bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary Results of NGS Gene Panel Test Using NSCLC Sputum Cytology and Therapeutic Effect Using Corresponding Molecular-Targeted Drugs
Authors: Morikawa Kei , Kinoshita Kohei , Kida Hirotaka , Inoue Takeo , Mineshita Masamichi
Published: May 2022

As more molecular-targeted drugs for advanced non-small cell lung cancer are brought to market, batch tests for the identification of gene mutations are needed at initial diagnosis. However, since current gene panel tests require a sufficient amount of tissue sample, there are many instances where panel tests cannot be performed. Therefore, we have developed a highly sensitive next generation sequencing (NGS) panel test to facilitate cytological specimens. Herein, we describe three cases positive for epidermal growth factor receptor (EGFR) exon 19 deletion, MET exon 14 skipping, and KRAS G12A using NGS analysis from sputum. In each case, genetic information was consistent with companion diagnostic analysis obtained from tissue samples collected under bronchoscopy. In cases of EGFR and MET mutations, the corresponding tyrosine kinase inhibitors were highly effective. This is the first report to demonstrate that a novel panel test could detect gene mutations in sputum samples in clinical practice and compare the gene allele ratio with the sample directly collected from the lesion.
The Communication Challenges and Strength of Nurses’ Intensive Corona Care during the Two First Pandemic Waves: A Qualitative Descriptive Phenomenology Study
Authors: Green Gizell , Sharon Cochava , Gendler Yulia
Published: May 2022

Intensive care nurses working with patients with severe COVID-19 illness are at the center and frontline of the dynamic pandemic, which poses communication challenges and demands of unusual strength on their part. The study aim was to capture the lived experience of intensive care COVID nurses’ communication challenges and strengths as they cared for COVID-19 intensive care patients during the two first pandemic waves. The study used qualitative descriptive-phenomenology research designs. Twenty-two nurses were selected using snowball sampling, and online interviews were conducted with them. Data were recorded and transcribed, then reflexively double-coded for increased rigor. Four major themes emerged from the data. The first two expressed the communication challenges and difficulties communicating with patients due to the extreme protection needed and/or their medical condition. However, the other two themes expressed the nurses’ strengths—sharing feelings with other caregivers and family. Accordingly, we recommend using simple language and ensuring patient comprehension, as well as creating an optimistic environment for fostering caregiver bonding.
Inhibition of Poly (ADP-Ribose) Glycohydrolase Accelerates Osteoblast Differentiation in Preosteoblastic MC3T3-E1 Cells
Authors: Sasaki Yuka , Nakatsuka Ryusuke , Inouchi Takuma , Masutani Mitsuko , Nozaki Tadashige
Published: May 2022

Poly ADP-ribosylation (PARylation) is a post-translational modification catalyzed by poly (ADP-ribose) polymerase (PARP) family proteins such as PARP1. Although PARylation regulates important biological phenomena such as DNA repair, chromatin regulation, and cell death, little is known about the relationship between osteoblast differentiation and the PARylation cycle involving PARP1 and the poly (ADP-ribose)-degrading enzyme poly (ADP-ribose) glycohydrolase (PARG). Here, we examined the effects of PARP inhibitor olaparib, an approved anti-cancer agent, and PARG inhibitor PDD00017273 on osteoblast differentiation. Olaparib decreased alkaline phosphatase (ALP) activity and suppressed mineralized nodule formation evaluated by Alizarin Red S staining in preosteoblastic MC3T3-E1 cells, while PDD00017273 promoted ALP activity and mineralization. Furthermore, PDD00017273 up-regulated the mRNA expression levels of osteocalcin and bone sialoprotein, as osteoblast differentiation markers, and osterix as transcription inducers for osteoblast differentiation, whereas olaparib down-regulated the expression of these genes. These findings suggest that PARG inhibition by PDD00017273 accelerates osteoblast differentiation in MC3T3-E1 cells. Thus, PARG inhibitor administration could provide therapeutic benefits for metabolic bone diseases such as osteoporosis.
Dental Pulp Response to Different Types of Calcium-Based Materials Applied in Deep Carious Lesion Treatment—A Clinical Study
Authors: Covaci Antoanela , Ciocan Lucian Toma , Gălbinașu Bogdan , Bucur Mirela Veronica , Matei Mădălina , Didilescu Andreea Cristiana
Published: May 2022

Dental pulp vitality preservation in dental caries treatment is a major goal in odontotherapy. The main objective of this study was to compare dental pulp tissue responses to vital therapies in deep carious lesions, using different calcium-based materials. An ambispective study was conducted on 47 patients. Ninety-five teeth with deep carious lesions were treated. Among them, 25 (26.32%) were diagnosed with pulpal exposures and treated by direct pulp capping. Indirect pulp capping was applied when pulp exposure was absent (n = 70; 73.68%). Fifty teeth (52.63%) were treated with TheraCal LC (prospective study), 31 teeth (32.63%) with Calcimol LC, and 14 teeth (14.74%) with Life Kerr AC (retrospective study). The results show that the survival rate for dental pulp was 100% for Life Kerr AC, 92% for TheraCal LC, and 83.87% for Calcimol LC, without significant differences. Apparently, self-setting calcium hydroxide material provided better dental pulp response than the two light-cured materials, regardless of their composition, that is, either calcium -hydroxide or calcium silicate-based. We will need a significant number of long-term clinical studies with the highest levels of evidence to determine the most adequate biomaterials for vital pulp therapies.
Prediction of Surface Roughness Using Machine Learning Approach in MQL Turning of AISI 304 Steel by Varying Nanoparticle Size in the Cutting Fluid
Authors: Dubey Vineet , Sharma Anuj Kumar , Pimenov Danil Yurievich
Published: May 2022

