bluuebunny/crossref_metadata_2025 huggingface dataset:
Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration
Authors: Lee Junyeop , Kim You Na , Kim June-Gone
Published: March 2022

We investigated the efficacy of monthly alternating injections of aflibercept and bevacizumab (MAAB) for maintenance treatment in patients with neovascular age-related macular degeneration (AMD) who showed improvement with the initial monthly injections but presented with rapid worsening after conversion to bimonthly injections. We included 72 patients with neovascular AMD who showed improvement with loading injections of aflibercept. For maintenance treatment, bevacizumab was administered every alternate month between the bimonthly aflibercept injections in 24 (33.3%) eyes showing worsening (MAAB group). The other eyes were treated with aflibercept (BiA group) bimonthly. Baseline low retinal thickness, thick choroid, and presence of intraretinal fluid were associated with worsening after extending the injection intervals. Visual improvement was lower in the MAAB group than in the BiA group, but the final visual outcomes were comparable. Additional bevacizumab stabilized the early fluctuation of retinal thickness, thus maintaining long-term visual stability without increasing the risk of geographic atrophy or disciform scar until the second year. Previously treated eyes or those with polypoidal choroidal vasculopathy responded less to the initial loading doses and showed worsening under the bimonthly regimen. MAAB was effective in preventing anatomical and functional deterioration when bimonthly aflibercept proved insufficient for the maintenance treatment of neovascular AMD.
Outcomes of COVID-19 Critically Ill Extremely Elderly Patients: Analysis of a Large, National, Observational Cohort
Authors: Andrei Stefan , Valeanu Liana , Stefan Mihai Gabriel , Longrois Dan , Popescu Mihai , Stefan Gabriel , Balan Cosmin , Arafat Raed , Corneci Dan , Droc Gabriela , Bubenek-Turconi Serban-Ion ,   on behalf of the COVATI-RO Collaborative
Published: March 2022

Background. During the COVID-19 pandemic, resource allocation became a major problem in globally overwhelmed ICUs. The main goal of this study was to describe the clinical characteristics of the very elderly patients (aged ≥ 80 years) with COVID-19 admitted in Romanian ICUs. The study objectives were to evaluate and determine the factors associated with ICU mortality. Methods. We designed a national, multicentric, observational platform with prospective enrolment. This study included patients aged ≥ 80 years admitted in Romanian ICUs with SARS-CoV-2 infection from March 2020 to December 2021. Results. We included 1666 patients with a median age of 83 years and 78% ICU mortality. Male sex, dyspnoea, lower Glasgow Coma Scale and lower SpO2 at ICU admission, the need for mechanical ventilation (MV), and corticosteroid use were independently associated with mortality. A total of 886/1666 (53%) elderly patients underwent invasive mechanical ventilation, with a mortality of 97%. The age impact on mortality was confirmed by a 1:1 propensity matching with less elderly ICU patients. Conclusion. In extremely elderly patients with COVID-19 admitted in the ICU, mortality is high, particularly when requiring MV. Therapy should be directed towards the optimization of less invasive ventilatory methods and the use of MV and corticosteroids only in highly selected patients.
Thoracic Curve Correction Ratio: An Objective Measure to Guide against Overcorrection of a Main Thoracic Curve in the Setting of a Structural Proximal Thoracic Curve
Authors: Landrum Matthew R. , Milby Andrew H. , Yaszay Burt , Parent Stefan , Nelson Susan E. , Pahys Joshua M. , Samdani Amer F. , Capraro Anthony C. , Flynn John M. , Cahill Patrick J. ,   on behalf of the Harms Study Group and Harms Non-Fusion Study Group
Published: March 2022

Purpose: The correction of double thoracic (Lenke 2) curves has been associated with higher rates of postoperative shoulder imbalance that may compromise long-term outcomes following spinal deformity correction. A number of methods have been proposed to mitigate this risk, though no accepted standard measurement exists. The purpose of this study is to validate a novel quantitative method of determining the relative curve correction magnitude in double thoracic curves. Methods: Retrospective data from a multi-center database of patients undergoing surgical correction of left-proximal thoracic, right-main thoracic Lenke 2 curves were analyzed. A novel measurement tool, the Thoracic Curve Correction Ratio (TCCR), was applied for the purposes of validation against historical data. Results: A total of 305 patients with complete two-year follow-up data were included. The TCCR, or the ratio of postoperative percent correction of the thoracic curves divided by the ratio of the preoperative curve magnitudes, displayed a significant negative correlation (Pearson R = −0.66; p < 0.001) with T1 tilt at two years postoperatively. Conclusions: The TCCR could be added as an important factor in the preoperative planning process and intraoperative assessment in order to reduce postoperative T1 tilt. While T1 tilt remains an imperfect surrogate measure for clinical shoulder balance, it serves as one of many potential measures that the surgeon may evaluate quantitatively and radiographically.
Characteristics and Outcomes of COVID-19-Related Hospitalization among PLWH
Authors: Gagliardini Roberta , Vergori Alessandra , Lorenzini Patrizia , Cicalini Stefania , Pinnetti Carmela , Mazzotta Valentina , Mondi Annalisa , Mastrorosa Ilaria , Camici Marta , Lanini Simone , Fusto Marisa , Paulicelli Jessica , Plazzi Maria Maddalena , Marchioni Luisa , Agrati Chiara , Garbuglia Anna Rosa , Piselli Pierluca , Nicastri Emanuele , Taglietti Fabrizio , Palmieri Fabrizio , D’Offizi Gianpiero , Girardi Enrico , Vaia Francesco , Antinori Andrea
Published: March 2022

