bluuebunny/crossref_metadata_2025 huggingface dataset:
Vanadium Complexes with Thioanilide Derivatives of Amino Acids: Inhibition of Human Phosphatases and Specificity in Various Cell Models of Metabolic Disturbances
Authors: Kazek Grzegorz , Głuch-Lutwin Monika , Mordyl Barbara , Menaszek Elżbieta , Kubacka Monika , Jurowska Anna , Cież Dariusz , Trzewik Bartosz , Szklarzewicz Janusz , Papież Monika A.
Published: March 2024

In the text, the synthesis and characteristics of the novel ONS-type vanadium(V) complexes with thioanilide derivatives of amino acids are described. They have shown inhibition of human protein tyrosine phosphatases (PTP1B, LAR, SHP1 and SHP2) in the submicromolar range, as well as inhibition of non-tyrosine phosphatases (CDC25A and PPA2) similar to bis(maltolato)oxovanadium(IV)(BMOV). The ONS complexes increased [14C]-deoxy-D-glucose transport into C2C12 myocytes, and one of them, VC070, also enhanced this transport in 3T3-L1 adipocytes. These complexes inhibited gluconeogenesis in hepatocytes HepG2, but none of them decreased lipid accumulation in the non-alcoholic fatty liver disease model using the same cells. Compared to the tested ONO-type vanadium complexes with 5-bromosalicylaldehyde and substituted benzhydrazides as Schiff base ligand components, the ONS complexes revealed stronger inhibition of protein tyrosine phosphatases, but the ONO complexes showed greater activity in the cell models in general. Moreover, the majority of the active complexes from both groups showed better effects than VOSO4 and BMOV. Complexes from both groups activated AKT and ERK signaling pathways in hepatocytes to a comparable extent. One of the ONO complexes, VC068, showed activity in all of the above models, also including glucose utilization in the myocytes and glucose transport in insulin-resistant hepatocytes. The discussion section explicates the results within the wider scope of the knowledge about vanadium complexes.
Phylogenetic Analysis of Pyruvate-Ferredoxin Oxidoreductase, a Redox Enzyme Involved in the Activation of Nitro-Based Prodrugs in Bacteria and Protozoa
Authors: Duwor Seth , Brites Daniela , Mäser Pascal
Published: March 2024

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.
Reliability of IL-6 Alone and in Combination for Diagnosis of Late Onset Sepsis: a Systematic Review
Authors: Eichberger Julia , Resch Elisabeth , Resch Bernhard
Published: March 2024

Diagnosis of neonatal sepsis is difficult as signs and symptoms are nonspecific. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in term and preterm infants after 72 hours of life (late-onset sepsis-LOS). We searched for IL-6 diagnostic accuracy studies between 1990 and 2020 using the PubMed database. Study selection was performed. The range of reported IL-6 sensitivities and specificities was 68% to 100% and 28% to 100%, respectively, the median values were 85.7% and 82% from 15 studies including 1306 infants. Subgroup analysis was performed. Sensitivity (87% vs 82%), but not specificity (both 86%), was better in preterm infants than in preterm and term infants. Early sample collection had the highest sensitivity (84%), but the lowest specificity (86%). To assess quality we used a STARD checklist adapted for septic neonates. Limitation of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarker. We concluded that IL-6 had a good performance especially in the preterm infant population and best results are achieved by measurements at the time of LOS suspicion.
Cultural Heritage Tourism in Tanzania: A Systematic Literature Review
Authors: Bakari Stephen
Published: March 2024

Cultural tourism in Tanzania presents a diverse tapestry of traditions, varied ethnic groups, and historical accounts. This article aims to pinpoint areas for further exploration in the cultural tourism sector of Tanzania and analyze their potential impacts. The study conducted a systematic review of the literature following established inclusion criteria as well as the Preferred Reporting Items for Systematic Reviews and meta-analysis guidelines. A total of 21 articles focused on Tanzania Cultural Heritage Tourism from sources such as Google Scholar and web databases were examined, revealing several research gaps, including theoretical, contextual and methodological aspects. Furthermore, the research offers insights into theoretical implications and recommends avenues for future studies that could advance the field by addressing these knowledge gaps providing valuable direction to new researchers interested in exploring these specific areas as well as practitioners seeking a comprehensive understanding of various aspects related to Tanzania's cultural heritage tourism
Nutrient Removal and Recovery from Municipal Wastewater
Authors: Derco Jan , Žgajnar Gotvajn Andreja , Guľašová Patrícia , Kassai Angelika , Šoltýsová Nikola
Published: March 2024