Surface roughness is considered as an important measuring parameter in the machining industry that aids in ensuring the quality of the finished product. In turning operations, the tool and workpiece contact develop friction and cause heat generation, which in turn affects the machined surface. The use of cutting fluid in the machining zone helps to minimize the heat generation. In this paper, minimum quantity lubrication is used in turning of AISI 304 steel for determining the surface roughness. The cutting fluid is enriched with alumina nanoparticles of two different average particle sizes of 30 and 40 nm. Among the input parameters chosen for investigation are cutting speed, depth of cut, feed rate, and nanoparticle concentration. The response surface approach is used in the design of the experiment (RSM). For the purpose of estimating the surface roughness and comparing the experimental value to the predicted values, three machine learning-based models, including linear regression (LR), random forest (RF), and support vector machine (SVM), are utilized in addition. For the purpose of evaluating the accuracy of the predicted values, the coefficient of determination (R2), mean absolute percentage error (MAPE), and mean square error (MSE) were all used. Random forest outperformed the other two models in both the particle sizes of 30 and 40 nm, with R-squared of 0.8176 and 0.7231, respectively. Thus, this study provides a novel approach in predicting the surface roughness by varying the particle size in the cutting fluid using machine learning, which can save time and wastage of material and energy.
Friction and Wear Characteristics of Polydimethylsiloxane under Water-Based Lubrication Conditions
Authors: Lee Sung-Jun , Sohn Yoon-Chul , Kim Chang-Lae
Published: May 2022

In this study, the friction and wear characteristics of polydimethylsiloxane (PDMS) were evaluated when using lubricants created by adding surfactants at various ratios to deionized (DI) water. When pure DI water is used as a lubricant, the repulsion of water from the hydrophobic PDMS surface is large and the interfacial affinity is low; thus, the lubrication properties cannot be significantly improved. However, when a lubricant with a surfactant is added to DI water, the interfacial affinity with the PDMS surface increases to form a lubricating film, and the friction coefficient is greatly reduced. In this study, under dry and pure DI water conditions, severe wear tracks were formed on the PDMS surface after 10,000 cycles of reciprocating sliding motion under a vertical load of 100 mN, whereas in the case of the surfactant-based and water-based lubricant, no severe wear tracks occurred. The friction and wear characteristics of the PDMS were evaluated by increasing the normal loads and sliding cycles with a water-based lubricant containing 1 wt % surfactant. Under normal loads of 300 mN and 500 mN, only minor scratches occurred on the PDMS surface up to 10,000 and 100,000 cycles, respectively, but after 300,000 cycles, very severe pit wear tracks occurred.
Comparative Analysis of Domestic and International Test Guidelines for Various Concrete Repair Materials
Authors: Kim Tae-Kyun , Park Jong-Sup
Published: May 2022

The number of aged bridges among concrete structures is increasing. Therefore, to increase their lifespans, repair and reinforcement schemes ought to be implemented. This study selected various repair materials according to crack-surface treatment, crack-filling, and crack-injection methods. These repair materials were evaluated using various test methods proposed by the Korean Standards and the American Society for Testing and Materials for structure protection, structure restoration, and crack repair; the results were analyzed and compared. Consequently, the structure restoration material exhibited a similar freezing–thawing trend as that of chloride, while also exhibiting similar flexural, compressive, bond, and splitting-tensile strengths. However, chloride yielded performance differences (up to two-fold) depending on the type of material used for comparison. The crack-repair material yielded similar trends only for bond strength but yielded differences (up to 2–4-fold) in tensile, compressive, and flexural strengths depending on the material used for comparison. These results confirmed that crack-repair materials exhibit significant differences in performance depending on the manufacturer compared with structure protection and structure restoration materials. Therefore, it is expected that repair materials appropriate for usability, durability, and structure safety, while also being environmentally friendly, could be used in future bridge repairs based on these test evaluations.
Obstacle Detection for Autonomous Guided Vehicles through Point Cloud Clustering Using Depth Data
Authors: Pires Micael , Couto Pedro , Santos António , Filipe Vítor
Published: May 2022

Autonomous driving is one of the fastest developing fields of robotics. With the ever-growing interest in autonomous driving, the ability to provide robots with both efficient and safe navigation capabilities is of paramount significance. With the continuous development of automation technology, higher levels of autonomous driving can be achieved with vision-based methodologies. Moreover, materials handling in industrial assembly lines can be performed efficiently using automated guided vehicles (AGVs). However, the visual perception of industrial environments is complex due to the existence of many obstacles in pre-defined routes. With the INDTECH 4.0 project, we aim to develop an autonomous navigation system, allowing the AGV to detect and avoid obstacles based in the processing of depth data acquired with a frontal depth camera mounted on the AGV. Applying the RANSAC (random sample consensus) and Euclidean clustering algorithms to the 3D point clouds captured by the camera, we can isolate obstacles from the ground plane and separate them into clusters. The clusters give information about the location of obstacles with respect to the AGV position. In experiments conducted outdoors and indoors, the results revealed that the method is very effective, returning high percentages of detection for most tests.
Salt- and pH-Dependent Thermal Stability of Photocomplexes from Extremophilic Bacteriochlorophyll b-Containing Halorhodospira Species
Authors: Kimura Yukihiro , Nakata Kazuna , Nojima Shingo , Takenaka Shinji , Madigan Michael T. , Wang-Otomo Zheng-Yu
Published: May 2022

