and Treatment Adherence after One Year of Intermittent Bladder Catheterisation in Functional Urology Unit Patients
Authors: Fernandez-Lasquetty Blanc Blanca , Hernández Martínez Antonio , Lorenzo García Carlos , Baixauli Puig Montserrat , Estudillo González Francisco , Martin Bermejo Maria Victoria , Ortega Checa Maria Angustias , Alcaraz Zomeño Elena , Torres Bacete Arancha , Ferrández Franco Guillermina , Benito Santos Begoña , Fernández Llorente Guadalupe , Guerrero Andrádes Maria Carmen , Rodríguez Diaz Monica , Louis Lauture Mario Pierre , Jiménez Mayorga Isabel , Serrano-Abiétar Rosario , Garrido Mora Maria Asunción , Barcia Barrera Francisco , Asensio Malo Gemma , Morcillo Marín Montserrat , Lluesma Martinez Vicenta , Valero Escribá Maria Luisa , Tendero Ruiz Silvia , Romay Cea Rosa Ana , Marín Valero Mercedes , Rodríguez-Almagro Julián
Published: April 2023

Objective: To determine patient difficulties and concerns when performing IBC (Intermittent Bladder Catheterisation), as well as the evolution of adherence, quality of life, and emotional state of patients one year after starting IBC. Method: A prospective, observational, multicentre study conducted in 20 Spanish hospitals with a one-year follow-up. Data sources were patient records and the King’s Health Questionnaire on quality of life, the Mini-Mental State Examination (MMSE), and the Hospital Anxiety and Depression Scale (HADS). Perceived adherence was measured using the ICAS (Intermittent Catheterization Adherence Scale) and perceived difficulties with IBC were assessed using the ICDQ (Intermittent Catheterization Difficulty Questionnaire). For data analysis, descriptive and bivariate statistics were performed for paired data at three points in time (T1: one month, T2: three months, T3: one year). Results: A total of 134 subjects initially participated in the study (T0), becoming 104 subjects at T1, 91 at T2, and 88 at T3, with a mean age of 39 years (standard deviation = 22.16 years). Actual IBC adherence ranged from 84.8% at T1 to 84.1% at T3. After one year of follow-up, a statistically significant improvement in quality of life (p ≤ 0.05) was observed in all dimensions with the exception of personal relationships. However, there were no changes in the levels of anxiety (p = 0.190) or depression (p = 0.682) at T3 compared to T0. Conclusions: Patients requiring IBC exhibit good treatment adherence, with a significant proportion of them performing self-catheterisation. After one year of IBC, a significant improvement in quality of life was noted, albeit with a significant impact on their daily lives and their personal and social relationships. Patient support programmes could be implemented to improve their ability to cope with difficulties and thus enhance both their quality of life and the maintenance of their adherence.
Management of Steroid-Induced Glaucoma in a Patient with Pyoderma Gangrenosum
Authors: Byun Ji Yeon , Kang Yong Koo , Jang Yong Hyun , Kim Young Kook , Kim Dai Woo
Published: April 2023

Pyoderma gangrenosum (PG) is an uncommon inflammatory skin disorder typically presenting as painful skin ulcers, which may also exhibit extracutaneous findings. PG can occur at the site of trauma or surgery, which is known as the pathergic phenomenon. A 36-year-old man developed bilateral steroid-induced glaucoma after prolonged systemic immunosuppressive treatment for cutaneous pyoderma gangrenosum. After successful Ahmed glaucoma valve implantation surgery with donor scleral patch graft in the right eye, the same surgery failed repeatedly in the left eye and complicated with the prolonged conjunctival necrosis and the exposure of the donor scleral patch graft. Under the impression of ocular involvement of PG, microinvasive glaucoma surgery (MIGS) with XEN® Gel Stent was performed in the left eye; the conjunctival bleb was successfully formed without conjunctival necrosis, and intraocular pressure was well maintained. Ophthalmic surgery can be complicated in patients with PG, and the surgical option should be selected prudently to minimize surgical trauma. MIGS, as a minimally invasive surgical technique, could offer an advantage for patients with PG.
Efficacy, Safety, and Outcomes following Accelerated and Iontophoresis Corneal Crosslinking in Progressive Keratoconus
Authors: Saad Sami , Saad Rana , Goemaere Isabelle , Cuyaubere Roxane , Borderie Marie , Borderie Vincent , Bouheraoua Nacim
Published: April 2023

