bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic evaluation of two therapeutic sequences in the first-line treatment of moderate to severe active ulcerative rectocolitis in Italy
Authors: Armeni Patrizio , Compagnucci Elena , Fiorino Gionata , Lolli Vincenzo , Mazzone Grazia , Orlando Ambrogio , Principi Mariabeatrice , Ravasio Roberto , Rizzello Fernando , Savarino Edoardo Vincenzo , Tombari Francesca
Published: March 2024

Background: Vedolizumab (VDZ) and infliximab are used to treat moderate to severe ulcerative colitis (UC). The choice of the drug to use at first-line is often based on a combination of clinical and economic factors. The cost of treatment pathway is rarely considered. Therefore, this cost-consequence analysis (CCA) investigated the overall costs of treatment pathway for vedolizumab followed by infliximab (VDZ → IFX) compared to infliximab followed by vedolizumab (IFX → VDZ).
Methods: We used a published cost-consequence model (CCM), based on a targeted literature search reporting the time-on-treatment data for vedolizumab or infliximab in UC in first and second-line of treatment. CCM time horizon was defined by the length of treatment sequences. Considering the Italian hospital perspective, the CCA evaluated the biologic drugs acquisition costs, drug administration costs, hospitalization costs, switch costs, colectomy costs and third-line treatment costs. Third-line options included colectomy, tofacitinib, ustekinumab or dose escalation of second-line biologic.
Results: Over the 5.2-year time horizon (duration of the longer VDZ → IFX pathway), the mean cost per patient of VDZ → IFX pathway was slightly lower than the mean cost per patient of IFX → VDZ pathway (€ 86,339 vs 89,636). The CCM predicted that using VDZ as first-line treatment delayed the time to costly third-line therapies compared to first-line using IFX (VDZ-first-line median time-on-treatment 3.6-years and IFX-second-line 1.6-years; IFX-first-line 1.4-years and VDZ-second-line 2.3-years and third-line 1.5-years).
Conclusion: The CCA showed that a biologic treatment pathway that begins with first-line vedolizumab is not more expensive than one beginning with first-line infliximab and delayed the time to costly third-line.
Long-term response with the atypical reaction to nivolumab in microsatellite stability metastatic colorectal cancer: A case report
Authors: Babyshkina Nataliya , Popova Nataliya , Grigoryev Evgeny , Dronova Tatyana , Gervas Polina , Dobrodeev Alexey , Kostromitskiy Dmitry , Goldberg Victor , Afanasiev Sergei , Cherdyntseva Nadejda
Published: March 2024

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients. However, its efficacy is extremely limited in microsatellite stability (MSS)/mismatch repair proficient (pMMR) patients. We report a case of a 42-year-old man diagnosed with MSS/pMMR mCRC who has achieved a durable response to nivolumab after a progression under chemotherapy with antiangiogenic treatment. We observed for the first time an atypical response after 8 months of nivolumab treatment, with the regression of previous primary pulmonary lesions and the presence of new para-aortic lymph node lesions. This report demonstrates that a subset of pretreated mCRC patients with the MSS/pMMR phenotype may benefit from nivolumab and these patients need more attention.
STABILIZATION OF WATER-COAL COMPO­SITE FUELS USING CARBON MICRO-NANO­MATERIALS AND AMINO ALCOHOLS
Authors: Klishchenko Roman
Published: March 2024

The study investigated the potential of stabilizing composite water-coal fuel (CWCF) by adding carbon micro-nanomaterials obtained through the plasma-chemical conversion of organics-containing wastewater and amino alcohols. The study focused on systems based on anthracite with a solid phase concentration of 62%. Two amino alcohols, 2-amino-­2-methyl-1-propanol (AMP) and 2-amino-­2-ethyl-1,3-propanediol (AEPD) were used at concentrations of 0.25%, 0.5%, 1%, and 2.5% by weight of CWCF.

The low stability and heterogeneity of coal particle distribution in organic liquids cause an increase in the viscosity of dispersed systems in combined systems. To regulate the rheological properties and stabilize the CWCF, chemicals such as dispersants, plasticizers, and stabili­zers are added. The CWCF 's properties can be improved by using additives such as sodium, calcium, and magnesium lignosulfonates, and naphthalene sulfonic acids. However, these reagents may not provide the desired properties of coal slurries in organomineral environments. Therefore, substitutes for these pro­ducts need to be found.

