bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting Microbiome Growth Dynamics under Environmental Perturbations
Authors: Sun George , Zhou Yi-Hui
Published: June 2024

MicroGrowthPredictor is a model that leverages Long Short-Term Memory (LSTM) networks to predict dynamic changes in microbiome growth in response to varying environmental perturbations. In this article, we present the innovative capabilities of MicroGrowthPredictor, which include the integration of LSTM modeling with a novel confidence interval estimation technique. The LSTM network captures the complex temporal dynamics of microbiome systems, while the novel confidence intervals provide a robust measure of prediction uncertainty. We include two examples—one illustrating the human gut microbiota composition and diversity due to recurrent antibiotic treatment and the other demonstrating the application of MicroGrowthPredictor on an artificial gut dataset. The results demonstrate the enhanced accuracy and reliability of the LSTM-based predictions facilitated by MicroGrowthPredictor. The inclusion of specific metrics, such as the mean square error, validates the model’s predictive performance. Our model holds immense potential for applications in environmental sciences, healthcare, and biotechnology, fostering advancements in microbiome research and analysis. Moreover, it is noteworthy that MicroGrowthPredictor is applicable to real data with small sample sizes and temporal observations under environmental perturbations, thus ensuring its practical utility across various domains.
An Unlikely Match: Modernism and Feminism in Lynda Benglis’s Contraband
Authors: Bivens Becky
Published: June 2024

In 1969, Lynda Benglis withdrew her large latex floor painting, Contraband, from the exhibition Anti-Illusion: Procedures/Materials. Looking beyond the logistical problems that caused Benglis to pull the work, I suggest that it challenged the conceptual and formal parameters of the exhibition from its inception. Taking hints from feminism, modernist painting, camp aesthetics, psychedelic imagery, pop, and minimalism, Benglis’s latex pours unify an array of movements, styles, and political positions that have often been treated as antithetical. Although the refusal of traditional binaries was typical of the neo-avant-garde, Benglis’s work was “contraband” because it challenged the inflexible dictum that feminist art and modernist painting are mortal enemies. With Contraband, she drew on abstract expressionist techniques for communicating feeling by exploiting the dialectic of spontaneity and order in Pollock’s drip paintings. Simultaneously, she drew attention to gender through sexed-up colors and materials. Rather than suggesting that gender difference is repressed by abstract expressionist painting’s false universalizing, Benglis shows that modernist techniques for communicating feeling are crucial for the feminist project of understanding the public significance of seemingly private experience.
Analysis of Ionospheric VTEC Retrieved from Multi-Instrument Observations
Authors: Oztan Gurkan , Duman Huseyin , Alcay Salih , Ogutcu Sermet , Ozdemir Behlul Numan
Published: June 2024

This study examines the Vertical Total Electron Content (VTEC) estimation performance of multi-instruments on a global scale during different ionospheric conditions. For this purpose, GNSS-based VTEC data from Global Ionosphere Maps (GIMs), COSMIC (F7/C2)—Feng–Yun 3C (FY3C) radio occultation (RO) VTEC, SWARM–VTEC, and JASON–VTEC were utilized. VTEC assessments were conducted on three distinct days: geomagnetic active (17 March 2015), solar active (22 December 2021), and quiet (11 December 2021). The VTEC values of COSMIC/FY3C RO, SWARM, and JASON were compared with data retrieved from GIMs. According to the results, COSMIC RO–VTEC is more consistent with GIM–VTEC on a quiet day (the mean of the differences is 4.38 TECU), while the mean of FY3C RO–GIM differences is 7.33 TECU on a geomagnetic active day. The range of VTEC differences between JASON and GIM is relatively smaller on a quiet day, and the mean of differences on active/quiet days is less than 6 TECU. Besides the daily comparison, long-term results (1 January–31 December 2015) were also analyzed by considering active and quiet periods. Results show that Root Mean Square Error (RMSE) values of COSMIC RO, FY3C RO, SWARM, and JASON are 5.02 TECU, 6.81 TECU, 16.25 TECU, and 5.53 TECU for the quiet period, and 5.21 TECU, 7.07 TECU, 17.48 TECU, and 5.90 TECU for the active period, respectively. The accuracy of each data source was affected by solar/geomagnetic activities. The deviation of SWARM–VTEC is relatively greater. The main reason for the significant differences in SWARM–GIM results is the atmospheric measurement range of SWARM satellites (460 km–20,200 km (SWARM A, C) and 520 km–20,200 km (SWARM B), which do not contain a significant part of the ionosphere in terms of VTEC estimation.
Meta-Analytic Gene-Clustering Algorithm for Integrating Multi-Omics and Multi-Study Data
Authors: Kemmo Tsafack Ulrich , Ahn Kwang Woo , Kwitek Anne E. , Lin Chien-Wei
Published: June 2024

