bluuebunny/crossref_metadata_2025 huggingface dataset:
Sea Slug Mucus Production Is Supported by Photosynthesis of Stolen Chloroplasts
Authors: Lopes Diana , Cruz Sónia , Martins Patrícia , Ferreira Sónia , Nunes Cláudia , Domingues Pedro , Cartaxana Paulo
Published: August 2022

A handful of sea slugs of the order Sacoglossa are able to steal chloroplasts—kleptoplasts—from their algal food sources and maintain them functionally for periods ranging from several weeks to a few months. In this study, we investigated the role of kleptoplast photosynthesis on mucus production by the tropical sea slug Elysia crispata. Animals reared for 5 weeks in quasi dark (5 μmol photons m−2 s−1) showed similar growth to those under regular light (60–90 μmol photons m−2 s−1), showing that kleptoplast photosynthesis was not relevant for growth when sea slugs were fed ad libitum. However, when subjected to short-term desiccation stress, animals reared under regular light produced significantly more mucus. Furthermore, the carbohydrate content of secreted mucus was significantly lower in slugs limited in the photosynthetic activity of their kleptoplasts by quasi-dark conditions. This study indicates that photosynthesis supports the synthesis of protective mucus in kleptoplast-bearing sea slugs.
Data Incompleteness May form a Hard-to-Overcome Barrier to Decoding Life’s Mechanism
Authors: Kondratyeva Liya , Alekseenko Irina , Chernov Igor , Sverdlov Eugene
Published: August 2022

In this brief review, we attempt to demonstrate that the incompleteness of data, as well as the intrinsic heterogeneity of biological systems, may form very strong and possibly insurmountable barriers for researchers trying to decipher the mechanisms of the functioning of live systems. We illustrate this challenge using the two most studied organisms: E. coli, with 34.6% genes lacking experimental evidence of function, and C. elegans, with identified proteins for approximately 50% of its genes. Another striking example is an artificial unicellular entity named JCVI-syn3.0, with a minimal set of genes. A total of 31.5% of the genes of JCVI-syn3.0 cannot be ascribed a specific biological function. The human interactome mapping project identified only 5–10% of all protein interactions in humans. In addition, most of the available data are static snapshots, and it is barely possible to generate realistic models of the dynamic processes within cells. Moreover, the existing interactomes reflect the de facto interaction but not its functional result, which is an unpredictable emerging property. Perhaps the completeness of molecular data on any living organism is beyond our reach and represents an unsolvable problem in biology.
Distinct Phenotypic Variation of Blastocystis sp. ST3 from Urban and Orang Asli Population—An Influential Consideration during Sample Collection in Surveys
Authors: Rajamanikam Arutchelvan , Hooi Ho Shiaw , Kudva Madhav , Samudi Chandramathi , Govind Suresh Kumar
Published: August 2022

Blastocystis sp. is a globally distributed protozoan parasite with uncertain pathogenicity. Phenotypic variation in Blastocystis sp. suggests its adaptation; however, the phenotypic features of Blastocystis sp. ST3 from a distinct source of isolation is unknown. Blastocystis sp. isolated from individuals in urban and orang asli (indigenous population in Selangor, Malaysia) settlements were studied for phenotypic characteristics such as growth profile, morphology, ultrastructure, and resistance to harsh conditions. Subsequently, pathogenic potentials, such as in protease activity and the ability to stimulate the proliferation of cancer cells, were assessed. Higher parasite counts with granular and apoptotic forms were found in Blastocystis sp. from orang asli individuals. Cells with fuzzy coats and amoebic structures which seemingly implicate increased interaction with bacteria were seen predominantly in urban symptomatic persons. Also, Blastocystis sp. from orang asli isolates resisted harsh environments, suggesting longer co-adaptation to the hosts. Urban and orang asli symptomatic isolates possessed a predominance of only cysteine protease, whereas all the asymptomatic isolates showed significantly higher cysteine, serine, or aspartic protease activity. However, only solubilized antigen from urban symptomatic isolates showed significant stimulation of cancer cell proliferation. For the first time, our findings demonstrate significant phenotypic variation in a single subtype, ST3 of Blastocystis sp., isolated from urban and orang asli populations that are known to have distinct gut microbial compositions. The outcome emphasizes the importance of identifying people’s locations and lifestyles during sample collection before forming conclusions on the prevailing data and implicating subtypes to pathogenicity. The environment plays a significant role in Blastocystis sp. infection.
Keeping 21st Century Paleontology Grounded: Quantitative Genetic Analyses and Ancestral State Reconstruction Re-Emphasize the Essentiality of Fossils
Authors: Monson Tesla A. , Brasil Marianne F. , Mahaney Michael C. , Schmitt Christopher A. , Taylor Catherine E. , Hlusko Leslea J.
Published: August 2022