Background: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. Methods: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. Results: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75–322) cells/μL; CD4 at COVID-19 diagnosis was 272 cells/μL (127–468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2–17.3) in PLWH versus 18.9% (16.9–21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5–36.4) in PLWH versus 37.6% (35.1–40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12–1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53–2.00, p = 0.926). Conclusion: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected.
Multidimensional Family-Centred Early Intervention in Children with Hearing Loss: A Conceptual Model
Authors: Holzinger Daniel , Hofer Johannes , Dall Magdalena , Fellinger Johannes
Published: March 2022

At least two per thousand newborns are affected by hearing loss, with up to 40% with an additional disability. Early identification by universal newborn hearing screening and early intervention services are available in many countries around the world, with limited data on their effectiveness and a lack of knowledge about specific intervention-related determinants of child and family outcomes. This concept paper aimed to better understand the mechanisms by which multi-dimensional family-centred early intervention influences child outcomes, through parent behaviour, targeted by intervention by a review of the literature, primarily in the field of childhood hearing loss, supplemented by research findings on physiological and atypical child development. We present a conceptual model of influences of multi-disciplinary family-centred early intervention on family coping/functioning and parent–child interaction, with effects on child psycho-social and cognitive outcomes. Social communication and language skills are postulated as mediators between parent–child interaction and non-verbal child outcomes. Multi-disciplinary networks of professionals trained in family-centred practice and the evaluation of existing services, with respect to best practice guidelines for family-centred early intervention, are recommended. There is a need for longitudinal epidemiological studies, including specific intervention measures, family behaviours and multidimensional child outcomes.
Trans-Spinal Electrical Stimulation Therapy for Functional Rehabilitation after Spinal Cord Injury: Review
Authors: Rahman Md. Akhlasur , Tharu Niraj Singh , Gustin Sylvia M. , Zheng Yong-Ping , Alam Monzurul
Published: March 2022

Spinal cord injury (SCI) is one of the most debilitating injuries in the world. Complications after SCI, such as respiratory issues, bowel/bladder incontinency, pressure ulcers, autonomic dysreflexia, spasticity, pain, etc., lead to immense suffering, a remarkable reduction in life expectancy, and even premature death. Traditional rehabilitations for people with SCI are often insignificant or ineffective due to the severity and complexity of the injury. However, the recent development of noninvasive electrical neuromodulation treatments to the spinal cord have shed a ray of hope for these individuals to regain some of their lost functions, a reduction in secondary complications, and an improvement in their life quality. For this review, 250 articles were screened and about 150 were included to summarize the two most promising noninvasive spinal cord electrical stimulation methods of SCI rehabilitation treatment, namely, trans-spinal direct current stimulation (tsDCS) and trans-spinal pulsed current stimulation (tsPCS). Both treatments have demonstrated good success in not only improving the sensorimotor function, but also autonomic functions. Due to the noninvasive nature and lower costs of these treatments, in the coming years, we expect these treatments to be integrated into regular rehabilitation therapies worldwide.
Clinical Outcomes of an Innovative Cefazolin Delivery Program for MSSA Infections in OPAT
Authors: Herrera-Hidalgo Laura , Luque-Márquez Rafael , de Alarcon Aristides , Guisado-Gil Ana Belén , Gutierrez-Gutierrez Belen , Navarro-Amuedo Maria Dolores , Praena-Segovia Julia , Carmona-Caballero Juan Manuel , Fraile-Ramos Elena , Gutierrez-Valencia Alicia , Lopez-Cortes Luis Eduardo , Gil-Navarro Maria Victoria
Published: March 2022

Cefazolin is a recommended treatment for methicillin-susceptible Staphylococcus aureus (MSSA) infections that has been successfully used in outpatient parenteral antibiotic therapy (OPAT) programs. The aim of this study was to assess the clinical outcomes of cefazolin delivered each day (Group 24) vs. every two days (Group 48) for MSSA infections in OPAT programs. It was a prospective observational study with retrospective analysis of a cohort of MSSA infections attended in OPAT. The primary outcome was treatment success, defined as completing the antimicrobial regimen without death, treatment discontinuation, or readmission during treatment and follow-up. A univariate and multivariate logistic regression model was built. A two-sided p < 0.05 was considered statistically significant. Of the 149 MSSA infections treated with cefazolin 2 g/8 h in OPATs, 94 and 55 patients were included in the delivery Group 24 and Group 48, respectively. Treatment failure and unplanned readmission rates were similar in both groups (11.7% vs. 7.3% p = 0.752 and 8.5% vs. 5.5% p = 0.491). There was a significant increase in vascular access complications in Group 24 (33.0%) with respect to Group 48 (7.3%) (p < 0.001). Treating uncomplicated MSSA infection with cefazolin home-delivered every two days through an OPAT program is not associated with an increased risk of treatment failure and entails a significant reduction in resource consumption compared to daily delivery.
Signs, Symptoms, and Morphological Features of Idiopathic Condylar Resorption in Orthodontic Patients: A Survey-Based Study
Authors: Iwasa Akihiko , Tanaka Eiji
Published: March 2022