Purpose: To investigate the outcomes of accelerated (A-CXL) and iontophoresis (I-CXL) corneal crosslinking in a large retrospective cohort with progressive keratoconus. Methods: This retrospective observational cohort study included consecutive patients treated by A-CXL (9 mW/5.4 J/cm2) or I-CXL with a minimal follow-up of 12 months. Visual acuity, manifest refraction, topography, specular microscopy, and corneal optical coherence tomography (OCT) were evaluated at baseline and at the last visit. Progression was defined as an increase in the maximum topographic keratometry (Kmax) of 1D. Results: 302 eyes of 241 patients with a mean age of 25.2 ± 7.5 years were included from 2012 to 2019: 231 and 71 eyes in the A-CXL and I-CXL groups, respectively. The mean follow-up was 27.2 ± 13.2 months (maximum: 85.7 months). Preoperatively, the mean Kmax was 51.8 ± 4.0D, with no differences between groups. Mean topographic measurements and spherical equivalent remained stable during the follow-up. At the last visit, CXL failure was reported in 60 eyes (19.9%): 40 (14.7%) versus 20 (28.2%) in A-CXL versus I-CXL, respectively, p = 0.005. The likelihood of progression after CXL was significantly higher following I-CXL: RR = 1.62, CI95 = [1.02 to 2.59], p = 0.04. Demarcation line presence at 1 month was positively correlated with higher efficacy of CXL, p = 0.03. No endothelial damage was reported, especially in 51 thin corneas (range = 342–399 µm). Conclusions: A-CXL seems more effective than I-CXL in stabilizing keratoconus; this is to be taken into account when a therapeutic indication is posed according to the aggressiveness of the keratoconus.
Amyotrophic Lateral Sclerosis Mimic Syndrome in a 24-Year-Old Man with Chiari 1 Malformation and Syringomyelia: A Clinical Case
Authors: Al-Zamil Mustafa , Shnayder Natalia A. , Davydova Tatiana K. , Nasyrova Regina F. , Trefilova Vera V. , Narodova Ekaterina A. , Petrova Marina M. , Romanova Irina V. , Chumakova Galina A.
Published: April 2023

Chiari 1 Malformation (CM1) is classically defined as a caudal displacement of the cerebellar tonsils through the foramen magnum into the spinal cord. Modern imaging techniques and experimental studies disclose a different etiology for the development of CM1, but the main etiology factor is a structural defect in the skull as a deformity or partial reduction, which push down the lower part of the brain and cause the cerebellum to compress into the spinal canal. CM1 is classified as a rare disease. CM1 can present with a wide variety of symptoms, also non-specific, with consequent controversies on diagnosis and surgical decision-making, particularly in asymptomatic or minimally symptomatic. Other disorders, such as syringomyelia (Syr), hydrocephalus, and craniocervical instability can be associated at the time of the diagnosis or appear secondarily. Therefore, CM1-related Syr is defined as a single or multiple fluid-filled cavities within the spinal cord and/or the bulb. A rare CM1-related disorder is syndrome of lateral amyotrophic sclerosis (ALS mimic syndrome). We present a unique clinical case of ALS mimic syndrome in a young man with CM1 and a huge singular syringomyelic cyst with a length from segment C2 to Th12. At the same time, the clinical picture showed upper hypotonic-atrophic paraparesis in the absence of motor disorders in the lower extremities. Interestingly, this patient did not have a disorder of superficial and deep types of sensitivity. This made it difficult to diagnose CM1. For a long time, the patient’s symptoms were regarded as a manifestation of ALS, as an independent neurological disease, and not as a related disorder of CM1. Surgical treatment for CM1 was not effective, but it allowed to stabilize the course of CM1-related ALS mimic syndrome over the next two years.
Unexplained Hyperthyrotropinemia: A Biochemical and Clinical Challenge
Authors: Croce Laura , Chytiris Spyridon , Coperchini Francesca , Ferraro Giovanni , Minelli Linda , Navarra Antonella , Magri Flavia , Chiovato Luca , Trimboli Pierpaolo , Rotondi Mario
Published: April 2023

