bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomechanical Assessments of the Upper Limb for Determining Fatigue, Strain and Effort from the Laboratory to the Industrial Working Place: A Systematic Review
Authors: Brambilla Cristina , Lavit Nicora Matteo , Storm Fabio , Reni Gianluigi , Malosio Matteo , Scano Alessandro
Published: April 2023

Recent human-centered developments in the industrial field (Industry 5.0) lead companies and stakeholders to ensure the wellbeing of their workers with assessments of upper limb performance in the workplace, with the aim of reducing work-related diseases and improving awareness of the physical status of workers, by assessing motor performance, fatigue, strain and effort. Such approaches are usually developed in laboratories and only at times they are translated to on-field applications; few studies summarized common practices for the assessments. Therefore, our aim is to review the current state-of-the-art approaches used for the assessment of fatigue, strain and effort in working scenarios and to analyze in detail the differences between studies that take place in the laboratory and in the workplace, in order to give insights on future trends and directions. A systematic review of the studies aimed at evaluating the motor performance, fatigue, strain and effort of the upper limb targeting working scenarios is presented. A total of 1375 articles were found in scientific databases and 288 were analyzed. About half of the scientific articles are focused on laboratory pilot studies investigating effort and fatigue in laboratories, while the other half are set in working places. Our results showed that assessing upper limb biomechanics is quite common in the field, but it is mostly performed with instrumental assessments in laboratory studies, while questionnaires and scales are preferred in working places. Future directions may be oriented towards multi-domain approaches able to exploit the potential of combined analyses, exploitation of instrumental approaches in workplace, targeting a wider range of people and implementing more structured trials to translate pilot studies to real practice.
Fabrication of Hydrogel-Based Composite Fibers and Computer Simulation of the Filler Dynamics in the Composite Flow
Authors: Gruhn Thomas , Monsalve Camilo Ortiz , Müller Claudia , Heid Susanne , Boccaccini Aldo R. , Salehi Sahar
Published: April 2023

Fibrous structures with anisotropic fillers as composites have found increasing interest in the field of biofabrication since they can mimic the extracellular matrix of anisotropic tissues such as skeletal muscle or nerve tissue. In the present work, the inclusion of anisotropic fillers in hydrogel-based filaments with an interpenetrating polymeric network (IPN) was evaluated and the dynamics of such fillers in the composite flow were analyzed using computational simulations. In the experimental part, microfabricated rods (200 and 400 μm length, 50 μm width) were used as anisotropic fillers in extrusion of composite filaments using two techniques of wet spinning and 3D printing. Hydrogels such as oxidized alginate (ADA) and methacrylated gelatin (GelMA) were used as matrices. In the computational simulation, a combination of computational fluid dynamics and coarse-grained molecular dynamics was used to study the dynamics of rod-like fillers in the flow field of a syringe. It showed that, during the extrusion process, microrods are far from being well aligned. Instead, many of them tumble on their way through the needle leading to a random orientation in the fiber which was confirmed experimentally.
Human-Derived Cortical Neurospheroids Coupled to Passive, High-Density and 3D MEAs: A Valid Platform for Functional Tests
Authors: Muzzi Lorenzo , Di Lisa Donatella , Falappa Matteo , Pepe Sara , Maccione Alessandro , Pastorino Laura , Martinoia Sergio , Frega Monica
Published: April 2023

With the advent of human-induced pluripotent stem cells (hiPSCs) and differentiation protocols, methods to create in-vitro human-derived neuronal networks have been proposed. Although monolayer cultures represent a valid model, adding three-dimensionality (3D) would make them more representative of an in-vivo environment. Thus, human-derived 3D structures are becoming increasingly used for in-vitro disease modeling. Achieving control over the final cell composition and investigating the exhibited electrophysiological activity is still a challenge. Thence, methodologies to create 3D structures with controlled cellular density and composition and platforms capable of measuring and characterizing the functional aspects of these samples are needed. Here, we propose a method to rapidly generate neurospheroids of human origin with control over cell composition that can be used for functional investigations. We show a characterization of the electrophysiological activity exhibited by the neurospheroids by using micro-electrode arrays (MEAs) with different types (i.e., passive, C-MOS, and 3D) and number of electrodes. Neurospheroids grown in free culture and transferred on MEAs exhibited functional activity that can be chemically and electrically modulated. Our results indicate that this model holds great potential for an in-depth study of signal transmission to drug screening and disease modeling and offers a platform for in-vitro functional testing.
RVM-GSM: Classification of OCT Images of Genitourinary Syndrome of Menopause Based on Integrated Model of Local–Global Information Pattern
Authors: Song Kaiwen , Wang Haoran , Guo Xinyu , Sun Mingyang , Shao Yanbin , Xue Songfeng , Zhang Hongwei , Zhang Tianyu
Published: April 2023