Amino alcohols are commonly used as dispersants and stabilizers, especially in the production of water-based paints. They are low in cost, low in toxicity, and serve as anti-corrosive agents and pH stabilizers without causing excessive foaming. To strengthen the spatial structure, reactive particles such as carbon micro- and nanomaterials (CNM) can be introduced into the CWCF. Unlike polyelectrolytes and surfactants, CNM particles can have a varying number of active centers depending on the method of formation. By varying the properties of CNMs, it is possible to increase the number of contact centers and form a spatial grid without increasing the concentration of surfactants and polyelectrolytes. This is because contact interactions are activated during grinding, forming a new surface with energy-saturated active centers. As a result, the concentration of the system can be increased, and the calorific value of the fuel can be increased as well. However, the presence of an organic component can render mechanochemical activation ineffective by shielding active sites with large organic molecules. Therefore, identifying the most effective stabilizer reagents and deve­loping technology for their introduction into the dispersed system is a crucial and intricate problem in obtaining CWCF

The study revealed that the ξ potential of anthracite particles is 40–45 mV in the pre­sence of amino alcohols. Sedimentation stabi­lity in the presence of highly dispersed carbon additives increases from 5–6 to 10–14 days, i.e., almost twice. The introduction of highly dispersed carbon leads to an increase in the effective viscosity of the systems and can be recommended for controlling the fluidity of the CWCF. The technical and operational requirements are best met by the CWCF containing 0.25% AMR and 1% highly dispersed carbon.
Study on Advancements in Dielectric Testing in High Voltage Applications and Assessment of Effects of Ageing on Dielectric Properties
Authors: Vijay Ankit , Savla Gaurav , Nand Gagan Kishore , Pattanaik B. R.
Published: March 2024

The reliability of a power system relies heavily on the performance of insulation or dielectric materials used in various equipment like power cables, transformers, generators, switch gears, capacitors, reactors, and arresters. However, dielectrics can degrade over time due to various factors, including electrical stress, temperature, humidity, and other environmental conditions. The degradation or failure of insulation can lead to equipment malfunction, power outages, or even a catastrophic failure. Therefore, a periodic assessment and monitoring of insulation health and integrity through proper dielectric testing mechanisms serves as an essential tool for the safe and sustainable operation of an electrical power system. This paper also addresses the development of aging models and predictive tools for assessing the remaining life of dielectric materials in high-voltage applications, valuable insights into the long-term performance and reliability of dielectrics, enabling improved maintenance strategies and design guidelines for high-voltage systems.
Precision, High Stability High Voltage Module Power Supply for Analytical Instrumentation
Authors: Sahu Sunil Kumar , Abichandani P. G. , Malhotra S.
Published: March 2024

Analytical instruments like mass spectrometer1-4 require a highly stable environment for precise measurements. A minute fluctuation in supply can cause large errors in measurements. For accelerating the ions in a mass spectrometer, a highly stable high-voltage power supply is required. High voltage power supplies up to 30kV/10W with 10ppm short-term stability are extensively used in various analytical instruments like mass spectrometers, PMT and CEM, scanning electron microscope, electron spectroscopy etc. This paper will illustrate the design concept and implementation of an HV module based on a compound regulatory system, where a linear regulator feeds the power to the switching regulator (ZVS mode resonance converter fly-back topology, SMPS) operating around 100 kHz.
Review of High Voltage Pulsed Power Supplies and Power Electronics in Pulse Power Generation
Authors: Khan Khuban Lateef , Verma Rishi , Roy Amitava
Published: March 2024

Recently, pulse-shaped power supplies have become more popular. Pulsed power is versatile and useful as a supply method since it can take several shapes and has many pulse characteristics. The release of electrons, protons, and neutrons from an atom and the synthesis of molecules to generate ions or other molecules require a lot of immediate energy. Pulsed power is needed for decomposition, molecular fusion and material joining, radiation generation (e.g., electrons, lasers, radar), explosive processes for concrete recycling, wastewater and exhaust gas treatment, and material surface treatments. Industrial and environmental applications require pulsed power, which requires efficient and adaptive pulse modulators. Higher-quality repeating pulses are needed for plasma fusion and laser weapons. Marx Generators, Magnetic Pulse Compressors, Pulse Forming Networks, and Multistage Blumlein Lines have several uses. Pulse modulators use spark gap and hydrogen thyratron gas/magnetic switching technologies for their high voltage tolerance and low-rise times. These creatures are inefficient, unreliable, repetitious, and short-lived. These devices are heavy, bulky, and expensive. Solid-state switching technology can replace conventional devices, improving pulse supply. High-frequency switching repeats the pulsed power supply. These items are compact, efficient, affordable, reliable, and durable. Solid-state transistor applications may not meet switch voltage ratings and rise time constraints. Various power electronics configurations can produce solid-state high-voltage pulses.
Usage of Energy Storage Capacitors in TE Gas Laser Pulsers
Authors: Raote Pallavi , Nilaya J. P. , Biswas D. J.
Published: March 2024

An energy storage capacitor is crucial for both electrically pumped and optically pumped pulsed lasers. In electrically pumped lasers, the energy stored in the capacitors is directly deposited into the lasing medium, while in optically pumped lasers, it energizes the flash lamp that, in turn, pumps the lasing medium. We discuss here the application of energy storage capacitors in the operation of electrically pumped pulsed gas lasers. Increasing the operating pressure of the gain medium, a prerequisite for obtaining higher energy from the laser, has resulted in great advancements in the gas laser pulse technology. This progress has led to the development of transverse electric discharge pumping, enabling easy scalability of gas pressure and achievable output power. An ideal TE pulser efficiently charges the capacitor to an appropriate voltage with minimal energy dissipation on the charging element and facilitates a rapid and uniform transfer of this stored energy into the lasing medium before a glow-to-arc transition can set in. Various types of pulser circuits employed to energize pulsed gas lasers are described in this paper.
Use of Data Analytics for Power Plant Operation Optimization
Authors: Samal Arnada Prasad
Published: March 2024