With the ongoing amendment of the EU legislation on the treatment of urban wastewater, stricter requirements for the removal of pollutants are expected, which calls for the need for innovative wastewater treatment technologies. Biological systems are still the first choice. The survey of typical bioreactors applied in wastewater treatment is presented. Wastewater treatment objective, bio-chemical environment and microbial growth are selected as a main criterion for classification of these bioreactors. Hydraulic and kinetic aspects are considered, advantages and drawbacks of these bioreactors regarding the selection of appropriate type of the reactor as well as regarding operation of reactors are mentioned. The aim of this paper is to provide operators and designers with a brief overview of selected traditional and advanced processes, reactors, and technologies for nutrient removal from municipal wastewater. Another goal is to discuss the possibilities and limitations to comply with more strict effluent standards. From the evaluation of the published papers, it follows that the currently applied traditional methods of nutrients removal have the potential to convey also with the expected stricter limits.
Conserved Functions of Orthohepadnavirus X Proteins to Inhibit Type-I Interferon Signaling
Authors: Choonnasard Amonrat , Shofa Maya , Okabayashi Tamaki , Saito Akatsuki
Published: March 2024

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.
Effect of Heat Treatment on the Microstructure and Mechanical Properties of Plasma Cladded CoCrFeNiMn Coatings on Compacted Graphite Iron
Authors: Zhang Bo , Fu Rui-Tao , Gao Pei-Hu , Chen Bai-Yang , Naumov Anton , Li Fei , Zhao Da-Ming , Yang Zhong , Guo Yong-Chun , Li Jian-Ping , Chen Lei , Gong Jin-Yuan , Liu Jiawei , Li Yu
Published: March 2024

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.
An Optimization Model for Flight Rescheduling from an Airport’s Centralized Perspective for Better Management of Demand and Capacity Utilization
Authors: Seifi Abbas , Ponnambalam Kumaraswamy , Kudiakova Anna , Aultman-Hall Lisa
Published: March 2024

Over-capacity flight scheduling by commercial airlines due to the surging demand in recent years creates congestion and significant delays at major airports. This maximizing throughput attitude calls for tactical flight rescheduling to comply with airports’ capacity limitations and distribute the peak hour demand over the course of a day. Such displacements of flights may cause significant problems and costs for airlines and some cancellations or missed connections for the passengers. This paper presents an optimization model for flight rescheduling at a schedule-coordinated airport to minimize congestion and flight delays. The optimization model is used to make better scheduling intervention decisions considering the airport resource constraints and safety of operation. We have also developed a simulation method to replicate arrival and departure processes in such an airport. The simulation adheres to a first come first served (FCFS) discipline and enforces runway capacity constraints and minimum turnaround times. We compare the delays caused by an ad hoc FCFS operation with those obtained by the optimization model. Computational results from a case study demonstrate that a reduction of 40.7% and 61.6% in total delay times for the arrival and departure flights can be achieved by the optimization model. It also facilitates implementing a collaborative decision-making system for better coordination with commercial airlines.
Integration of GNSS Technology and Geometric Levelling for Accurate Height Determination in Uneven Terrains: A Case Study in Lebanon
Authors: Mustafin Murat , Moussa And Hiba
Published: March 2024

The technology for determining the point’s coordinates on the earth’s surface using the global navigation satellite system (GNSS) is becoming the norm along with ground-based methods. In this case, determining coordinates does not cause any particular difficulties. However, to identify normal heights using this technology with a given accuracy, special research is required. The fact is that satellite determinations of geodetic heights (h) over an ellipsoid surface differ from ground-based measurements of normal height (HN) over a quasi-geoid surface by a certain value called quasi-geoid height or height anomaly (ζ). In relation to determining heights of a certain territory, the concept of geoid height (N) is usually operated when dealing with a geoid model. In this work, geodetic and normal heights are determined for 5 control points in three different regions in Lebanon, where measurements are carried out using GNSS technology and geometric levelling. The obtained quasi-geoid heights are compared with geoid heights derived from the global Earth model EGM2008. The results obtained showed that, in the absence of gravimetric data, the combination of global Earth model data, geometric levelling for selected areas and satellite determinations allows the creation of a high accurate altitude network for mountainous areas.
Community Directed Vector Control to Accelerate Onchocerciasis Elimination
Authors: Jacob Benjamin , Michael Edwin , Unnasch Thomas Raymond
Published: March 2024

