bluuebunny/crossref_metadata_2025 huggingface dataset:
Traffic Light and Arrow Signal Recognition Based on a Unified Network
Authors: Yeh Tien-Wen , Lin Huei-Yung , Chang Chin-Chen
Published: August 2021

We present a traffic light detection and recognition approach for traffic lights that utilizes convolutional neural networks. We also introduce a technique for identifying arrow signal lights in multiple urban traffic environments. For detection, we use map data and two different focal length cameras for traffic light detection at various distances. For recognition, we propose a new algorithm that combines object detection and classification to recognize the light state classes of traffic lights. Furthermore, we use a unified network by sharing features to decrease computation time. The results reveal that the proposed approach enables high-performance traffic light detection and recognition.
Design of Inverted Nano-Cone Arrayed SERS Substrate for Rapid Detection of Pathogens
Authors: Jia Zixun , Asiri Sarah , Elsharif Asma , Alamoudi Widyan , Al-Suhaimi Ebtesam , Kim Sang-Gook
Published: August 2021

Rapid detection of bacteria is a very critical and important part of infectious disease treatment. Sepsis kills more than 25 percent of its victims, resulting in as many as half of all deaths in hospitals before identifying the pathogen for patients to get the right treatment. Raman spectroscopy is a promising candidate in pathogen diagnosis given its fast and label-free nature, only if the concentration of the pathogen is high enough to provide reasonable sensitivity. This work reports a new design of surface-enhanced Raman spectroscopy (SERS) substrate which will provide high enough sensitivity and fast and close contact of the target structure to the optical hot spots for immunomagnetic capturing-based bacteria-concentrating technique. The substrate uses inverted nanocone structure arrays made of transparent PDMS (Polydimethylsiloxane) to funnel the light from the bottom to the top of the cones where plasmonic gold nanorods are located. A high reflective and low loss layer is deposited on the outer surface of the cone. Given the geometry of cones, photons are multi-reflected by the outer layer and thus the number density of photons at hotspots increases by an order of magnitude, which could be high enough to detect immunomagnetically densified bacteria.
Probiotics in Oral Health and Disease: A Systematic Review
Authors: Saïz Perrine , Taveira Nuno , Alves Ricardo
Published: August 2021

Purpose: Probiotics may exclude or antagonize oral pathogens and be useful to prevent oral dysbiosis and treat oral diseases. The objective of this review was to assess the benefits of probiotics in oral health and disease, and in dental practice; Methods: Primary articles published between January 2012 and 30 December 2020 with full text available were searched in PubMed, ClinicalTrials.gov, ScienceDirect, Google Scholar, B-on, and SciELO; Results: The electronic search identified 361 references of which 91 (25.2%) met all the inclusion criteria. In total, data from 5374 participants with gingivitis, periodontitis, peri-implantitis, caries, orthodontic conditions, halitosis, or oral conditions associated with chemo-radiotherapy were included. Despite major inconsistencies between clinical trials, probiotics have been found to contribute to reduce S. mutans counts (L. paracasei SD1), reduce probing depth in chronic periodontitis (B. animalis subsp. lactis DN-173010 with L. reuteri), reduce levels of volatile sulfur compounds and halitosis (L. salivarius WB21), treat oral mucositis and improve the quality of life of patients undergoing cancer chemo-radiotherapy (L. brevis CD2). Combinations of probiotic bacteria tend to lead to higher clinical efficacy than any individual probiotic agent; Conclusion: Oral probiotics influence favorably the oral microbiota and provide benefits to the oral ecosystem in periodontal diseases, cariology, halitosis, orthodontics and management of oral mucositis resulting from cancer treatment. However, the use of probiotics in dental practice or in self-management preventive strategies requires additional well controlled clinical trials to determine the most effective probiotic combinations, the most appropriate probiotic vehicle, and the frequency of administration.
Multi-Objective Parameter Optimization of Flexible Support System of Optical Mirror
Authors: Jin Zujin , Cheng Gang , Pang Yusong , Xu Shichang , Yuan Dunpeng
Published: August 2021