Gene pathways and gene-regulatory networks are used to describe the causal relationship between genes, based on biological experiments. However, many genes are still to be studied to define novel pathways. To address this, a gene-clustering algorithm has been used to group correlated genes together, based on the similarity of their gene expression level. The existing methods cluster genes based on only one type of omics data, which ignores the information from other types. A large sample size is required to achieve an accurate clustering structure for thousands of genes, which can be challenging due to the cost of multi-omics data. Meta-analysis has been used to aggregate the data from multiple studies and improve the analysis results. We propose a computationally efficient meta-analytic gene-clustering algorithm that combines multi-omics datasets from multiple studies, using the fixed effects linear models and a modified weighted correlation network analysis framework. The simulation study shows that the proposed method outperforms existing single omic-based clustering approaches when multi-omics data and/or multiple studies are available. A real data example demonstrates that our meta-analytic method outperforms single-study based methods.
Agarose as a Tissue Mimic for the Porcine Heart, Kidney, and Liver: Measurements and a Springpot Model
Authors: Mishra Aadarsh , Cleveland Robin O.
Published: June 2024

Agarose gels are often used as a tissue mimic. The goal of this work was to determine the appropriate agarose concentrations that result in mechanical properties that match three different porcine organs. Strain tests were carried out with an amplitude varying from 0.01% to 10% at a frequency of 1 Hz on a range of agarose concentrations and porcine organs. Frequency sweep tests were performed from 0.1 Hz to a maximum of 9.5 Hz at a shear strain amplitude of 0.1% for agarose and porcine organs. In agarose samples, the effect of pre-compression of the samples up to 10% axial strain was considered during frequency sweep tests. The experimental measurements from agarose samples were fit to a fractional order viscoelastic (springpot) model. The model was then used to predict stress relaxation in response to a step strain of 0.1%. The prediction was compared to experimental relaxation data, and the results agreed within 12%. The agarose concentrations (by mass) that gave the best fit were 0.25% for the liver, 0.3% for the kidney, and 0.4% for the heart. At a frequency of 0.1 Hz and a shear strain of 0.1%, the agarose concentrations that best matched the shear storage modulus of the porcine organs were 0.4% agarose for the heart, 0.3% agarose for the kidney, and 0.25% agarose for the liver.
Preliminary Virtual Constraint-Based Control Evaluation on a Pediatric Lower-Limb Exoskeleton
Authors: Goo Anthony C. , Laubscher Curt A. , Wajda Douglas A. , Sawicki Jerzy T.
Published: June 2024

Pediatric gait rehabilitation and guidance strategies using robotic exoskeletons require a controller that encourages user volitional control and participation while guiding the wearer towards a stable gait cycle. Virtual constraint-based controllers have created stable gait cycles in bipedal robotic systems and have seen recent use in assistive exoskeletons. This paper evaluates a virtual constraint-based controller for pediatric gait guidance through comparison with a traditional time-dependent position tracking controller on a newly developed exoskeleton system. Walking experiments were performed with a healthy child subject wearing the exoskeleton under proportional-derivative control, virtual constraint-based control, and while unpowered. The participant questionnaires assessed the perceived exertion and controller usability measures, while sensors provided kinematic, control torque, and muscle activation data. The virtual constraint-based controller resulted in a gait similar to the proportional-derivative controlled gait but reduced the variability in the gait kinematics by 36.72% and 16.28% relative to unassisted gait in the hips and knees, respectively. The virtual constraint-based controller also used 35.89% and 4.44% less rms torque per gait cycle in the hips and knees, respectively. The user feedback indicated that the virtual constraint-based controller was intuitive and easy to utilize relative to the proportional-derivative controller. These results indicate that virtual constraint-based control has favorable characteristics for robot-assisted gait guidance.
Orthobiologic Management Options for Degenerative Disc Disease
Authors: de Oliveira Cezar Augusto Alves , Oliveira Bernardo Scaldini , Theodoro Rafael , Wang Joshua , Santos Gabriel Silva , Rodrigues Bruno Lima , Rodrigues Izair Jefthé , Jorge Daniel de Moraes Ferreira , Jeyaraman Madhan , Everts Peter Albert , Navani Annu , Lana José Fábio
Published: June 2024

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient’s own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.
Assessment of Thermal Osteonecrosis during Bone Drilling Using a Three-Dimensional Finite Element Model
Authors: Chen Yung-Chuan , Tsai Yi-Jung , Hsiao Hao-Yuan , Chiu Yen-Wei , Hong You-Yao , Tu Yuan-Kun , Hsiao Chih-Kun
Published: June 2024