Advances in genetics and developmental biology are revealing the relationship between genotype and dental phenotype (G:P), providing new approaches for how paleontologists assess dental variation in the fossil record. Our aim was to understand how the method of trait definition influences the ability to reconstruct phylogenetic relationships and evolutionary history in the Cercopithecidae, the Linnaean Family of monkeys currently living in Africa and Asia. We compared the two-dimensional assessment of molar size (calculated as the mesiodistal length of the crown multiplied by the buccolingual breadth) to a trait that reflects developmental influences on molar development (the inhibitory cascade, IC) and two traits that reflect the genetic architecture of postcanine tooth size variation (defined through quantitative genetic analyses: MMC and PMM). All traits were significantly influenced by the additive effects of genes and had similarly high heritability estimates. The proportion of covariate effects was greater for two-dimensional size compared to the G:P-defined traits. IC and MMC both showed evidence of selection, suggesting that they result from the same genetic architecture. When compared to the fossil record, Ancestral State Reconstruction using extant taxa consistently underestimated MMC and PMM values, highlighting the necessity of fossil data for understanding evolutionary patterns in these traits. Given that G:P-defined dental traits may provide insight to biological mechanisms that reach far beyond the dentition, this new approach to fossil morphology has the potential to open an entirely new window onto extinct paleobiologies. Without the fossil record, we would not be able to grasp the full range of variation in those biological mechanisms that have existed throughout evolution.
Design, Synthesis and Pharmacological Evaluation of Novel Conformationally Restricted N-arylpiperazine Derivatives Characterized as D2/D3 Receptor Ligands, Candidates for the Treatment of Neurodegenerative Diseases
Authors: da Silva Cunha Thayssa Tavares , Silva Rafaela Ribeiro , Rodrigues Daniel Alencar , de Sena Murteira Pinheiro Pedro , Kronenberger Thales , Sant’Anna Carlos Maurício R. , Noël François , Fraga Carlos Alberto Manssour
Published: August 2022

Most neurodegenerative diseases are multifactorial, and the discovery of several molecular mechanisms related to their pathogenesis is constantly advancing. Dopamine and dopaminergic receptor subtypes are involved in the pathophysiology of several neurological disorders, such as schizophrenia, depression and drug addiction. For this reason, the dopaminergic system and dopamine receptor ligands play a key role in the treatment of such disorders. In this context, a novel series of conformationally restricted N-arylpiperazine derivatives (5a–f) with a good affinity for D2/D3 dopamine receptors is reported herein. Compounds were designed as interphenylene analogs of the drugs aripiprazole (2) and cariprazine (3), presenting a 1,3-benzodioxolyl subunit as a ligand of the secondary binding site of these receptors. The six new N-arylpiperazine compounds were synthesized in good yields by using classical methodologies, and binding and guanosine triphosphate (GTP)-shift studies were performed. Affinity values below 1 μM for both target receptors and distinct profiles of intrinsic efficacy were found. Docking studies revealed that Compounds 5a–f present a different binding mode with dopamine D2 and D3 receptors, mainly as a consequence of the conformational restriction imposed on the flexible spacer groups of 2 and 3.
The HPV16E7 Affibody as a Novel Potential Therapeutic Agent for Treating Cervical Cancer Is Likely Internalized through Dynamin and Caveolin-1 Dependent Endocytosis
Authors: Zhang Qingyuan , Zhu Hua , Cui Zhouying , Li Yuxiao , Zhuo Jiaying , Ye Jingwei , Zhang Zhihui , Lian Zheng , Du Qianqian , Zhao Kong-Nan , Zhang Lifang , Jiang Pengfei
Published: August 2022

Affibodies targeting intracellular proteins have a great potential to function as ideal therapeutic agents. However, little is known about how the affibodies enter target cells to interact with intracellular target proteins. We have previously developed the HPV16E7 affibody (ZHPV16E7384) for HPV16 positive cervical cancer treatment. Here, we explored the underlying mechanisms of ZHPV16E7384 and found that ZHPV16E7384 significantly inhibited the proliferation of target cells and induced a G1/S phase cell cycle arrest. Furthermore, ZHPV16E7384 treatment resulted in the upregulation of retinoblastoma protein (Rb) and downregulation of phosphorylated Rb (pRb), E2F1, cyclin D1, and CDK4 in the target cells. Moreover, treatment with dynamin or the caveolin-1 inhibitor not only significantly suppressed the internalization of ZHPV16E7384 into target cells but also reversed the regulation of cell cycle factors by ZHPV16E7384. Overall, these results indicate that ZHPV16E7384 was likely internalized specifically into target cells through dynamin- and caveolin-1 mediated endocytosis. ZHPV16E7384 induced the cell cycle arrest in the G1/S phase at least partially by interrupting HPV16E7 binding to and degrading Rb, subsequently leading to the downregulation of E2F1, cyclin D1, CDK4, and pRb, which ultimately inhibited target cell proliferation. These findings provide a rationale of using ZHPV16E7384 to conduct a clinical trial for target therapy in cervical cancer.
Conformational Plasticity of Centrin 1 from Toxoplasma gondii in Binding to the Centrosomal Protein SFI1
Authors: Bombardi Luca , Favretto Filippo , Pedretti Marco , Conter Carolina , Dominici Paola , Astegno Alessandra
Published: August 2022