Optimized operation and maintenance of a power plant to improve the KPIs is the key to success. Forced outages not only make the unit unavailable but also increase the number of start-ups and hence high cost and deteriorated plant life. Fault diagnostics and prediction of future behavior of equipment by data analytic techniques will be very handy in improving reliability. On the other hand, the cost of generation depends upon how efficiently the plants are operated. Any deviation from the optimized design point, results in losses and hence as far as possible the deviations should be minimized. However, the deviations are unavoidable due to various reasons. Along with efficient operation, Environmental compliance, and flexibility is also to be ensured to meet the statutory requirements. With the advancement of computing techniques, data analytics, and Artificial Intelligence are being used for the optimization of many industrial processes. Given the background, the objective of this paper is to study and suggest how Data Analytics can be utilized for the optimization of power plant operations to improve reliability, efficiency, and flexibility, and minimize the impact on the environment. Many statistical methods are available to identify the hidden pattern in the data which can be used for optimisation of processes. AI is used for process control, diagnosing faults, and predicting of future behaviors so that advanced action can be taken to avoid surprises. The domain expertise along with data analytic methods can be utilized to find solutions to a variety of problems. In this paper, a comprehensive data analytic tool with four modules i.e., “Efficiency optimization”, “Plant Health monitoring and reporting”, “Optimization of life consumption” and “Environment protection” has been conceived for application. These Modules work in an integrated manner and shall monitor, optimize, control, and report/advise. The tool shall have a digital replica of the individual equipment for simulation individually as well as in combination with other related equipment for whole plant performance prediction and diagnosis. The replica shall use its database for machine learning and for running of diagnostic process.
Predicting cell population-specific gene expression from genomic sequence
Authors: Michielsen Lieke , Reinders Marcel J. T. , Mahfouz Ahmed
Published: March 2024

Most regulatory elements, especially enhancer sequences, are cell population-specific. One could even argue that a distinct set of regulatory elements is what defines a cell population. However, discovering which non-coding regions of the DNA are essential in which context, and as a result, which genes are expressed, is a difficult task. Some computational models tackle this problem by predicting gene expression directly from the genomic sequence. These models are currently limited to predicting bulk measurements and mainly make tissue-specific predictions. Here, we present a model that leverages single-cell RNA-sequencing data to predict gene expression. We show that cell population-specific models outperform tissue-specific models, especially when the expression profile of a cell population and the corresponding tissue are dissimilar. Further, we show that our model can prioritize GWAS variants and learn motifs of transcription factor binding sites. We envision that our model can be useful for delineating cell population-specific regulatory elements.
Failure behavior and mechanical properties of prefabricated cantilever retaining under dynamic effect
Authors: Du Yihan , Du Xuze , Han Wei , Huang Bo , Huang Songtao , Liang Peng , Zhang Mo
Published: March 2024

Prefabricated retaining wall is in line with the development trend of greening and environmental protection of civil engineering, and has a broad application prospect. However, the seismic response of prefabricated retaining wall has not been systematically revealed. Therefore, in this study, a simple fabricated cantilever retaining wall with connecting plate was proposed, and the mechanical properties of prefabricated cantilever retaining under dynamic effect was investigated by the experimental and numerical methods. At first, the physical model experiments of prefabricated cantilever retaining with different vertical plate thicknesses were carried out. Subsequently, the mechanical properties of the prefabricated cantilever retaining were investigated. The research results show that the thickness of retaining wall significantly affects the failure pattern, the larger the thickness, the more complete the broken pattern. In addition, the connection between the vertical plate and the bottom plate is prone to cracks induced by stress concentration, eventually leading to damage. As the thickness of the vertical plate increases, the top stress of the vertical plate decreases but the bottom stress increases. The greater the embedded depth of the vertical plate, the larger the stress at bottom of the vertical plate. Furthermore, the effect of concrete strength on mechanical properties is not obvious. This study provides an idea for the dynamic response research of prefabricated retaining structure.
Detection of infectious SARS-CoV-2 in ocular samples is linked to viral load in the nasopharynx
Authors: Kimpel Janine , Rössler Annika , Bante David , Borena Wegene , von Laer Dorothee , Zehetner Claus , Rauchegger Teresa , Seiwald Stefanie , Falkensammer Barbara
Published: March 2024

Introduction

SARS-CoV-2 is known to infect respiratory tissue cells. However, less is known about infection of ocular tissue and potential infectivity of lacrimal fluid. With this study, we want to compare viral loads in eye and nasopharyngeal swabs and analyze these for infectious virus.

Methods

Between May 2020 and April 2021 ocular and nasopharyngeal swabs were collected from 28 SARS-CoV-2 infected patients treated on the corona virus disease 2019 (COVID-19)-ward of the University Hospital of Innsbruck, Austria. Samples with PCR detectable SARS-CoV-2 were analyzed via whole genome sequencing and an attempt was made to isolate infectious virus.