Bone drilling is a common procedure used to create pilot holes for inserting screws to secure implants for fracture fixation. However, this process can increase bone temperature and the excessive heat can lead to cell death and thermal osteonecrosis, potentially causing early fixation failure or complications. We applied a three-dimensional dynamic elastoplastic finite element model to evaluate the propagation and distribution of heat during bone drilling and assess the thermally affected zone (TAZ) that may lead to thermal necrosis. This model investigates the parameters influencing bone temperature during bone drilling, including drill diameter, rotational speed, feed force, and predrilled hole. The results indicate that our FE model is sufficiently accurate in predicting the temperature rise effect during bone drilling. The maximum temperature decreases exponentially with radial distance. When the feed forces are 40 and 60 N, the maximum temperature does not exceed 45 °C. However, with feed forces of 10 and 20 N, both the maximum temperatures exceed 45 °C within a radial distance of 0.2 mm, indicating a high-risk zone for potential thermal osteonecrosis. With the two-stage drilling procedure, where a 2.5 mm pilot hole is predrilled, the maximum temperature can be reduced by 14 °C. This suggests that higher feed force and rotational speed and/or using a two-stage drilling process could mitigate bone temperature elevation and reduce the risk of thermal osteonecrosis during bone drilling.
Conceptualizing Scaffold Guided Breast Tissue Regeneration in a Preclinical Large Animal Model
Authors: Cheng Matthew , Janzekovic Jan , Finze Ronja , Mohseni Mina , Saifzadeh Siamak , Savi Flavia M. , Ung Owen , Wagels Michael , Hutmacher Dietmar W.
Published: June 2024

Scaffold-guided breast tissue regeneration (SGBTR) can transform both reconstructive and cosmetic breast surgery. Implant-based surgery is the most common method. However, there are inherent limitations, as it involves replacement of tissue rather than regeneration. Regenerating autologous soft tissue has the potential to provide a more like-for-like reconstruction with minimal morbidity. Our SGBTR approach regenerates soft tissue by implanting additively manufactured bioresorbable scaffolds filled with autologous fat graft. A pre-clinical large animal study was conducted by implanting 100 mL breast scaffolds (n = 55) made from medical-grade polycaprolactone into 11 minipigs for 12 months. Various treatment groups were investigated where immediate or delayed autologous fat graft, as well as platelet rich plasma, were added to the scaffolds. Computed tomography and magnetic resonance imaging were performed on explanted scaffolds to determine the volume and distribution of the regenerated tissue. Histological analysis was performed to confirm the tissue type. At 12 months, we were able to regenerate and sustain a mean soft tissue volume of 60.9 ± 4.5 mL (95% CI) across all treatment groups. There was no evidence of capsule formation. There were no immediate or long-term post-operative complications. In conclusion, we were able to regenerate clinically relevant soft tissue volumes utilizing SGBTR in a pre-clinical large animal model.
Targets to Search for New Pharmacological Treatment in Idiopathic Parkinson’s Disease According to the Single-Neuron Degeneration Model
Authors: Huenchuguala Sandro , Segura-Aguilar Juan
Published: June 2024

One of the biggest problems in the treatment of idiopathic Parkinson’s disease is the lack of new drugs that slow its progression. L-Dopa remains the star drug in the treatment of this disease, although it induces severe side effects. The failure of clinical studies with new drugs depends on the use of preclinical models based on neurotoxins that do not represent what happens in the disease since they induce rapid and expansive neurodegeneration. We have recently proposed a single-neuron degeneration model for idiopathic Parkinson’s disease that requires years to accumulate enough lost neurons for the onset of motor symptoms. This single-neuron degeneration model is based on the excessive formation of aminochrome during neuromelanin synthesis that surpass the neuroprotective action of the enzymes DT-diaphorase and glutathione transferase M2-2, which prevent the neurotoxic effects of aminochrome. Although the neurotoxic effects of aminochrome do not have an expansive effect, a stereotaxic injection of this endogenous neurotoxin cannot be used to generate a preclinical model in an animal. Therefore, the aim of this review is to evaluate the strategies for pharmacologically increasing the expression of DT diaphorase and GSTM2-2 and molecules that induce the expression of vesicular monoamine transporter 2, such as pramipexole.
Multi-Omics Insights into Disulfidptosis-Related Genes Reveal RPN1 as a Therapeutic Target for Liver Cancer
Authors: He Yan , Hu Yue , Cheng Yunsheng , Li Xutong , Chen Chuanhong , Zhang Shijie , He Huihu , Cao Feng
Published: June 2024