Centrins are calcium (Ca2+)-binding proteins that are involved in many cellular functions including centrosome regulation. A known cellular target of centrins is SFI1, a large centrosomal protein containing multiple repeats that represent centrin-binding motifs. Recently, a protein homologous to yeast and mammalian SFI1, denominated TgSFI1, which shares SFI1-repeat organization, was shown to colocalize at centrosomes with centrin 1 from Toxoplasma gondii (TgCEN1). However, the molecular details of the interaction between TgCEN1 and TgSFI1 remain largely unknown. Herein, combining different biophysical methods, including isothermal titration calorimetry, nuclear magnetic resonance, circular dichroism, and fluorescence spectroscopy, we determined the binding properties of TgCEN1 and its individual N- and C-terminal domains to synthetic peptides derived from distinct repeats of TgSFI1. Overall, our data indicate that the repeats in TgSFI1 constitute binding sites for TgCEN1, but the binding modes of TgCEN1 to the repeats differ appreciably in terms of binding affinity, Ca2+ sensitivity, and lobe-specific interaction. These results suggest that TgCEN1 displays remarkable conformational plasticity, allowing for the distinct repeats in TgSFI1 to possess precise modes of TgCEN1 binding and regulation during Ca2+ sensing, which appears to be crucial for the dynamic association of TgCEN1 with TgSFI1 in the centrosome architecture.
The Role of Nutraceutical Supplements, Monacolin K and Astaxanthin, and Diet in Blood Cholesterol Homeostasis in Patients with Myopathy
Authors: Villano Ines , La Marra Marco , Allocca Salvatore , Ilardi Ciro Rosario , Polito Rita , Porro Chiara , Chieffi Sergio , Messina Giovanni , Monda Vincenzo , Di Maio Girolamo , Messina Antonietta
Published: August 2022

Several studies suggest that different combinations of nutraceutical supplements may improve the lipid profile, representing a viable alternative to statins. However, their effects on individuals with myopathy need to be investigated. The aim of our study was to explore the mid- and long-term physiological effects of monacolin k (5 mg) and astaxanthin (0.1 mg) supplements in association with a low-energy/fat diet in a group of subjects with mild myopathy. Eighty subjects (44 women) took part in this observational study. Participants were assigned to the experimental group (EG, n = 40, 24 women) treated with a low-energy/fat diet (1200–1500 Kcal/day and 15–20% lipids) in combination with monacolin k (5 mg) and astaxanthin (0.1 mg) supplementation, and to the control group (CG, n = 40, 20 women) treated only with a low-energy/fat diet (1200–1500 Kcal/day and 15–20% lipids). BMI and biochemical parameters (blood glucose, total cholesterol, HDL, LDL, triglycerides, C-reactive protein (CRP) and creatine phosphokinase-CPK) were collected at baseline (T0), after 12 (T1) and 24 (T2) weeks. A mixed factorial ANOVA was performed to determine if there were significant main effects and/or interactions between time and treatment. Treatment (EG vs. CG) was entered as the between-subjects factor and time (T0 vs. T1 vs. T2) as the within-subject factor. We found a significant improvement in total cholesterol, HDL, LDL, PCR and CPK parameters in EG compared with CG. Our results highlight the efficacy and safety of combined use of monacolin k (5 mg) and astaxanthin (0.1 mg) in combination with a low-energy/fat diet in the treatment of dyslipidemia.
Thrust Improvement of a Biomimetic Robotic Fish by Using a Deformable Caudal Fin
Authors: Shao Hua , Dong Bingbing , Zheng Changzhen , Li Te , Zuo Qiyang , Xu Yaohui , Fang Haitao , He Kai , Xie Fengran
Published: August 2022

In nature, live fish has various deformable fins which are capable to promote the swimming speed, efficiency, stability, and thrust generation. However, this feature is rarely possessed by current man-made biomimetic robotic fishes. In this paper, a novel deformable caudal fin platform is proposed to improve thrust generation of biomimetic robotic fish. First, the design of the deformable caudal fin is given, which includes a servo motor, a gear-based transmission mechanism, fin bones, and silica membrane. Second, an improved Central Pattern Generator (CPG) model was developed to coordinately control the flapping of the tail and the deformation of the caudal fin. More specifically, three deformation patterns, i.e., conventional nondeformable mode, sinusoidal-based mode, instant mode, of the caudal fin are investigated. Third, extensive experiments are conducted to explore the effects of deformation of the caudal fin on the thrust generation of the biomimetic robotic fish. It was found that the instant mode of the caudal fin has the largest thrust, which sees a 27.5% improvement compared to the conventional nondeformable mode, followed by the sinusoidal-based mode, which also sees an 18.2% improvement. This work provides a novel way to design and control the deformation of the caudal fin, which sheds light on the development of high-performance biomimetic robotic fish.
Applying Multiple Functional Connectivity Features in GCN for EEG-Based Human Identification
Authors: Tian Wenli , Li Ming , Ju Xiangyu , Liu Yadong
Published: August 2022

EEG-based human identification has gained a wide range of attention due to the further increase in demand for security. How to improve the accuracy of the human identification system is an issue worthy of attention. Using more features in the human identification system is a potential solution. However, too many features may cause overfitting, resulting in the decline of system accuracy. In this work, the graph convolutional neural network (GCN) was adopted for classification. Multiple features were combined and utilized as the structure matrix of the GCN. Because of the constant signal matrix, the training parameters would not increase as the structure matrix grows. We evaluated the classification accuracy on a classic public dataset. The results showed that utilizing multiple features of functional connectivity (FC) can improve the accuracy of the identity authentication system, the best results of which are at 98.56%. In addition, our methods showed less sensitivity to channel reduction. The method proposed in this paper combines different FCs and reaches high classification accuracy for unpreprocessed data, which inspires reducing the system cost in the actual human identification system.
The Contributions of Cognitive Abilities to the Relationship between ADHD Symptoms and Academic Achievement
Authors: Tsantilas Demi , Ilie Alzena , Waldon Jessica , McGonnell Melissa , Corkum Penny
Published: August 2022