Halorhodospira (Hlr.) species are the most halophilic and alkaliphilic of all purple bacteria. Hlr. halochloris exhibits the lowest LH1 Qy transition energy among phototrophic organisms and is the only known triply extremophilic anoxygenic phototroph, displaying a thermophilic, halophilic, and alkaliphilic phenotype. Recently, we reported that electrostatic charges are responsible for the unusual spectroscopic properties of the Hlr. halochloris LH1 complex. In the present work, we examined the effects of salt and pH on the spectroscopic properties and thermal stability of LH1-RCs from Hlr. halochloris compared with its mesophilic counterpart, Hlr. abdelmalekii. Experiments in which the photocomplexes were subjected to different levels of salt or variable pH revealed that the thermal stability of LH1-RCs from both species was largely retained in the presence of high salt concentrations and/or at alkaline pH but was markedly reduced by lowering the salt concentration and/or pH. Based on the amino acid sequences of LH1 polypeptides and their composition of acidic/basic residues and the Hofmeister series for cation/anion species, we discuss the importance of electrostatic charge in stabilizing the Hlr. halochloris LH1-RC complex to allow it to perform photosynthesis in its warm, hypersaline, and alkaline habitat.
Facile and Green Synthesis of Highly Fluorescent Carbon Quantum Dots from Water Hyacinth for the Detection of Ferric Iron and Cellular Imaging
Authors: Zhao Pei , Zhang Qin , Cao Juanjuan , Qian Cheng , Ye Jing , Xu Siyuan , Zhang Yonggui , Li Yanbin
Published: May 2022

Natural biomass is used for facile synthesis of carbon quantum dots (CQDs) with high fluorescence, owing to its abundance, low cost, and eco-friendliness. In this study, a bottom-up hydrothermal method was used to prepare CQDs from water hyacinth (wh) at a constant temperature of 180 °C for 12 h. The synthesized wh-CQDs had uniform size, amorphous graphite structure, high water solubility (containing multiple hydroxyl and carboxyl groups on the surface), excitation light-dependent characteristics, and high photostability. The results showed that the aqueous solution of CQDs could detect Fe3+ rapidly, sensitively, and highly selectively with a detection limit of 0.084 μM in the linear range of 0–330 μM, which is much lower than the detection limit of 0.77 μM specified by the World Health Organization. More importantly, because the wh-CQDs were synthesized without any additives, they exhibited low toxicity to Klebsiella sp. cells even at high concentrations. Moreover, wh-CQDs emitted bright blue fluorescence in Klebsiella sp. cells, indicating its strong penetrating ability. Correspondingly, the fluorescent cell sorting results also revealed that the proportion of cell internalization reached 41.78%. In this study, wh-CQDs derived from natural biomass were used as high-performance fluorescent probes for Fe3+ detection and Klebsiella sp. imaging. This study is expected to have great significance for the application of biomass carbon spots in the field of cellular imaging and biology.
Responsivity of Fractal Nanoparticle Assemblies to Multiple Stimuli: Structural Insights on the Modulation of the Optical Properties
Authors: Capocefalo Angela , Bizien Thomas , Sennato Simona , Ghofraniha Neda , Bordi Federico , Brasili Francesco
Published: May 2022

Multi-responsive nanomaterials based on the self-limited assembly of plasmonic nanoparticles are of great interest due to their widespread employment in sensing applications. We present a thorough investigation of a hybrid nanomaterial based on the protein-mediated aggregation of gold nanoparticles at varying protein concentration, pH and temperature. By combining Small Angle X-ray Scattering with extinction spectroscopy, we are able to frame the morphological features of the formed fractal aggregates in a theoretical model based on patchy interactions. Based on this, we established the main factors that determine the assembly process and their strong correlation with the optical properties of the assemblies. Moreover, the calibration curves that we obtained for each parameter investigated based on the extinction spectra point out to the notable flexibility of this nanomaterial, enabling the selection of different working ranges with high sensitivity. Our study opens for the rational tuning of the morphology and the optical properties of plasmonic assemblies to design colorimetric sensors with improved performances.
Application of Nanopore Sequencing in the Detection of Foodborne Microorganisms
Authors: Zhou You , Ren Meishen , Zhang Pengfei , Jiang Dike , Yao Xueping , Luo Yan , Yang Zexiao , Wang Yin
Published: May 2022

Foodborne pathogens have become the subject of intense interest because of their high incidence and mortality worldwide. In the past few decades, people have developed many methods to solve this challenge. At present, methods such as traditional microbial culture methods, nucleic acid or protein-based pathogen detection methods, and whole-genome analysis are widely used in the detection of pathogenic microorganisms in food. However, these methods are limited by time-consuming, cumbersome operations or high costs. The development of nanopore sequencing technology offers the possibility to address these shortcomings. Nanopore sequencing, a third-generation technology, has the advantages of simple operation, high sensitivity, real-time sequencing, and low turnaround time. It can be widely used in the rapid detection and serotyping of foodborne pathogens. This review article discusses foodborne diseases, the principle of nanopore sequencing technology, the application of nanopore sequencing technology in foodborne pathogens detection, as well as its development prospects.
Study on the Characteristics of the Dispersion and Conductivity of Surfactants for the Nanofluids
Authors: Kim Sedong
Published: May 2022