Disulfidptosis, a newly identified mode of programmed cell death, is yet to be comprehensively elucidated with respect to its multi-omics characteristics in tumors, specific pathogenic mechanisms, and antitumor functions in liver cancer. This study included 10,327 tumor and normal tissue samples from 33 cancer types. In-depth analyses using various bioinformatics tools revealed widespread dysregulation of disulfidptosis-related genes (DRGs) in pan-cancer and significant associations with prognosis, genetic variations, tumor stemness, methylation levels, and drug sensitivity. Univariate and multivariate Cox regression and LASSO regression were used to screen and construct prognosis-related hub DRGs and predictive models in the context of liver cancer. Subsequently, single cell analysis was conducted to investigate the subcellular localization of RPN1, a hub DRG, in various solid tumors. Western blotting was performed to validate the expression of RPN1 at both cellular and tissue levels. Additionally, functional experiments, including CCK8, EdU, clone, and transwell assays, indicated that RPN1 knockdown promoted the proliferative and invasive capacities of liver cancer cells. Therefore, this study elucidated the multi-omics characteristics of DRGs in pan-cancer and established a prognostic model for liver cancer. Additionally, this study revealed the molecular functions of RPN1 in liver cancer, suggesting its potential as a therapeutic target for this disease.
The Wnt/β-catenin/TCF/Sp5/Zic4 Gene Network That Regulates Head Organizer Activity in Hydra Is Differentially Regulated in Epidermis and Gastrodermis
Authors: Iglesias Ollé Laura , Perruchoud Chrystelle , Sanchez Paul Gerald Layague , Vogg Matthias Christian , Galliot Brigitte
Published: June 2024

Hydra head formation depends on an organizing center in which Wnt/β-catenin signaling, that plays an inductive role, positively regulates Sp5 and Zic4, with Sp5 limiting Wnt3/β-catenin expression and Zic4 triggering tentacle formation. Using transgenic lines in which the HySp5 promoter drives eGFP expression in either the epidermis or gastrodermis, we show that Sp5 promoter activity is differentially regulated in each epithelial layer. In intact animals, epidermal HySp5:GFP activity is strong apically and weak along the body column, while in the gastrodermis, it is maximal in the tentacle ring region and maintained at a high level along the upper body column. During apical regeneration, HySp5:GFP is activated early in the gastrodermis and later in the epidermis. Alsterpaullone treatment induces a shift in apical HySp5:GFP expression towards the body column where it forms transient circular figures in the epidermis. Upon β-catenin(RNAi), HySp5:GFP activity is down-regulated in the epidermis while bud-like structures expressing HySp5:GFP in the gastrodermis develop. Sp5(RNAi) reveals a negative Sp5 autoregulation in the epidermis, but not in the gastrodermis. These differential regulations in the epidermis and gastrodermis highlight the distinct architectures of the Wnt/β-catenin/TCF/Sp5/Zic4 network in the hypostome, tentacle base and body column of intact animals, as well as in the buds and apical and basal regenerating tips.
TAFRO Syndrome: Guidance for Managing Patients Presenting Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly
Authors: Miura Katsuhiro , Nishimaki-Watanabe Haruna , Takahashi Hiromichi , Nakagawa Masaru , Otake Shimon , Hamada Takashi , Koike Takashi , Iizuka Kazuhide , Takeuchi Yuuichi , Kurihara Kazuya , Endo Toshihide , Ito Shun , Nukariya Hironao , Namiki Takahiro , Hayashi Yoshiyuki , Nakamura Hideki
Published: June 2024

TAFRO syndrome is an inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly. Despite great advancements in research on the TAFRO syndrome in the last decade, its diagnosis and treatment are still challenging for most clinicians because of its rarity and severity. Since the initial proposal of the TAFRO syndrome as a distinct disease entity in 2010, two independent diagnostic criteria have been developed. Although these are different in the concept of whether TAFRO syndrome is a subtype of idiopathic multicentric Castleman disease or not, they are similar except for the magnitude of lymph node histopathology. Because there have been no specific biomarkers, numerous diseases must be ruled out before the diagnosis of TAFRO syndrome is made. The standard of care has not been fully established, but interleukin-6 blockade therapy with siltuximab or tocilizumab and anti-inflammatory therapy with high-dose corticosteroids are the most commonly applied for the treatment of TAFRO syndrome. The other immune suppressive agents or combination cytotoxic chemotherapies are considered for patients who do not respond to the initial treatment. Whereas glowing awareness of this disease improves the clinical outcomes of patients with TAFRO syndrome, further worldwide collaborations are warranted.
The Blood Plasma Lipidomic Profile in Atherosclerosis of the Brachiocephalic Arteries
Authors: Lomonosova Anastasiia , Gognieva Daria , Suvorov Aleksandr , Silantyev Artemy , Abasheva Alina , Vasina Yana , Abdullaev Magomed , Nartova Anna , Eroshchenko Nikolay , Kazakova Viktoriia , Komarov Roman , Dzyundzya Andrey , Danilova Elena , Shchekochikhin Dmitry , Kopylov Philipp
Published: June 2024