Results

At the time point of sample collection, 22 individuals were still PCR positive in nasopharyngeal samples and in 6 of these patients one or both ocular samples were additionally positive. CT-values in eyes were generally higher compared to corresponding nasopharyngeal samples and we observed a tendency for lower CT-values, i.e. increased viral load, in nasopharyngeal swabs of individuals with at least one infected eye, compared to those where ocular samples were PCR negative. Ocular and nasopharyngeal sequences from the same patient were assigned to the same variant, either the D614G or the Alpha variant. Infectious virus was successfully isolated from 9 nasopharyngeal swabs, however only from one of the seven PCR positive ocular samples.

Conclusion

We could detect SARS-CoV-2 in eyes of some of the infected patients albeit at lower levels compared to nasopharyngeal swabs. However, our results also indicate that lacrimal fluid might be infectious in patients with high viral load.
Airway necrosis and granulation tissue formation caused by Rhizopus oryzae leading to severe upper airway obstruction: a case report
Authors: Chen Geng-Jia , Chen Xiao-Bo , Rao Wan-Yuan , Pan Xiao-Yi , Li Shi-Yue , Su Zhu-Quan
Published: March 2024

Pulmonary Mucormycosis is a fatal infectious disease with high mortality rate. The occurrence of Mucormycosis is commonly related to the fungal virulence and the host’s immunological defenses against pathogens. Mucormycosis infection and granulation tissue formation occurred in the upper airway was rarely reported. This patient was a 60-year-old male with diabetes mellitus, who was admitted to hospital due to progressive cough, sputum and dyspnea. High-resolution computed tomography (HRCT) and bronchoscopy revealed extensive tracheal mucosal necrosis, granulation tissue proliferation, and severe airway stenosis. The mucosal necrotic tissue was induced by the infection of Rhizopus Oryzae, confirmed by metagenomic next-generation sequencing (mNGS) in tissue biopsy. This patient was treated with the placement of a covered stent and local instillation of amphotericin B via bronchoscope. The tracheal mucosal necrosis was markedly alleviated, the symptoms of cough, shortness of breath, as well as exercise tolerance were significantly improved. The placement of airway stent and transbronchial microtube drip of amphotericin B could conduce to rapidly relieve the severe airway obstruction due to Mucormycosis infection.
Contemporary evaluation and treatment of tricuspid regurgitation
Authors: Minciunescu Andrei , Emaminia Abbas
Published: March 2024

Valvular heart disease is a global health burden with substantial mortality. The left-sided valvular diseases have been extensively described using the robust treatment strategies available. By contrast, the right-sided diseases, particularly the tricuspid valve (TV) and associated regurgitation, still have much to be delineated. Worsening tricuspid regurgitation (TR) is associated with increased mortality; the non-invasive management is suboptimal; and surgical approaches carry significant risk. With advances in multimodality imaging, 3D echocardiography, improved understanding of TV anatomy, and pathophysiological mechanisms of primary and secondary regurgitation, as well as favorable data with transcatheter therapies, the field of TV management is rapidly evolving. This review aims to highlight pathophysiological mechanisms of TR, describe echocardiographic approaches to diagnosis and TV interrogation, and outline the latest transcatheter developments.
Multiscale physics-based in silico modelling of nanocarrier-assisted intravascular drug delivery
Authors: Buchete Nicolae-Viorel , Cicha Iwona , Dutta Sutapa , Neofytou Panagiotis
Published: March 2024

A rational design of drug nanocarriers supported by in silico modelling tools can improve the efficacy of nanosystem-based intravascular drug delivery (IVDD). Computational model development stems from the vision of replacing conventional (pre)clinical trials with advanced simulations and applies to the development of more efficient nanocarriers for intravascular therapies. To establish a standardized framework for in silico preclinical trials, it is necessary to include in silico tools that can model each experimental stage of a preclinical trial for a respective nanocarrier system and give accurate and verifiable results. This review paper highlights the status of intravascular drug delivery supported by nanocarriers and discusses the modelling stages of a physics-based multiscale modelling framework that should be developed, validated and exploited to address the need for an effective preclinical assessment of nanocarriers for IVDD.
Early Pleistocene depositional and environmental conditions at Dachangliang, Nihewan Basin, NE China
Authors: H. Moghazi Ahmed , Zhao Hailong , Zhang Chengjun , Eythorsdottir Elísabet A. , Mischke Steffen
Published: March 2024