Onchocerciasis, or river blindness, has historically been one of the most important causes of blindness worldwide, and a major cause of socio-economic disruption, particularly in sub-Saharan Africa. Its importance as a cause of morbidity and an impediment to economic development in some of the poorest countries in the world motivated the international community to implement several programs to control or eliminate this scourge. Initially, these involved reducing transmission of the causative agent Onchocerca volvulus through controlling the vector population. When ivermectin was found to be a very effective drug for treating onchocerciasis, the strategy shifted to mass drug administration (MDA) of endemic communities. In some countries, both vector control and ivermectin MDA have been used together. However, traditional vector control methods involve treating rivers in which the black fly vectors breed with insecticides, a process which is expensive, requires trained personnel to administer, and is ecologically harmful. In this review, we discuss recent research into alternatives to riverine insecticide treatment, which are inexpensive, ecologically less harmful and which can be implemented by the affected communities themselves. These can dramatically reduce vector densities and, when combined with ivermectin MDA, can accelerate the time to elimination when compared to MDA alone.
Design and Implementation of a MIMO Integral Resonant Control for Active Vibration Control of Pedestrian Structures
Authors: Pereira Emiliano , Wang Xidong , Díaz Iván M. , Aphale Sumeet S.
Published: March 2024

In contemporary construction, the prevalence of vibration serviceability issues in lightweight and slender structures has become increasingly common, owing to advancements in building materials and construction methods. While these structures often meet the criteria for ultimate limit states, they can still elicit complaints due to excessive vibrations induced by human activity. To address this challenge, the Integral Resonant Control (IRC) technique has emerged as a favored approach for actively damping vibrations in various systems. This study introduces a fresh perspective on implementing a multi-input multi-output (MIMO) IRC scheme for active vibration control (AVC) specifically tailored for pedestrian structures utilizing inertial mass actuators. Building upon a common framework and design methodology outlined in previous research, this work presents a novel application of MIMO IRC for AVC. The designed controller is rigorously tested and implemented on a laboratory floor structure to validate its efficacy.
An Insight into Knowledge, Perspective, and Practices of Indian Optometrists Towards Childhood Myopia
Authors: Naik Archana , Karthikeyan Siddharth K , Ramesh Jivitha Jyothi , Bhaskar Shwetha , Ganapathi Chinnappa A , Biswas Sayantan
Published: March 2024

Knowledge of clinical approaches and barriers in managing childhood myopia is limited. This study explores optometrists' knowledge, attitude, and practice towards childhood myopia. A 26-item survey was circulated online among practising optometrists in India. The questionnaire assessed the demographics, knowledge, self-reported clinical practice behaviour, barriers, source of information guiding their management, and extent of adult caregiver engagement for childhood myopia. Of 393 responses, a significant proportion of respondents (32.6%–92.4%) were unaware of the ocular complications associated with high myopia, with less than half (46.5%) routinely measuring axial length in clinical practice. Despite the improved awareness of emerging myopia management options, the uptake remains generally poor, with single-vision distance full correction spectacles (70.3%) being the most common mode of vision correction. Barriers to adopting emerging evidence are medico-legal concerns and the absence of clinical practice guidelines. Original research articles were the primary source of information supporting clinical practice. Most (>70%) respondents considered involving the adult caregiver in their child's clinical decision-making process. While practitioner knowledge, perspective, and practice are improving, childhood myopia management evidence is constantly evolving and remains inconclusive. Evidence-based practice guidelines and continuing education on myopia control might be helpful for practitioners in improving their clinical decision-making skills.
Animal Health Discourse during Ecological Crisis in the Media. Lessons Learnt from the Flood in Thessaly from the One Health Perspective
Authors: Meletis Eleftherios , Jarynowski Andrzej , Maksymowicz Stanislaw , Kostoulas Polychronis , Belik Vitaly
Published: March 2024