Genitourinary syndrome of menopause (GSM) is a group of syndromes, including atrophy of the reproductive tract and urinary tract, and sexual dysfunction, caused by decreased levels of hormones, such as estrogen, in women during the transition to, or late stage of, menopause. GSM symptoms can gradually become severe with age and menopausal time, seriously affecting the safety, and physical and mental health, of patients. Optical coherence tomography (OCT) systems can obtain images similar to “optical slices” in a non-destructive manner. This paper presents a neural network, called RVM-GSM, to implement automatic classification tasks for different types of GSM-OCT images. The RVM-GSM module uses a convolutional neural network (CNN) and a vision transformer (ViT) to capture local and global features of the GSM-OCT images, respectively, and, then, fuses the two features in a multi-layer perception module to classify the image. In accordance with the practical needs of clinical work, lightweight post-processing is added to the final surface of the RVM-GSM module to compress the module. Experimental results showed that the accuracy rate of RVM-GSM in the GSM-OCT image classification task was 98.2%. This result is better than those of the CNN and Vit models, demonstrating the promise and potential of the application of RVM-GSM in the physical health and hygiene fields for women.
Reproducing during Heat Waves: Influence of Juvenile and Adult Environment on Fecundity of a Pest Mite and Its Predator
Authors: Tscholl Thomas , Nachman Gösta , Spangl Bernhard , Serve Hanna Charlotte , Walzer Andreas
Published: April 2023

The thermal history of arthropod predators and their prey may affect their reproductive performance during heat waves. Thus, a matching juvenile and adult environment should be beneficial as it enables the individuals to acclimate to extreme conditions. Prey fecundity, however, is also affected by a second stressor, namely predation risk. Here, we assessed the impact of extreme and mild heat waves on the reproductive output of acclimated (juvenile and adult heat wave conditions are matching) and non-acclimated females of the biocontrol agent Phytoseiulus persimilis, a predatory mite, and its herbivorous prey, the two-spotted spider mite Tetranychus urticae, on bean leaves. Their escape and oviposition rates and egg sizes were recorded over 10 days. Additionally, ovipositing prey females were exposed to predator cues and heat waves. Acclimation changed the escape rates and egg sizes of both species, whereas fecundity was only influenced by the adult thermal environment via increased egg numbers under extreme heat waves. Acclimation reduced predator and prey escape rates, which were higher for the predator. Pooled over acclimation, both species deposited more but smaller eggs under extreme heat waves. Acclimation dampened this effect in prey eggs, whereas acclimation resulted in smaller female eggs of the predator. Prey deposited larger male and female eggs. Predator cues reduced prey oviposition, but the effect was small compared to the large increase gained under extreme heat waves. We argue that the success of predators in controlling spider mites during heat waves mainly depends on the fates of escaping predators. A permanent absence of predators may result in the numerical dominance of prey.
Population Genetics of Manila Clam (Ruditapes philippinarum) in China Inferred from Microsatellite Markers
Authors: Zheng Sichen , Zhang Tianshi , Tu Kang , Li Li , Liu Zhihong , Wu Biao , Zhou Liqing , Sun Xiujun
Published: April 2023

The Manila clam (Ruditapes philippinarum) is one of the most commercially important bivalves along the coast of China. With the continuous expansion of clam farming scale, it may lead to some serious problems, including loss of genetic variation, inbreeding depression, and reduced effective population size (Ne). In the present study, eleven microsatellite markers were used to investigate the genetic diversity and differentiation among 13 clam populations along the coast of China. As a result, 150 alleles were detected according to the genotyping results of eleven microsatellite loci. The observed heterozygosity (Ho) was estimated to be ranging from 0.437 to 0.678, while the expected heterozygosity (He) was calculated to be varying from 0.587 to 0.700. Fst values between populations ranged from 0.0046-0.1983. In particular, the Laizhou population had the highest genetic variability, which was significantly different from the others (all Fst values > 0.1). For all the clam populations, there was no significant linear regression between genetic and geographic distance, indicating that these populations do not follow a pattern of isolation by distance (IBD). Genetic structure was estimated according to NJ, principal coordinates (PCoA), and structure-based clustering. Estimates of effective population size range from dozens to thousands among different populations, based on linkage-disequilibrium and molecular coancestry methods. The results reveal the genetic diversity of clams and verify the hypothesis that clam population differentiation may be influenced by the mode of southern breeding and northern culture, providing guiding information for natural resource conservation and genetic breeding of clams.
Humanin and Its Pathophysiological Roles in Aging: A Systematic Review
Authors: Coradduzza Donatella , Congiargiu Antonella , Chen Zhichao , Cruciani Sara , Zinellu Angelo , Carru Ciriaco , Medici Serenella
Published: April 2023