According to the World Health Organization, ischemic stroke is the second leading cause of death in the world. Frequently, it is caused by brachiocephalic artery (BCA) atherosclerosis. Timely detection of atherosclerosis and its unstable course can allow for a timely response to potentially dangerous changes and reduce the risk of vascular complications. Omics technologies allow us to identify new biomarkers that we can use in diagnosing diseases. This research included 90 blood plasma samples. The study group comprised 52 patients with severe atherosclerotic lesions BCA, and the control group comprised 38 patients with no BCA atherosclerosis. Targeted and panoramic lipidomic profiling of their blood plasma was carried out. There was a statistically significant difference (p < 0.05) in the values of the indices saturated fatty acids (FAs), unsaturated FAs, monounsaturated FAs, omega-3, and omega-6. Based on the results on the blood plasma lipidome, we formed models that have a fairly good ability to determine atherosclerotic lesions of the brachiocephalic arteries, as well as a model for identifying unstable atherosclerotic plaques. According only to the panoramic lipidome data, divided into groups according to stable and unstable atherosclerotic plaques, a significant difference was taken into account: p value < 0.05 and abs (fold change) > 2. Unfortunately, we did not observe significant differences according to the established plasma panoramic lipidome criteria between patients with stable and unstable plaques. Omics technologies allow us to obtain data about any changes in the body. According to our data, statistically significant differences in lipidomic profiling were obtained when comparing groups with or without BCA atherosclerosis.
The Obesogenic Gut Microbiota as a Crucial Factor Defining the Depletion of Predicted Enzyme Abundance for Vitamin B12 Synthesis in the Mouse Intestine
Authors: Zabolotneva Anastasia A. , Kolesnikova Irina M. , Vasiliev Ilya Yu. , Grigoryeva Tatiana V. , Roumiantsev Sergei A. , Shestopalov Aleksandr V.
Published: June 2024

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet well understood. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesized that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower predicted abundance of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(−/−) (db/db) mice, which developed severe obesity. The predicted abundance of enzymes involved in cobalamin synthesis is strongly correlated with the representation of several microbes in high-fat diet-fed mice, while there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.
Biped Robots Control in Gusty Environments with Adaptive Exploration Based DDPG
Authors: Zhang Yilin , Sun Huimin , Sun Honglin , Huang Yuan , Hashimoto Kenji
Published: June 2024

As technology rapidly evolves, the application of bipedal robots in various environments has widely expanded. These robots, compared to their wheeled counterparts, exhibit a greater degree of freedom and a higher complexity in control, making the challenge of maintaining balance and stability under changing wind speeds particularly intricate. Overcoming this challenge is critical as it enables bipedal robots to sustain more stable gaits during outdoor tasks, thereby increasing safety and enhancing operational efficiency in outdoor settings. To transcend the constraints of existing methodologies, this research introduces an adaptive bio-inspired exploration framework for bipedal robots facing wind disturbances, which is based on the Deep Deterministic Policy Gradient (DDPG) approach. This framework allows the robots to perceive their bodily states through wind force inputs and adaptively modify their exploration coefficients. Additionally, to address the convergence challenges posed by sparse rewards, this study incorporates Hindsight Experience Replay (HER) and a reward-reshaping strategy to provide safer and more effective training guidance for the agents. Simulation outcomes reveal that robots utilizing this advanced method can more swiftly explore behaviors that contribute to stability in complex conditions, and demonstrate improvements in training speed and walking distance over traditional DDPG algorithms.
Biological Surface Layer Formation on Bioceramic Particles for Protein Adsorption
Authors: Kimura Reo , Noda Daichi , Liu Zizhen , Shi Wanyu , Akutsu Ryota , Tagaya Motohiro
Published: June 2024

In the biomedical fields of bone regenerative therapy, the immobilization of proteins on the bioceramic particles to maintain their highly ordered structures is significantly important. In this review, we comprehensively discussed the importance of the specific surface layer, which can be called “non-apatitic layer”, affecting the immobilization of proteins on particles such as hydroxyapatite and amorphous silica. It was suggested that the water molecules and ions contained in the non-apatitic layer can determine and control the protein immobilization states. In amorphous silica particles, the direct interactions between proteins and silanol groups make it difficult to immobilize the proteins and maintain their highly ordered structures. Thus, the importance of the formation of a surface layer consisting of water molecules and ions (i.e., a non-apatitic layer) on the particle surfaces for immobilizing proteins and maintaining their highly ordered structures was suggested and described. In particular, chlorine-containing amorphous silica particles were also described, which can effectively form the surface layer of protein immobilization carriers. The design of the bio-interactive and bio-compatible surfaces for protein immobilization while maintaining the highly ordered structures will improve cell adhesion and tissue formation, thereby contributing to the construction of social infrastructures to support super-aged society.
Microbial Biofilms: Features of Formation and Potential for Use in Bioelectrochemical Devices
Authors: Perchikov Roman , Cheliukanov Maxim , Plekhanova Yulia , Tarasov Sergei , Kharkova Anna , Butusov Denis , Arlyapov Vyacheslav , Nakamura Hideaki , Reshetilov Anatoly
Published: June 2024

