bluuebunny/crossref_metadata_2025 huggingface dataset:
Heat Shock Protein Upregulation Supplemental to Complex mRNA Alterations in Autoimmune Glaucoma
Authors: Reinehr Sabrina , Safaei Armin , Grotegut Pia , Guntermann Annika , Tsai Teresa , Hahn Stephan A. , Kösters Steffen , Theiss Carsten , Marcus Katrin , Dick H. Burkhard , May Caroline , Joachim Stephanie C.
Published: October 2022

Glaucomatous optic neuropathy is a common cause for blindness. An elevated intraocular pressure is the main risk factor, but also a contribution of the immune system seems likely. In the experimental autoimmune glaucoma model used here, systemic immunization with an optic nerve homogenate antigen (ONA) leads to retinal ganglion cell (RGC) and optic nerve degeneration. We processed retinae for quantitative real-time PCR and immunohistology 28 days after immunization. Furthermore, we performed mRNA profiling in this model for the first time. We detected a significant RGC loss in the ONA retinae. This was accompanied by an upregulation of mRNA expression of genes belonging to the heat shock protein family. Furthermore, mRNA expression levels of the genes of the immune system, such as C1qa, C1qb, Il18, and Nfkb1, were upregulated in ONA animals. After laser microdissection, inner retinal layers were used for mRNA microarrays. Nine of these probes were significantly upregulated in ONA animals (p < 0.05), including Hba-a1 and Cxcl10, while fifteen probes were significantly downregulated in ONA animals (p < 0.05), such as Gdf15 and Wwox. Taken together, these findings provide further insights into the pivotal role of the immune response in glaucomatous optic neuropathy and could help to identify novel diagnostic or therapeutic strategies.
New Multifunctional Agents for Potential Alzheimer’s Disease Treatment Based on Tacrine Conjugates with 2-Arylhydrazinylidene-1,3-Diketones
Authors: Elkina Natalia A. , Grishchenko Maria V. , Shchegolkov Evgeny V. , Makhaeva Galina F. , Kovaleva Nadezhda V. , Rudakova Elena V. , Boltneva Natalia P. , Lushchekina Sofya V. , Astakhova Tatiana Y. , Radchenko Eugene V. , Palyulin Vladimir A. , Zhilina Ekaterina F. , Perminova Anastasiya N. , Lapshin Luka S. , Burgart Yanina V. , Saloutin Victor I. , Richardson Rudy J.
Published: October 2022

Alzheimer’s disease (AD) is considered a modern epidemic because of its increasing prevalence worldwide and serious medico-social consequences, including the economic burden of treatment and patient care. The development of new effective therapeutic agents for AD is one of the most urgent and challenging tasks. To address this need, we used an aminoalkylene linker to combine the well-known anticholinesterase drug tacrine with antioxidant 2-tolylhydrazinylidene-1,3-diketones to create 3 groups of hybrid compounds as new multifunctional agents with the potential for AD treatment. Lead compounds of the new conjugates effectively inhibited acetylcholinesterase (AChE, IC50 0.24–0.34 µM) and butyrylcholinesterase (BChE, IC50 0.036–0.0745 µM), with weak inhibition of off-target carboxylesterase. Anti-AChE activity increased with elongation of the alkylene spacer, in agreement with molecular docking, which showed compounds binding to both the catalytic active site and peripheral anionic site (PAS) of AChE, consistent with mixed type reversible inhibition. PAS binding along with effective propidium displacement suggest the potential of the hybrids to block AChE-induced β-amyloid aggregation, a disease-modifying effect. All of the conjugates demonstrated metal chelating ability for Cu2+, Fe2+, and Zn2+, as well as high antiradical activity in the ABTS test. Non-fluorinated hybrid compounds 6 and 7 also showed Fe3+ reducing activity in the FRAP test. Predicted ADMET and physicochemical properties of conjugates indicated good CNS bioavailability and safety parameters acceptable for potential lead compounds at the early stages of anti-AD drug development.
Periodontitis and Its Inflammatory Changes Linked to Various Systemic Diseases: A Review of Its Underlying Mechanisms
Authors: Bhuyan Ruchi , Bhuyan Sanat Kumar , Mohanty Jatindra Nath , Das Srijit , Juliana Norsham , Juliana Izuddin Fahmy
Published: October 2022

Periodontitis is a chronic inflammatory disease of the gums. The incidence of periodontitis is increasing all over the world. In patients with periodontitis, there is gradual destruction of the periodontal ligament and the alveolar bone, and later, in advanced stages, there is tooth loss. Different microorganisms, the host’s immune response, and various environmental factors interact in the progression of this chronic inflammatory disease. In the present review, we discuss the epidemiology, clinical features, diagnosis, and complications of periodontitis. We also discuss the association of chronic inflammation found in periodontitis with various other systemic diseases, which include cardiovascular, respiratory, diabetes, Alzheimer’s, cancer, adverse pregnancy, and multiple myeloma, and also highlight microbial carcinogenesis and the microRNAs involved. The latest updates on the molecular mechanism, possible biomarkers, and treatment procedures may be beneficial for diagnostic and therapeutic purposes.
Associations of Warfarin Use with Risks of Ischemic Cerebrovascular Events and Major Bleeding in Patients with Hyperthyroidism-Related Atrial Fibrillation
Authors: Liu Sian-De , Lin Shwu-Jiuan , Ray Chin-Ying , Lin Fang-Tsyr , Lin Weei-Chin , Wang Li-Hsuan
Published: October 2022