Background: Idiopathic condylar resorption (ICR) is an aggressive degenerative disease of the temporomandibular joint that is most frequently observed in teenage girls. However, no specific cause of ICR has been identified. To explore the specific causes of the onset and progression of ICR, we performed a survey-based study on ICR in orthodontic patients and described its subjective symptoms, clinical signs, and condylar morphological features. Methods: A total of 1735 participants were recruited from 2193 orthodontic patients. For each participant, subjective symptoms and clinical signs of temporomandibular disorders (TMDs) were evaluated through clinical examination and a questionnaire. Furthermore, three-dimensional computed tomography (CT) was performed to diagnose ICR. Results: Among the 1735 patients evaluated, ICR was present in two male and ten female patients. All 12 patients had maxillary protrusion and an anterior open bite. Four patients with ICR underwent orthodontic treatment. Based on CT findings, patients with ICR had significantly different condylar sizes and shapes from patients with TMDs alone. Conclusions: The coexistence of intrinsic and extrinsic factors, such as sex-hormone imbalance and a history of orthodontic treatment, might lead to the onset of ICR. We suggest that growing patients suspected of having ICR should undergo CT evaluation because CT findings may precede clinical symptoms and signs.
Adjunct Non-Elastic Hip Taping Improves Gait Stability in Cane-Assisted Individuals with Chronic Stroke: A Randomized Controlled Trial
Authors: Wang Ray-Yau , Lin Chieh-Yu , Chen Jyue-Liang , Lee Chun-Shou , Chen Yun-Ju , Yang Yea-Ru
Published: March 2022

Cane-assisted individuals with chronic stroke may perform with an abnormal gait pattern. One of the important factors of gait training for cane-assisted individuals is inducing improvement in lower limb muscle activity of the paretic side. Non-elastic taping on the hip may be used as an adjunct therapy for improving gait. The objective of this study was to investigate effects of non-elastic hip taping combined with exercise on gait in cane-assisted individuals with chronic stroke. This study is a single-blinded, randomized controlled trial. A total of 21 cane-assisted ambulators with chronic stroke were enrolled. Participants in both groups received a therapeutic exercise program, with the experimental and control groups having adjunct non-elastic taping and sham taping on the hip, respectively. The gait, Berg Balance Scale, 6-min walk test, and Fall Efficacy Scale–International were measured at pre-intervention, post-intervention, and 1-month follow-up. The experimental group resulted in significantly better performance in double-support time compared with the control group. Furthermore, the experimental group showed a significant improvement in double-support time and spatial symmetry at post-intervention and 1-month follow-up compared with pre-intervention. This study demonstrated that non-elastic hip taping combined with exercise could improve gait stability in cane-assisted ambulators. Non-elastic hip taping would be a useful adjunct to rehabilitation strategies for individuals with chronic stroke.
Wave Forces on a Partially Reflecting Wall by Oblique Bragg Scattering with Porous Breakwaters over Uneven Bottoms
Authors: Chang Jen-Yi , Tsai Chia-Cheng
Published: March 2022

In this study, the scattering of oblique water waves by multiple variable porous breakwaters near a partially reflecting wall over uneven bottoms are investigated using the eigenfunction matching method (EMM). In the solution procedure, the variable breakwaters and bottom profiles are sliced into shelves separated steps and the solutions on the shelves are composed of eigenfunctions with unknown coefficients representing the wave amplitudes. Using the conservations of mass and momentum as well as the condition for the partially reflecting sidewall, a system of linear equations is resulted that can be solved by a sparse-matrix solver. The proposed EMM is validated by comparing its results with those in the literature. Then, the EMM is applied for studying oblique Bragg scattering by periodic porous breakwaters near a partially reflecting wall over uneven bottoms. The constructive and destructive Bragg scattering are discussed. Numerical results suggest that the partially reflecting wall should be separated from the last breakwater by half wavelength of the periodic breakwaters to migrate the wave force on the vertical wall.
A 2D Model for 3D Periodic Deep-Water Waves
Authors: Chalikov Dmitry
Published: March 2022

The paper is devoted to further development of an accelerated method for simulation of the two-dimensional surface waves at infinite depth with the use of a two-dimensional model derived with simplifications of the three-dimensional equations for potential periodic deep-water waves. A 3D full wave model (FWM) is based on a numerical solution of a 3D Poisson equation written in the surface-fitted coordinates for a nonlinear component of the velocity potential. For sufficient vertical resolution used for the Poisson equation, the 3D model provides very high accuracy. The simplified model is based on the 2D Poisson equation written for a free surface. This exact equation contains both the first and second derivatives of the velocity potential, i.e., it is unclosed. The analysis of the accurate solutions for the 3D velocity potential obtained with the 3D model shows that those variables are linearly connected to each other. This property allows us to obtain a 2D equation for the first derivative of the velocity potential (i.e., vertical velocity on surface), which gives the closed 2D formulation for a 3D problem of two-dimensional waves. The previously developed scheme was not universal since the parameters of the closure scheme had to be adjusted to the specific setting. The current paper offers a new formulation of a closing scheme based on the integral parameters of wave field. The method of closing the equations, as well as the numerical parameters, were chosen on the basis of the multiple numerical experiments with the full nonlinear wave model (FWM) and selection of a suitable closing scheme. That is why the given model can be called Heuristic Wave Model (HWM). The connection between the first and second variables is not precise; hence, the method as a whole cannot be exact. However, the derived 2D model is able to reproduce different statistical characteristics of the 2D wave field with good accuracy. The main advantage of the model developed is its high performance exceeding that of 3D model by about two decimal orders.
Updating the Methodology of Identifying Maize Hybrids Resistant to Ear Rot Pathogens and Their Toxins—Artificial Inoculation Tests for Kernel Resistance to Fusarium graminearum, F. verticillioides, and Aspergillus flavus
Authors: Mesterhazy Akos , Szieberth Denes , Toldine Eva Tóth , Nagy Zoltan , Szabó Balázs , Herczig Beata , Bors Istvan , Tóth Beata
Published: March 2022