Given the importance of nanofluid dispersion and stability, a number of approaches were proposed and applied to the nanofluid preparation process. Among these approaches, the noncovalent chemical process was intensively utilized because of its effective dispersion ability. For the noncovalent dispersion method, polymers and surfactants are typically used. In order to find an effective noncovalent dispersion method, several types of solutions were prepared in this study. The widely used naturally cellulose nanocrystal (CNC) aqueous solution was compared with several surfactant aqueous solutions. The dispersion characteristics of the prepared fluids were examined by UV/VIS spectroscopy at operating wavelengths ranging from 190 to 500 nm. Furthermore, the heat capacity and the electrical and thermal conductivity of the fluids were analyzed to evaluate their heat transfer performance and conductivity. The Lambda system was utilized for thermal conductivity measurement with operation at proper temperature ranges. The electrical conductivity of the fluids was measured by a conductivity meter. This experimental study revealed that the cellulose nanocrystal was an effective source of the noncovalent dispersion agent for thermal characteristics and was more eco-friendly than other surfactants. Moreover, cellulose aqueous solution can be used as a highly thermal efficient base fluid for nanofluid preparation.
An Investigation of Social Ecological Barriers to and Facilitators of WIC Farmers Market Nutrition Program Voucher Redemption
Authors: Blumberg Renata , Fowler Emily , Bai Yeon , Lal Pankaj , Smolen Alyssa , Dubrovsky Ilana
Published: May 2022

In the United States, many communities lack sufficient access to fresh produce. To improve access to fresh fruits and vegetables, the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides eligible participants vouchers through the Farmers Market Nutrition Program (FMNP) that can be redeemed directly from farmers at markets or farm stands. However, FMNP voucher redemption rates in New Jersey remain lower than those in neighboring states. This article used the social ecological model to examine differences between FMNP participants who redeem vouchers (Redeemers) and those who do not (non-Redeemers) in the areas of: produce procurement practices and consumption frequency, and barriers to and facilitators of FMNP voucher redemption. This cross-sectional study included WIC FMNP participants (N = 329) in northern New Jersey, USA. Analyses were conducted using descriptive statistics, independent sample t-tests, and one-way ANOVA. Compared to Redeemers, non-Redeemers consumed fewer average daily vegetable servings, were more likely to shop at small grocery/corner stores, and encountered significant barriers to FMNP redemption, e.g., difficulty finding time to redeem vouchers.
Nutritionists’ Practices and Knowledge about the Risks of Alcohol Consumption during Pregnancy: An Israeli Survey
Authors: Hen-Herbst Liat , Ron El Levin Meital , Senecky Yehuda , Frishman Sigal , Berger Andrea
Published: May 2022

Fetal alcohol spectrum disorders (FASDs) are lifelong disabilities and the leading preventable cause of developmental disabilities. Antenatal care providers may influence pregnant women’s dietary practices and their awareness of the risks of alcohol consumption during pregnancy. This study aimed to assess nutritionists’ self-reported knowledge about the risks of drinking alcohol during pregnancy, professional practices in this respect, and self-perceived competence to assess and guide women about alcohol consumption during pregnancy in Israel. A sample of 526 professional nutritionists completed an anonymous online questionnaire. Results showed significant differences between the nutritionists’ knowledge and professional practices scores. About 349 (66.3%) of the sample agreed (to any degree) that they did not have enough knowledge to guide pregnant women regarding drinking alcohol. The number of years of experience, combined with self-perceived competence and the mean knowledge score, explained 18% of the variance in professional practices. Nutritionists and other health professionals may have a crucial role in preventing FASD and should prioritize appropriate screening for prenatal alcohol use. Eliminating alcohol consumption at any point in pregnancy would reduce the risk for FASDs.
The Effect of Enteral Immunonutrition in the Intensive Care Unit: Does It Impact on Outcomes?
Authors: Lopez-Delgado Juan Carlos , Grau-Carmona Teodoro , Trujillano-Cabello Javier , García-Fuentes Carlos , Mor-Marco Esther , Bordeje-Laguna Maria Luisa , Portugal-Rodriguez Esther , Lorencio-Cardenas Carol , Vera-Artazcoz Paula , Macaya-Redin Laura , Martinez-Carmona Juan Francisco , Mateu-Campos Lidón , Gero-Escapa Maria , Gastaldo-Simeon Rosa , Vila-García Belen , Flordelis-Lasierra José Luis , Montejo-Gonzalez Juan Carlos , Servia-Goixart Lluís ,   the ENPIC Study Group
Published: May 2022