Background: Senescence is a cellular aging process in all multicellular organisms. It is characterized by a decline in cellular functions and proliferation, resulting in increased cellular damage and death. These conditions play an essential role in aging and significantly contribute to the development of age-related complications. Humanin is a mitochondrial-derived peptide (MDP), encoded by mitochondrial DNA, playing a cytoprotective role to preserve mitochondrial function and cell viability under stressful and senescence conditions. For these reasons, humanin can be exploited in strategies aiming to counteract several processes involved in aging, including cardiovascular disease, neurodegeneration, and cancer. Relevance of these conditions to aging and disease: Senescence appears to be involved in the decay in organ and tissue function, it has also been related to the development of age-related diseases, such as cardiovascular conditions, cancer, and diabetes. In particular, senescent cells produce inflammatory cytokines and other pro-inflammatory molecules that can participate to the development of such diseases. Humanin, on the other hand, seems to contrast the development of such conditions, and it is also known to play a role in these diseases by promoting the death of damaged or malfunctioning cells and contributing to the inflammation often associated with them. Both senescence and humanin-related mechanisms are complex processes that have not been fully clarified yet. Further research is needed to thoroughly understand the role of such processes in aging and disease and identify potential interventions to target them in order to prevent or treat age-related conditions. Objectives: This systematic review aims to assess the potential mechanisms underlying the link connecting senescence, humanin, aging, and disease.
Tubulin Post-Translational Modifications: The Elusive Roles of Acetylation
Authors: Carmona Bruno , Marinho H. Susana , Matos Catarina Lopes , Nolasco Sofia , Soares Helena
Published: April 2023

Microtubules (MTs), dynamic polymers of α/β-tubulin heterodimers found in all eukaryotes, are involved in cytoplasm spatial organization, intracellular transport, cell polarity, migration and division, and in cilia biology. MTs functional diversity depends on the differential expression of distinct tubulin isotypes and is amplified by a vast number of different post-translational modifications (PTMs). The addition/removal of PTMs to α- or β-tubulins is catalyzed by specific enzymes and allows combinatory patterns largely enriching the distinct biochemical and biophysical properties of MTs, creating a code read by distinct proteins, including microtubule-associated proteins (MAPs), which allow cellular responses. This review is focused on tubulin-acetylation, whose cellular roles continue to generate debate. We travel through the experimental data pointing to α-tubulin Lys40 acetylation role as being a MT stabilizer and a typical PTM of long lived MTs, to the most recent data, suggesting that Lys40 acetylation enhances MT flexibility and alters the mechanical properties of MTs, preventing MTs from mechanical aging characterized by structural damage. Additionally, we discuss the regulation of tubulin acetyltransferases/desacetylases and their impacts on cell physiology. Finally, we analyze how changes in MT acetylation levels have been found to be a general response to stress and how they are associated with several human pathologies.
Diverse Functions of Multiple Bdnf Transcripts Driven by Distinct Bdnf Promoters
Authors: You He , Lu Bai
Published: April 2023

The gene encoding brain-derived neurotrophic factor (Bdnf) consists of nine non-coding exons driven by unique promoters, leading to the expression of nine Bdnf transcripts that play different roles in various brain regions and physiological stages. In this manuscript, we present a comprehensive overview of the molecular regulation and structural characteristics of the multiple Bdnf promoters, along with a summary of the current knowledge on the cellular and physiological functions of the distinct Bdnf transcripts produced by these promoters. Specifically, we summarized the role of Bdnf transcripts in psychiatric disorders, including schizophrenia and anxiety, as well as the cognitive functions associated with specific Bdnf promoters. Moreover, we examine the involvement of different Bdnf promoters in various aspects of metabolism. Finally, we propose future research directions that will enhance our understanding of the complex functions of Bdnf and its diverse promoters.
Diagnostic Problems in C3 Glomerulopathy
Authors: Niepolski Leszek , Czekała Anna , Seget-Dubaniewicz Monika , Frydrychowicz Magdalena , Talarska-Markiewicz Patrycja , Kowalska Angelika , Szmelter Jagoda , Salwa-Żurawska Wiesława , Sirek Tomasz , Sobański Dawid , Grabarek Beniamin Oskar , Żurawski Jakub
Published: April 2023

Background: C3 glomerulopathies (C3GN) are a group of rare kidney diseases associated with impaired complement regulation. The effects of this disease include the accumulation of complement C3 in the kidneys. Based on the clinical data, as well as light, fluorescence, and electron microscopy results, the diagnoses were verified. The study group consisted of biopsy specimens, which were obtained from 332 patients who were diagnosed with C3 glomerulopathy. In all cases, histopathological examinations were performed; deposits of complement C3 and C1q components, as well as the immunoglobulins IgA, IgG, and IgM, were identified using immunofluorescence. Furthermore, electron microscopy was also performed. Results: The histopathological examination results presented cases of C3GN (n = 111) and dense deposit disease (DDD; n = 17). The non-classified (NC) group was the most numerous (n = 204). The lack of classification was due to the poor severity of the lesions, even on the electron microscopic examination or in the presence of intense sclerotic lesions. Conclusions: In cases of suspected C3 glomerulopathies, we believe an electron microscopy examination is necessary. This examination is beneficial in mild-to-extremely-severe cases of this glomerulopathy, where the lesions are barely discernible when using immunofluorescence microscopy.
The DASciS Software for BSI Calculation as a Valuable Prognostic Tool in mCRPC Treated with 223RaCl2: A Multicenter Italian Study
Authors: De Feo Maria Silvia , Frantellizzi Viviana , Bauckneht Matteo , Farcomeni Alessio , Filippi Luca , Rizzini Elisa Lodi , Lavelli Valentina , Stazza Maria Lina , Di Raimondo Tania , Fornarini Giuseppe , Rebuzzi Sara Elena , Filippo Mammini , Mammucci Paolo , Marongiu Andrea , Monari Fabio , Rubini Giuseppe , Spanu Angela , De Vincentis Giuseppe
Published: April 2023