The main objective of this study was to examine whether increased levels of inattentive (INA) and hyperactive/impulsive (H/I) behaviours were associated with lower scores on standardized tests of achievement in basic reading, spelling, and math skills, after accounting for certain known background risk factors and cognitive processes. Clinical assessment data from a rigorously diagnosed, stimulant-medication-naïve sample of 354 elementary school-aged children experiencing academic difficulties and behavioural symptoms of inattention and/or hyperactivity/impulsivity were analyzed. Although higher scores of INA were significantly associated with lower scores in reading, spelling, and math, these associations did not persist when cognitive variables were added to the models. H/I was associated with math achievement, along with cognitive and background variables. Overall, cognitive variables accounted for the majority of the variance across basic reading, spelling, and math skills. Additionally, the only background demographic variables associated with academic achievement were age and sex for spelling and math. This finding highlights the importance of looking beyond observable INA and H/I behaviours to determine the underlying factors influencing academic achievement. Accurate identification of deficits in specific academic skills and the underlying factors influencing achievement in these skills are essential components in determining appropriate recommendations and targeted interventions.
Voxel-Mirrored Homotopic Connectivity Is Altered in Meibomian Gland Dysfunction Patients That Are Morbidly Obese
Authors: Shi Yi-Dan , Shu Hui-Ye , Liu Li-Qi , Li Shi-Qi , Liao Xu-Lin , Pan Yi-Cong , Su Ting , Zhang Li-Juan , Kang Min , Ying Ping , Shao Yi
Published: August 2022

Purpose: To investigate the altered functional connectivity (FC) of the cerebral hemispheres in patients with morbid obesity (MO) with meibomian gland dysfunction (MGD) by voxel-mirrored homotopic connectivity (VMHC). Methods: Patients and matched healthy controls (HCs) were recruited, and all subjects underwent functional resonance magnetic imaging (fMRI), and VMHC results were processed statistically to assess the differences in FC in different brain regions between the two groups. We further used ROC curves to evaluate the diagnostic value of these differences. We also used Pearson’s correlation analysis to explore the relationship between changes in VMHC values in specific brain regions, visual acuity, and Mini-Mental State Examination (MMSE) score. Conclusions: Patients with morbid obesity and MGD had abnormal FC in the cerebral hemispheres in several specific brain areas, which were mainly concentrated in pathways related to vision and perception and may correlate to some extent with the clinical presentations of the patients.
A Decoding Prediction Model of Flexion and Extension of Left and Right Feet from Electroencephalogram
Authors: AlArfaj Abeer Abdulaziz , Hosni Mahmoud Hanan A. , Hafez Alaaeldin M.
Published: August 2022

Detection of limb motor functions utilizing brain signals is a significant technique in the brain signal gain model (BSM) that can be effectively employed in various biomedical applications. Our research presents a novel technique for prediction of feet motor functions by applying a deep learning model with cascading transfer learning technique to use the electroencephalogram (EEG) in the training stage. Our research deduces the electroencephalogram data (EEG) of stroke incidence to propose functioning high-tech interfaces for predicting left and right foot motor functions. This paper presents a transfer learning with several source input domains to serve a target domain with small input size. Transfer learning can reduce the learning curve effectively. The correctness of the presented model is evaluated by the abilities of motor functions in the detection of left and right feet. Extensive experiments were performed and proved that a higher accuracy was reached by the introduced BSM-EEG neural network with transfer learning. The prediction of the model accomplished 97.5% with less CPU time. These accurate results confirm that the BSM-EEG neural model has the ability to predict motor functions for brain-injured stroke therapy.
Potential for Exposure to Particles and Gases throughout Vat Photopolymerization Additive Manufacturing Processes
Authors: Bowers Lauren N. , Stefaniak Aleksandr B. , Knepp Alycia K. , LeBouf Ryan F. , Martin Stephen B. , Ranpara Anand C. , Burns Dru A. , Virji M. Abbas
Published: August 2022

Vat photopolymerization (VP), a type of additive manufacturing process that cures resin to build objects, can emit potentially hazardous particles and gases. We evaluated two VP technologies, stereolithography (SLA) and digital light processing (DLP), in three separate environmental chambers to understand task-based impacts on indoor air quality. Airborne particles, total volatile organic compounds (TVOCs), and/or specific volatile organic compounds (VOCs) were monitored during each task to evaluate their exposure potential. Regardless of duration, all tasks released particles and organic gases, though concentrations varied between SLA and DLP processes and among tasks. Maximum particle concentrations reached 1200 #/cm3 and some aerosols contained potentially hazardous elements such as barium, chromium, and manganese. TVOC concentrations were highest for the isopropyl alcohol (IPA) rinsing, soaking, and drying post-processing tasks (up to 36.8 mg/m3), lowest for the resin pouring pre-printing, printing, and resin recovery post-printing tasks (up to 0.1 mg/m3), and intermediate for the curing post-processing task (up to 3 mg/m3). Individual VOCs included, among others, the potential occupational carcinogen acetaldehyde and the immune sensitizer 2-hydroxypropyl methacrylate (pouring, printing, recovery, and curing tasks). Careful consideration of all tasks is important for the development of strategies to minimize indoor air pollution and exposure potential from VP processes.
Review of Mechanical and Temperature Properties of Fiber Reinforced Recycled Aggregate Concrete
Authors: Yao Xinglong , Pei Zhiyang , Zheng Haoyuan , Guan Qizhou , Wang Fupeng , Wang Shuo , Ji Yongcheng
Published: August 2022