The use of oral anticoagulants for patients with new-onset hyperthyroidism-related atrial fibrillation (AF) is controversial. We aimed to evaluate the clinical benefits of warfarin therapy in this population. This retrospective cohort study used a data-cut of Taiwan Health and Welfare Database between 2000 and 2016. We compared warfarin users and nonusers among AF patients with hyperthyroidism. We used 1:2 propensity score matching to balance covariates and Cox regression model to calculate hazard ratios (HRs). The primary outcome was risk of ischemic stroke/transient ischemic attack (TIA), and the secondary outcome was major bleeding. After propensity score matching, we defined 90 and 168 hyperthyroidism-related AF patients with mean (SD) age of 59.9 ± 13.5 and 59.2 ± 14.6 in the warfarin-treated group and untreated group separately. The mean (SD) CHA2DS2-VASc scores for the two groups were 2.1 ± 1.6 and 1.8 ± 1.5, respectively. Patients with hyperthyroidism-related AF receiving warfarin had no significant risk of ischemic stroke/TIA (adjusted HR: 1.16, 95% confidence interval [CI]: 0.52–2.56, p = 0.717) compared to nonusers. There was a comparable risk of major bleeding between those receiving warfarin or not (adjusted HR: 0.91, 95% CI: 0.56–1.47, p = 0.702). The active-comparator design also demonstrated that warfarin use had no significant association with the risk of stroke/TIA versus aspirin use (adjusted HR: 2.43; 95% CI: 0.68–8.70). In conclusion, anticoagulation therapy did not have a statistically significant benefit on ischemic stroke/TIA nor risk of bleeding, among patients with new-onset hyperthyroidism-related AF under a low CHA2DS2-VASc score, by comparing those without use.
Changes in Circadian Variations in Blood Pressure, Pain Pressure Threshold and the Elasticity of Tissue after a Whole-Body Photobiomodulation Treatment in Patients with Fibromyalgia: A Tripled-Blinded Randomized Clinical Trial
Authors: Navarro-Ledesma Santiago , Carroll James , González-Muñoz Ana , Pruimboom Leo , Burton Patricia
Published: October 2022

This study analysed circadian variation changes in blood pressure (BP), the pain pressure threshold (PPT) and the elasticity of tissue in patients with fibromyalgia (FM) after a whole-body photobiomodulation (PBM) treatment. This was a tripled-blinded randomized clinical trial including forty participants with FM. Participants using validated self-measurement BP devices attained readings that were used to calculate the circadian variation. Additionally, a standard pressure algometer of 1cm2 was used to assess 13 tender points by exerting a pressure of up to 4 kg, and strain elastography assessed the elasticity of tissue. Circadian variations in BP showed significant differences after the PBM intervention (p = 0.036). When comparing PPT between groups, statistically significant differences were found in the occiput (p = 0.039), low cervical (p = 0.035), trapezius (p = 0.037), second rib (p < 0.001) and medial epicondyle points (p = 0.006). Furthermore, there were statistically significant differences in both the trapezius and the forearm at the distal dorsal third SEL values (p ≤ 0.001) when comparing groups. Whole-body PBM produces changes in circadian blood pressure, the pain pressure threshold and the elasticity of tissue after a treatment program was carried out. However, more studies are needed to corroborate our findings as well as to better understand the underlying mechanisms.
Synthesis, Biophysical Interaction of DNA/BSA, Equilibrium and Stopped-Flow Kinetic Studies, and Biological Evaluation of bis(2-Picolyl)amine-Based Nickel(II) Complex
Authors: Ramzy Esraa , Ibrahim Mohamed M. , El-Mehasseb Ibrahim M. , Ramadan Abd El-Motaleb M. , Elshami Fawzia I. , Shaban Shaban Y. , van Eldik Rudi
Published: October 2022

Reaction of bis(2-picolyl)amine (BPA) with Ni(II) salt yielded [(BPA)NiCl2(H2O)] (NiBPA). The Ni(II) in NiBPA bound to a BPA ligand, two chloride, and one aqua ligands. Because most medications inhibit biological processes by binding to a specific protein, the stopped-flow technique was used to investigate DNA/protein binding in-vitro, and a mechanism was proposed. NiBPA binds to DNA/protein more strongly than BPA via a static quenching mechanism. Using the stopped-flow technique, a mechanism was proposed. BSA interacts with BPA via a fast reversible step followed by a slow irreversible step, whereas NiBPA interacts via two reversible steps. DNA, on the other hand, binds to BPA and NiBPA via the same mechanism through two reversible steps. Although BSA interacts with NiBPA much faster, NiBPA has a much higher affinity for DNA (2077 M) than BSA (30.3 M). Compared to NiBPA, BPA was found to form a more stable BSA complex. When BPA and NiBPA bind to DNA, the Ni(II) center was found to influence the rate but not the mechanism, whereas, for BSA, the Ni(II) center was found to change both the mechanism and the rate. Additionally, NiBPA exhibited significant cytotoxicity and antibacterial activity, which is consistent with the binding constants but not the kinetic stability. This shows that in our situation, biological activity is significantly more influenced by binding constants than by kinetic stability. Due to its selectivity and cytotoxic activity, complex NiBPA is anticipated to be used in medicine.
Glucose Incorporated Graphite Matrix for Electroanalysis of Trimethoprim
Authors: Sawkar Rakesh R. , Shanbhag Mahesh M. , Tuwar Suresh M. , Veerapur Ravindra S. , Shetti Nagaraj P.
Published: October 2022