Due to the increasing risk of extreme events caused by climate change (i.e. floods, fires, hurricanes) or wars, European veterinary public health may need some improvement. Utilizing a mix of qualitative (participatory observation) and quantitative methods (Internet mining), we analyzed the Greek media responses to the millennial flood in Thessaly (September 2023), focusing on animal health (including wild, companion animals and livestock) and public sentiment towards epizootic/epidemic threats. The study revealed a gap in crisis management plans regarding veterinary-related issues, emphasizing the need for comprehensive emergency response strategies. Our findings show how: (i) lay-referral system is projecting perception of epidemic threats into the population; (ii) emotional load of images of animal carcasses is misused by media creators aiming for big audience; (iii) pets owners are creating on-line communities for searching and treatment of their pets. Our results stress the importance of integrating crisis communication in consecutive phases of the discourse, such as (i) weather change; (ii) acute flood; (iii) recovery; (iv) outbreaks, into veterinary practices to better prepare for such disasters.
Starting DNA Synthesis: Initiation Processes during the Replication of Chromosomal DNA in Humans
Authors: Nasheuer Heinz P. , Meaney Anna Marie
Published: March 2024

The initiation reactions of DNA synthesis are central processes during human chromosomal DNA replication. They are separated into two main processes: the initiation events at replication origins, the start of the leading strand synthesis for each replicon, and the numerous initiation events taking place during lagging strand DNA synthesis. In addition, a third mechanism is the re-initiation of DNA synthesis after replication fork stalling, which takes place when DNA lesions hinder the progression of DNA synthesis. The initiation of leading strand synthesis at replication origin is regulated at multiple levels, from the origin recognition to the assembly and activation of replicative helicase, the Cdc45-MCM2-7-GINS (CMG) complex. In addition, the multiple interactions of the CMG complex with the eukaryotic replicative DNA polymerases such as DNA polymerase α-primase (Pol α), DNA polymerase δ and ε at replication forks play pivotal roles in the mechanism of initiation reactions including the initiation of signalling unperturbed and stalled replication forks, ‘replication stress’ events, via ATR (ATM-Rad 3-related protein kinase). All these processes are essential for the accurate transfer of the cells’ genetic information to their daughters. Failures and dysfunctions in these processes gives rise to genome instability followed by genetic diseases including cancer. Thus, in their review ‘Hallmarks of Cancer: New Dimensions‘ Hanahan and Weinberg (2022) called genome instability a fundamental function in the development process of cancer cells. In recent years, the understanding of the initiation processes and mechanisms of human DNA replication has made substantial progress at all levels which will be discussed in the review.
The Influence of Geometry on the Energy Capture of a Point Absorber Wave Energy Converter in the Coast of Mexico
Authors: Martinez Flores Alejandro , Medina Rodríguez Ayrton Alfonso , Mendoza Edgar , Silva Rodolfo
Published: March 2024

The wave energy converter (WEC) technology constantly develops new designs and models. To encourage its development within the energy sector, research is required to improve current designs and create durable and effective devices. However, it is also crucial to investigate the suitability of a WEC to a site-specific sea condition as this can impact its optimal power absorption and constructability. This study evaluates and compares the efficiency of a heaving buoy with varied geometries in one of the most energetic places along the Mexican coast. A statistical analysis of the wave climate on the coast of Ensenada during the last 42 years is performed to define the conditions to which the device is subjected. The location of the WEC in shallow waters is chosen using a computational model which solves the modified mild slope equation in its elliptic shape. The heaving buoy floater is studied using three distinct geometries: a semi-sphere, a cylinder, and a proposed rounded semi-rectangle. The hydrodynamic response of the three geometries is then analysed in the frequency and time domain using ANSYS AQWA. The hydrodynamic study involves the assessment of the floating body dynamics, exerted forces, the power absorbed as well as the suitability of the proposed power take-off (PTO) system. Findings reveal that the proposed geometry absorbs the most energy, with an annual power of 135.11 MW, and that the transmission PTO design is appropriate for this type of technology.
Unlocking the Long-Term Effectiveness of Benralizumab in Severe Eosinophilic Asthma: A Three-Year Real-Life Study
Authors: Pini Laura , Bagnasco Diego , Beghe Bianca , Braido Fulvio , Cameli Paolo , Caminati Marco , Caruso Cristiano , Crimi Claudia , Guarnieri Gabriella , Latorre Manuela , Menzella Francesco , Micheletto Claudio , Vianello Andrea , Visca Dina , Bondi Benedetta , El Masri Yehia , Giordani Jordan , Mastrototaro Andrea , Maule Matteo , Pini Alessandro , Piras Stefano , Zappa Martina , Senna Gianenrico , Spanevello Antonio , Paggiaro Pierluigi , Blasi Francesco , Canonica Giorgio Walter
Published: March 2024