The Pleistocene sediments of Nihewan Basin in NE China are intensively studied since ca. 100 years because of its rich mammalian fossil record and abundant stone-artifact-bearing layers. To better understand the mechanisms underlying past climate and environmental changes in the basin, three sediment sections at the Dachangliang location were investigated using a multi-proxy toolbox of sedimentological, magnetic susceptibility (MS) and micropalaeontological analyses. The exposed sediments are lithologically mostly relatively homogeneous, with grain sizes in a relatively small range. However, variations in colour, bedding structures, concentrations of magnetic minerals and the ostracod assemblage were used to correlate the three sections to form the synthetic NH-T section of 86.2-m total length. The sediments mainly represent varicoloured silt of probably reworked loess deposits, partially interbedded with fine sand layers and minor contributions of clay particles. These sediments are interpreted to have accumulated in wetlands alternating with deposition on an alluvial plain, and with a lacustrine setting which probably existed from time to time. These different depositional settings are expressed in the three dominant fine to coarse silt-sized components and the ostracod-assemblage changes (mostly Limnocythere flexa, Ilyocypris spp. and Leucocythere sp.). The recorded ostracods of laterally apparently consistent white marl beds (dominantly Cytherissa lacustris) were used to stratigraphically correlate these sections. The resulting NH-T section was further correlated with the three proximal artefact-bearing sections Majuangou, Banshan and Xiantai which have published magnetostratigraphic data. The correlation shows that the investigated sedimentary sequence was probably formed between ca. 1.7 and 0.9 Ma. The relatively continuous synthetic sequence NH-T represents three main wetter periods with three intervening drier intervals, possibly synchronous with interglacial (S23-S20, S15-S13 and S10-S9) and glacial (L20-L18, L17-L16 and L13-L11) periods which were previously inferred from the palaeoclimatic records of the Chinese Loess Plateau (CLP) in the SW of the Nihewan Basin.
Eye tracking in a teaching context: comparative study of the professional vision of university supervisor trainers and pre-service teachers in initial training for secondary education in French-speaking Belgium
Authors: Duvivier Valérie , Derobertmasure Antoine , Demeuse Marc
Published: March 2024

This study explores the visual strategies of University Supervisor Trainers (UST) for teachers [Upper Secondary Education Teaching Certification—Agrégation de l’Enseignement Secondaire Supérieur (AESS)] in French-speaking Belgium and the pre-service teachers (PT) they train. It aims to understand how these two groups observe a teaching situation, on video, using an eye-tracking device. The video shows the start of a geography lesson given by a trainee in a primary school class. Three research questions were formulated, examining (a) the actor observed (the trainee, the pupil working groups and 4 pupil profiles present in the scene), (b) the visual strategies used to access these actors, and (c) the visual itineraries when a planning error by the trainee is presented on the screen. To answer, we chose to carry out an analysis based on oculometric indicators (fixing, visit, and first view). The results show that UST and PT focus their attention on the same groups of students. However, they do not do so in the same way. UST adopt visual strategies that are distinct from those of PT, thus aligning their approaches with those of expert teachers in other studies using eye tracking. Within these strategies, we highlight two important points: (a) the emergence of dynamic and floating visual strategies in the UST, characterized by more frequent revisits (significantly validated) and fixations of shorter duration than in PT; and (b) less fixation of UST in observing students who are very active in class compared to PT. Finally, the specific analysis of the UST gaze itineraries at the time of the trainee’s planning error reflected both common elements (e.g., teaching tools) and divergent elements (e.g., checking pupils).
A randomized feasibility trial of the modified Atkins diet in older adults with mild cognitive impairment due to Alzheimer’s disease
Authors: Buchholz Alison , Deme Pragney , Betz Joshua F. , Brandt Jason , Haughey Norman , Cervenka Mackenzie C.
Published: March 2024

Background

Alzheimer’s disease (AD) is increasing in prevalence, but effective treatments for its cognitive impairment remain severely limited. This study investigates the impact of ketone body production through dietary manipulation on memory in persons with mild cognitive impairment due to early AD and explores potential mechanisms of action.

Methods

We conducted a 12-week, parallel-group, controlled feasibility trial of a ketogenic diet, the modified Atkins diet (MAD), compared to a control diet in patients with cognitive impairments attributed to AD. We administered neuropsychological assessments, including memory tests, and collected blood samples at baseline and after 12 weeks of intervention. We performed untargeted lipidomic and targeted metabolomic analyses on plasma samples to detect changes over time.

Results

A total of 839 individuals were screened to yield 38 randomized participants, with 20 assigned to receive MAD and 18 assigned to receive a control diet. Due to attrition, only 13 in the MAD arm and nine in the control arm were assessed for the primary endpoint, with two participants meeting ketosis levels used to define MAD adherence criteria. The average change from baseline in the Memory Composite Score was 1.37 (95% CI: −0.87, 4.90) points higher in the MAD group compared to the control group. The effect size of the intervention on baseline MAD change was moderate (Cohen’s D = 0.57, 95% CI: −0.67, 1.33). In the 15 participants (nine MAD, six control) assessed for lipidomic and metabolomic-lipidomics and metabolomics, 13 metabolites and 10 lipids showed significant changes from baseline to 12 weeks, including triacylglycerols (TAGs, 50:5, 52:5, and 52:6), sphingomyelins (SM, 44:3, 46:0, 46:3, and 48:1), acetoacetate, fatty acylcarnitines, glycerol-3-phosphate, and hydroxy fatty acids.