Microbial biofilms present one of the most widespread forms of life on Earth. The formation of microbial communities on various surfaces presents a major challenge in a variety of fields, including medicine, the food industry, shipping, etc. At the same time, this process can also be used for the benefit of humans—in bioremediation, wastewater treatment, and various biotechnological processes. The main direction of using electroactive microbial biofilms is their incorporation into the composition of biosensor and biofuel cells This review examines the fundamental knowledge acquired about the structure and formation of biofilms, the properties they have when used in bioelectrochemical devices, and the characteristics of the formation of these structures on different surfaces. Special attention is given to the potential of applying the latest advances in genetic engineering in order to improve the performance of microbial biofilm-based devices and to regulate the processes that take place within them. Finally, we highlight possible ways of dealing with the drawbacks of using biofilms in the creation of highly efficient biosensors and biofuel cells.
Comparing the Mechanical Properties of Rice Cells and Protoplasts under PEG6000 Drought Stress Using Double Resonator Piezoelectric Cytometry
Authors: Yan Yu , Zhou Tiean , Zhang Yu , Kong Zhicheng , Pan Weisong , Tan Chengfang
Published: June 2024

Plant cells’ ability to withstand abiotic stress is strongly linked to modifications in their mechanical characteristics. Nevertheless, the lack of a workable method for consistently tracking plant cells’ mechanical properties severely restricts our comprehension of the mechanical alterations in plant cells under stress. In this study, we used the Double Resonator Piezoelectric Cytometry (DRPC) method to dynamically and non-invasively track changes in the surface stress (ΔS) generated and viscoelasticity (storage modulus G′ and loss modulus G″) of protoplasts and suspension cells of rice under a drought stress of 5–25% PEG6000. The findings demonstrate that rice suspension cells and protoplasts react mechanically differently to 5–15% PEG6000 stress, implying distinct resistance mechanisms. However, neither of them can withstand 25% PEG6000 stress; they respond mechanically similarly to 25% PEG6000 stress. The results of DRPC are further corroborated by the morphological alterations of rice cells and protoplasts observed under an optical microscope. To sum up, the DRPC technique functions as a precise cellular mechanical sensor and offers novel research tools for the evaluation of plant cell adversity and differentiating between the mechanical reactions of cells and protoplasts under abiotic stress.
Acetaminophen Adsorption on Carbon Materials from Citrus Waste
Authors: Gatrouni Marwa , Asses Nedra , Bedia Jorge , Belver Carolina , Molina Carmen B. , Mzoughi Nadia
Published: June 2024

Biochar and carbon adsorbents from citrus waste have been prepared by thermal and chemical treatments; they have been used in the aqueous phase adsorption of acetaminophen (ACE) as a model emerging pollutant. These materials were fully characterized by elemental analysis, X-ray fluorescence (TXRF), adsorption/desorption of nitrogen, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), point of zero charge (pHpzc), scanning electron microscopy (SEM), and thermogravimetric analyses (TGA/DTG/DTA). A magnetic carbon adsorbent was obtained by FeCl3 activation under an inert atmosphere, giving rise to the best results in ACE adsorption. Adsorption equilibrium data were obtained at 298, 318, and 338 K and fitted to different models, corresponding to the best fitting to the Redlich–Peterson model. The maximum adsorption capacity at equilibrium resulted in 45 mg ACE·g−1 carbon at 338 K. The free energy values were calculated, and values between −21.03 and −23.00 kJ·mol−1 were obtained; the negative values confirmed the spontaneity of the process. The enthalpy and entropy of the adsorption process were obtained, giving rise to −6.4 kJ·mol−1 and 49 J·mol−1·K−1, respectively, indicating a slightly exothermic process and an increase in the randomness at the solid–liquid interface upon adsorption, respectively. The adsorption kinetics were also studied, with the Elovich model being the one that gave rise to the best-fitting results.
Dose Optimization of Targeted Therapies for Oncologic Indications
Authors: Zettler Marjorie E.
Published: June 2024

Therapeutic advances in oncology in the 21st century have contributed to significant declines in cancer mortality. Notably, targeted therapies comprised the largest proportion of oncology drugs approved by the United States (US) Food and Drug Administration (FDA) over the past 25 years and have become the standard of care for the treatment of many cancers. However, despite the metamorphosis of the therapeutic landscape, some aspects of cancer drug development have remained essentially unchanged. In particular, the dose-finding methodology originally developed for cytotoxic chemotherapy drugs continues to be implemented, even though this approach no longer represents the most appropriate strategy for modern cancer therapies. In recognition of the need to reconsider assumptions, adapt the dose selection process for newer drugs, and design alternative strategies, the FDA has undertaken several initiatives in recent years to address these concerns. These actions include the launch of Project Optimus in 2021 and the issuance of draft guidance for industry on dose optimization of oncology drugs in 2023. Amid this evolving regulatory environment, the present manuscript reviews case studies for six different targeted cancer therapies, highlighting how dose-finding challenges have been managed to date by oncologists, sponsors, and regulators.
Emerging Prognostic Markers in Patients Undergoing Liver Resection for Hepatocellular Carcinoma: A Narrative Review
Authors: Panettieri Elena , Campisi Andrea , De Rose Agostino M. , Mele Caterina , Giuliante Felice , Vauthey Jean-Nicolas , Ardito Francesco
Published: June 2024