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p
Reconsidering Leadership Development: From Programs to Developmental Systems
Authors: Day David V , Dannhäuser Laura
Published: March 2024

We argue for reconsidering leadership development based on systems design principles. A primary advantage of systems thinking is that it encourages holistic approaches to development and avoids episodic program-based training and piecemeal thinking. The latter approaches are both limited and limiting yet tend to be the preferred approach to leadership development in organizations. Systems approaches to development offer numerous advantages both conceptually and pragmatically, especially through the incorporation of ongoing feedback cycles. Core practices that define a leadership development system are presented and implications are discussed.
Could Phosphorous MR Spectroscopy Help Predict the Severity of Vasospasm? A Pilot Study
Authors: Galijasevic Malik , Steiger Ruth , Treichl Stephanie Alice , Ho Wing Man , Mangesius Stephanie , Ladenhauf Valentin , Deeg Johannes , Gruber Leonhard , Ouaret Miar , Regodic Milovan , Lenhart Lukas , Pfausler Bettina , Grams Astrid Ellen , Petr Ondra , Thomé Claudius , Gizewski Elke Ruth
Published: March 2024

One of the main causes of the dismal prognosis in patients who survive the initial bleeding after aneurysmal subarachnoidal hemorrhage is the delayed cerebral ischaemia caused by vasospasm. Studies suggest that cerebral magnesium and pH may potentially play a role in the pathophysiology of this adverse event. Using phosphorous magnetic resonance spectrocopy (31P-MRS) we calculated the cerebral magnesium (Mg) and pH level in 13 patients who suffered aSAH. The values between the group that developed clinically significant vasospasm (n=7) and the group that did not (n=6) were compared. The results of this study showed significantly lower cerebral Mg levels (p=0.019) and higher pH (p<0.001) in cumulative group (all brain voxels together) in patients who developed clinically significant vasospasm. Further clinical studies on a larger group of carefully selected patients are needed in order to predict clinically significant vasospasm.
A Nationwide Study of the Delayed Diagnosis and the Clinical Manifestations of Predominantly Antibody Deficiencies and CTLA4-Mediated Immune Dysregulation Syndrome in Greece
Authors: Kapousouzi Androniki , Kalala Fani , Sarrou Styliani , Farmaki Evangelia , Antonakos Nikolaos , Kakkas Ioannis , Kourakli Alexandra , Labropoulou Vasiliki , Kelaidi Charikleia , Tsiouma Georgia , Dimou Maria , Vassilakopoulos Theodoros , VOULGARELIS MICHAEL , Onoufriadis Ilias , Papadimitriou Eleni , Polychronopoulou Sophia , Giamarellos-Bourboulis Evangelos J , Symeonidis Argiris , Hadjichristodoulou Christos , Germenis Anastasios E. , Speletas Matthaios
Published: March 2024

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients
The Quantum Ratio
Authors: Konishi Kenichi , Elze Hans-Thomas
Published: March 2024

The concept of {\it quantum ratio} emerged in the recent efforts to
understand how Newton's equations appear for the center of mass (CM) of an isolated macroscopic body at finite body-temperatures, as the first approximation to quantum-mechanical equations.
It is defined as $Q\equiv R_q/L_0$, where the quantum fluctuation range $R_q$ is the spatial extension of the pure-state CM wave function, whereas $L_0$ stands for the body's linear size (the space support of the internal, bound-state wave function). The two cases $R_q /L_0 \lesssim 1$ or $R_q/ L_0 \gg 1$, roughly correspond to the body's CM behaving classically or quantum mechanically, respectively. In the present note we elaborate more on this concept, illustrating it in several examples. An important notion following from introduction of the quantum ratio is that the elementary particles (thus the electron and the photon) are quantum mechanical, even when the environment-induced decoherence turns them into a mixed state. Decoherence and classical state should not be identified. This simple observation, further illustrationed by the consideration of a few atomic or molecular processes, may have significant implications on the way quantum mechanics works in biological systems.
A Comprehensive Review of Secondary Movement Disorders
Authors: R. Santos Eduardo
Published: March 2024