Background: The present research aimed to evaluate the effect on outcomes of immunonutrition (IMN) enteral formulas during the intensive care unit (ICU) stay. Methods: A multicenter prospective observational study was performed. Patient characteristics, disease severity, nutritional status, type of nutritional therapy and outcomes, and laboratory parameters were collected in a database. Statistical differences were analyzed according to the administration of IMN or other types of enteral formulas. Results: In total, 406 patients were included in the analysis, of whom 15.02% (61) received IMN. Univariate analysis showed that patients treated with IMN formulas received higher mean caloric and protein intake, and better 28-day survival (85.2% vs. 73.3%; p = 0.014. Unadjusted Hazard Ratio (HR): 0.15; 95% CI (Confidence Interval): 0.06–0.36; p < 0.001). Once adjusted for confounding factors, multivariate analysis showed a lower need for vasopressor support (OR: 0.49; 95% CI: 0.26–0.91; p = 0.023) and continuous renal replacement therapies (OR: 0.13; 95% CI: 0.01–0.65; p = 0.049) in those patients who received IMN formulas, independently of the severity of the disease. IMN use was also associated with higher protein intake during the administration of nutritional therapy (OR: 6.23; 95% CI: 2.59–15.54; p < 0.001), regardless of the type of patient. No differences were found in the laboratory parameters, except for a trend toward lower triglyceride levels (HR: 0.97; 95% CI: 0.95–0.99; p = 0.045). Conclusion: The use of IMN formulas may be associated with better outcomes (i.e., lower need for vasopressors and continuous renal replacement), together with a trend toward higher protein enteral delivery during the ICU stay. These findings may ultimately be related to their modulating effect on the inflammatory response in the critically ill. NCT Registry: 03634943.
Large-Scale Data Analysis for Glucose Variability Outcomes with Open-Source Automated Insulin Delivery Systems
Authors: Shahid Arsalan , Lewis Dana M.
Published: May 2022

Open-source automated insulin delivery (AID) technologies use the latest continuous glucose monitors (CGM), insulin pumps, and algorithms to automate insulin delivery for effective diabetes management. Early community-wide adoption of open-source AID, such as OpenAPS, has motivated clinical and research communities to understand and evaluate glucose-related outcomes of such user-driven innovation. Initial OpenAPS studies include retrospective studies assessing high-level outcomes of average glucose levels and HbA1c, without in-depth analysis of glucose variability (GV). The OpenAPS Data Commons dataset, donated to by open-source AID users with insulin-requiring diabetes, is the largest freely available diabetes-related dataset with over 46,070 days’ worth of data and over 10 million CGM data points, alongside insulin dosing and algorithmic decision data. This paper first reviews the development toward the latest open-source AID and the performance of clinically approved GV metrics. We evaluate the GV outcomes using large-scale data analytics for the n = 122 version of the OpenAPS Data Commons. We describe the data cleaning processes, methods for measuring GV, and the results of data analysis based on individual self-reported demographics. Furthermore, we highlight the lessons learned from the GV outcomes and the analysis of a rich and complex diabetes dataset and additional research questions that emerged from this work to guide future research. This paper affirms previous studies’ findings of the efficacy of open-source AID.
Sarcopenia as an Independent Risk Factor for Specific Cancers: A Propensity Score-Matched Asian Population-Based Cohort Study
Authors: Sun Ming-Yang , Chang Chia-Lun , Lu Chang-Yun , Wu Szu-Yuan , Zhang Jia-Qiang
Published: May 2022

Purpose: Whether preexisting sarcopenia is an independent risk factor for cancer incidence remains unclear. Therefore, we performed this propensity score (PS)-matched (PSM) population-based cohort study to compare the incidence rate ratios (IRRs) of specific cancers between patients with and without sarcopenia. Patients and Methods: The patients were categorized into two groups according to the presence or absence of sarcopenia, matched at a 4:1 ratio. Results: PS matching yielded a final cohort of 77,608 patients (15,527 in the sarcopenia and 62,081 nonsarcopenia groups) eligible for further analysis. In our multivariate Cox regression analysis, compared with the nonsarcopenia group, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for cancer risk in the sarcopenia group was 1.277 (1.10 to 1.36; p < 0.001). Furthermore, the adjusted IRRs (95% CIs) for sarcopenia patients were pancreatic cancer 3.77 (1.79 to 4.01), esophageal cancer 3.38 (1.87 to 4.11), lung cancer 2.66 (1.15 to 2.90), gastric cancer 2.25 (1.54 to 3.23), head and neck cancer 2.15 (1.44 to 2.53), colorectal cancer 2.04 (1.77 to 2.30), hepatocellular carcinoma 1.84 (1.30 to 2.36), breast cancer 1.56 (1.12 to 1.95), and ovarian cancer 1.43 (1.10 to 2.29), respectively. Conclusions: Sarcopenia might be a significant cancer risk factor for lung, colorectal, breast, head and neck, pancreas, gastric, esophageal, and ovarian cancer, as well as hepatocellular carcinoma.
Effectiveness of Reminiscence Therapy versus Cognitive Stimulation Therapy in Older Adults with Cognitive Decline: A Quasi-Experimental Pilot Study
Authors: Gil Isabel , Santos-Costa Paulo , Bobrowicz-Campos Elzbieta , Silva Rosa , de Lurdes Almeida Maria , Apóstolo João
Published: May 2022