In patients with hepatocellular carcinoma (HCC), liver resection is potentially curative. Nevertheless, post-operative recurrence is common, occurring in up to 70% of patients. Factors traditionally recognized to predict recurrence and survival after liver resection for HCC include pathologic factors (i.e., microvascular and capsular invasion) and an increase in alpha-fetoprotein level. During the past decade, many new markers have been reported to correlate with prognosis after resection of HCC: liquid biopsy markers, gene signatures, inflammation markers, and other biomarkers, including PIVKA-II, immune checkpoint molecules, and proteins in urinary exosomes. However, not all of these new markers are readily available in clinical practice, and their reproducibility is unclear. Liquid biopsy is a powerful and established tool for predicting long-term outcomes after resection of HCC; the main limitation of liquid biopsy is represented by the cost related to its technical implementation. Numerous patterns of genetic expression capable of predicting survival after curative-intent hepatectomy for HCC have been identified, but published findings regarding these markers are heterogenous. Inflammation markers in the form of prognostic nutritional index and different blood cell ratios seem more easily reproducible and more affordable on a large scale than other emerging markers. To select the most effective treatment for patients with HCC, it is crucial that the scientific community validate new predictive markers for recurrence and survival after resection that are reliable and widely reproducible. More reports from Western countries are necessary to corroborate the evidence.
Quick Plant Sample Preparation Methods Using a Micro-Homogenizer for the Detection of Multiple Citrus Pathogens
Authors: Liu Chia-Wei , Bodaghi Sohrab , Vidalakis Georgios , Tsutsui Hideaki
Published: June 2024

Effective pathogen detection is essential for plant disease control. However, plant sample preparation for downstream assays, such as quantitative polymerase chain reaction (qPCR), is challenging to perform outside of a laboratory. This paper reports two sample preparation methods featuring chemical and mechanical lysis and nucleic acid extraction using a micro-homogenizer, followed by serial dilution or nucleic acid purification with a paper disk before assay. Five minutes of lysis and extraction resulted in DNA and RNA yields of up to 76.5% and 63.3%, respectively, compared to mortar and pestle controls. Crude lysates were unsuitable for direct use in qPCR assays; however, serial dilution or quick wash using chromatography paper rendered samples ready for such assays. Additionally, the nucleic acids stored on paper disks under various storage conditions remained stable for one month. These methods can facilitate the in-field preparation of citrus samples and allow for both onsite and mail-in diagnostics for growers.
An In-Depth Look at Nutrition Support and Adequacy for Critically Ill Children with Organ Dysfunction
Authors: Knebusch Nicole , Hong-Zhu Paola , Mansour Marwa , Daughtry Jennifer N. , Fogarty Thomas P. , Stein Fernando , Coss-Bu Jorge A.
Published: June 2024

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2–18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days 1 and 3 of admission, with OD defined as a score > 5. Of 4199 patient admissions, 164 children were included. The prevalence of OD for days 1 and 3 was 79.3% and 78.7%, respectively. On day 3, when pSOFA scores trended upward, decreased, or remained unchanged, median (IQR) caloric intake was 0 (0–15), 9.2 (0–25), and 22 (1–43) kcal/kg/day, respectively (p = 0.0032); when pSOFA scores trended upward, decreased, or remained unchanged, protein intake was 0 (0–0.64), 0.44 (0–1.25), and 0.66 (0.04–1.67) g/kg/day, respectively (p = 0.0023). Organ dysfunction was prevalent through the first 72 h of a PICU stay. When the pSOFA scores trended downward or remained unchanged, caloric and protein intakes were higher than those that trended upward.
Feasibility of Achieving Nutritional Adequacy in Critically Ill Children with Critical Neurological Illnesses (CNIs)?—A Quaternary Hospital Experience
Authors: Mansour Marwa , Knebusch Nicole , Daughtry Jennifer , Fogarty Thomas P. , Lam Fong Wilson , Orellana Renan A. , Lai Yi-Chen , Erklauer Jennifer , Coss-Bu Jorge A.
Published: June 2024