During the processing of an optical mirror, the performance parameters of the bottom support system would affect the surface forming accuracy of the mirror. The traditional bottom support system has a large unadjustable support stiffness, which increases the difficulty of unloading the impact force generated by the grinding disc. In response to this scenario, a flexible support system (FSS) consisting of 36 support cylinders with beryllium bronze reeds (BBRs) and rolling diaphragms (RDs) as key components is designed. It is necessary to analyze the key components of the support cylinder to reduce its axial movement resistance, ensure a consistent force output of each support point. First, the internal resistance model of a flexible support cylinder is established, and the main factors of internal resistance are then analyzed. Thereafter, the multi-objective structural parameters of the BBR and RD are simulated in ANSYS using the control variable method. The optimal structural parameters of BBR and RD are determined by simulation. Finally, experiments are performed on the RD ultimate pressure, internal resistance of the support cylinder, and consistency of the force output of the FSS. The experimental results show that the support cylinder with the optimized design has good force output consistency, which provides a theoretical basis for the application of FSS in optical mirror processing.
Development of Knowledge Base Using Human Experience Semantic Network for Instructive Texts
Authors: Gabbar Hossam A. , Jabar Sk Sami Al , Hassan Hassan A. , Ren Jing
Published: August 2021

An organized knowledge structure or knowledge base plays a vital role in retaining knowledge where data are processed and organized so that machines can understand. Instructive text (iText) consists of a set of instructions to accomplish a task or operation. Hence, iText includes a group of texts having a title or name of the task or operation and step-by-step instructions on how to accomplish the task. In the case of iText, storing only entities and their relationships with other entities does not always provide a solution for capturing knowledge from iTexts as it consists of parameters and attributes of different entities and their action based on different operations or procedures and the values differ for every individual operation or procedure for the same entity. There is a research gap in iTexts that created limitations to learn about different operations, capture human experience and dynamically update knowledge for every individual operation or instruction. This research presents a knowledge base for capturing and retaining knowledge from iTexts existing in operational documents. From each iTexts, small pieces of knowledge are extracted and represented as nodes linked to one another in the form of a knowledge network called the human experience semantic network (HESN). HESN is the crucial component of our proposed knowledge base. The knowledge base also consists of domain knowledge having different classified terms and key phrases of the specific domain.
How to Quantify the Dynamics of Single (Straight or Sinuous) and Multiple (Anabranching) Channels from Imagery for River Restoration
Authors: Arnaud-Fassetta Gilles , Melun Gabriel , Passy Paul , Brousse Guillaume , Theureaux Olivier
Published: August 2021

Since the 2000s, European rivers have undergone restoration works to give them back a little more ‘freedom space’ and consolidate the hydro-sedimentary continuum and biological continuity as required by the Water Framework Directive (WFD). In high-energy rivers, suppression of lateral constraints (embankment removal) leads to geomorphological readjustments in the modification of both the active-channel length and active-channel width. The article provides a new methodological development to overcome the shortcomings of traditional methods (based on diachronic cross-section analysis) unable to simultaneously take into account these geometric adjustments after active-channel restoration. It allows us to follow and precisely quantify the geomorphological changes of the active channel faced to the stakes (i.e., structures or urbanized, recreation or agricultural areas) in the floodplain. The methodology proposes three new indicators (distance from active channel to stakes or floodplain margins as indicator 1; distance from stakes to active channel as indicator 2; diachronic distance as indicator 3) and a metric analysis grid in the 2D Euclidean space. It is applied to the Clamoux River (order 4, Strahler; bankfull, specific stream power: 280 W/m2) in the Aude watershed (Mediterranean France). The paper shows the full potential of this methodological protocol to be able to meet managers’ expectations as closely as possible within the framework of the multi-annual active-channel monitoring.
Freundlich Isotherm: An Adsorption Model Complete Framework
Authors: Vigdorowitsch Michael , Pchelintsev Alexander , Tsygankova Liudmila , Tanygina Elena
Published: August 2021