Resistance to toxigenic fungi and their toxins in maize is a highly important research topic, as mean global losses are estimated at about 10% of the yield. Resistance and toxin data of the hybrids are mostly not given, so farmers are not informed about the food safety risks of their grown hybrids. According to the findings aflatoxin regularly occurs at preharvest in Hungary and possibly other countries in the region can be jeopardized. We tested, with an improved methodology (two isolates, three pathogens, and a toxin control), 18 commercial hybrids (2017–2020) for kernel resistance (%), and for toxin contamination separately by two–two isolates of F. graminearum, F. verticillioides (mg/kg), and A. flavus (μg/kg). The preharvest toxin contamination was measured in the controls. Highly significant kernel resistance and toxin content differences were identified between hybrids to the different fungi. Extreme high toxin production was found for each toxic species. Only about 10–15% of the hybrids showed higher resistance to the fungal species tested and lower contamination level of their toxins. The lacking correlations between resistance to different fungi and toxins suggest that resistance to different fungi and response to toxin contamination inherits independently, so a toxin analysis is necessary. For safety risk estimation, separated artificial and natural kernel infection and toxin data are needed against all pathogens. Higher resistance to A. flavus and F. verticillioides stabilizes or improves feed safety in hot and dry summers, balancing the harmful effect of climate changes. Resistance and toxin tests during variety registration is an utmost necessity. The exclusion of susceptible or highly susceptible hybrids from commercial production results in reduced toxin contamination.
Sex and Age Differences Modulate Association of Vitamin D with Serum Triglyceride Levels
Authors: Cheng Ying-Lien , Lee Ting-Wei , Lee Ting-I , Kao Yu-Hsun , Wu Chih-Yin , Chen Yi-Jen
Published: March 2022

The sex and age differences in the relationship between vitamin D and lipid levels remain unclear. This retrospective study investigated the correlations between serum 25-hydroxyvitamin D levels and various biomarkers, along with the sex and age differences in these associations, among 573 men and 436 women during physical check-ups. The mean age of the study population was 51.4 years, and 66% of people had serum 25(OH)D levels below 30 ng/mL. People aged over 65 years had higher 25(OH)D levels than those younger than 65 years, and women had lower 25(OH)D levels than men. Younger age (odds ratio (OR) per year = 1.044, 95% CI, 1.029–1.059, p < 0.0001), female sex (OR = 1.779, 95% CI, 1.149–2.755, p = 0.0097), and elevated serum triglyceride (TG) levels (OR per 1 mg/dL = 1.005, 95% CI, 1.002–1.007, p = 0.0002) were all independent risk factors for vitamin D deficiency. Serum 25(OH)D levels were inversely associated with TG levels. The positive association between vitamin D deficiency and hypertriglyceridemia was significant in men (not in women) and in those aged between 50 and 65 years. In conclusion, younger individuals, women, and middle-aged men with hypertriglyceridemia are at higher risk of vitamin D deficiency.
Use of Long-Acting Injectable Antipsychotics in Inpatients with Schizophrenia Spectrum Disorder in an Academic Psychiatric Hospital in Switzerland
Authors: Reymann Stephan , Schoretsanitis Georgios , Egger Stephan T. , Mohonko Alexey , Kirschner Matthias , Vetter Stefan , Homan Philipp , Seifritz Erich , Burrer Achim
Published: March 2022

Long-acting injectable antipsychotics (LAIs) offer many benefits to patients with schizophrenia spectrum disorder (SSD). They are used with very different frequencies due to questions of eligibility or patients and prescribers’ attitudes towards LAI use. We assessed the prescribing rates of LAIs in a large academic psychiatric hospital with a public service mandate in Switzerland and compared them with other countries and health care systems. To our knowledge, this study is the first to investigate inpatient LAI use in Europe. Medical records of all patients diagnosed with SSD discharged from the Clinic of Adult Psychiatry of the University Hospital of Psychiatry Zurich over a 12 month period from January to December 2019 were evaluated regarding the prescribed antipsychotics at the time of discharge. The rates of use of LAIs among all patients and among patients receiving LAI-eligible antipsychotic substances were assessed retrospectively. We assessed records of 885 patients with SSD. Among all cases, 13.9% received an LAI. Among patients who received antipsychotic medication that was eligible for LAI use (n = 434), 28.1% received an agent as an LAI. LAI use included paliperidone palmitate (69.9%), aripiprazole monohydrate (14.6%), risperidone (4.9%) and first-generation LAIs (9.8%). Compared to international frequencies of LAI administration, the prescription rate of LAIs in SSD patients was low. Further studies will evaluate patient- and prescriber-related reasons for this low rate.
Circulating Tumor Cell Detection during Neoadjuvant Chemotherapy to Predict Early Response in Locally Advanced Oropharyngeal Cancers: A Prospective Pilot Study
Authors: Gauthier Arnaud , Philouze Pierre , Lauret Alexandra , Alphonse Gersende , Malesys Céline , Ardail Dominique , Payen Léa , Céruse Philippe , Wozny Anne-Sophie , Rodriguez-Lafrasse Claire
Published: March 2022