Background/Aim: Radium-223 dichloride (223RaCl2) represents a therapeutic option for metastatic castration-resistant prostate cancer (mCRPC) patients dealing with symptomatic bone metastases. The identification of baseline variables potentially affecting the life-prolonging role of 223RaCl2 is still ongoing. Bone scan index (BSI) defines the total load of bone metastatic disease detected on a bone scan (BS) and is expressed as a percentage value of the whole bone mass. The aim of this multicenter study was to assess the impact of baseline BSI on overall survival (OS) in mCRPC patients treated with 223RaCl2. For this purpose, the DASciS software developed by the Sapienza University of Rome for BSI calculation was shared between six Italian Nuclear Medicine Units. Methods: 370 pre-treatment BS were analyzed through the DASciS software. Other clinical variables relevant to OS analysis were taken into account for the statistical analysis. Results: Of a total of 370 patients, 326 subjects had died at the time of our retrospective analysis. The median OS time from the first cycle of 223RaCl2 to the date of death from any cause or last contact was 13 months (95%CI 12–14 months). The mean BSI value resulted in 2.98% ± 2.42. The center-adjusted univariate analysis showed that baseline BSI was significantly associated with OS as an independent risk factor (HR 1.137, 95%CI: 1.052–1.230, p = 0.001), meaning that patients with higher BSI values had worse OS. When adjusting for other measures on multivariate analysis, in addition to Gleason score and baseline values of Hb, tALP, and PSA, baseline BSI was confirmed to be a statistically significant parameter (HR 1.054, 95%CI: 1.040–1.068, p < 0.001). Conclusions: Baseline BSI significantly predicts OS in mCRPC treated with 223RaCl2. The DASciS software was revealed to be a valuable tool for BSI calculation, showing rapid processing time and requiring no more than a single demonstrative training for each participating center.
Neuroinflammation, Oxidative Stress, Apoptosis, Microgliosis and Astrogliosis in the Cerebellum of Mice Chronically Exposed to Waterpipe Smoke
Authors: Hamadi Naserddine , Beegam Sumaya , Zaaba Nur Elena , Elzaki Ozaz , Altamimi Mariam Abdulla , Nemmar Abderrahim
Published: April 2023

Waterpipe smoking (WPS) is prevalent in Asian and Middle Eastern countries and has recently gained worldwide popularity, especially among youth. WPS has potentially harmful chemicals and is associated with a wide range of adverse effects on different organs. However, little is known regarding the impact of WPS inhalation on the brain and especially on the cerebellum. Presently, we aimed at investigating inflammation, oxidative stress and apoptosis as well as microgliosis and astrogliosis in the cerebellum of BALB/C mice chronically (6 months) exposed to WPS compared with air-exposed mice (control). WPS inhalation augmented the concentrations of proinflammatory cytokines tumor necrosis factor, interleukin (IL)-6 and IL-1β in cerebellar homogenates. Likewise, WPS increased oxidative stress markers including 8-isoprostane, thiobarbituric acid reactive substances and superoxide dismutase. In addition, compared with the air-exposed group, WPS caused an increase in the oxidative DNA damage marker, 8-hydroxy-2′-deoxyguanosine, in cerebellar homogenates. Similarly, in comparison with the air group, WPS inhalation elevated the cerebellar homogenate levels of cytochrome C, cleaved caspase-3 and nuclear factor-κB (NF-κB). Immunofluorescence analysis of the cerebellum showed that WPS exposure significantly augmented the number of ionized calcium-binding adaptor molecule 1 and glial fibrillary acidic protein-positive microglia and astroglia, respectively. Taken together, our data show that chronic exposure to WPS is associated with cerebellar inflammation, oxidative stress, apoptosis, microgliosis and astrogliosis. These actions were associated with a mechanism involving NF-κB activation.
Transcriptomic Approaches in Studies on and Applications of Chimeric Antigen Receptor T Cells
Authors: Pierzynowska Karolina , Gaffke Lidia , Zaucha Jan , Węgrzyn Grzegorz
Published: April 2023

Chimeric antigen receptor T (CAR-T) cells are specifically modified T cells which bear recombinant receptors, present at the cell surface and devoted to detect selected antigens of cancer cells, and due to the presence of transmembrane and activation domains, able to eliminate the latter ones. The use of CAR-T cells in anti-cancer therapies is a relatively novel approach, providing a powerful tool in the fight against cancer and bringing new hope for patients. However, despite huge possibilities and promising results of preclinical studies and clinical efficacy, there are various drawbacks to this therapy, including toxicity, possible relapses, restrictions to specific kinds of cancers, and others. Studies desiring to overcome these problems include various modern and advanced methods. One of them is transcriptomics, a set of techniques that analyze the abundance of all RNA transcripts present in the cell at certain moment and under certain conditions. The use of this method gives a global picture of the efficiency of expression of all genes, thus revealing the physiological state and regulatory processes occurring in the investigated cells. In this review, we summarize and discuss the use of transcriptomics in studies on and applications of CAR-T cells, especially in approaches focused on improved efficacy, reduced toxicity, new target cancers (like solid tumors), monitoring the treatment efficacy, developing novel analytical methods, and others.
Do Epilepsy Patients with Cognitive Impairment Have Alzheimer’s Disease-like Brain Metabolism?
Authors: He Michael , Kolesar Tiffany A. , Goertzen Andrew L. , Ng Marcus C. , Ko Ji Hyun
Published: April 2023