Background: A raised serum TSH in the absence of a clear etiology, or “unexplained hyperthyrotropinemia” (UH), can be challenging for clinicians. The aim of the present study was to evaluate potential strategies aimed at a clinical and biochemical characterization of UH patients. Methods: We compared 36 patients with UH with a control group of 14 patients with chronic autoimmune thyroiditis (CAT) and subclinical hypothyroidism. The two groups were compared in terms of the following: (i) the rate of normalization of TSH after repeating with another assay; (ii) the rate of normalization of TSH over time with the same assay; (iii) the reduction in TSH after precipitation with polyethilenglycole (PEG); and (iv) free thyroxine (FT4) levels. Results: Similar TSH levels were observed in UH [5.65 (5.21–6.37)] and CAT [5.62 (5.17–8.50)] (p = 0.489). TSH measurement with another assay method showed a normal TSH value in 41.9% of UH vs. 46.1% of CAT patients (p = 0.797). After repeating the TSH measurement in time with the same assay method, an increased TSH value was confirmed in all cases, in both groups (0% in the UH group vs. 0% in the CAT group, p = 1.000). TSH recovery after PEG precipitation was similar in the two groups (% precipitable post-PEG: 68.75 ± 3.14 in UH vs. 68.67 ± 7.18 in CAT, p = 0.960). FT4 levels were similar in the two groups (FT4 1.02 ± 0.20 ng/dl in UH vs. 1.00 ± 0.20 ng/dl in CAT, p = 0.789). Conclusions: The results do not support the concept that laboratory interferences are more frequent in UH patients, suggesting that patients with UH should be managed in the same way as patients with CAT until proven otherwise.
Zinc Oxide–Incorporated Chitosan–Poly(methacrylic Acid) Polyelectrolyte Complex as a Wound Healing Material
Authors: Sathya Seeli David , Das Abinash , Prabaharan Mani
Published: April 2023

A novel type of porous films based on the ZnO-incorporated chitosan–poly(methacrylic acid) polyelectrolyte complex was developed as a wound healing material. The structure of porous films was established by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and energy dispersive X-ray (EDX) analysis. Scanning electron microscope (SEM) and porosity studies revealed that the pore size and porosity of the developed films increased with the increase in zinc oxide (ZnO) concentration. The porous films with maximum ZnO content exhibited improved water swelling degree (1400%), controlled biodegradation (12%) for 28 days, a porosity of 64%, and a tensile strength of 0.47 MPa. Moreover, these films presented antibacterial activity toward Staphylococcus aureus and Micrococcus sp. due to the existence of ZnO particles. Cytotoxicity studies demonstrated that the developed films had no cytotoxicity against the mouse mesenchymal stem (C3H10T1/2) cell line. These results reveal that ZnO-incorporated chitosan-poly(methacrylic acid) films could be used as an ideal material for wound healing application.
Investigation of the Biosafety of Antibacterial Mg(OH)2 Nanoparticles to a Normal Biological System
Authors: Wang Ying , Liu Yanjing , Li Xiyue , Wang Fuming , Huang Yaping , Liu Yuezhou , Zhu Yimin
Published: April 2023

The toxicity of Mg(OH)2 nanoparticles (NPs) as antibacterial agents to a normal biological system is unclear, so it is necessary to evaluate their potential toxic effect for safe use. In this work, the administration of these antibacterial agents did not induce pulmonary interstitial fibrosis as no significant effect on the proliferation of HELF cells was observed in vitro. Additionally, Mg(OH)2 NPs caused no inhibition of the proliferation of PC-12 cells, indicating that the brain’s nervous system was not affected by Mg(OH)2 NPs. The acute oral toxicity test showed that the Mg(OH)2 NPs at 10,000 mg/kg induced no mortality during the administration period, and there was little toxicity in vital organs according to a histological analysis. In addition, the in vivo acute eye irritation test results showed little acute irritation of the eye caused by Mg(OH)2 NPs. Thus, Mg(OH)2 NPs exhibited great biosafety to a normal biological system, which was critical for human health and environmental protection.
Retinal Disease Detection Using Deep Learning Techniques: A Comprehensive Review
Authors: Muchuchuti Stewart , Viriri Serestina
Published: April 2023