Cognitive impairment can represent a predecessor to neuro-degenerative processes; however, evidence suggests that non-pharmacologic interventions such as reminiscence therapy (RT) and cognitive stimulation therapy (CST) can potentially stabilize or reverse this trend. Community-based settings are widely regarded as the key area of intervention by healthcare professionals in this field. Thus, this study aimed to assess the effects of an RT and a CST program in the cognition, depressive symptomatology, and quality of life (QoL) of older adults with cognitive decline who attend community support structures (CSS) in central Portugal. A quasi-experimental study with two arms (RT and CST program) was conducted for seven weeks. Participants were allocated to each arm based on the CSS they attended. Of the 109 older adults initially screened, 76 completed the intervention (50 in the RT program and 26 in the CST program). A pre- and post-intervention analysis showed statistically significant differences in older adults’ cognition, especially in their delayed recall ability, in both groups. Older adults in the RT program evidence improved QoL scores post-intervention. Both the RT and CST programs implemented throughout the study are beneficial to older adults’ cognitive performance, although results are more pronounced in the earlier stages of cognitive decline. Participation in the RT program was associated with improvements in older adults’ QoL scores.
Photonic and Optomechanical Thermometry
Authors: Briant Tristan , Krenek Stephan , Cupertino Andrea , Loubar Ferhat , Braive Rémy , Weituschat Lukas , Ramos Daniel , Martin Maria Jose , Postigo Pablo A. , Casas Alberto , Eisermann René , Schmid Daniel , Tabandeh Shahin , Hahtela Ossi , Pourjamal Sara , Kozlova Olga , Kroker Stefanie , Dickmann Walter , Zimmermann Lars , Winzer Georg , Martel Théo , Steeneken Peter G. , Norte Richard A. , Briaudeau Stéphan
Published: May 2022

Temperature is one of the most relevant physical quantities that affects almost all processes in nature. However, the realization of accurate temperature standards using current temperature references, like the triple point of water, is difficult due to the requirements on material purity and stability of the environment. In addition, in harsh environments, current temperature sensors with electrical readout, like platinum resistors, are difficult to implement, urging the development of optical temperature sensors. In 2018, the European consortium Photoquant, consisting of metrological institutes and academic partners, started investigating new temperature standards for self-calibrated, embedded optomechanical sensor applications, as well as optimised high resolution and high reliability photonic sensors, to measure temperature at the nano and meso-scales and as a possible replacement for the standard platinum resistant thermometers. This article presents an overview of the results obtained with sensor prototypes that exploit photonic and optomechanical techniques for sensing temperatures over a large temperature range (5 K to 300 K). Different concepts are demonstrated, including ring resonators, ladder-like resonators and suspended membrane optomechanical thermometers, highlighting initial performance and challenges, like self-heating that need to be overcome to realize photonic and optomechanical thermometry applications.
Borrelia burgdorferi Migration Assays for Evaluation of Chemoattractants in Tick Saliva
Authors: Jacobs Mary B. , Grasperge Britton J. , Doyle-Meyers Lara A. , Embers Monica E.
Published: May 2022

Uptake of the Lyme disease spirochete by its tick vector requires not only chemical signals present in the tick’s saliva but a responsive phenotype by the Borrelia burgdorferi living in the mammalian host. This is the principle behind xenodiagnosis, wherein pathogen is detected by vector acquisition. To study migration of B. burgdorferi toward Ixodes scapularis tick saliva, with the goal of identifying chemoattractant molecules, we tested multiple assays and compared migration of host-adapted spirochetes to those cultured in vitro. We tested mammalian host-adapted spirochetes, along with those grown in culture at 34 °C, for their relative attraction to tick saliva or the nutrient N-acetyl-D-glucosamine (D-GlcNAc) and its dimer chitobiose using two different experimental designs. The host-adapted B. burgdorferi showed greater preference for tick saliva over the nutrients, whereas the cultured incubator-grown B. burgdorferi displayed no significant attraction to saliva versus a significant response to the nutrients. Our results not only describe a validated migration assay for studies of the Lyme disease agent, but provide a further understanding of how growth conditions and phenotype of B. burgdorferi are related to vector acquisition.
Impact of Theaflavins-Enriched Tea Leaf Extract TY-1 against Surrogate Viruses of Human Norovirus: In Vitro Virucidal Study
Authors: Mohamed Israa M. A. , Jamsransuren Dulamjav , Matsuda Sachiko , Ogawa Haruko , Takeda Yohei
Published: May 2022

Using an effective natural virucidal substance may be a feasible approach for preventing food-borne viral contamination. Here, the virucidal efficacy of theaflavins (TFs)-enriched tea leaf extract (TY-1) against feline calicivirus (FCV) and murine norovirus (MNV), surrogates of human norovirus (HuNoV), was evaluated. The virus solutions were mixed with various dosages of TY-1 and incubated at 25 °C for different contact times. TY-1 reduced the viral titer of both surrogate viruses in a time- and dosage-dependent manner. A statistically significant reduction in the viral titer of FCV by 5.0 mg/mL TY-1 and MNV by 25.0 mg/mL TY-1 was observed in 10 s and 1 min, respectively. Furthermore, TY-1 reduced the viral titer of FCV and MNV on the dry surface in 10 min. The multiple compounds in TY-1, including TFs and catechins, contributed to its overall virucidal activity. Furthermore, the effect of TY-1 on viral proteins and genome was analyzed using Western blotting, RT-PCR, and transmission electron microscopy. TY-1 was found to promote the profound disruption of virion structures, including the capsid proteins and genome. Our finding demonstrates the potential of using TY-1 as a nature-derived disinfectant in food processing facilities and healthcare settings to reduce viral load and HuNoV transmission.
Refining Glioblastoma Surgery through the Use of Intra-Operative Fluorescence Imaging Agents
Authors: Netufo Oluwakanyinsolami , Connor Kate , Shiels Liam P. , Sweeney Kieron J. , Wu Dan , O’Shea Donal F. , Byrne Annette T. , Miller Ian S.
Published: May 2022