The literature on the nutritional needs and outcomes of critically ill children is scarce, especially on those with critical neurological illnesses (CNIs). Current evidence shows a lower mortality in patients who achieve two-thirds of their nutritional needs during the first week of pediatric intensive care unit (PICU) admission. We hypothesized that achieving 60% of the recommended dietary intake during the first week of a PICU stay is not feasible in patients with CNI. We designed an observational retrospective cohort study where we included all index admissions to the PICU in our institution of children (1 month to 18 years) with CNI from January 2018 to June 2021. We collected patient demographics, anthropometric measures, and caloric and protein intake (enteral and parenteral) information during the first week of PICU admission. Goal adequacy for calories and protein was defined as [(intake/recommended) × 100] ≥ 60%. A total of 1112 patients were included in the nutrition assessment, 12% of whom were underweight (weight for age z score < −2). Of this group, 180 met the criteria for nutrition support evaluation. On the third day of admission, 50% of the patients < 2 years achieved caloric and protein goal adequacy, compared to 25% of patients > 2 years, with p-values of 0.0003 and 0.0004, respectively. Among the underweight patients, 60% achieved both caloric and protein goal adequacy by day 3 vs. 30% of non-underweight patients with p-values of 0.0006 and 0.002, respectively. The results show that achieving 60% of the recommended dietary intake by days 5 and 7 of admission was feasible in more than half of the patients in this cohort. Additionally, children who were evaluated by a clinical dietician during the first 48 h of PICU admission reached higher nutrition adequacy.
Genomic Evolution Strategy in SARS-CoV-2 Lineage B: Coevolution of Cis Elements
Authors: Tamayo-Ordóñez Yahaira de J. , Rosas-García Ninfa M. , Tamayo-Ordoñez Francisco A. , Ayil-Gutiérrez Benjamín A. , Bello-López Juan M. , Sosa-Santillán Gerardo de J. , Acosta-Cruz Erika , Anguebes-Franseschi Francisco , Damas-Damas Siprian , Domínguez-May Angel V. , Córdova-Quiroz Atl Victor , Tamayo-Ordóñez María Concepción
Published: June 2024

In the SARS-CoV-2 lineage, RNA elements essential for its viral life cycle, including genome replication and gene expression, have been identified. Still, the precise structures and functions of these RNA regions in coronaviruses remain poorly understood. This lack of knowledge points out the need for further research to better understand these crucial aspects of viral biology and, in time, prepare for future outbreaks. In this research, the in silico analysis of the cis RNA structures that act in the alpha-, beta-, gamma-, and deltacoronavirus genera has provided a detailed view of the presence and adaptation of the structures of these elements in coronaviruses. The results emphasize the importance of these cis elements in viral biology and their variability between different viral variants. Some coronavirus variants in some groups, depending on the cis element (stem-loop1 and -2; pseudoknot stem-loop1 and -2, and s2m), exhibited functional adaptation. Additionally, the conformation flexibility of the s2m element in the SARS variants was determined, suggesting a coevolution of this element in this viral group. The variability in secondary structures suggests genomic adaptations that may be related to replication processes, genetic regulation, as well as the specific pathogenicity of each variant. The results suggest that RNA structures in coronaviruses can adapt and evolve toward different viral variants, which has important implications for viral adaptation, pathogenicity, and future therapeutic strategies.
Experimental Study on the Process of Submerged Arc Welding for Nickel-Based WC Flux-Cored Wire on Descaling Roll
Authors: Li Chang , Feng Lei , Han Xing , Luo Fenghua , Sun Han
Published: June 2024

Descaling roll is a key component used to remove iron oxide on billet surface in hot rolling production lines, and its surface properties have a significant effect on the quality of hot rolling products. The descaling roll is in bad service condition and subjected to the dynamic impact caused by high-pressure water erosion and high temperature billet descaling process for a long time. Under the action of high temperature, strong wear, multi-cycle heat, force, flow and multi-field strong coupling, the surface is prone to wear and corrosion failure, which affects the continuous rolling production. Submerged arc welding provides an effective way to repair and strengthen the descaling roll surface. The content of WC hard phase has a significant effect on welding quality. At the same time, direct submerged arc welding of Ni based WC wire on the descaling roll surface is easy to cause cracks, and a gradient synergistic strengthening effect can be formed by setting the transition bottom layer in welding. At present, there is a lack of experiments related to the preparation of flux-cored wire with different contents and the overlaying for the bottom submerged arc welding. Relevant studies are urgently needed to further reveal the welding process mechanism to provide significant theoretical support for the preparation of wire materials and the improvement of welding quality. In this paper, 30% and 60% WC flux-cored wires were prepared by employing Ni-Cr-B-Si alloy powder as the base powder, and submerged arc welding tests were conducted on the descaling roll, preparing three welding layers, namely 70% NiCrBSi + 30% WC without the bottom layer, 70% NiCrBSi + 30% WC with the bottom layer, and 40% NiCrBSi + 60% WC with the bottom layer. The properties of the welding layer were evaluated by SEM, XRD, EDS, hardness, friction and wear, corrosion and impact experiments. The results show that the WC hard phase added in the filler metal has dissolved and formed a new phase with other elements in the melting pool. The surfacing layer mainly contains Fe-Ni, Cr-C, Fe3Si, Ni3C and other phases. The surfacing layer prepared by a different amount of WC flux-cored wire and the surfacing layer with or without the bottom layer have great differences in microstructure and properties. This study lays a significant theoretical foundation for optimizing the submerged arc welding process and preparing welding materials for the descaling roll and has significant practical significance and application value.