The antibiotic drug trimethoprim (TMP) is used to treat bacterial infections in humans and animals, and frequently TMP is used along with sulfonamides. However, a large portion of TMP is excreted in its active state, which poses a severe problem to humans and the environment. A sensitive, rapid, cost-effective analytical tool is required to monitor the TMP concentration in biological and environmental samples. Hence, this study proposed an analytical methodology to analyze TMP in clinical, biological and environmental samples. The investigations were carried out using a glucose-modified carbon paste electrode (G-CPE) employing voltammetric techniques. Electrochemical behavior was examined with 0.5 mM TMP solution at optimum pH 3.4 (Phosphate Buffer Solution, I = 0.2 M). The influence of scan rate on the electro-oxidation of TMP was studied within the range of 0.05 to 0.55 V/s. The effect of pH and scan rate variations revealed proton transfer during oxidation. Moreover, diffusion phenomena governed the irreversibility of the electrode reaction. A probable and suitable electrode interaction and reaction mechanism was proposed for the electrochemical oxidation of TMP. Further, the TMP was quantitatively estimated with the differential pulse voltammetry (DPV) technique in the concentration range from 9.0 × 10−7 to 1.0 × 10−4 M. The tablet, spiked water and urine analysis demonstrated that the selected method and developed electrode were rapid, simple, sensitive, and cost-effective.
Efficient Entrapment of Alpha-Synuclein Biotinylated Antibody in KCC-1-NH-CS2 and Application for the Sensitive Diagnosis of Parkinson’s Using Recognition of Biomarker: An Innovative Electrochemical Label-Free Immunosensor for the Biomedical Analysis of Neurodegenerative Diseases
Authors: Navay Baghban Hossein , Hasanzadeh Mohammad , Liu Yuqian , Seidi Farzad
Published: October 2022

The early detection of Parkinson’s disease (PD) is a critical issue in terms of efficiency. Alpha-synuclein (α-Syn) is a biomarker in PD checks. Alpha-synuclein (α-syn) is the major constituent of Lewy bodies and a pathogenic hallmark of all synucleinopathies, including PDs, dementia with Lewy bodies, and multiple system atrophy. In this study, KCC-1-NH-CS2 was conjugated with biotinylated Ab and entrapped in P(β-CD) polymer cavities. Using this approach, a novel electrochemical label-free immunosensor was designed for the quantification of α-syn in real human samples. For this purpose, the glassy carbon electrode electropolymerized with P(β-CD) biopolymer provided an excellent matrix for entrapping of KCC-1-NH-CS2 loaded with the biotinylated antibody of α-syn. Using the chronoamperometric technique, the proposed immunosensor shows a suitable range of 0.02 to 64 ng/mL for the determination of α-syn. Additionally, a low limit of quantification of the engineered biosensor was obtained at 0.02 ng/mL. The developed immunosensor’s adequate stability, sensitivity, and selectivity, together with its ease of manufacture, make it a promising diagnostic technique for further research. This study also will pave the way for further applications of the synergetic effect of β-CD and KCC-1-NH-CS2 for biomedical analysis in the near future.
Highly Specific Peptide-Mediated Cuvette-Form Localized Surface Plasmon Resonance (LSPR)-Based Fipronil Detection in Egg
Authors: Yoo Jingon , Han Soobin , Park Bumjun , Sonwal Sonam , Alhammadi Munirah , Kim Eunsu , Aliya Sheik , Lee Eun-Seon , Jeon Tae-Joon , Oh Mi-Hwa , Huh Yun Suk
Published: October 2022

Herein, we have developed peptide-coated gold nanoparticles (AuNPs) based on localized surface plasmon resonance (LSPR) sensor chips that can detect fipronil with high sensitivity and selectivity. The phage display technique has been exploited for the screening of highly specific fipronil-binding peptides for the selective detection of the molecule. LSPR sensor chips are fabricated initially by attaching uniformly synthesized AuNPs on the glass substrate, followed by the addition of screened peptides. The parameters, such as the peptide concentration of 20 µg mL−1 and the reaction time of 30 min, are further optimized to maximize the efficacy of the fabricated LSPR sensor chips. The sensing analysis is performed systematically under standard fipronil solutions and spike samples from eggs. The developed sensor has shown excellent sensitivity towards both standard solutions and spike samples with limit of detection (LOD) values of 0.01 ppb, respectively. Significantly, the developed LSPR sensor chips offer distinct features, such as a facile fabrication approach, on-site sensing, rapid analysis, cost-effectiveness, and the possibility of mass production, in which the chips can be effectively used as a promising and potential on-site detection tool for the estimation of fipronil.
Label-Free and Bioluminescence-Based Nano-Biosensor for ATP Detection
Authors: Karimi Elham , Nikkhah Maryam , Hosseinkhani Saman
Published: October 2022