Although not classically considered together, there is emerging evidence that Alzheimer’s disease (AD) and epilepsy share a number of features and that each disease predisposes patients to developing the other. Using machine learning, we have previously developed an automated fluorodeoxyglucose positron emission tomography (FDG-PET) reading program (i.e., MAD), and demonstrated good sensitivity (84%) and specificity (95%) for differentiating AD patients versus healthy controls. In this retrospective chart review study, we investigated if epilepsy patients with/without mild cognitive symptoms also show AD-like metabolic patterns determined by the MAD algorithm. Scans from a total of 20 patients with epilepsy were included in this study. Because AD diagnoses are made late in life, only patients aged ≥40 years were considered. For the cognitively impaired patients, four of six were identified as MAD+ (i.e., the FDG-PET image is classified as AD-like by the MAD algorithm), while none of the five cognitively normal patients was identified as MAD+ (χ2 = 8.148, p = 0.017). These results potentially suggest the usability of FDG-PET in prognosticating later dementia development in non-demented epilepsy patients, especially when combined with machine learning algorithms. A longitudinal follow-up study is warranted to assess the effectiveness of this approach.
Comorbidities and Malignancy among NAFLD Patients Compared to the General Population, A Nation-Based Study
Authors: Abu-Freha Naim , Cohen Bracha , Gordon Michal , Weissmann Sarah , Fich Alexander , Munteanu Daniela , Yardeni David , Etzion Ohad
Published: April 2023

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Aims: We aimed to investigate the frequency of comorbidities and malignancies among NAFLD patients compared to the general population. (2) Methods: A retrospective study included adult patients with a NAFLD diagnosis. A control group was matched for age and gender. Demographics, comorbidities, malignancies, and mortality were collected and compared. (3) Results: 211,955 NAFLD patients were analyzed in comparison to 452,012 matched general population controls. Significantly higher rates of diabetes mellitus (23.2% vs. 13.3%), obesity (58.8% vs. 27.8%), hypertension (57.2% vs. 39.9%), chronic ischemic heart disease (24.7% vs. 17.3%), and CVA (3.2% vs. 2.8%) were found among NAFLD patients. Patients with NAFLD had significantly higher rates of the following malignancies: prostate cancer (1.6% vs. 1.2%), breast cancer (2.6% vs. 1.9%), colorectal cancer (1.8% vs. 1.4%), uterine cancer (0.4 vs. 0.2%), kidney cancer (0.8% vs. 0.5%), but a lower rate of lung cancer (0.9% vs. 1.2%) and stomach cancer (0.3% vs. 0.4%). The all-cause mortality rate among NAFLD patients was significantly lower in comparison to the general population (10.8% vs. 14.7%, p < 0.001). (4) Conclusions: Higher rates of comorbidities and malignancies among NAFLD patients were observed, but a lower rate of all-cause mortality was found.
Immediate Autogenous Bone Transplantation Using a Novel Kinetic Bioactive Screw 3D Design as a Dental Implant
Authors: Andreucci Carlos Aurelio , Fonseca Elza M. M. , Jorge Renato N.
Published: April 2023

The restoration of osseous defects is accomplished by bone grafts and bone substitutes, which are also called biomaterials. Autogenous grafts, which are derived from the same individual, can retain the viability of cells, mainly the osteoblasts and osteoprogenitor stem cells, and they do not lead to an immunologic response, which is known as the gold standard for bone grafts. There are both different techniques and devices that can be used to obtain bone grafts according to the needs of the patients, the location, and the size of the bone defect. Here, an innovative technique is presented in which the patient’s own bone is removed from the trigone retromolar region of the mandible and is inserted into a dental alveolus after the extraction and immediate insertion of an innovative dental implant, the BKS. The first step of the technique creates the surgical alveolus; the second step perforates the BKS in the retromolar region, and shortly after, the BKS containing the bone to be grafted is removed; the third step screws the BKS bone that collects in the created surgical alveolus. Experimental studies have shown the feasibility and practicality of this new technique and the new dental implant model for autogenous transplants.
Evaluation of Transmembrane Protein Structural Models Using HPMScore
Authors: Téletchéa Stéphane , Esque Jérémy , Urbain Aurélie , Etchebest Catherine , de Brevern Alexandre G.
Published: April 2023