Secondary movement disorders (SMDs) represent a heterogeneous group of neurological conditions characterized by abnormal, involuntary movements resulting from various underlying causes. This comprehensive review aims to thoroughly understand SMDs, including their epidemiology, pathophysiology, clinical manifestations, diagnostic approach, and management strategies. SMDs encompass a spectrum of movement abnormalities, including dystonia, chorea, athetosis, myoclonus, tics, and tremors. They can arise from a multitude of etiologies, such as drug-induced effects, post-infectious processes, metabolic disturbances, and structural brain lesions. The epidemiology of SMDs varies depending on the underlying cause, with some conditions being more prevalent in specific populations or age groups. Understanding the pathophysiology of SMDs is crucial for accurate diagnosis and targeted management. Diagnosing SMDs requires a comprehensive approach, including a detailed history, physical examination, laboratory investigations, neuroimaging studies, and sometimes electrophysiological studies. Management of SMDs is multifaceted and may involve pharmacological, non-pharmacological, and surgical interventions. Individualized treatment plans are essential, considering the underlying cause, severity of symptoms, and patient preferences. Emerging concepts in the field of SMDs include advancements in genetic research, identification of biomarkers, and development of novel therapeutic approaches. There is a growing focus on patient-centered care and improving the quality of life for individuals with SMDs. In conclusion, SMDs pose diagnostic and therapeutic challenges, requiring a multidisciplinary approach for optimal management. Continued research and collaboration are essential for advancing our understanding and treatment of these complex disorders.
DNA Contamination during Extraction of Dried Blood Spots from Whatman Filter Paper
Authors: Maiga Hamma , Gorres Patrict J , Duffy Patrick E
Published: March 2024

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.
EASY-NET Program: Effectiveness of an Audit and Feedback Intervention in the Emergency Care for Acute Conditions in Lazio Region
Authors: Angelici Laura , Angioletti Carmen , Pinnarelli Luigi , Colais Paola , De Belvis Antonio Giulio , Melnyk Andriy , La Gatta Emanuele , Farchi Sara , Davoli Marina , Agabiti Nera , Acampora Anna
Published: March 2024

The EASY-NET network program (NET-2016-02364191 - Effectiveness of Audit and Feedback (A&F) strategies to improve health practice and equity in various clinical and organizational set-tings), piloted a new and more structured A&F strategy. This study compared the effectiveness of the new strategy versus the periodic publication of indicators alone in improving the appropri-ateness and timeliness of emergency health interventions in patients with Acute Miocardial In-farction (AMI) and ischemic stroke in the Lazio Region. Efficacy was evaluated according to a prospective quasi-experimental design of pre-post (2021-2022) intervention type with control group. The exposed are hospitals in the Lazio Region where professional teams voluntarily par-ticipated in the intervention. The control group is involved only in the usual reporting activities. Effectiveness analysis was conducted at the patient level. Regional health information systems were used to calculate process and outcome indicators. The effectiveness of the intervention was assessed with Difference In Difference models, comparing pre-post intervention periods between exposures and controls. Estimates were calculated in terms of the difference in percentage points (pp) between absolute risks. Sixteen facilities for the IMA pathway and 13 for the stroke pathway joined the intervention. The intervention reduced the proportion of 30-days readmissions after a hospitalization for ischemic stroke by 0.54 pp in the exposed patients with a significant difference of -3.80 pp (IC95% -6.57; -1.03; 5453 patients, 63.7% cases) in the exposed compared to controls. There were no statistically significant differences attributable to the implemented A&F interven-tion in the other indicators considered. The results show, for the first time in Italy, the impact of A&F interventions in an emergency setting using aggregated data from hospitals involved in the Lazio Region emergency network.
Impact of Deep Learning Denoising Algorithm on Diffusion Tensor Imaging of the Growth Plate on Different Spatial Resolutions
Authors: Santos Laura A , Hsu Hao-Yun , Jambawalikar Sachin , Nelson Ronald , Sullivan Brendan , Shin Jaemin , Fung Maggie , Lebel R. Marc , Jaramillo Diego
Published: March 2024