A bioluminescence-based assay for ATP can measure cell viability. Higher ATP concentration indicates a higher number of living cells. Thus, it is necessary to design an ATP sensor that is low-cost and easy to use. Gold nanoparticles provide excellent biocompatibility for enzyme immobilization. We investigated the effect of luciferase proximity with citrate-coated gold, silver, and gold–silver core–shell nanoparticles, gold nanorods, and BSA–Au nanoclusters. The effect of metal nanoparticles on the activity of luciferases was recorded by the luminescence assay, which was 3–5 times higher than free enzyme. The results showed that the signal stability in presence of nanoparticles improved and was reliable up to 6 h for analytes measurements. It has been suggested that energy is mutually transferred from luciferase bioluminescence spectra to metal nanoparticle surface plasmons. In addition, we herein report the 27-base DNA aptamer for adenosine-5′-triphosphate (ATP) as a suitable probe for the ATP biosensor based on firefly luciferase activity and AuNPs. Due to ATP application in the firefly luciferase reaction, the increase in luciferase activity and improved detection limits may indicate more stability or accessibility of ATP in the presence of nanoparticles. The bioluminescence intensity increased with the ATP concentration up to 600 µM with a detection limit of 5 µM for ATP.
Modeling Cognitive Load as a Self-Supervised Brain Rate with Electroencephalography and Deep Learning
Authors: Longo Luca
Published: October 2022

The principal reason for measuring mental workload is to quantify the cognitive cost of performing tasks to predict human performance. Unfortunately, a method for assessing mental workload that has general applicability does not exist yet. This is due to the abundance of intuitions and several operational definitions from various fields that disagree about the sources or workload, its attributes, the mechanisms to aggregate these into a general model and their impact on human performance. This research built upon these issues and presents a novel method for mental workload modelling from EEG data employing deep learning. This method is self-supervised, employing a continuous brain rate, an index of cognitive activation, and does not require human declarative knowledge. The aim is to induce models automatically from data, supporting replicability, generalisability and applicability across fields and contexts. This specific method is a convolutional recurrent neural network trainable with spatially preserving spectral topographic head-maps from EEG data, aimed at fitting a novel brain rate variable. Findings demonstrate the capacity of the convolutional layers to learn meaningful high-level representations from EEG data since within-subject models had, on average, a test Mean Absolute Percentage Error of around 11%. The addition of a Long-Short Term Memory layer for handling sequences of high-level representations was not significant, although it did improve their accuracy. These findings point to the existence of quasi-stable blocks of automatically learnt high-level representations of cognitive activation because they can be induced through convolution and seem not to be dependent on each other over time, intuitively matching the non-stationary nature of brain responses. Additionally, across-subject models, induced with data from an increasing number of participants, thus trained with data containing more variability, obtained a similar accuracy to the within-subject models. This highlights the potential generalisability of the induced high-level representations across people, suggesting the existence of subject-independent cognitive activation patterns. This research contributes to the body of knowledge by providing scholars with a novel computational method for mental workload modelling that aims to be generally applicable and does not rely on ad hoc human crafted models.
The Effect of Menstrual Cycle Phases on Approach–Avoidance Behaviors in Women: Evidence from Conscious and Unconscious Processes
Authors: Li Danyang , Zhang Lepu , Wang Xiaochun
Published: October 2022

The menstrual cycle affects women’s emotional states, with estrogen and progesterone having predominant roles. However, it remains unclear whether the phases of the menstrual cycle also affect women’s motivational behaviors. In this study, the main aim was to investigate how the menstrual cycle influences approach–avoidance behavior under conditions of conscious versus unconscious processing of emotions. Briefly, after recruitment by advertisement and screening with a menstrual cycle survey questionnaire, 27 naturally cycling, healthy women participated in an improved “manikin task” and were presented both positive and negative emotional stimuli during early follicular, late follicular, and mid-luteal phases. Estrogen and progesterone levels were measured. Women in the late follicular phase exhibited the shortest response times for approaching positive stimuli, while women in the mid-luteal phase exhibited the shortest response times for avoiding negative stimuli. Estrogen and progesterone levels significantly correlated with the speed of the approach–avoidance responses observed for the women, indicating the important role that sex hormones have in mediating emotionally motivated behavior. Overall, these findings suggest that the menstrual cycle has strong and specific influences on women’s approach–avoidance behaviors that are in part mediated by estrogen and progesterone. By identifying characteristics of these behaviors in the late follicular and mid-luteal phases, greater insight can be provided to women regarding the physiological influences of the menstrual cycle on their personal growth and security.
Cerebral Blood Deoxygenation by a Postural Change Detected by Near-Infrared Spectroscopy Has a Close Association with Cerebral Infarction
Authors: Irisawa Hiroshi , Inui Naoki , Mizushima Takashi , Watanabe Hiroshi
Published: October 2022