Patients with locally advanced oropharyngeal carcinoma treated with neoadjuvant chemotherapy are reassessed both radiologically and clinically to adapt their treatment after the first cycle. However, some responders show early tumor progression after adjuvant radiotherapy. This cohort study evaluated circulating tumor cells (CTCs) from a population of locally advanced oropharyngeal carcinoma patients treated with docetaxel, cisplatin, and 5-fluorouracil (DCF) induction chemotherapy or DCF with a modified dose and fractioned administration. The counts and phenotypes of CTCs were assessed at baseline and at day 21 of treatment, after isolation using the RosetteSepTM technique based on negative enrichment. At baseline, 6 out of 21 patients had CTCs (28.6%). On day 21, 5 out of 11 patients had CTCs (41.6%). There was no significant difference in the overall and progression-free survival between patients with or without CTCs at baseline (p = 0.44 and 0.78) or day 21 (p = 0.88 and 0.5). Out of the 11 patients tested at day 21, 4 had a positive variation of CTCs (33%). Patients with a positive variation of CTCs display a lower overall survival. Our findings suggest that the variation in the number of CTCs would be a better guide to the management of treatment, with possible early changes in treatment strategy.
Measures of Volatility, Crises, Sentiment and the Role of U.S. ‘Fear’ Index (VIX) on Herding in BRICS (2007–2021)
Authors: Zhang Hang , Giouvris Evangelos
Published: March 2022

We look into determinants (volatility, crises, sentiment and the U.S. ‘fear’ index) of herding using BRICS as our sample. Investors herd selectively to crises and herding is a short-lived phenomenon. Herding was highest during the global financial crisis (only China was affected). There was no herding during the European debt crisis and COVID. With regard to the relationship between volatility and CSAD (cross sectional absolute deviation)/herding, a lower CSAD (movement in a specific direction) brings about less volatility. However, a high volatility amplifies herding (reduces CSAD), especially in China. Russia and South Africa are unresponsive to volatility levels (low/high) and herding. We also observe volatility heterogeneity. Different volatility measures have different effects on different markets. There is limited evidence to suggest that sentiment (based on principal component) Granger causes herding/CSAD. Herding is a period and market variant and unrelated to crises. The U.S. ‘fear’ index has a short-lived, limited effect on CSAD/herding (during COVID only) for all countries except China. In addition, Granger causality analysis indicates a two-way relationship between the U.S. ‘fear’ index and CSAD/herding, unrelated to crises.
The Interplay between Digitalization, Education and Financial Development: A European Case Study
Authors: Horobet Alexandra , Mnohoghitnei Irina , Zlatea Emanuela Marinela Luminita , Belascu Lucian
Published: March 2022

The paper explores the relationship between education, digitalization, and financial development between 1996 and 2019 with the aim of showcasing the differences between developed and emerging economies in Europe. We use a Bayesian VAR framework that includes variables related to education, digitalization, and financial development, as well as several endogenous variables to control for differences between countries in terms of nominal GDP growth, unemployment rate, and trade openness. Our findings clearly demonstrate the dynamic interdependence between financial development—including its two main components, financial institutions, and financial markets, digitalization, and education. Furthermore, we find that education is a leading variable in the financial development–education–digitalization nexus, whereas financial development and digitalization are laggard variables. These findings open possibilities for influencing joint policies on digitalization, education, and financial development, particularly in emerging European countries.
Urban Parks Hydrological Regime in the Context of Climate Change—A Case Study of Štěpánka Forest Park (Mladá Boleslav, Czech Republic)
Authors: Kupec Petr , Marková Jana , Pelikán Petr , Brychtová Martina , Autratová Sabina , Fialová Jitka
Published: March 2022

The paper presents the results of a case study that was prepared as a basis for decision-making processes in the context of the impacts of global climate change. The article is focused on a very important part of the urban environment, namely urban forests. When taking planning measures in periurban forests, two realities must always be addressed, i.e., adaptation measures to mitigate the effects of climate change on the forest complex in question and its use to mitigate the effects of climate change in its surroundings must both be considered. It is a well-known fact that forest communities (of any kind) are on the one hand affected by the impacts of climate change, but on the other hand are able to mitigate its effects on their surroundings. The case study was of land near the town of Mladá Boleslav. The aim was to analyse the hydrological regime of the Štěpánka Forest Park, nicknamed “the lungs of Mladá Boleslav”. Modelling of the runoff coefficient was made for the whole park area, as well as for the part on the left bank of the Klenice River (forested part). The runoff conditions of the site and their subparameters are addressed in the study by comparing the current state with the modelled state after deforestation of the site, e.g., due to drought. As far as the spatial layout of the forest is concerned, it is absolutely essential to maintain an integrated stand on the site with a lower stem cover (fewer individuals per plot) and a lower regeneration period. These aspects of a growing matrix forest stand will ensure its sustainability, in particular the sustainable water management of the trees in the context of lower water reserves in the rhizosphere and the greater ability of younger individuals to adapt to changes in site conditions (replacement of stress-resistant types by resilient types).
Coupling Coordination of Urban Pseudo and Reality Human Settlements
Authors: Tian Shenzhen , Yang Bing , Liu Zhangli , Li Xueming , Zhang Wei
Published: March 2022