Transmembrane proteins (TMPs) are a class of essential proteins for biological and therapeutic purposes. Despite an increasing number of structures, the gap with the number of available sequences remains impressive. The choice of a dedicated function to select the most probable/relevant model among hundreds is a specific problem of TMPs. Indeed, the majority of approaches are mostly focused on globular proteins. We developed an alternative methodology to evaluate the quality of TMP structural models. HPMScore took into account sequence and local structural information using the unsupervised learning approach called hybrid protein model. The methodology was extensively evaluated on very different TMP all-α proteins. Structural models with different qualities were generated, from good to bad quality. HPMScore performed better than DOPE in recognizing good comparative models over more degenerated models, with a Top 1 of 46.9% against DOPE 40.1%, both giving the same result in 13.0%. When the alignments used are higher than 35%, HPM is the best for 52%, against 36% for DOPE (12% for both). These encouraging results need further improvement particularly when the sequence identity falls below 35%. An area of enhancement would be to train on a larger training set. A dedicated web server has been implemented and provided to the scientific community. It can be used with structural models generated from comparative modeling to deep learning approaches.
Pediatric Slow-Progressive, but Not Non-Progressive Cerebellar Ataxia Delays Intra-Limb Anticipatory Postural Adjustments in the Upper Arm
Authors: Marchese Silvia Maria , Esposti Roberto , Farinelli Veronica , Ciaccio Claudia , De Laurentiis Arianna , D’Arrigo Stefano , Cavallari Paolo
Published: April 2023

We recently investigated the role of the cerebellum during development, reporting that children with genetic slow-progressive ataxia (SlowP) show worse postural control during quiet stance and gait initiation compared to healthy children (H). Instead, children with genetic non-progressive ataxia (NonP) recalled the behavior of H. This may derive from compensatory networks, which are hindered by disease progression in SlowP while free to develop in NonP. In the aim of extending our findings to intra-limb postural control, we recorded, in 10 NonP, 10 SlowP and 10 H young patients, Anticipatory Postural Adjustments (APAs) in the proximal muscles of the upper-limb and preceding brisk index finger flexions. No significant differences in APA timing occurred between NonP and H, while APAs in SlowP were delayed. Indeed, the excitatory APA in Triceps Brachii was always present but significantly delayed with respect to both H and NonP. Moreover, the inhibitory APAs in the Biceps Brachii and Anterior Deltoid, which are normally followed by a late excitation, could not be detected in most SlowP children, as if inhibition was delayed to the extent where there was overlap with a late excitation. In conclusion, disease progression seems to be detrimental for intra-limb posture, supporting the idea that inter- and intra-limb postures seemingly share the same control mechanism.
A Projectile Concussive Impact Model Produces Neuroinflammation in Both Mild and Moderate-Severe Traumatic Brain Injury
Authors: Michalovicz Lindsay T. , Kelly Kimberly A. , Craddock Travis J. A. , O’Callaghan James P.
Published: April 2023

Traumatic brain injury (TBI) is a major cause of death and disability and is experienced by nearly 3 million people annually as a result of falls, vehicular accidents, or from being struck by or against an object. While TBIs can range in severity, the majority of injuries are considered to be mild. However, TBI of any severity has the potential to have long-lasting neurological effects, including headaches, cognitive/memory impairments, mood dysfunction, and fatigue as a result of neural damage and neuroinflammation. Here, we modified a projectile concussive impact (PCI) model of TBI to deliver a closed-head impact with variable severity dependent on the material of the ball-bearing projectile. Adult male Sprague Dawley rats were evaluated for neurobehavioral, neuroinflammatory, and neural damage endpoints both acutely and longer-term (up to 72 h) post-TBI following impact with either an aluminum or stainless-steel projectile. Animals that received TBI using the stainless-steel projectile exhibited outcomes strongly correlated to moderate-severe TBI, such as prolonged unconsciousness, impaired neurobehavior, increased risk for hematoma and death, as well as significant neuronal degeneration and neuroinflammation throughout the cortex, hippocampus, thalamus, and cerebellum. In contrast, rats that received TBI with the aluminum projectile exhibited characteristics more congruous with mild TBI, such as a trend for longer periods of unconsciousness in the absence of neurobehavioral deficits, a lack of neurodegeneration, and mild neuroinflammation. Moreover, alignment of cytokine mRNA expression from the cortex of these rats with a computational model of neuron–glia interaction found that the moderate-severe TBI produced by the stainless-steel projectile strongly associated with the neuroinflammatory state, while the mild TBI existed in a state between normal and inflammatory neuron–glia interactions. Thus, these modified PCI protocols are capable of producing TBIs that model the clinical and experimental manifestations associated with both moderate-severe and mild TBI producing relevant models for the evaluation of the potential underlying roles of neuroinflammation and other chronic pathophysiology in the long-term outcomes associated with TBI.
Cortical Layer Markers Expression and Increased Synaptic Density in Interstitial Neurons of the White Matter from Drug-Resistant Epilepsy Patients
Authors: Yang Jiachao , Wang Mi , Lv Yang , Chen Jiadong
Published: April 2023