Millions of people are affected by retinal abnormalities worldwide. Early detection and treatment of these abnormalities could arrest further progression, saving multitudes from avoidable blindness. Manual disease detection is time-consuming, tedious and lacks repeatability. There have been efforts to automate ocular disease detection, riding on the successes of the application of Deep Convolutional Neural Networks (DCNNs) and vision transformers (ViTs) for Computer-Aided Diagnosis (CAD). These models have performed well, however, there remain challenges owing to the complex nature of retinal lesions. This work reviews the most common retinal pathologies, provides an overview of prevalent imaging modalities and presents a critical evaluation of current deep-learning research for the detection and grading of glaucoma, diabetic retinopathy, Age-Related Macular Degeneration and multiple retinal diseases. The work concluded that CAD, through deep learning, will increasingly be vital as an assistive technology. As future work, there is a need to explore the potential impact of using ensemble CNN architectures in multiclass, multilabel tasks. Efforts should also be expended on the improvement of model explainability to win the trust of clinicians and patients.
Kerf Geometry and Surface Roughness Optimization in CO2 Laser Processing of FFF Plates Utilizing Neural Networks and Genetic Algorithms Approaches
Authors: Kechagias John D. , Fountas Nikolaos A. , Ninikas Konstantinos , Vaxevanidis Nikolaos M.
Published: April 2023

This work deals with the experimental investigation and multi-objective optimization of mean kerf angle (A) and mean surface roughness (Ra) in laser cutting (LC) fused filament fabrication (FFF) 3D-printed (3DP), 4 mm-thick polylactic acid (PLA) plates by considering laser feed (F) and power (P) as the independent control parameters. A CO2 laser apparatus was employed to conduct machining experiments on 27 rectangular workpieces. An experimental design approach was adopted to establish the runs according to full-combinatorial design with three repetitions, resulting in 27 independent experiments. A customized response surface experiment was formulated to proceed with regression equations to predict the responses and examine the solution domain continuously. After examining the impact of F and P on mean A and mean Ra, two reliable prediction models were generated to model the process. Furthermore, since LC is a highly intricate, non-conventional machining process and its control variables affect the responses in a nonlinear manner, A and Ra were also predicted using an artificial neural network (NN), while its resulting performance was compared to the predictive regression models. Finally, the regression models served as objective functions for optimizing the responses with an intelligent algorithm adopted from the literature.
Systematic Approach for Investigating Temporal Variability in Production Systems to Improve Production Planning and Control
Authors: Telatko Rocky , Reichelt Dirk
Published: April 2023

Including the inherent temporal variability in a production system in planning and control processes can ensure the fulfillment of the production schedule and increase key performance indicators. This benefits the sustainable and efficient use of the system. The current lack of consideration of this inherent temporal variability in production planning leads to optimistic estimates and calculations of planned values that cannot be met. To complete this information, the inherent temporal variability in a production system is investigated using a systematic approach. This approach detects, identifies, and quantifies inherent temporal variability and is applied to a data base created via an automated, event-driven procedure. The approach is tested in a smart factory laboratory. The results to date on improving production planning and control are promising as key performance indicators have been increased. There is still a need for action to ensure the fulfillment of the production schedule. Concluding, work on this topic has just begun, as can be seen from the discussion section. More data need to be collected and aggregated for future research. This publication is intended to motivate researchers to address this issue and better manage the existing uncertainty in production through the use of data.
Freeform Hybrid Manufacturing: Binderjet, Structured Light Scanning, Confocal Microscopy, and CNC Machining
Authors: Dvorak Jake , Gilmer Dustin , Zameroski Ross , Cornelius Aaron , Schmitz Tony
Published: April 2023