Urban pseudo and reality human settlements (PHSs and RHSs) are important components of the human–land relationship regional system. To explore the coupling and coordination relationship and principle among them is an important approach to high-quality coordinated urban development. Based on the three-dimensional development of human settlements, the theoretical system of a “three states” dynamic frame diagram is constructed. The spatio-temporal heterogeneity and driving principle of coupling coordination among PHSs and RHSs in 34 prefecture-level cities in northeast China from 2011 to 2019 were explained by using the coupling coordination degree, spatial trend surface analysis and geographic detector techniques, and the evolution principle of spatio-temporal coordination was revealed. The results show that: (1) in the temporal dimension, the coupling coordination degree among PHSs and RHSs in the three provinces shows a smooth growth from “slight disadjustment” to “near disadjustment”; (2) With Shenyang, Dalian, Changchun and Harbin as the center, the coordination degree shows a circular pattern decreasing from the transition area to peripheral area. In the direction of south and north, the spatial evolution trend shows a gradual change from a “—” shape to “U” shape. There is spatio-temporal variation of the trend surface from an inverted “U” shape to “—” shape in the east–west direction; (3) The socioeconomic situation is an important driving factor, and the tool system is a new driving system for the coupling and coordinated development of urban PHSs and RHSs.
From the Structural and (Dys)Function of ATP Synthase to Deficiency in Age-Related Diseases
Authors: Garone Caterina , Pietra Andrea , Nesci Salvatore
Published: March 2022

The ATP synthase is a mitochondrial inner membrane complex whose function is essential for cell bioenergy, being responsible for the conversion of ADP into ATP and playing a role in mitochondrial cristae morphology organization. The enzyme is composed of 18 protein subunits, 16 nuclear DNA (nDNA) encoded and two mitochondrial DNA (mtDNA) encoded, organized in two domains, FO and F1. Pathogenetic variants in genes encoding structural subunits or assembly factors are responsible for fatal human diseases. Emerging evidence also underlines the role of ATP-synthase in neurodegenerative diseases as Parkinson’s, Alzheimer’s, and motor neuron diseases such as Amyotrophic Lateral Sclerosis. Post-translational modification, epigenetic modulation of ATP gene expression and protein level, and the mechanism of mitochondrial transition pore have been deemed responsible for neuronal cell death in vivo and in vitro models for neurodegenerative diseases. In this review, we will explore ATP synthase assembly and function in physiological and pathological conditions by referring to the recent cryo-EM studies and by exploring human disease models.
Genetic Workup for Charcot–Marie–Tooth Neuropathy: A Retrospective Single-Site Experience Covering 15 Years
Authors: Gemelli Chiara , Geroldi Alessandro , Massucco Sara , Trevisan Lucia , Callegari Ilaria , Marinelli Lucio , Ursino Giulia , Hamedani Mehrnaz , Mennella Giulia , Stara Silvia , Maggi Giovanni , Mori Laura , Schenone Cristina , Gotta Fabio , Patrone Serena , Mammi Alessia , Origone Paola , Prada Valeria , Nobbio Lucilla , Mandich Paola , Schenone Angelo , Bellone Emilia , Grandis Marina
Published: March 2022

Charcot–Marie–Tooth (CMT) disease is the most commonly inherited neurological disorder. This study includes patients affected by CMT during regular follow-ups at the CMT clinic in Genova, a neuromuscular university center in the northwest of Italy, with the aim of describing the genetic distribution of CMT subtypes in our cohort and reporting a peculiar phenotype. Since 2004, 585 patients (447 index cases) have been evaluated at our center, 64.9% of whom have a demyelinating neuropathy and 35.1% of whom have an axonal neuropathy. A genetic diagnosis was achieved in 66% of all patients, with the following distribution: CMT1A (48%), HNPP (14%), CMT1X (13%), CMT2A (5%), and P0-related neuropathies (7%), accounting all together for 87% of all the molecularly defined neuropathies. Interestingly, we observe a peculiar phenotype with initial exclusive lower limb involvement as well as lower limb involvement that is maintained over time, which we have defined as a “strictly length-dependent” phenotype. Most patients with this clinical presentation shared variants in either HSPB1 or MPZ genes. The identification of distinctive phenotypes such as this one may help to address genetic diagnosis. In conclusion, we describe our diagnostic experiences as a multidisciplinary outpatient clinic, combining a gene-by-gene approach or targeted gene panels based on clinical presentation.
Possible Ribose Synthesis in Carbonaceous Planetesimals
Authors: Paschek Klaus , Kohler Kai , Pearce Ben K. D. , Lange Kevin , Henning Thomas K. , Trapp Oliver , Pudritz Ralph E. , Semenov Dmitry A.
Published: March 2022