Background: The recent introduction of near-infrared spectroscopy has enabled the monitoring of cerebral blood flow in real-time. Previous studies have shown that blood flow velocity is a predictor of cardiovascular disease. We hypothesized that cerebral oxygenation with a change in posture is a predictor for cerebral infarction. We designed a cross-sectional study to investigate the relationship between postural-related changes in cerebral oxygenation and a history of chronic cerebral infarction. Methods: A total of 100 consecutive participants were enrolled in this study. We evaluated changes in cerebral oxygenation with a change in posture from the supine to the upright position in the bilateral forehead. The association between a decline in cerebral oxygenation and chronic cerebral infarction was analyzed with multiple logistic regression adjusted for covariates. Results: Cerebral blood oxygenation increased in 52 participants and decreased in 48 participants with a postural change. The prevalence of decreased cerebral oxygenation was 76.3% in participants with chronic cerebral infarction. Multiple logistic regression analysis showed that a decline in cerebral oxygenation upon a postural change was strongly associated with chronic cerebral infarction (adjusted odds ratio: 3.42, p = 0.025). Conclusions: Cerebral blood oxygenation upon a postural change could be a useful predictor for cerebral infarction.
Profile of Service Use and Barriers to Access to Care among Brazilian Children and Adolescents with Autism Spectrum Disorders
Authors: Araripe Beatriz , Montiel-Nava Cecilia , Bordini Daniela , Cunha Graccielle R. , Garrido Gabriela , Cukier Sebastián , Garcia Ricardo , Rosoli Analia , Valdez Daniel , Caetano Sheila C. , Rattazzi Alexia , Paula Cristiane S.
Published: October 2022

Delayed diagnosis and a lack of adequate care for people with autism spectrum disorder (ASD) are related to worse outcomes and quality of life. This study aimed to identify the profile of service use, barriers to access care, and factors related to those barriers in Brazilian families with children with ASD. A total of 927 families with children with ASD (3–17 years) from five Brazilian regions completed an online version of the Caregivers Needs Survey. Results showed that the most used services were behavioral interventions and pharmacotherapy, while the most used professionals were neurologists, nutritionists, speech therapists, psychiatrists, psychologists, and pediatricians. The main barriers included waiting lists, costs, and the absence of services or treatment. Service use varied according to age, the region of residence, type of health care system used, and the parents/caregivers’ education. Access to behavioral interventions was more frequent among users of the private system/health insurance and families whose caregivers had higher education. The absence of specialized services/treatments was less frequent among residents of state capitals and families whose caregivers had higher levels of education. This study highlights how families with children/adolescents with ASD in Brazil face significant barriers to access care related to sociodemographic factors.
Neuroprotective Effect of Angiopoietin2 Is Associated with Angiogenesis in Mouse Brain Following Ischemic Stroke
Authors: Lv Ling-Ling , Du Yi-Ting , Chen Xiao , Lei Yu , Sun Feng-Yan
Published: October 2022

Angiogenic factors play an important role in protecting, repairing, and reconstructing vessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34+ vascular length and area. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury, and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.
Use of Eco-Friendly Materials in the Stabilization of Expansive Soils
Authors: Bekkouche Souhila Rehab , Benzerara Mohammed , Zada Umar , Muhammad Ghulam , Ali Zulfiqar
Published: October 2022

Volume change of expansive soils is a challenging issue, which affects various engineering structures all over the world. Consequently, we need environmentally-friendly and cost-effective soil stabilizers to address the challenges related to expansive soils. The utilization of natural fibers allows for the reduction in environmental impact since they are renewable and biodegradable raw materials. Moreover, the current article presents an experimental approach to study the effect of natural fibers on the mechanical behavior of expansive soils. Various experimental tests—such as Atterberg limits, standard compaction, direct shear, swelling potential, and swelling pressure—were conducted on control and treated soil samples using different percentages of fibers. The results of measurements of the physico-mechanical properties after reinforcement of the soil with 1%, 5%, and 10% of natural fibers indicate that the mechanical behavior of expansive soils is greatly influenced by the addition of natural fibers. To conclude, 86% reduction was observed in the swelling coefficient of treated soil. Future research can be done to check the durability of the current practice in detail.
CCTV Camera Array for the Displacement and Strain Measurement of a Beam Specimen in a Laboratory
Authors: Tuladhar Rujika , Thammarak Punchet , Elias Said
Published: October 2022

The available conventional sensors, like displacement transducers, used in the Structural Engineering Laboratory are expensive. In addition to that, the need for data acquisition devices also escalates the expense invested in point contact measurement systems. The recent appeal of vision-based measurement and the search for cost-effectiveness has led to an exploration of the established sampling moiré method using cheap closed-circuit television (CCTV) cameras as a viable option. The sampling moiré method is simple and analyzes the displacements from grating images by a phase-shifting method. Several trial experiments were conducted, which demonstrated that the setup is at least as accurate as the traditional measuring system. An experiment was conducted on a steel I-beam for displacement measurement, which displayed satisfactory results. In addition, the setup was also tested for strain measurement, and it has yielded promising results that need fine-tuning. This paper discusses the challenges, findings, and the possibility of incorporating vision-based displacement measurements in laboratory platforms.
Load Distribution Optimization of Steel Storage Rack Based on Genetic Algorithm
Authors: Deng Tianyang , Niu Yu , Yin Lingfeng , Lin Zhiqiang , Li Zhanjie
Published: October 2022