The interstitial neurons in the white matter of the human and non-human primate cortex share a similar developmental origin with subplate neurons and deep-layer cortical neurons. A subset of interstitial neurons expresses the molecular markers of subplate neurons, but whether interstitial neurons express cortical layer markers in the adult human brain remains unexplored. Here we report the expression of cortical layer markers in interstitial neurons in the white matter of the adult human brain, supporting the hypothesis that interstitial neurons could be derived from cortical progenitor cells. Furthermore, we found increased non-phosphorylated neurofilament protein (NPNFP) expression in interstitial neurons in the white matter of drug-resistant epilepsy patients. We also identified the expression of glutamatergic and g-aminobutyric acid (GABAergic) synaptic puncta that were distributed in the perikarya and dendrites of interstitial neurons. The density of glutamatergic and GABAergic synaptic puncta was increased in interstitial neurons in the white matter of drug-resistant epilepsy patients compared with control brain tissues with no history of epilepsy. Together, our results provide important insights of the molecular identity of interstitial neurons in the adult human white matter. Increased synaptic density of interstitial neurons could result in an imbalanced synaptic network in the white matter and participate as part of the epileptic network in drug-resistant epilepsy.
Residual Shear Capacity of Post-Fire RC Beams under Indirect Loading
Authors: Song Yamin , Fu Chuanguo , Liang Shuting , Topilin Ivan , Song Xuanzhen
Published: April 2023

Building fire is one of the most frequent disasters. The mechanical properties of concrete and steel will deteriorate to different degrees under fire exposure, thus weakening the bearing capacity of reinforced concrete (RC) members. Therefore, it is of great theoretical and practical significance to carry out research on the bearing capacity of RC members subjected to fire. To study the residual shear capacity of post-fire RC beams under indirect loading, static load tests were carried out on six full-scale RC beams to investigate the development of diagonal cracks and failure modes under an indirect load. Numerical models were established with ABAQUS to study the effect of the shear span-to-depth ratio and stirrup ratio on the residual shear capacity of the tested beams after fire exposure, and the shear capacity calculation method of indirectly loaded beams after high temperature is proposed. The results indicate that although the fire had no obvious affect on the failure mode of the beam under indirect loading, the fire aggravated the failure degree of the beams without additional transverse reinforcement. Moreover, the ultimate bending capacity of beams with additional transverse reinforcement decreased obviously after fire. The residual shear capacity of indirectly-loaded beams subjected to fire decreased compared with the directly-loaded beams due to the variation in the shear span-to-depth ratio and stirrup ratio. The shear capacity theoretical calculation results of the indirectly-loaded beam after high temperature were in good agreement with the tested results, and the average absolute error was 3.88%. Therefore, this calculation method for an indirectly loaded beam with a shear span-to-depth ratio less than 3.0 after fire as proposed in this paper was effective. The findings of this study are expected to provide a reference for the improved fire-resistant design of RC structures under indirect loading.
Thermal Characterization of Buildings with as-is Thermal-Building Information Modelling
Authors: Pérez-Andreu Víctor , Oliver Antonio Adán , Aparicio-Fernández Carolina , Bono José-Luis Vivancos
Published: April 2023

Developing methodologies to accurately characterise the energy conditions of existing building stock is a fundamental aspect of energy consumption reduction strategies. To that end, a case study using a thermal information modelling method for existing buildings (as-is T-BIM) is reported. This proposed new method is based on the automatic processing of 3D thermal clouds of interior zones of a building that generates a semantic proprietary model that contains time series of surface temperatures assigned to its surface elements. The proprietary as-is T-BIM automatically generates an as-is BEM model with gbXML standards for energy simulation. This is a multi-zone energy model of the building. In addition, the surface temperature data series of the as-is T-BIM model elements permit the calculation of their thermal transmittances, increasing the calibration options of the obtained as-is BEM model. To test the as-is TBIM method, a case study compares the as-is BEM model obtained by as-is T-BIM methods with the one obtained by standard methods for the same building. The results demonstrate differences in geometry, transmittance, and infiltration values, as well as insignificant differences in annual air conditioning energy consumption or the comfort parameters tested. This seems to indicate shorter modelling times and greater accuracy of the as-is T-BIM model.
Simulation-Assisted Project Data Integration for Development and Analysis of As-Built Schedules
Authors: Fagiar Muaz , Mohamed Yasser , AbouRizk Simaan
Published: April 2023

As-built schedules are an essential tool for evaluating contractors’ schedule performance and analyzing delay and lost productivity claims. Yet, most often construction schedules are not updated frequently and/or accurately as required, which limit the availability of as-built schedules. Furthermore, the retrospective development of as-built schedules, when sufficient and reliable project data is available, is a lengthy and costly process. This study describes a simulation-assisted modeling approach that automatically processes and integrates schedules progress data and develops as-built schedules at the activity level. The proposed method uses conceptual entities that are central to the operation of simulation models and whose content changes as they route through the schedule network model. The approach introduces (1) an entity information model that records relevant schedule information either in a materialized or virtual form, and (2) an entity lifecycle model that imitates the possible routes an entity instance may maneuver through in a schedule network model which, together, simultaneously respond to schedule logic and invoking duration changes. To demonstrate its effectiveness, a prototype based on the framework was developed using Excel and MS Project and was tested with a real case study. The study is expected to facilitate the development of as-built schedules for the analysis of delay and time extension claims.
Timber Construction as a Solution to Climate Change: A Systematic Literature Review
Authors: Tupenaite Laura , Kanapeckiene Loreta , Naimaviciene Jurga , Kaklauskas Arturas , Gecys Tomas
Published: April 2023