The origin of life might be sparked by the polymerization of the first RNA molecules in Darwinian ponds during wet-dry cycles. The key life-building block ribose was found in carbonaceous chondrites. Its exogenous delivery onto the Hadean Earth could be a crucial step toward the emergence of the RNA world. Here, we investigate the formation of ribose through a simplified version of the formose reaction inside carbonaceous chondrite parent bodies. Following up on our previous studies regarding nucleobases with the same coupled physico-chemical model, we calculate the abundance of ribose within planetesimals of different sizes and heating histories. We perform laboratory experiments using catalysts present in carbonaceous chondrites to infer the yield of ribose among all pentoses (5Cs) forming during the formose reaction. These laboratory yields are used to tune our theoretical model that can only predict the total abundance of 5Cs. We found that the calculated abundances of ribose were similar to the ones measured in carbonaceous chondrites. We discuss the possibilities of chemical decomposition and preservation of ribose and derived constraints on time and location in planetesimals. In conclusion, the aqueous formose reaction might produce most of the ribose in carbonaceous chondrites. Together with our previous studies on nucleobases, we found that life-building blocks of the RNA world could be synthesized inside parent bodies and later delivered onto the early Earth.
Special Issue “Structure, Activity, and Function of Protein Methyltransferases”
Authors: Dhayalan Arunkumar , Jeltsch Albert
Published: March 2022

Post-translational modifications (PTMs) largely expand the functional diversity of the proteome [...]
2-Fluorofucose Attenuates Hydrogen Peroxide-Induced Oxidative Stress in HepG2 Cells via Nrf2/keap1 and NF-κB Signaling Pathways
Authors: Tu Mengjue , Fan Xingshuo , Shi Jianan , Jing Shengnan , Xu Xiaole , Wang Yuqin
Published: March 2022

Fucosylation is one of the most important glycan terminal modifications that affects multiple biological activities of proteins. 2-Fluorofucose (2FF), its specific inhibitor, has recently been reported to reveal numerous biological effects by blocking fucosylation both in vitro and in vivo. The current study aimed to evaluate the effect of 2FF on hydrogen peroxide (H2O2)-induced oxidative damage in vitro. In our study, treatment with H2O2 increased the level of fucosylation, and 2FF improved the cell viability in H2O2-treated HepG2 cells. Our study also showed that 2FF significantly decreased the overproduction of reactive oxygen species (ROS) induced by H2O2 and the activities of catalase, glutathione and Mn-superoxide dismutase were remarkably increased by 2FF pretreatment. Furthermore, 2FF attenuated H2O2-induced early mitochondria dysfunction. The second part of the study revealed that 2FF enhanced antioxidant capacity by affecting Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Being pretreated with 2FF significantly increased the nuclear translocation of Nrf2 and simultaneously promoted the expression of downstream proteins, such as HO-1 and NQO1. Moreover, 2FF remarkably suppressed the expression of inflammation-associated proteins. Taken together, these data suggest that 2FF might have a potential therapeutic effect for oxidative stress.
Efficacy and Safety of Da-Chai-Hu-Tang in Lipid Profiles in High-Risk, Statin-Treated Patients with Residual HyperTG: A 12-Week, Randomized, Active-Control, Open Clinical Study
Authors: Lee Young-Shin , Lee Jung-Myung , Chung Hyemoon , Woo Jong-Shin , Lee Byung-Cheol , Kim Weon
Published: March 2022

Da-Chai-Hu-Tang (DCHT) is a herbal extract that has been shown to reduce serum triglyceride (TG) levels in animal experiments as well as small clinical trials. This study aimed to evaluate the efficacy and safety of DCHT in high-risk, statin-treated patients with residual hypertriglyceridemia (hyperTG). This was a 12-week, randomized, active-controlled, open-label, single-center trial. Of these patients, 42 had high cardiovascular risks whose LDL cholesterol levels were controlled by statin treatment; however, with TG levels of 200 to 500 mg/dL they were randomly assigned 1:1 to the OMEGA3 or DCHT group. The primary endpoint was defined as the percentage change in TG at 12 weeks, and changes in other lipid profiles and endothelial cell function were included as secondary endpoints. Safety analyses were also conducted. In the OMEGA3 group, the average TG level decreased from 294.5 ± 72.0 to 210.0 ± 107.8 mg/dL (p = 0.004), and in the DCHT group, from 288.7 ± 59.1 to 227.5 ± 98.1 mg/dL (p = 0.001). The percentage change in TG was −27.6 ± 33.6 and −22.4 ± 24.1 (p = 0.58), respectively, and there was no significant difference between the two groups. There were no severe adverse events in either group. In high-risk, statin-treated patients with residual hyperTG, the administration of OMEGA3 or DCHT for 12 weeks resulted in a significant reduction in TG, and the effect of DCHT was not inferior to that of OMEGA3.
Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors
Authors: Zhang Xin , Li Huiqin , Lv Xiupeng , Hu Li , Li Wen , Zi Meiting , He Yonghan
Published: March 2022