To assess the impact of a deep learning (DL) denoising reconstruction algorithm applied to identical patient scans acquired with two different voxel dimensions, representing distinct spatial resolutions. This IRB approved prospective study was conducted at a tertiary pediatric center in compliance with the Health Insurance Portability and Accountability Act. We used a General Electric Signa Premier unit (GE Medical Systems, Milwaukee, WI) to acquire two DTI sequences of the left knee on each child at 3T: an in-plane 2.0 x 2.0 mm2 with section thickness of 3.0 mm and a 2 mm3 isovolumetric voxel, neither had an inter-section gap. We used a multi-band DTI acquisi-tion with fat-suppressed single-shot spin-echo echo-planar sequence (20 non-collinear directions; b-values of 0 and 600 sec/mm2). The MR vendor-provided a commercially available DL model applied with 75% noise reduction settings to same subject DTI sequences at different spatial res-olutions. We compared DTI tract metrics from both DL-reconstructed scans and non-denoised scans for femur and tibia, at each spatial resolution. Differences were evaluated using Wilcox-on-signed ranked test and Bland-Altman plots. When comparing DL versus non-denoised diffu-sion metrics in femur and tibia using the 2 mm x 2mm x 3 mm voxel dimension there were no significant differences between tract count (p = 0.1, p =0.14) tract volume (p = 0.14, p = 0.29), or tibial tract length (p=0.16); femur tract length exhibited a significant difference (p
Sustainable VAT harmonization theory for cross-border e-commerce transactions in the European Union
Authors: Becsky-Nagy Patrícia , Póta Cserne Panka
Published: March 2024

Current VAT rules for cross-border e-commerce companies in the EU are not sustainable, because they are extremely complex and often opaque, due to the lack of tax harmonization. The aim of the research is to explore, using a qualitative method, what kind of harmonization would make the current legislation more uniform, simpler, more transparent, and easier to understand, without conflicting with the rules of any Member State. To this end, the aspects of the new platform regulation introduced on 1 July 2021 and its potential for expansion are assessed through information from possible sales models. The research suggests that the rules on platforms do not cover all possible sales models, which in our view imposes an unnecessary extra administrative burden on some businesses and makes their tax activities less transparent. In the light of the results of the research, we propose that the current EU platform regulation should be extended to cover B2B, B2C transactions and services. As a result of this suggested harmonization, a simpler, more transparent, uniform and sustainable tax system would contribute to the whitening of the economy, generating additional tax revenue for Member States.
Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities
Authors: Di Maio Attilio , Olleik Hamza , Courvoisier-Dezord Elise , Guillier Sophie , Neulat-Ripoll Fabienne , Haudecoeur Romain , Bolla Jean-Michel , Casanova Magali , Cavalier Jean-François , Canaan Stéphane , Pique Valérie , Charmasson Yolande , Baydoun Elias , Hijazi Akram , Perrier Josette , Maresca Marc , Robin Maxime
Published: March 2024

The development of new and effective antimicrobial compounds is an urgent need with the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 have the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess a large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safest compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.
Proton-Pump Inhibitors in Eosinophilic Esophagitis: A Review Focused on the Role of Pharmacogenetics
Authors: Rodríguez-Alcolado Leticia , Navarro Pilar , Arias-González Laura , Grueso-Navarro Elena , Lucendo Alfredo J , Laserna-Mendieta Emilio J
Published: March 2024