Glioblastoma (GBM) is the most aggressive adult brain tumour with a dismal 2-year survival rate of 26–33%. Maximal safe resection plays a crucial role in improving patient progression-free survival (PFS). Neurosurgeons have the significant challenge of delineating normal tissue from brain tumour to achieve the optimal extent of resection (EOR), with 5-Aminolevulinic Acid (5-ALA) the only clinically approved intra-operative fluorophore for GBM. This review aims to highlight the requirement for improved intra-operative imaging techniques, focusing on fluorescence-guided imaging (FGS) and the use of novel dyes with the potential to overcome the limitations of current FGS. The review was performed based on articles found in PubMed an.d Google Scholar, as well as articles identified in searched bibliographies between 2001 and 2022. Key words for searches included ‘Glioblastoma’ + ‘Fluorophore’+ ‘Novel’ + ‘Fluorescence Guided Surgery’. Current literature has favoured the approach of using targeted fluorophores to achieve specific accumulation in the tumour microenvironment, with biological conjugates leading the way. These conjugates target specific parts overexpressed in the tumour. The positive results in breast, ovarian and colorectal tissue are promising and may, therefore, be applied to intracranial neoplasms. Therefore, this design has the potential to produce favourable results in GBM by reducing the residual tumour, which translates to decreased tumour recurrence, morbidity and ultimately, mortality in GBM patients. Several preclinical studies have shown positive results with targeted dyes in distinguishing GBM cells from normal brain parenchyma, and targeted dyes in the Near-Infrared (NIR) emission range offer promising results, which may be valuable future alternatives.
Galactosylated Prodrugs: A Strategy to Improve the Profile of Nonsteroidal Anti-Inflammatory Drugs
Authors: Sodano Federica , Cristiano Claudia , Rolando Barbara , Marini Elisabetta , Lazzarato Loretta , Cuozzo Mariarosaria , Albrizio Stefania , Russo Roberto , Rimoli Maria Grazia
Published: May 2022

Carbohydrates are one of the most abundant and important classes of biomolecules. The variety in their structures makes them valuable carriers that can improve the pharmaceutical phase, pharmacokinetics and pharmacodynamics of well-known drugs. D-galactose is a simple, naturally occurring monosaccharide sugar that has been extensively studied for use as a carrier and has proven to be valuable in this role. With the aim of validating the galactose-prodrug approach, we have investigated the galactosylated prodrugs ibuprofen, ketoprofen, flurbiprofen and indomethacin, which we have named IbuGAL, OkyGAL, FluGAL and IndoGAL, respectively. Their physicochemical profiles in terms of lipophilicity, solubility and chemical stability have been evaluated at different physiological pH values, as have human serum stability and serum protein binding. Ex vivo intestinal permeation experiments were performed to provide preliminary insights into the oral bioavailability of the galactosylated prodrugs. Finally, their anti-inflammatory, analgesic and ulcerogenic activities were investigated in vivo in mice after oral treatment. The present results, taken together with those of previous studies, undoubtedly validate the galactosylated prodrug strategy as a problem-solving technique that can overcome the disadvantages of NSAIDs.
Hematological and Extra-Hematological Autoimmune Complications after Checkpoint Inhibitors
Authors: Fattizzo Bruno , Rampi Nicolò , Barcellini Wilma
Published: May 2022

Checkpoint inhibitors (CPI) represent a novel therapeutical strategy with a high efficacy both in solid and hematological cancers. They act by reactivating the immune system against neoplastic cells but may, in turn, cause immune-related adverse events (IRAEs) involving several organs with variable frequency and severity. Up to 10% of CPI-treated patients experience hematological IRAEs, mainly cytopenias. The differential diagnosis is challenging due to underlying disease, previous treatments and the variable liability of available tests (i.e., the direct antiglobulin test, anti-platelet antibodies, etc.). Among extra-hematological IRAEs, cutaneous and endocrine ones are the most frequent (up to 30–50%), ranging from mild (pruritus, eczema and thyroid dysfunctions) to severe forms (bullous disorders, hypophysitis and diabetes), mostly requiring topic or replacement therapy. Gastroenteric and kidney toxicities occur in about 5% of patients, biopsies may support the diagnosis, and immunosuppressive treatment is required in severe cases. Finally, neurologic and cardiologic IRAEs, although rare, may be life-threatening and require prompt intervention. By reviewing the most recent literature on post-CPI IRAEs, it emerged that clinical suspicion and monitoring of laboratory markers of organ damage is pivotal to a prompt diagnosis. In severe cases, CPI should be discontinued and immunosuppressive therapy started, whilst rechallenge is anecdotal and should be carefully evaluated.
Significant Sex Differences in the Efficacy of the CSF1R Inhibitor-PLX5622 on Rat Brain Microglia Elimination
Authors: Sharon Aviv , Erez Hadas , Spira Micha E.
Published: May 2022

Microglia play pivotal roles in central nervous system development, homeostasis, responses to trauma, and neurodegenerative and neuropsychiatric disorders with significant sex-bias in their symptoms and prevalence. Survival of the microglia in adult brains depends on the expression of the colony-stimulating factor 1 receptor (CSF1R). The inhibition of CSF1R by brain-permeant PLX5622 in the chow eliminates, within 5–10 days, ~90% of the microglia in female and male mice, thereby enabling the investigation of the roles of the microglia in health and pathological mice models. Because of a prevailing “impression” that PLX5622 is ineffective in rats, it has hardly been used in studies of adult rats. Here, we report that effective microglia elimination by PLX5622-chow in rats is highly sex-dependent. Our observations provide missing information for the limited use and interpretation of PLX5622 in biomedical studies of the microglia in rat models. The sex differences that are too often overlooked must be carefully considered and clearly emphasized.
Development and Evaluation of a PSMA-Targeted Nanosystem Co-Packaging Docetaxel and Androgen Receptor siRNA for Castration-Resistant Prostate Cancer Treatment
Authors: Zhang Yingying , Duan Hongxia , Zhao Heming , Qi Lingling , Liu Yanhong , Zhang Zheao , Liu Chao , Chen Liqing , Jin Mingji , Guan Youyan , Gao Zhonggao , Huang Wei
Published: May 2022