Immunotherapy has revolutionized the established therapeutics against tumors. As the major immunotherapy approach, immune checkpoint inhibitors (ICIs) achieved remarkable success in the treatment of malignancies. However, the clinical gains are far from universal and durable, because of the primary and secondary resistance of tumors to the therapy, or side effects induced by ICIs. There is an urgent need to find safe combinatorial strategies that enhance the response of ICIs for tumor treatment. Diets have an excellent safety profile and have been shown to play pleiotropic roles in tumor prevention, growth, invasion, and metastasis. Accumulating evidence suggests that dietary regimens bolster not only the tolerability but also the efficacy of tumor immunotherapy. In this review, we discussed the mechanisms by which tumor cells evade immune surveillance, focusing on describing the intrinsic and extrinsic mechanisms of resistance to ICIs. We also summarized the impacts of different diets and/or nutrients on the response to ICIs therapy. Combinatory treatments of ICIs therapy with optimized diet regimens own great potential to enhance the efficacy and durable response of ICIs against tumors, which should be routinely considered in clinical settings.
Design, Synthesis and 5-HT1A Binding Affinity of N-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propyl)tricyclo[3.3.1.13,7]decan-1-amine and N-(3-(4-(2-Methoxyphenyl)piperazin-1-yl)propyl)-3,5-dimethyl-tricylo[3.3.1.13,7]decan-1-amine
Authors: Zoidis Grigoris , Loza María Isabel , Catto Marco
Published: March 2022

Based on previously highlighted structural features, the development of highly selective 5-HT1A receptor inhibitors is closely linked to the incorporation of a 4-alkyl-1-arylpiperazine scaffold on them. In this paper, we present the synthesis of two new compounds bearing the 2-MeO-Ph-piperazine moiety linked via a three carbon atom linker to the amine group of 1-adamantanamine and memantine, respectively. Both were tested for their binding affinity against 5-HT1A receptor. N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)tricyclo[3.3.1.13,7]decan-1-amine fumarate (8) and N-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-3,5-dimethyl-tricylo[3.3.1.13,7]decan-1-amine fumarate (10) proved to be highly selective ligands towards 5-HT1A receptor with a binding constant of 1.2 nM and 21.3 nM, respectively, while 5-carboxamidotriptamine (5-CT) (2) was used as an internal standard for this assay with a measured Ki = 0.5 nM.
Grain Refinement of Inconel 718 Superalloy—The Effect of Rotating Magnetic Field
Authors: Silva Rui Pedro , Soares Rui , Neto Rui , Reis Ana , Paiva Ricardo , Madureira Rui , Silva José
Published: March 2022

The effect of the application of a rotating magnetic field on the average grain size of IN718 castings was experimentally studied. For the purpose, four parts were produced by investment casting and characterized. The first casting was produced without application of RMF for comparison. The remaining ones were submitted to different RMF frequencies for 15 min and subsequently to the pouring of the nickel-based superalloy. In these three castings, the RMF frequencies applied were, respectively, 15 Hz, 75 Hz and 150 Hz. All the other process parameters were kept constant during the execution of the experimental procedure. The average grain size of the samples was determined according to the ASTM E112-13 standard, using intercept methods. Macro hardness measurements, tensile testing and SEM-EDS analysis were conducted in order to evaluate the casting’s mechanical properties and microstructures. The results demonstrate a noticeable grain size reduction in the samples submitted to rotating magnetic field. An average grain area reduction, greater than 96%, was achieved in the castings where RMF frequencies of 75 Hz and 150 Hz were applied. The application of RMF also caused a morphological change in the casting’s dendrites from cellular to almost equiaxed. Additionally, it originated the decrease of the size and amount of needle-like δ phase. Regarding mechanical properties of the cast parts, no major differences were verified.
Fe3O4@PDA@PEI Core-Shell Microspheres as a Novel Magnetic Sorbent for the Rapid and Broad-Spectrum Separation of Bacteria in Liquid Phase
Authors: Zhang Yueqi , Du Bin , Wu Yuting , Liu Zhiwei , Wang Jiang , Xu Jianjie , Tong Zhaoyang , Mu Xihui , Liu Bing
Published: March 2022

Bacterial infection is a significant cause of morbidity and mortality to humans worldwide. Thus, a method for nonspecific, sensitive, and rapid enrichment of such bacteria is essential for bacteria detection and treatment. This study demonstrates a self-made core-shell Fe3O4@Polydopamine@Polyethyleneimine magnetic beads (Fe3O4@PDA@PEI MBs) with a high density positive charge-based magnetic separation scheme for the broad-spectrum rapid enrichment of microorganisms in the liquid phase. MBs with a high-density positive charge have a strong electrostatic attraction to most microorganisms in nature. Our scheme is as follows: (1) wrapping dopamine (DA) on the iron oxide through self-polymerization and wrapping PEI on the outermost shell layer in a mode of crosslinking with the PDA; (2) subsequently, the Fe3O4@PDA@PEI MBs were used to concentrate microorganisms from the sample solution; (3) performing magnetic separation and calculating the adsorption efficiency. The as-prepared Fe3O4@PDA@PEI MBs composite was carefully characterized by zeta potential analysis, Value stream-mapping (VSM), transmission electron microscopy (TEM), and Fourier transforms infrared spectrometry (FT-IR). In this study, both gram-positive and gram-negative bacteria could be captured in three minutes through electrostatic interaction. Furthermore, the adsorption efficiency on gram-negative (>98%) is higher than that on gram-positive (>95%), allowing for a simple, rapid assay to enrich organisms in resource-limited settings.