Conclusions

Attrition was greatest between baseline and week 6. All participants retained at week 6 completed the study. Despite low rates of adherence by criteria defined a priori, lipidomic and metabolomic analyses indicate significant changes from baseline in circulating lipids and metabolites between MAD and control participants at 12-week postrandomization, and MAD participants showed greater, albeit nonsignificant, improvement in memory.
Nighttime warming promotes copper translocation from root to shoot of wheat (Triticum aestivum L.) through enlarging root systems
Authors: Qi Lin , Li Chunxia , Lai Lukuan , Kou Taiji , Deng Yi
Published: March 2024

This study aimed to investigate whether and how nighttime warming (NW) influences the copper (Cu) bioaccumulation of wheat (Triticum aestivum L.) under Cu pollution. We examined plant growth, Cu concentration, and antioxidant enzymes of wheat after 6 months of Cu exposure (0, 100, 400, and 800 mg/kg) under NW. The results indicated that, NW of 1.54°C significantly promoted Cu translocation from root to shoot through an increasing root system under increased Cu treatments (p < 0.05). The Cu contents of grains were significantly increased by NW under 800 mg/kg Cu treatment (p < 0.05). NW decreased superoxide dismutase (SOD) activity under increased Cu treatments (p < 0.05). There were significantly negative correlations between biomass and Cu concentrations of the same part under NW (p < 0.05). The root biomass significantly increased by 51% in NW compared with nonnighttime warming (CK) (p < 0.05). These results provided evidence that wheat might respond to NW by altering their roots so that they were larger, thinner, and longer, suggesting that soil Cu translocation from root to shoot would be accelerated resulting from the expanded roots under elevated temperatures, and thus forewarned the food safety risks of climate change in agricultural ecosystem.
Casting light on the European anchovy: from biology to conservation and industry
Authors: Mutalipassi Mirko , D’Anza Emanuele , Pugliano Mariagiulia , Firmamento Roberto , Murano Carola , Ruocco Nadia , Pennesi Chiara , Procaccini Gabriele , Romeo Teresa , Terlizzi Antonio , Peretti Vincenzo
Published: March 2024

This manuscript explores the role of European anchovies (Engraulis encrasicolus) in the central Mediterranean Region, shedding light on their ecological significance, conservation challenges, and sustainable utilization. The European anchovy is one of Europe’s most important fish resources in the Mediterranean basin, and it is considered a keystone species, playing a pivotal role in both ecological and socio-economic dimensions. However, in recent decades, European anchovy, together with Sardina pilchardus (commonly known as European sardine), has suffered a population decline for several reasons. Consequently, it is necessary to improve the management of anchovy fisheries by understanding the reproductive modes and characteristics, the influence of currents on the passive transport of eggs and larvae, the feeding habits, the environmental adaptability (e.g., salinity), and the distribution of ecotypes along the Italian coasts. Such information is fundamental for the management of fisheries, especially artisanal ones, and to control frauds, especially in protected, geographically referred, and traditional high-quality commercial products. Various aspects, ranging from their population dynamics to their industrial processing and the ecological implications of these activities were delved, highlighting the knowledge about anchovy populations and ecotypes and its importance in maintaining ecosystem balance and sustaining human communities. The ecological interaction of anchovies within the food web, as essential data in the conservation actions and management of these resources was emphasized. In addition, the metabolic and stomach contents diversity among anchovy populations and ecotypes was discussed, enhancing our understanding of their adaptability to varying environmental conditions. The manuscript then explores the traditional and industrial processing of anchovies, encompassing aspects ranging from fishing techniques (i.e., methods of capture) to their industrial significance, sustainability concerns, issues of fraud, and the establishment of geographical traceability. Finally, the opportunities for sustainable and biotechnological utilization of anchovy discards were also further explored, demonstrating the potential for waste reduction and resource optimization.
Unraveling the skin; a comprehensive review of atopic dermatitis, current understanding, and approaches
Authors: Afshari Moeina , Kolackova Martina , Rosecka Michaela , Čelakovská Jarmila , Krejsek Jan
Published: March 2024

Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin disease characterized by red pruritic skin lesions, xerosis, ichthyosis, and skin pain. Among the social impacts of atopic dermatitis are difficulties and detachment in relationships and social stigmatization. Additionally, atopic dermatitis is known to cause sleep disturbance, anxiety, hyperactivity, and depression. Although the pathological process behind atopic dermatitis is not fully known, it appears to be a combination of epidermal barrier dysfunction and immune dysregulation. Skin is the largest organ of the human body which acts as a mechanical barrier to toxins and UV light and a natural barrier against water loss. Both functions face significant challenges due to atopic dermatitis. The list of factors that can potentially trigger or contribute to atopic dermatitis is extensive, ranging from genetic factors, family history, dietary choices, immune triggers, and environmental factors. Consequently, prevention, early clinical diagnosis, and effective treatment may be the only resolutions to combat this burdensome disease. Ensuring safe and targeted drug delivery to the skin layers, without reaching the systemic circulation is a promising option raised by nano-delivery systems in dermatology. In this review, we explored the current understanding and approaches of atopic dermatitis and outlined a range of the most recent therapeutics and dosage forms brought by nanotechnology. This review was conducted using PubMed, Google Scholar, and ScienceDirect databases.
The efflux pumps Rv1877 and Rv0191 play differential roles in the protection of Mycobacterium tuberculosis against chemical stress
Authors: Sao Emani Carine , Reiling Norbert
Published: March 2024

Background

It was previously shown that GlnA3sc enabled Streptomyces coelicolor to survive in excess polyamines. However, subsequent studies revealed that Rv1878, the corresponding Mycobacterium tuberculosis (M.tb) ortholog, was not essential for the detoxification of spermine (Spm), in M.tb. On the other hand, the multi-drug efflux pump Rv1877 was previously shown to enable export of a wide range of compounds, while Rv0191 was shown to be more specific to chloramphenicol.