The distribution of load has high uncertainty, which is the main cause of a rack structure’s instabilities. The objective of this study was to identify the most unfavorable and favorable load distributions on steel storage racks with and without bracings under seismic loading through a stochastic optimization—a genetic algorithm (GA). This paper begins with optimizing the most unfavorable and favorable load distributions on the steel storage racks with and without bracings using GA. Based on the optimization results, the failure position and seismic performance influencing factors, such as the load distributions on the racks and at hazardous positions, are then identified. In addition, it is demonstrated that the maximum stress ratio of the uprights under the most unfavorable load distribution is higher than that under the full-load normal design, and it is not the case that the higher the center of gravity the more dangerous the steel storage rack is, demonstrating that the load distribution pattern has a significant impact on the structural safety of steel storage racks. The statistics of the distributions of the load generated during the optimization of the GA and the contours of the probability distributions of the load are generated. Combining the probability distribution contours and the GA’s optimization findings, the “convex” distribution hazard model and the “concave” distribution safety model for a steel storage rack with bracings are identified. In addition, the features of the distribution hazard model and the load distribution safety model are also identified for steel storage racks without bracings.
Low-Dose Computed Tomography Scanning Protocols for Online Adaptive Proton Therapy of Head-and-Neck Cancers
Authors: Nesteruk Konrad P. , Bobić Mislav , Sharp Gregory C. , Lalonde Arthur , Winey Brian A. , Nenoff Lena , Lomax Antony J. , Paganetti Harald
Published: October 2022

Purpose: To evaluate the suitability of low-dose CT protocols for online plan adaptation of head-and-neck patients. Methods: We acquired CT scans of a head phantom with protocols corresponding to CT dose index volume CTDIvol in the range of 4.2–165.9 mGy. The highest value corresponds to the standard protocol used for CT simulations of 10 head-and-neck patients included in the study. The minimum value corresponds to the lowest achievable tube current of the GE Discovery RT scanner used for the study. For each patient and each low-dose protocol, the noise relative to the standard protocol, derived from phantom images, was applied to a virtual CT (vCT). The vCT was obtained from a daily CBCT scan corresponding to the fraction with the largest anatomical changes. We ran an established adaptive workflow twice for each low-dose protocol using a high-quality daily vCT and the corresponding low-dose synthetic vCT. For a relative comparison of the adaptation efficacy, two adapted plans were recalculated in the high-quality vCT and evaluated with the contours obtained through deformable registration of the planning CT. We also evaluated the accuracy of dose calculation in low-dose CT volumes using the standard CT protocol as reference. Results: The maximum differences in D98 between low-dose protocols and the standard protocol for the high-risk and low-risk CTV were found to be 0.6% and 0.3%, respectively. The difference in OAR sparing was up to 3%. The Dice similarity coefficient between propagated contours obtained with low-dose and standard protocols was above 0.982. The mean 2%/2 mm gamma pass rate for the lowest-dose image, using the standard protocol as reference, was found to be 99.99%. Conclusion: The differences between low-dose protocols and the standard scanning protocol were marginal. Thus, low-dose CT protocols are suitable for online adaptive proton therapy of head-and-neck cancers. As such, considering scanning protocols used in our clinic, the imaging dose associated with online adaption of head-and-neck cancers treated with protons can be reduced by a factor of 40.
The Optimal Therapy after Progression on Immune Checkpoint Inhibitors in MSI Metastatic Gastrointestinal Cancer Patients: A Multicenter Retrospective Cohort Study
Authors: Chen Mifen , Wang Zhenghang , Liu Zimin , Liu Ning , Fang Weijia , Zhang Hangyu , Jin Xuan , Li Jiayi , Zhao Weifeng , Qu Huajun , Song Fanghua , Chang Zhiwei , Li Yi , Tang Yong , Xu Chunlei , Zhang Xiaotian , Wang Xicheng , Peng Zhi , Cai Jinping , Li Jian , Shen Lin
Published: October 2022

Background: In microsatellite instability (MSI)/mismatch repair-deficient (dMMR) gastrointestinal cancers, the optimum therapy after the progression of immune checkpoint inhibitors (ICIs) is yet unknown. Here, we compared the efficacy of programmed death 1 (PD1)/programmed death ligand-1 (PD-L1) inhibitors plus other therapy and chemotherapy with or without targeted therapy in MSI/dMMR gastrointestinal cancer patients after progression on anti-PD1/PD-L1 monotherapy. Methods: We retrospectively recruited MSI/dMMR gastrointestinal cancer patients who had progressed on anti-PD1/PD-L1 monotherapy. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and PFS ratio (PFSr) were compared between patients who received anti-PD1/PD-L1 plus other therapy (ICI-plus group) and patients who received chemotherapy with or without targeted therapy (chemo-targeted group). Results: In total, 26 and 25 patients were recruited in the ICI-plus group and chemo-targeted group, respectively. Significantly better DCR (80.8% vs. 44.0%, p = 0.007), PFS (median PFS 6.9 months vs. 3.0 months, p = 0.001), OS (median OS NR vs. 14.1 months, p = 0.043), and PFSr (2.4 vs. 0.9, p = 0.021), along with a numerically higher ORR (23.1% vs. 12.0%, p = 0.503) were observed in the ICI-plus group compared with the chemo-targeted group. Multivariate analyses identified the therapy regimen as an important prognostic factor in gastrointestinal cancers. Conclusions: Compared to conventional chemotherapy with or without targeted therapy, continuing anti-PD1/PD-L1 in combination with other treatments showed better clinical outcomes in MSI/dMMR gastrointestinal cancer patients who progressed on PD1/PD-L1 blockade, which should be validated prospectively in clinical trials.
Higher Risk of Recurrence in Patients Treated for Head and Neck Cancer with Low BMI and Elevated Levels of C-Reactive Protein
Authors: Spiegelberg Diana , Malmberg Christer , Tiblom Ehrsson Ylva , Laurell Göran
Published: October 2022