Recycled aggregate concrete has received increasing attention owing to its broad development prospects in recent years. This study discusses the enhancement mechanism of various fibers on the mechanical properties, high-temperature resistance, and freeze–thaw cycle resistance of recycled aggregate concrete. It reviews the effects of fiber types and content on the strength, failure state, and resistance to recycled aggregate concrete’s high and low temperatures. The results indicate that fibers can significantly improve the flexural strength and tensile strength of recycled aggregate concrete in the bridging effect but have little effect on compressive strength. Regarding high-temperature resistance, fibers with a lower melting point can form channels in the concrete, reducing the internal pressure of water vapor. Fibers with higher melting points can act as bridges, inhibiting the generation and propagation of cracks in recycled aggregate concrete. Therefore, fiber-reinforced recycled aggregate concrete can perform better at higher temperatures than ordinary recycled aggregate concrete. Due to the high water absorption rate in recycled aggregate concrete, which is approximately 7–10 times that of natural aggregate concrete, it is easier to reach the critical water saturation of freeze–thaw damage. Results show that 0.2 kg/m3 polypropylene fiber and 1.2 kg/m3 basalt fiber show excellent performance in improving the frost resistance of recycled aggregate concrete.
A Kano–IS Model for the Sustainable Renovation of Living Environments in Rural Settlements in China
Authors: Xu Yanqing , Li Shengcai , Juan Yi-Kai , Guo Hongxia , Lin Hanfei
Published: August 2022

By 2020, there will be 2.36 million natural villages in China, with more than 500 million people living in them. Although China’s 2018 “National Rural Revitalization Strategy” has clarified the importance of the rural environment, the sustainability of living environments in rural settlements is generally ignored. However, current renovation work is implemented as per the same set of standards and is not sufficient to reach the highest satisfaction levels and sustainable development because the optimal renovation indicators are not selected according to local conditions. To address these issues, this work carried out a series of literature reviews and expert interviews to propose indicators applicable to the sustainable renovation of living environments in rural settlements in China. The questionnaire survey was conducted in a typical Chinese village in order to verify the feasibility of this decision model. Furthermore, the Kano model was organically combined with the importance–satisfaction (IS) model from the villagers’ point of view to establish a model analyzing the optimal indicators of the sustainable renovation. The results show that this model determines the priority of elements that need to be improved or maintained, based on which village administrators can make better management decisions and which government managers can invest limited government resources in key sectors, thus creating sustainable living environments in rural settlements and enhancing the satisfaction of villagers. It is suggested that the opinions of village administrators and planners be considered to optimize this model further.
Sound Insulation of Façade Element with Triple IGU
Authors: Bliūdžius Raimondas , Miškinis Kęstutis , Buhagiar Vincent , Banionis Karolis
Published: August 2022

Sound insulation design for structural glazed façade is an important task in environmental noise control, as increased continuously repeated noise is a significant factor impacting on people’s well-being and is associated with a negative impact on their health. For façades, in addition to sound insulation, requirements for safe use and high energy efficiency are also usually raised, which partly determine the composition of the glazing: triple insulating glass unit (IGU) with inner safety laminated glass sheet. Therefore, the aim of the research was to investigate the structural sealed façade structure with triple IGU and to determine the effect of the thickness of ordinary and laminated glasses, their position in the IGU, the thickness of the gas cavities, and the mass of the structural frame on the sound insulation level of structural glazing. Experimental measurements of the sound insulation index of the investigated façade elements with IGU of various constructions were performed in an acoustic reverberation chamber according to standard procedures. The result of the study indicated that the use of the second laminated glass in a triple IGU is inefficient, the highest sound insulation indicators are achieved by increasing the thicknesses of the external glass sheet and the gas cavity; increasing the mass of the frame also has only little effect on the sound insulation of the structural glazing.
Effect of a Polyglycolic Acid Mesh Sheet (Neoveil™) in Thyroid Cancer Surgery: A Prospective Randomized Controlled Trial
Authors: Kim Seong Hoon , Ahn Jong Hyuk , Yoon Hye Jeong , Kim Jae Hwan , Hwang Young Mi , Choi Yun Suk , Yi Jin Wook
Published: August 2022

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Surgery for PTC involves resection of the thyroid gland and central lymph node dissection. Central lymph node dissection is associated with an increased amount of fluid from the dissection area and chyle leakage due to thoracic duct injury. There are few studies that deal with reducing fluid drainage and preventing chyle leakage after thyroid surgery with central lymph node dissection. A polyglycolic acid mesh sheet (Neoveil™) has been demonstrated to prevent postoperative fluid leakage in other surgeries. This study aims to evaluate whether a polyglycolic acid mesh sheet can reduce postoperative drainage and chyle leakage in papillary thyroid cancer surgery, and this study was designed as a prospective, open-label, randomized controlled trial in a single university hospital. The patients were randomly assigned to having only fibrin glue used in the central node dissection area (control group) or to having a polyglycolic acid mesh sheet applied after fibrin glue (treatment group). A total of 330 patients were enrolled, of which 5 patients were excluded. A total of 161 patients were included in the treatment group, and 164 patients were included in the control group. The primary outcome was the drainage amount from the Jackson-Pratt drain, and the secondary outcome was the triglyceride level in the drained fluid on the 1st and 2nd postoperative days. The drainage amount was significantly lower in the treatment group on the 2nd postoperative day (60.9 ± 34.9 mL vs. 72.3 ± 38.0 mL, p = 0.005). The sum of drainage amount during the whole postoperative days (1st and 2nd days) was also significantly lower in the treatment group (142.7 ± 71.0 mL vs. 162.5 ± 71.5 mL, p = 0.013). The postoperative triglyceride levels were lower in the treatment group but were not statistically significant (92.1 ± 60.1 mg/dL vs. 81.3 ± 58.7 mg/dL on postoperative day 1, p = 0.104 and 67.6 ± 99.2 mg/dL vs. 53.6 ± 80.4 mg/dL on postoperative day 2, p = 0.162). No adverse effects were observed in the treatment groups during the postoperative 9-month follow-up. Our study suggests that polyglycolic acid mesh sheets can be safely applied to reduce postoperative drainage amount in thyroidectomy patients who need lymph node dissection.
Improvements in Quality Control and Library Preparation for Targeted Sequencing Allowed Detection of Potentially Pathogenic Alterations in Circulating Cell-Free DNA Derived from Plasma of Brain Tumor Patients
Authors: Szadkowska Paulina , Roura Adria-Jaume , Wojtas Bartosz , Wojnicki Kamil , Licholai Sabina , Waller Tomasz , Gubala Tomasz , Zukowski Kacper , Karpeta Michal , Wilkus Kinga , Kaspera Wojciech , Nawrocki Sergiusz , Kaminska Bozena
Published: August 2022