Primary prostate cancer (PC) progresses to castration-resistant PC (CRPC) during androgen deprivation therapy (ADR) in early stages of prostate cancer. Thus, rather than blocking the androgen-related pathway further, docetaxel (DTX)-based therapy has become the most effective and standard first-line chemotherapy for CRPC. Although the therapy is successful in prolonging the survival of patients with CRPC, chemotherapy resistance develops due to the abnormal activation of the androgen receptor (AR) signaling pathway. Thus, to optimize DTX efficacy, continued maximum suppression of androgen levels and AR signaling is required. Here, we designed a prostate-specific membrane antigen (PSMA)-targeted nanosystem to carry both DTX and AR siRNA (Di-PP/AR-siRNA/DTX) for CRPC treatment. Specifically, DTX was encapsulated into the hydrophobic inner layer, and the AR siRNA was then condensed with the cationic PEI block in the hydrophilic outer layer of the PEI-PLGA polymeric micelles. The micelles were further coated with PSMA-targeted anionic polyethylene glycol-polyaspartic acid (Di-PEG-PLD). In vitro and in vivo results demonstrated that the resulting Di-PP/AR-siRNA/DTX exhibited prolonged blood circulation, selective targeting, and enhanced antitumor effects. Consequently, Di-PP/AR-siRNA/DTX holds great potential for efficient CRPC treatment by combining chemotherapy and siRNA silencing of androgen-related signaling pathways.
Nonclinical Pharmacokinetics and Pharmacodynamics Characterization of Anti-CD79b/CD3 T Cell-Dependent Bispecific Antibody Using a Surrogate Molecule: A Potential Therapeutic Agent for B Cell Malignancies
Authors: Yadav Rajbharan , Sukumaran Siddharth , Zabka Tanja S. , Li Jinze , Oldendorp Amy , Morrow Gary , Reyes Arthur , Cheu Melissa , Li Jessica , Wallin Jeffrey J. , Tsai Siao , Sun Laura , Wang Peiyin , Ellerman Diego , Spiess Christoph , Polson Andy , Stefanich Eric G. , Kamath Amrita V. , Ovacik Meric A.
Published: May 2022

The T cell-dependent bispecific (TDB) antibody, anti-CD79b/CD3, targets CD79b and CD3 cell-surface receptors expressed on B cells and T cells, respectively. Since the anti-CD79b arm of this TDB binds only to human CD79b, a surrogate TDB that binds to cynomolgus monkey CD79b (cyCD79b) was used for preclinical characterization. To evaluate the impact of CD3 binding affinity on the TDB pharmacokinetics (PK), we utilized non-tumor-targeting bispecific anti-gD/CD3 antibodies composed of a low/high CD3 affinity arm along with a monospecific anti-gD arm as controls in monkeys and mice. An integrated PKPD model was developed to characterize PK and pharmacodynamics (PD). This study revealed the impact of CD3 binding affinity on anti-cyCD79b/CD3 PK. The surrogate anti-cyCD79b/CD3 TDB was highly effective in killing CD79b-expressing B cells and exhibited nonlinear PK in monkeys, consistent with target-mediated clearance. A dose-dependent decrease in B cell counts in peripheral blood was observed, as expected. Modeling indicated that anti-cyCD79b/CD3 TDB’s rapid and target-mediated clearance may be attributed to faster internalization of CD79b, in addition to enhanced CD3 binding. The model yielded unbiased and precise curve fits. These findings highlight the complex interaction between TDBs and their targets and may be applicable to the development of other biotherapeutics.
A High-Energy and High-Intensity Inverse Compton Scattering Source Based on CompactLight Technology
Authors: Mușat Vlad , Latina Andrea , D’Auria Gerardo
Published: May 2022

An inverse Compton scattering source based on the CompactLight injector and capable of producing MeV gamma-rays with a brilliance several orders of magnitude larger than existing sources is proposed. The CompactLight injector can operate at a bunch repetition rate of 1 kHz, with trains of 50 bunches and a bunch spacing of 5 ns, giving a maximum total flux of 8.62 × 1011 photons/s. For a normalised emittance of 0.3 mm mrad, an average brilliance of 1.85 × 1014 photons/(s mm2 mrad2 0.1%BW) could be obtained. A 1 kW colliding laser was considered, corresponding to a laser pulse energy of 50 mJ. Given the electron beam energy up to 300 MeV provided by the CompactLight photoinjector, a maximum photon energy of 2 MeV is obtained. Simulations of inverse Compton scattering were performed using the RF-Track particle tracking software. Parametric scans were used to derive the electron and laser spot sizes maximising the total flux. The accelerator optic components were also determined from the final focus design, which was optimised for a micrometer-level electron beam size at the interaction point. Given a maximum total flux in the order of 1012 photons/s and a maximum output photon energy in the MeV range, the proposed source could be used for various applications, including X-ray imaging.