This prospective study identifies high-risk groups for recurrence of head and neck cancer by BMI and circulating inflammatory response markers. Head and neck cancer patients from three Swedish hospitals were included (n = 272). Leukocyte and thrombocyte counts, CRP levels, and BMI were measured pre-treatment and post-treatment. Associations between the four factors and treatment failure (residual tumor, loco-regional failure, general failure/distant metastasis) were assessed using a Cox proportional hazards model adjusted for sex, age at the initial visit, smoking status, cancer stage, and hemoglobin count. CRP level was the only significant single variable, with an average increase in risk of recurrence of 74% (p = 0.018) for every doubling. The predictive power of a combined model using all variables was highest during the initial months after treatment, with AUC under the ROC curve 0.75 at the 0–3 month timepoints. Patients with elevated pre- and post-treatment CRP levels are at higher risk for recurrence of disease. Male patients with low post-treatment BMI, advanced stage, and high CRP at any time post treatment are at high risk for recurrence. The combined model may be useful for stratifying post-treatment patients into low and high-risk groups, to enable more detailed follow-up or additional treatment regimens.
Risk and Status of Gastrointestinal Cancer According to the International Standard Industrial Classification in Korean Workers
Authors: Shin Soonsu , Choi Jun-Hyeok , Lee Kyung-Eun , Yoon Jin-Ha , Lee Wanhyung
Published: October 2022

To compare the risk of developing gastrointestinal (GI) cancer according to industrial groups, we performed a retrospective cohort study using the database of the Korea National Health Insurance Service (NHIS). We calculated the age-standardized incidence ratios (SIRs) and 95% confidence intervals (95% CIs) for the types of GI cancers according to the Korean Standard Industrial Classification (KSIC) compared with the whole employee population. The highest SIR for all GI cancer was found in the “Mining and quarrying” section (SIR, 1.30; 95% CI, 1.14–1.47), followed by the “Transportation and storage” section (SIR, 1.27; 95% CI, 1.24–1.30). Miners and quarriers had the highest risk of developing gastric cancer (SIR, 1.29; 95% CI, 1.06–1.55) and cancer of the liver and intrahepatic bile ducts (SIR, 1.48; 95% CI, 1.17–1.86). Transportation workers had the highest SIR of cancer of the lip, oral cavity, and pharynx (SIR, 1.27; 95% CI, 1.13–1.43) and cancers of the rectum, anus, and anal canal (SIR, 1.27; 95% CI, 1.19–1.35). There were distinct GI cancers with an elevated risk in each industry group. Our findings imply that distinct cancer prevention programs should be developed for each industrial sector.
Stereotactic Body Radiotherapy Boost with the CyberKnife for Locally Advanced Cervical Cancer: Dosimetric Analysis and Potential Clinical Benefits
Authors: Gao Jiaxiang , Xu Benhua , Lin Yibin , Xu Zhenhang , Huang Miaoyun , Li Xiaobo , Wu Xiaodong , Chen Yuangui
Published: October 2022

(1) Aim: To compare the treatment plans of stereotactic body radiotherapy (SBRT) with CyberKnife (CK) and high-dose-rate (HDR) intracavitary/interstitial brachytherapy (IC/ISBT) and examine the feasibility of CK-SBRT as a viable alternative to BT in patients with locally advanced cervical cancer (LACC). (2) Methods: A BT plan of 28 Gy in four fractions delivered previously to 20 patients with LACC was compared with a CK plan based on the same CT images with structures delineation for BT. The SBRT treatment plan was further divided according to two different approaches, with the high-risk planning target volume (HR-PTV) defined by the high-risk clinical target volume (HR-CTV) without and with a 5 mm margin, which were named CK-CTV plan and CK-PTV plan, respectively. The dose distributions and dosimetric parameters of the target volumes and organs at risk (OARs) were recorded and compared for the three boost plans. Radiobiological metrics were calculated based on the EUD for the hybrid plans. Additionally, the relationship between tumor volume and tolerance doses for the OARs in the BT plan and CK-PTV plan was investigated. (3) Results: Target coverage was better with the CK plan than with the BT plan, as the D95%, D98%, HI and CI of the CK-CTV plan and CK-PTV plan were higher than those of the BT plan; an exception was the D50%. Similarly, the TCP of the target was also significantly in favor of the CK hybrid plans (p < 0.01). For the OARs, the CK-CTV plan was superior to the BT plan as regards the rectum D2cc, bladder D2cc and bladder Dmax. The CK-PTV plan could achieve dosimetric parameters comparable to those of the BT plan for OARs concerning the small residual tumor volume. The NTCP of the rectum for the WPI+CK-CTV plans was significantly lower than that of the WPI+BT plans (p < 0.01). (4) Conclusions: CK-based SBRT can achieve better target coverage, dose sparing for the OARs and radiobiological effects compared with the BT plan for tumors that are not excessively large. CK-based SBRT could be an alternative option to administer a radiation boost for patients with LACC.
Precision Medicine in the Treatment of Locally Advanced or Metastatic Urothelial Cancer: New Molecular Targets and Pharmacological Therapies
Authors: Vitiello Antonio , Ferrara Francesco , Lasala Ruggero , Zovi Andrea
Published: October 2022