Malignant gliomas are the most frequent primary brain tumors in adults. They are genetically heterogenous and invariably recur due to incomplete surgery and therapy resistance. Circulating tumor DNA (ctDNA) is a component of circulating cell-free DNA (ccfDNA) and represents genetic material that originates from the primary tumor or metastasis. Brain tumors are frequently located in the eloquent brain regions, which makes biopsy difficult or impossible due to severe postoperative complications. The analysis of ccfDNA from a patient’s blood presents a plausible and noninvasive alternative. In this study, freshly frozen tumors and corresponding blood samples were collected from 84 brain tumor patients and analyzed by targeted next-generation sequencing (NGS). The cohort included 80 glioma patients, 2 metastatic cancer patients, and 2 primary CNS lymphoma (PCNSL) patients. We compared the pattern of genetic alterations in the tumor DNA (tDNA) with that of ccfDNA. The implemented technical improvements in quality control and library preparation allowed for the detection of ctDNA in 8 out of 84 patients, including 5 out of 80 glioma patients. In 32 out of 84 patients, we found potentially pathogenic genetic alterations in ccfDNA that were not detectable in tDNA. While sequencing ccfDNA from plasma has a low efficacy as a diagnostic tool for glioma patients, we concluded that further improvements in sample processing and library preparation can make liquid biopsy a valuable diagnostic tool for glioma patients.
Radiomic Signatures Derived from Hybrid Contrast-Enhanced Ultrasound Images (CEUS) for the Assessment of Histological Characteristics of Breast Cancer: A Pilot Study
Authors: Bene Ioana , Ciurea Anca Ileana , Ciortea Cristiana Augusta , Ștefan Paul Andrei , Ciule Larisa Dorina , Lupean Roxana Adelina , Dudea Sorin Marian
Published: August 2022

The purpose of this study was to evaluate the diagnostic performance of radiomic features extracted from standardized hybrid contrast-enhanced ultrasound (CEUS) data for the assessment of hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, tumor grade and Ki-67 in patients with primary breast cancer. Methods: This prospective study included 72 patients with biopsy-proven breast cancer who underwent CEUS examinations between October 2020 and September 2021. Results: A radiomic analysis found the WavEnHH_s_4 parameter as an independent predictor associated with the HER2+ status with 76.92% sensitivity, and 64.41% specificity and a prediction model that could differentiate between the HER2 entities with 76.92% sensitivity and 84.75% specificity. The RWavEnLH_s-4 parameter was an independent predictor for estrogen receptor (ER) status with 55.93% sensitivity and 84.62% specificity, while a prediction model (RPerc01, RPerc10 and RWavEnLH_s_4) could differentiate between the progesterone receptor (PR) status with 44.74% sensitivity and 88.24% specificity. No texture parameter showed statistically significant results at the univariate analysis when comparing the Nottingham grade and the Ki-67 status. Conclusion: Our preliminary data indicate a potential that hybrid CEUS radiomic features allow the discrimination between breast cancers of different receptor and HER2 statuses with high specificity. Hybrid CEUS radiomic features might have the potential to provide a noninvasive, easily accessible and contrast-agent-safe method to assess tumor biology before and during treatment.
Management of Patients with Newly Diagnosed Desmoid Tumors in a First-Line Setting
Authors: Testa Stefano , Bui Nam Q. , Charville Gregory W. , Avedian Raffi S. , Steffner Robert , Ghanouni Pejman , Mohler David G. , Ganjoo Kristen N.
Published: August 2022