Rationale

Therefore, we first wanted to determine if detoxification of Spm by efflux can be achieved by any efflux pump, or if that was dependent upon the function of the pump. Next, since Rv1878 was found not to be essential for the detoxification of Spm, we sought to follow-up on the investigation of the physiological role of Rv1878 along with Rv1877 and Rv0191.

Approach

To evaluate the specificity of efflux pumps in the mycobacterial tolerance to Spm, we generated unmarked ∆rv1877 and ∆rv0191 M.tb mutants and evaluated their susceptibility to Spm. To follow up on the investigation of any other physiological roles they may have, we characterized them along with the ∆rv1878 M.tb mutant.

Results

The ∆rv1877 mutant was sensitive to Spm stress, while the ∆rv0191 mutant was not. On the other hand, the ∆rv1878 mutant grew better than the wild-type during iron starvation yet was sensitive to cell wall stress. The proteins Rv1877 and Rv1878 seemed to play physiological roles during hypoxia and acidic stress. Lastly, the ∆rv0191 mutant was the only mutant that was sensitive to oxidative stress.

Conclusion

The multidrug MFS-type efflux pump Rv1877 is required for Spm detoxification, as opposed to Rv0191 which seems to play a more specific role. Moreover, Rv1878 seems to play a role in the regulation of iron homeostasis and the reconstitution of the cell wall of M.tb. On the other hand, the sensitivity of the ∆rv0191 mutant to oxidative stress, suggests that Rv0191 may be responsible for the transport of low molecular weight thiols.
Impact of olfactory function on the trajectory of cognition, motor function, and quality of life in Parkinson’s disease
Authors: Lin Chia-Yen , Tsai Yu-Shan , Chang Ming-Hong
Published: March 2024

Background

Olfactory dysfunction in Parkinson’s disease (PD) is associated with more severe phenotypes, but trajectories of cognitive function, disease severity, and subdomains of quality-of-life measurements in patients with distinct olfactory profiles remain underexplored.

Objective

To analyze the influence of olfaction on trajectories of clinical parameters in patients with PD.

Design

Retrospective cohort study.

Subjects

From October 2016 to May 2021, the study tracked 58 participants over 3 years. Participants completed follow-up assessments using tools including the Chinese version of the University of Pennsylvania’s Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale, and the Chinese translation of the 39-item Parkinson’s Disease Questionnaire (PDQ-39).

Methods

Participants were divided into anosmia (UPSIT < 19) and non-anosmia (UPSIT ≥ 19) groups based on initial scores. Generalized estimating equations and repeated measures correlations were used to examine longitudinal associations and correlations between olfaction and clinical parameters.

Results

Divergent cognitive trajectories were observed between groups. The anosmia group exhibited a faster cognitive decline (adjusted B [beta coefficient] = −1.8, p = 0.012) according to the interaction effect of olfaction and time on the MoCA score. The anosmia group exhibited no longitudinal correlation between cognition and olfactory function but showed correlations with age (rrm [coefficient of repeated measures correlation] = −0.464, p = 0.004) and disease duration (rrm = −0.457, p = 0.005). The non-anosmia group’s UPSIT scores decreased over time (B = −2.3, p = 0.005) alongside a significant correlation with motor function (rrm = −0.479, p = 0.006).

Conclusion

The anosmia group’s accelerated cognitive decline correlated with age and disease duration, but not olfactory function, suggesting a poor cognitive outcome in this population despite the lack of longitudinal correlation between cognition and olfaction. The non-anosmia group exhibited progressive olfactory degradation and notable correlations between motor function and UPSIT scores, implying pathological accumulation in the olfactory structure and basal ganglia.
Case report: A novel ACTA1 variant in a patient with nemaline rods and increased glycogen deposition
Authors: Piga Daniela , Rimoldi Martina , Magri Francesca , Zanotti Simona , Napoli Laura , Ripolone Michela , Pagliarani Serena , Ciscato Patrizia , Velardo Daniele , D’Amico Adele , Bertini Enrico , Comi Giacomo Pietro , Ronchi Dario , Corti Stefania
Published: March 2024

Background

Congenital myopathies are a group of heterogeneous inherited disorders, mainly characterized by early-onset hypotonia and muscle weakness. The spectrum of clinical phenotype can be highly variable, going from very mild to severe presentations. The course also varies broadly resulting in a fatal outcome in the most severe cases but can either be benign or lead to an amelioration even in severe presentations. Muscle biopsy analysis is crucial for the identification of pathognomonic morphological features, such as core areas, nemaline bodies or rods, nuclear centralizations and congenital type 1 fibers disproportion. However, multiple abnormalities in the same muscle can be observed, making more complex the myopathological scenario.