The built environment significantly contributes to climate change. There is pressure on the construction industry to find and use alternative sustainable environmentally friendly building materials to reduce the climate impact. Timber is increasingly being considered in the literature and used as a viable alternative for steel and concrete in both residential and non-residential building projects as it is a renewable material and has multiple benefits for reducing carbon (CO2) emissions and consequently climate change. This study aims to research the benefits of sustainable timber construction in terms of climate change. To achieve this aim, a systematic literature review was performed based on the research conducted between 1998 and 2022. For this purpose, research papers were searched from the Web of Science database and screened by applying a combination of keywords and the criteria for academic publication selection, including climate change, timber or wooden building, renewable material, sustainable material, carbon sink, carbon reduction, embodied energy, lifecycle assessment, and the circular economy. Further, a quantitative analysis of publications was performed using a science mapping approach, and qualitative content analysis was then conducted in three areas of research: timber as a sustainable construction material, the carbon storage of and reduction in GHG/CO2 emissions, and the circular economy. Research trends, general findings, and knowledge gaps were identified, and future research directions were indicated. The literature review proves that timber construction is a potential solution to reduce climate change.
Non-Coding RNAs Derived from Extracellular Vesicles Promote Pre-Metastatic Niche Formation and Tumor Distant Metastasis
Authors: Cheng Jin , Zhang Kun , Qu Chunhui , Peng Jinwu , Yang Lifang
Published: April 2023

Metastasis is a critical stage of tumor progression, a crucial challenge of clinical therapy, and a major cause of tumor patient death. Numerous studies have confirmed that distant tumor metastasis is dependent on the formation of pre-metastatic niche (PMN). Recent studies have shown that extracellular vesicles (EVs) play an important role in PMN formation. The non-coding RNAs (ncRNAs) derived from EVs mediate PMN formation and tumor-distant metastasis by promoting an inflammatory environment, inhibiting anti-tumor immune response, inducing angiogenesis and permeability, and by microenvironmental reprogramming. Given the stability and high abundance of ncRNAs carried by EVs in body fluids, they have great potential for application in tumor diagnosis as well as targeted interventions. This review focuses on the mechanism of ncRNAs derived from EVs promoting tumor PMN formation and distant metastasis to provide a theoretical reference for strategies to control tumor metastasis.
Towards a Synthesis of the Non-Genetic and Genetic Views of Cancer in Understanding Pancreatic Ductal Adenocarcinoma Initiation and Prevention
Authors: Gopalan Vishaka , Hannenhalli Sridhar
Published: April 2023

While much of the research in oncogenesis and cancer therapy has focused on mutations in key cancer driver genes, more recent work suggests a complementary non-genetic paradigm. This paradigm focuses on how transcriptional and phenotypic heterogeneity, even in clonally derived cells, can create sub-populations associated with oncogenesis, metastasis, and therapy resistance. We discuss this complementary paradigm in the context of pancreatic ductal adenocarcinoma. A better understanding of cellular transcriptional heterogeneity and its association with oncogenesis can lead to more effective therapies that prevent tumor initiation and slow progression.
Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice
Authors: Dima Danai , Ullah Fauzia , Mazzoni Sandra , Williams Louis , Faiman Beth , Kurkowski Austin , Chaulagain Chakra , Raza Shahzad , Samaras Christy , Valent Jason , Khouri Jack , Anwer Faiz
Published: April 2023

Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.
Lung Cancer Incidence by Detailed Race–Ethnicity
Authors: Cranford Hannah , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo
Published: April 2023

Lung cancer (LC) incidence rates and tumor characteristics among (non-Hispanic) Black and Hispanic detailed groups, normally characterized in aggregate, have been overlooked in the US. We used LC data from the Florida state cancer registry, 2012–2018, to compute LC age-adjusted incidence rates (AAIR) for US-born Black, Caribbean-born Black, Mexican, Puerto Rican, Cuban, Dominican, and Central and South American populations. We analyzed 120,550 total LC cases. Among Hispanics, Cuban males had the highest AAIR (65.6 per 100,000; 95%CI: 63.6–67.6), only 8% [Incidence Rate Ratio (IRR): 0.92; 95%CI: 0.89–0.95] lower than Whites, but 2.7 (IRR 95%CI: 2.31-3.19) times higher than Central Americans. Among Blacks, the AAIR for US-born Black males was over three times that of those Caribbean-born (IRR: 3.12; 95%CI: 2.80–3.40) and 14% higher than White males (IRR: 1.14; 95%CI: 1.11–1.18). Among women, US-born Blacks (46.4 per 100,000) and foreign-born Mexicans (12.2 per 100,000) had the highest and lowest rates. Aggregation of non-Hispanic Blacks or Hispanics obscures inherent disparities within groups. Understanding the distinct LC rates in US populations is crucial for targeting public health measures for LC diagnosis, prevention, and treatment. Further LC research exploring detailed race–ethnicity regarding LC in never-smokers is necessary, particularly among females and considering pertinent environmental factors.