The initial management of desmoid tumors (DTs) is shifting from surgery towards active surveillance, with systemic and locally ablative treatments reserved for enlarging and/or symptomatic disease. However, it remains unclear which patients would benefit most from an initial conservative rather than interventional approach. To answer this question, we retrospectively analyzed adult and pediatric patients with DTs treated at a tertiary academic cancer center between 1992 and 2022. Outcomes measured were progression-free survival (PFS) and time to next treatment (TTNT) after first-line therapy. A total of 262 treatment-naïve patients were eligible for analysis with a median age of 36.5 years (range, 0–87 years). The 5-year PFS and the median TTNT (months) after first-line treatment were, respectively: 50.6% and 69.1 mo for surgery; 64.9% and 149.5 mo for surgery plus adjuvant radiotherapy; 57.1% and 44.7 mo for surgery plus adjuvant systemic therapy; 24.9% and 4.4 mo for chemotherapy; 26.7% and 5.3 mo for hormonal therapy; 41.3% and 29.6 mo for tyrosine kinase inhibitors (TKIs); 44.4% and 8.9 mo for cryoablation and high intensity focused ultrasound; and 43.1% and 32.7 mo for active surveillance. Age ≤ 40 years (p < 0.001), DTs involving the extremities (p < 0.001), a maximum tumor diameter > 60 mm (p = 0.04), and hormonal therapy (p = 0.03) predicted a higher risk of progression. Overall, our results suggest that active surveillance should be considered initially for patients with smaller asymptomatic DTs, while upfront TKIs, local ablation, and surgery achieve similar outcomes in those with more aggressive disease.
Adipose Tissue-Derived Mesenchymal Stromal/Stem Cells, Obesity and the Tumor Microenvironment of Breast Cancer
Authors: Ritter Andreas , Kreis Nina-Naomi , Hoock Samira Catharina , Solbach Christine , Louwen Frank , Yuan Juping
Published: August 2022

Breast cancer is the most frequently diagnosed cancer and a common cause of cancer-related death in women. It is well recognized that obesity is associated with an enhanced risk of more aggressive breast cancer as well as reduced patient survival. Adipose tissue is the major microenvironment of breast cancer. Obesity changes the composition, structure, and function of adipose tissue, which is associated with inflammation and metabolic dysfunction. Interestingly, adipose tissue is rich in ASCs/MSCs, and obesity alters the properties and functions of these cells. As a key component of the mammary stroma, ASCs play essential roles in the breast cancer microenvironment. The crosstalk between ASCs and breast cancer cells is multilateral and can occur both directly through cell–cell contact and indirectly via the secretome released by ASC/MSC, which is considered to be the main effector of their supportive, angiogenic, and immunomodulatory functions. In this narrative review, we aim to address the impact of obesity on ASCs/MSCs, summarize the current knowledge regarding the potential pathological roles of ASCs/MSCs in the development of breast cancer, discuss related molecular mechanisms, underline the possible clinical significance, and highlight related research perspectives. In particular, we underscore the roles of ASCs/MSCs in breast cancer cell progression, including proliferation and survival, angiogenesis, migration and invasion, the epithelial–mesenchymal transition, cancer stem cell development, immune evasion, therapy resistance, and the potential impact of breast cancer cells on ASCS/MSCs by educating them to become cancer-associated fibroblasts. We conclude that ASCs/MSCs, especially obese ASCs/MSCs, may be key players in the breast cancer microenvironment. Targeting these cells may provide a new path of effective breast cancer treatment.
Sequential Hypofractionated versus Concurrent Twice-Daily Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis
Authors: Zhou Wei , Wang Pang , Ti Xinyu , Yin Yutian , Huang Shigao , Yang Zhi , Li Jie , Chai Guangjin , Lyu Bo , Li Zhaohui , Zhou Yan , Xiao Feng , Xu Lin , Shi Mei , Zhao Lina
Published: August 2022

Background: As there are no randomized trials comparing twice-daily with sequential hypofractionated (sequential hypo) radiotherapy regimens for limited-stage small-cell lung cancer (LS-SCLC). This study aimed to compare these two regimens for LS-SCLC by propensity score-matched analysis (PSM). Methods: We retrospectively analyzed 108 LS-SCLC patients between January 2015 and July 2019. All patients received concurrent twice-daily or sequential hypo radiotherapy. The survival, failure patterns, and toxicities were evaluated before and after PSM. Results: Before PSM, multivariate analysis showed that patients treated with sequential hypo had a significantly better overall survival (OS) and distant metastasis-free survival (DMFS) (HR = 0.353, p = 0.009; HR = 0.483, p = 0.039, respectively). Total radiotherapy time ≥ 24 days and stage III (HR = 2.454, p = 0.004; HR = 2.310, p = 0.004, respectively) were poor prognostic indicators for OS. Patients with a total radiotherapy time ≥ 24 days and N2–3 were more likely to recur than others (HR = 1.774, p = 0.048; HR = 2.369, p = 0.047, respectively). N2–3 (HR = 3.032, p = 0.011) was a poor prognostic indicator for DMFS. After PSM, being aged ≥65 years was associated with poorer OS, relapse-free survival (RFS) and DMFS (p < 0.05). A total radiotherapy time of ≥24 days was a poor prognostic indicator for OS and RFS (HR = 2.671, p = 0.046; HR = 2.370, p = 0.054, respectively). Although there was no significant difference, the patients in the sequential hypo group had a trend towards a better OS. The failure pattern between the two groups showed no difference. More patients had grade 1–2 esophagitis in the twice-daily group (p = 0.001). Conclusions: After propensity matching, no difference was shown in survival and failure. The sequential hypo schedule was associated with comparable survival and less toxicity and may be used as an alternative to concurrent twice-daily regimens.
Integrating Structure Propagation Uncertainties in the Optimization of Online Adaptive Proton Therapy Plans
Authors: Nenoff Lena , Buti Gregory , Bobić Mislav , Lalonde Arthur , Nesteruk Konrad P. , Winey Brian , Sharp Gregory Charles , Sudhyadhom Atchar , Paganetti Harald
Published: August 2022