This paper describes a hybrid manufacturing approach for silicon carbide (SiC) freeform surfaces using binder jet additive manufacturing (BJAM) to print the preform and machining to obtain the design geometry. Although additive manufacturing (AM) techniques such as BJAM allow for the fabrication of complex geometries, additional machining or grinding is often required to achieve the desired surface finish and shape. Hybrid manufacturing has been shown to provide an effective solution. However, hybrid manufacturing also has its own challenges, depending on the combination of processes. For example, when the subtractive and additive manufacturing steps are performed sequentially on separate systems, it is necessary to define a common coordinate system for part transfer. This can be difficult because AM preforms do not inherently contain features that can serve as datums. Additionally, it is important to confirm that the intended final geometry is contained within the AM preform. The approach described here addresses these challenges by using structured light scanning to create a stock model for machining. Results show that a freeform surface was machined with approximately 70 µm of maximum deviation from that which was planned.
Bisection Method for the Heavy Fuel Oil Tank Filling Problem at a Liquefied Natural Gas Carrier
Authors: Mrzljak Vedran , Poljak Igor , Kosor Mate , Čulin Jelena
Published: April 2023

The commingling of the two types of heavy fuel oils (fuel remaining in the tanks and fuel loaded) is determined by the company’s guidance and safety management system. Remained heavy fuel oil must be distributed in the heavy fuel oil tanks before bunkering efficiently, in order to obtain maximum bunker loading. This paper proposes the use of the bisection method to calculate the distribution of the remaining fuel in heavy fuel oil tanks on the liquefied natural gas carrier. The use of this method is illustrated by three examples. The first and second examples show that the iterations converge quickly to the solution. It is found that maximum tank filling with fuel commingling is achievable if the bunker intervals satisfy the company policy of 10% as a lower limit of tank filling, and 90% to 100% as an upper limit. The third example illustrates a situation when the proposed mathematical model does not allow maximization of the total tank capacity without risk assessment. The mathematical spectrum of the possible tank filling solution is presented. Despite its limitations, the bisection method is suitable for onboard applications because it is simple and fast, and can be easily programmed.
Needs and Demands for eHealth Pain Management Interventions in Chronic Pain Patients
Authors: Stoppok Paula , Frewer Anna-Lena , Schweda Adam , Geiger Sheila , Skoda Eva-Maria , Müßgens Diana , Bingel Ulrike , Teufel Martin , Bäuerle Alexander
Published: April 2023

Although chronic pain is a global health problem, the current care situation is often inadequate. eHealth offers many advantages as an additional option for treating chronic pain. Yet, an intervention’s efficacy can only be fully exhausted if patients intend to use it. This study aims to identify the needs and demands of patients with chronic pain regarding intervention concepts and frameworks to develop specifically tailored eHealth pain management interventions. A cross-sectional study was conducted, including 338 individuals with chronic pain. Within the cohort, a distinction between a high- and a low-burden group was made. Respondents generally preferred a permanently accompanying mobile app, but the preferred content varied with group. According to the majority, interventions should be made available on smartphones, offer sessions once per week with a duration from 10 to 30 min, and be recommended by experts. These results can provide the basis for future eHealth pain management interventions tailored to the patients’ needs and demands.
Effects and Safety of Wearable Exoskeleton for Robot-Assisted Gait Training: A Retrospective Preliminary Study
Authors: Park Gwang-Min , Cho Su-Hyun , Hong Jun-Taek , Kim Dae-Hyun , Shin Ji-Cheol
Published: April 2023

Background: Wearable devices for robot-assisted gait training (RAGT) provide overground gait training for the rehabilitation of neurological injuries. We aimed to evaluate the effectiveness and safety of RAGT in patients with a neurologic deficit. Methods: Twenty-eight patients receiving more than ten sessions of overground RAGT using a joint-torque-assisting wearable exoskeletal robot were retrospectively analyzed in this study. Nineteen patients with brain injury, seven patients with spinal cord injury and two patients with peripheral nerve injury were included. Clinical outcomes, such as the Medical Research Council scale for muscle strength, Berg balance scale, functional ambulation category, trunk control tests, and Fugl–Meyer motor assessment of the lower extremities, were recorded before and after RAGT. Parameters for RAGT and adverse events were also recorded. Results: The Medical Research Council scale scores for muscle strength (36.6 to 37.8), Berg balance scale (24.9 to 32.2), and functional ambulation category (1.8 to 2.7) significantly improved after overground RAGT (p < 0.05). The familiarization process was completed within six sessions of RAGT. Only two mild adverse events were reported. Conclusions: Overground RAGT using wearable devices can improve muscle strength, balance, and gait function. It is safe in patients with neurologic injury.