Case presentation

Here, we describe an Italian newborn presenting with severe hypotonia, respiratory insufficiency, inability to suck and swallow, requiring mechanical ventilation and gastrostomy feeding. Muscle biopsy analyzed by light microscopy showed the presence of vacuoles filled with glycogen, suggesting a metabolic myopathy, but also fuchsinophilic inclusions. Ultrastructural studies confirmed the presence of normally structured glycogen, and the presence of minirods, directing the diagnostic hypothesis toward a nemaline myopathy. An expanded Next Generation Sequencing analysis targeting congenital myopathies genes revealed the presence of a novel heterozygous c.965 T > A p. (Leu322Gln) variant in the ACTA1 gene, which encodes the skeletal muscle alpha-actin.

Conclusion

Our case expands the repertoire of molecular and pathological features observed in actinopathies. We highlight the value of ultrastructural examination to investigate the abnormalities detected at the histological level. We also emphasized the use of expanded gene panels in the molecular analysis of neuromuscular patients, especially for those ones presenting multiple bioptic alterations.
Behavioral disinhibition in stroke
Authors: Tang Wai Kwong , Hui Edward , Leung Thomas Wai Hong
Published: March 2024

Background

Post-stroke behavioral disinhibition (PSBD) is common in stroke survivors and often presents as impulsive, tactless or vulgar behavior. However, it often remains undiagnosed and thus untreated, even though it can lead to a longer length of stay in a rehabilitation facility. The proposed study will aim to evaluate the clinical, neuropsychological and magnetic resonance imaging (MRI) correlates of PSBD in a cohort of stroke survivors and describe its 12-month course.

Methods

This prospective cohort study will recruit 237 patients and will be conducted at the Neurology Unit of the Prince of Wales Hospital. The project duration will be 24 months. The patients will be examined by multiple MRI methods, including diffusion-weighted imaging, within 1 week after stroke onset. The patients and their caregivers will receive a detailed assessment at a research clinic at 3, 9 and 15 months after stroke onset (T1, T2 and T3, respectively). The disinhibition subscale of the Frontal Systems Behavior Scale (FrSBe) will be completed by each subject and caregiver, and scores ≥65 will be considered to indicate PSBD.

A stepwise logistic regression will be performed to assess the importance of lesions in the regions of interest (ROIs), together with other significant variables identified in the univariate analyses. For patients with PSBD at T1, the FrSBe disinhibition scores will be compared between the groups of patients with and without ROI infarcts, using covariance analysis. The demographic, clinical and MRI variables of remitters and non-remitters will be examined again at T2 and T3 by logistic regression.

Discussion

This project will be the first MRI study on PSBD in stroke survivors. The results will shed light on the associations of lesions in the orbitofrontal cortex, anterior temporal lobe and subcortical brain structures with the risk of PSBD. The obtained data will advance our understanding of the pathogenesis and clinical course of PSBD in stroke, as well as other neurological conditions. The findings are thus likely to be applicable to the large population of patients with neurological disorders at risk of PSBD and are expected to stimulate further research in this field.
An ultrasound-based nomogram model in the assessment of pathological complete response of neoadjuvant chemotherapy in breast cancer
Authors: Liu Jinhui , Leng Xiaoling , Liu Wen , Ma Yuexin , Qiu Lin , Zumureti Tuerhong , Zhang Haijian , Mila Yeerlan
Published: March 2024

Introduction

We aim to predict the pathological complete response (pCR) of neoadjuvant chemotherapy (NAC) in breast cancer patients by constructing a Nomogram based on radiomics models, clinicopathological features, and ultrasound features.

Methods

Ultrasound images of 464 breast cancer patients undergoing NAC were retrospectively analyzed. The patients were further divided into the training cohort and the validation cohort. The radiomics signatures (RS) before NAC treatment (RS1), after 2 cycles of NAC (RS2), and the different signatures between RS2 and RS1 (Delta-RS/RS1) were obtained. LASSO regression and random forest analysis were used for feature screening and model development, respectively. The independent predictors of pCR were screened from clinicopathological features, ultrasound features, and radiomics models by using univariate and multivariate analysis. The Nomogram model was constructed based on the optimal radiomics model and clinicopathological and ultrasound features. The predictive performance was evaluated with the receiver operating characteristic (ROC) curve.

Results

We found that RS2 had better predictive performance for pCR. In the validation cohort, the area under the ROC curve was 0.817 (95%CI: 0.734-0.900), which was higher than RS1 and Delta-RS/RS1. The Nomogram based on clinicopathological features, ultrasound features, and RS2 could accurately predict the pCR value, and had the area under the ROC curve of 0.897 (95%CI: 0.866-0.929) in the validation cohort. The decision curve analysis showed that the Nomogram model had certain clinical practical value.

Discussion

The Nomogram based on radiomics signatures after two cycles of NAC, and clinicopathological and ultrasound features have good performance in predicting the NAC efficacy of breast cancer.