Many variants of urothelial cancer present diagnostic challenges and carry clinical implications that influence prognosis and treatment decisions. The critical issues of treatment-resistant clones are a crucial barrier to care in individuals affected by urothelial carcinoma. Laying the foundations for the resistance evolution, a wide mutational heterogeneity characterizes urothelial carcinoma, noticeable also in patients affected by a early stage disease. In recent years the growing knowledge of the pathogenesis and molecular paths underlying the onset and progression of urothelial cancer are leading to the development of new therapies based on immune checkpoints. Chemotherapy and immunotherapy both operate selectively by shaping the developmental trajectory of urothelial carcinoma in the course of the illness. To date, a promising new therapeutic treatment is represented by antibody-drug conjugates, therapeutic tools that exploit the targeted ability of an antibody to administer cytotoxic drugs directly to the tumor. Indeed, nowadays in the clinical setting there are several treatments available for the treatment of locally advanced or metastatic urothelial cancer, from classic chemotherapeutics such as Gemcitabine, Cisplatin and Carboplatin, Paclitaxel and Docetaxel, to Programmed cell death protein 1 (PD-1) or Programmed death-ligand 1 (PD-L1) inhibitors such as Atezolizumab, Avelumab, Nivolumab, Pembrolizumab, up to anti-nectin 4 Enfortumab Vedotin and Sacituzumab govitecan, which binds Tumor-associated calcium signal transducer 2 (Trop-2) and activates as a topoisomerase inhibitor. The aim of this work is to describe the molecular mechanisms underlying the onset of the urothelial cancer and provide an overview of the immunotherapies that can be used in the clinical setting to counteract it, deepening the efficacy and safety results of the pivotal studies and the place in therapy of these treatments.
Glioblastoma-Derived Three-Dimensional Ex Vivo Models to Evaluate Effects and Efficacy of Tumor Treating Fields (TTFields)
Authors: Nickl Vera , Schulz Ellina , Salvador Ellaine , Trautmann Laureen , Diener Leopold , Kessler Almuth F. , Monoranu Camelia M. , Dehghani Faramarz , Ernestus Ralf-Ingo , Löhr Mario , Hagemann Carsten
Published: October 2022

Glioblastoma (GBM) displays a wide range of inter- and intra-tumoral heterogeneity contributing to therapeutic resistance and relapse. Although Tumor Treating Fields (TTFields) are effective for the treatment of GBM, there is a lack of ex vivo models to evaluate effects on patients’ tumor biology or to screen patients for treatment efficacy. Thus, we adapted patient-derived three-dimensional tissue culture models to be compatible with TTFields application to tissue culture. Patient-derived primary cells (PDPC) were seeded onto murine organotypic hippocampal slice cultures (OHSC), and microtumor development with and without TTFields at 200 kHz was observed. In addition, organoids were generated from acute material cultured on OHSC and treated with TTFields. Lastly, the effect of TTFields on expression of the Ki67 proliferation marker was evaluated on cultured GBM slices. Microtumors exhibited increased sensitivity towards TTFields compared to monolayer cell cultures. TTFields affected tumor growth and viability, as the size of microtumors and the percentage of Ki67-positive cells decreased after treatment. Nevertheless, variability in the extent of the response was preserved between different patient samples. Therefore, these pre-clinical GBM models could provide snapshots of the tumor to simulate patient treatment response and to investigate molecular mechanisms of response and resistance.
The Prognostic and Therapeutic Implications of the Chemoresistance Gene BIRC5 in Triple-Negative Breast Cancer
Authors: Adinew Getinet M. , Messeha Samia , Taka Equar , Soliman Karam F. A.
Published: October 2022

Chemoresistance affects TNBC patient treatment responses. Therefore, identifying the chemoresistant gene provides a new approach to understanding chemoresistance in TNBC. BIRC5 was examined in the current study as a tool for predicting the prognosis of TNBC patients and assisting in developing alternative therapies using online database tools. According to the examined studies, BIRC5 was highly expressed in 45 to 90% of TNBC patients. BIRC5 is not only abundantly expressed but also contributes to resistance to chemotherapy, anti-HER2 therapy, and radiotherapy. Patients with increased expression of BIRC5 had a median survival of 31.2 months compared to 85.8 months in low-expression counterparts (HR, 1.73; CI, 1.4–2.13; p = 2.5 × 10−7). The overall survival, disease-free survival, relapse-free survival, distant metastasis-free survival, and the complete pathological response of TNBC patients with high expression of BIRC5 who received any chemotherapy (Taxane, Ixabepilone, FAC, CMF, FEC, Anthracycline) and anti-HER2 therapy (Trastuzumab, Lapatinib) did not differ significantly from those patients receiving any other treatment. Data obtained indicate that the BIRC5 promoter region was substantially methylated, and hypermethylation was associated with higher BIRC5 mRNA expression (p < 0.05). The findings of this study outline the role of BIRC5 in chemotherapy-induced resistance of TNBC, further indicating that BIRC5 may serve as a promising prognostic biomarker that contributes to chemoresistance and could be a possible therapeutic target. Meanwhile, several in vitro studies show that flavonoids were highly effective in inhibiting BIRC5 in genetically diverse TNBC cells. Therefore, flavonoids would be a promising strategy for preventing and treating TNBC patients with the BIRC5 molecule.