Currently, adaptive strategies require time- and resource-intensive manual structure corrections. This study compares different strategies: optimization without manual structure correction, adaptation with physician-drawn structures, and no adaptation. Strategies were compared for 16 patients with pancreas, liver, and head and neck (HN) cancer with 1–5 repeated images during treatment: ‘reference adaptation’, with structures drawn by a physician; ‘single-DIR adaptation’, using a single set of deformably propagated structures; ‘multi-DIR adaptation’, using robust planning with multiple deformed structure sets; ‘conservative adaptation’, using the intersection and union of all deformed structures; ‘probabilistic adaptation’, using the probability of a voxel belonging to the structure in the optimization weight; and ‘no adaptation’. Plans were evaluated using reference structures and compared using a scoring system. The reference adaptation with physician-drawn structures performed best, and no adaptation performed the worst. For pancreas and liver patients, adaptation with a single DIR improved the plan quality over no adaptation. For HN patients, integrating structure uncertainties brought an additional benefit. If resources for manual structure corrections would prevent online adaptation, manual correction could be replaced by a fast ‘plausibility check’, and plans could be adapted with correction-free adaptation strategies. Including structure uncertainties in the optimization has the potential to make online adaptation more automatable.
Novel Biotransformation of Maslinic Acid to MA-2-O-β-D-Glucoside by UDP-Glycosyltransferases from Bacillus subtilis
Authors: Hu Fen , Chen Jiaxin , Zhang Yunfeng , Sun Yuxi , Liu Yan , Yu Yuan , Xu Ke , Cai Haifeng
Published: August 2022

Maslinic acid (MA) is a pentacyclic triterpenoid which originates from olive and other plants. Though MA possesses multiple biological activities, it has limitations due to its poor water solubility. YojK, YjiC, and UGT109A3 UDP-glycosyltransferases (UGTs) from Bacillus subtilis (B. subtilis) were utilized to catalyze the conjugation of MA with UDP-Glucose to generate a new MA glycosylation product, MA-2-O-β-D-glucoside (MA-2-O-β-D-Glu). The experimental results indicated that the resultant water solubility of MA-2-O-β-D-Glu is 1.69 times higher than that of MA. In addition, the recombinant YojK showed maximum activity at 40 °C with a pH range of 8.0−10.0, while the recombinant YjiC showed maximum activity at 45 °C with a pH of 8.0, and the recombinant UGT109A3 showed maximum activity at 40 °C with a pH of 8.0. Mg2+ is an important factor for efficient catalysis by three recombinant glycosyltransferases. The chemical conversion rate of the recombinant YojK, YjiC, and UGT109A3 is nearly 100% at their optimum pH, temperature, and metal ions. Furthermore, eight essential residues of three UGTs for MA glycosylation modification were further determined by molecular docking and site-directed mutagenesis. Thus, efficient glycosylation modification improves the water solubility of MA and provides a new potential method for the glycosylation modification of other pentacyclic triterpenoids.
Catalytic Performance of Bimetallic Systems (Cu-Fe, Cu-Mn, Fe-Mn) Based on Spherical MCM-41 Modified by Template Ion-Exchange in NH3-SCR Process
Authors: Jankowska Aleksandra , Kowalczyk Andrzej , Rutkowska Małgorzata , Michalik Marek , Chmielarz Lucjan
Published: August 2022

Mesoporous silica of MCM-41 type with spherical morphology was modified with copper, iron, or manganese as well as pairs of these metals by template ion-exchange (TIE) method. The obtained samples were characterized with respect to their structure (XRD), morphology (SEM-EDS), textural parameters (low-temperature N2 sorption), surface acidity (NH3-TPD), transition metal loadings (ICP-OES), their deposited forms (UV-vis DRS) and reducibility (H2-TPR). The catalytic performance of monometallic and bimetallic samples in the selective catalytic reduction of NO with ammonia (NH3-SCR) was tested. The best catalytic results presented a bimetallic copper-manganese sample, which was significantly more active than the mechanical mixture of monometallic copper and manganese catalysts. The synergistic cooperation of manganese and copper species is possibly related to charge relocation between them, resulting in activation of the catalyst in oxidation of NO to NO2, which is necessary for the fast NH3-SCR reaction.
The CREC Fluidized Riser Simulator a Unique Tool for Catalytic Process Development
Authors: de Lasa Hugo
Published: August 2022

The CREC Riser Simulator is a mini-fluidized bench scale unit invented and implemented in 1992, at the CREC (Chemical Reactor Engineering Centre), University of Western Ontario The CREC Riser Simulator can be operated at short reaction times, in the 3 s to 20 s range. The present review describes and evaluates the original basic concept of the 1992-CREC Riser Simulator Unit, and the improved design of the 2019-CREC Riser Simulator. Both the initial and the enhanced units are specially engineered to allow the rigorous assessment of both catalyst performance and catalytic reaction kinetics. Kinetic parameters of relatively simple and accurate mathematical models can be calculated using experimental data from the CREC Riser Simulator. Since its inception in 1992, the CREC Riser Simulator has been licensed to and manufactured for a significant number of universities and companies around the world. Several examples of scenarios where the CREC Riser Simulator can be employed to develop fluidized bed catalytic and heterogeneous reactor simulations are reported in this review. Among others, they include (a) hydrocarbon catalytic cracking, (b) the catalytic conversion of tar derived biomass chemical species, (c) steam and dry catalytic methane reforming, (d) the catalytic oxydehydrogenation of light paraffins, (e) the catalytic desulfurization of gasoline, and (f) biomass derived syngas combustion via chemical looping. In this review, special emphasis is given to the application of the CREC Riser Simulator to TIPB (tri-iso-propyl-benzene) catalytic cracking and the light paraffins catalytic oxydehydrogenation (PODH).