Proton-pump inhibitors (PPIs) are the most administered first-line treatment for eosinophilic esophagitis (EoE). However, only around half of EoE patients respond histologically to PPI at double dosage. In addition, 70% of responders maintain EoE in remission after tapering the PPI dose. In order to avoid endoscopy with biopsies − the only accurate method of assessing PPI response − efforts have been made to identify PPI responder patients. Clinical or endoscopic features and biomarkers evaluated so far however, have not proved good enough in predicting PPI response. Although new approaches based on omics technologies have uncovered promising biomarkers, the specialized and complex procedures required are difficult to implement in clinical settings. Alternatively, PPI pharmacogenetics based on identifying variations in CYP2C19 and STAT6 genes have shown promising results in EoE, and could easily be performed in most laboratories. Other genetic variations have also been associated with PPI response and may explain those cases not related to CYP2C19 or STAT6. Here, we give an overview of PPI treatment in EoE and evidence of how genetic variations in CYP2C19 and other genes could affect PPI effectiveness, and also discuss studies evaluating the role of pharmacogenetics in predicting PPI response in patients with EoE.
Optimizing Flexible Microelectrode Designs for Enhanced Efficacy in Electrical Stimulation Therapy
Authors: Qi Lihong , Yu Ying , Tao Zeru , Liu Mujie , Jiang Yongwei , Yao Kai , Wang Yuheng
Published: March 2024

To investigate the impact of electrode structure on Electrical Stimulation Therapy (EST) for chronic wound healing, this study designed three variants of flexible microelectrodes (FMs) with Ag-Cu coverings (ACCs), each exhibiting distinct geometrical configurations: hexagonal, cross-shaped, and serpentine. These were integrated with PPY@PDA/PANI (3/6) hydrogel dressings. Comprehensive animal studies, coupled with detailed electrical and mechanical modeling and simulations, were conducted to assess their performance. Results indicated that the serpentine-shaped FM outperformed its counterparts in terms of flexibility and safety, exhibiting minimal thermal effects and a reduced risk of burns. Notably, FMs with metal coverings under 3% demonstrated promising potential for optoelectronic self-powering capabilities. Additionally, simulation data highlighted the significant influence of hydrogel non-uniformity on the distribution of electrical properties across the skin surface, providing critical insights for optimizing EST protocols when employing hydrogel dressings.
Critical View of Business Architecture: Current and Future State
Authors: Díaz Velásquez María Fernanda , Tavera Romero Carlos Andrés , Gamboa-Cruzado Javier , Ortiz Monedero Jesús Hamilton
Published: March 2024

This article presents a critical review of the current and future state of “business architecture” within the enterprise architecture frameworks. The review is conducted in the following four stages. In the first stage of analysis, the research and publication questions are established. In the second stage, the search for information is designed and implemented using the Prisma methodology, and once the selection criteria were applied, 75 article-type documents were selected from Scopus, WoS, and Dimensions databases. In the third stage, the information analysis is conducted, and then it is synthesized. Finally, in fourth stage, the discussion is elaborated. This research contributes in understanding the current and future trends of business architecture in Industry 4.0. Considering the challenges of the changing market, the results show the need to implement architectures and dynamic business models, including their artifacts, in a globalized context immersed in new technologies.
Coccomyxa Kj Components Enhance the Expression of Metallothioneins and Th17 Cytokines during Human T Cell Activation
Authors: Seki Toshiro , Oshima Shino , Komatsu Satoko , Yamada Soga , Kashiwagi Hirofumi , Goto Yumiko , Tsuda Banri , Kanno Akiko , Yasuda Atsushi , Kuno Hitoshi , Tsuji Noriko , Shiina Takashi , Kametani Yoshie
Published: March 2024

Coccomyxa subellipsoidea KJ (C-KJ) is a green alga with unique immunoregulatory characteristics. Here, we investigated the mechanism underlying the modification of T cell function by C-KJ components. The water-soluble extract of C-KJ was fractionated into protein (P) and sugar (S) fractions [acidic (AS), basic (BS), and neutral (NS)]. These fractions were used for the treatment of peripheral blood mononuclear cells stimulated with toxic shock syndrome toxin-1. Transcriptome analysis revealed that both P and AS enhanced the expression of the genes encoding metallothionein (MT) family proteins, inflammatory factors, and T helper (Th) 17 cytokine and suppressed that of those encoding Th2 cytokines in stimulated T cells. The kinetics of MT1 and MT2A gene expression showed a transient increase in MT1 and maintenance of MT2A mRNA after T cell stimulation in the presence of AS. The kinetics of Th17-related cytokine secretion in the early period were comparable to those of MT2A mRNA. Furthermore, our findings revealed that static, a STAT-3 inhibitor, significantly suppressed MT2A gene expression. These findings suggest that the expression of MTs is involved in the immune regulatory function of C-KJ components, which is partially regulated by Th17 responses, and may help develop innovative immunoregulatory drugs or functional foods.