The absolute majority of modern studies dealing with the interpretation of experimental data on the basis of the Freundlich isotherm ignore the fact that the data obtained for regions of low and moderate adsorbate concentration/pressure can be analytically continued within the Freundlich adsorption model to the adsorptive saturation area with coverages tending to 100%. Needless to say, this would give valuable extended information about the corresponding adsorption process. This message proposes a framework to comprehensively analyse experimental data first recognised as complying with the Freundlich adsorption model. An algorithm-driven method is presented which enables one to translate the data obtained in the area of small and moderate the coverages of the area of adsorptive saturation regime. As examples, three sets of experimental data for adsorption of mercury (II) on N-rich porous organic polymers and of protein on carrier nano-Mg(OH)2 have been processed and presented according to the framework developed.
Accuracy and Feasibility of a Zero-Setup Implant Guide System Made of a Light-Cured Composite Resin with Simultaneous Flapless Sinus Augmentation: A Pilot Study
Authors: Park Jin-Young , Lee Joo-Yeon , Kim Joo-Nyeon , Paik Jeong-Won , Lee Jung-Seok , Jung Ui-Won , Choi Seong-Ho , Cha Jae-Kook
Published: August 2021

The aim of this study was to evaluate the accuracy and feasibility of flapless implant placement using a light-cured surgical template made of composite resin comprising dimethacrylate and diurethane, performed simultaneously with crestal sinus augmentation. This pilot study was a prospective, single-armed, controlled clinical trial. Four patients having an edentulous region in the posterior maxilla with 4 to 8 mm of residual ridge height were enrolled. Flapless fully-guided implant placement was performed using a zero-setup surgical template with simultaneous crestal sinus graft. Horizontal, vertical, and angular deviations of the placed implants from the planned positions were measured. Clinical observations were made, and implant stability was measured up to 3 months postoperatively. All four implants were placed and maintained successfully without complication. The mean deviations of the four implants were 1.27 and 1.85 mm horizontally at platform and apex, respectively, 0.84 mm vertically at apex, and 4.76° in angle. Satisfactory implant stability was obtained in all implants at placement and 3 months. Fully-guided implant placement and crestal sinus graft using a zero-setup surgical template can be a safe and feasible method with acceptable accuracy. A randomized controlled trial should be performed in the future to validate its clinical performance in terms of surgical time, accuracy, and patient-reported outcomes.
Plane Machining by Inner-Jet Electrochemical Milling of TiB2/7050 Aluminum Matrix Composite
Authors: He Binsen , Li Hansong , Ma Xin , Li Jie , Fan Shukai
Published: August 2021

Electrochemical milling (ECM) is an ideal technique for machining thin-walled structural parts of aluminum matrix composites. Adopting a reasonable tool cathode structure, feed rate, and processing method can improve the machining efficiency. In this study, a tool cathode with a reasonable structure was selected through flow field simulation. Then, the material removal rate (MRR) and surface roughness were studied using various ECM parameters. Finally, the transverse movement and processing method in which the starting position was rotated 90° were studied, and a plane of 59 × 59 mm was machined. The experimental results show that using an appropriate tool cathode can create a more uniform flow field. The MRR was 168.6 mm3/min and the surface roughness (Ra) was 3.329 µm at a feed rate of 30 mm/min. For machining larger plane structures, a transverse movement of 7 mm is verified to be the most suitable because of the best smoothness in the middle of the two processes. By using the same machining method and rotating the starting position 90°, the flatness of the processing plane decreased from 0.296 mm to 0.251 mm, a reduction of 15.2% compared to that obtained in the first processing.
Theoretical Studies on the Reaction Mechanism and Kinetics of Ethylbenzene-OH Adduct with O2 and NO2
Authors: Lu Tingting , Huang Mingqiang , Lin Xin , Zhang Wei , Zhao Weixiong , Hu Changjin , Gu Xuejun , Zhang Weijun
Published: August 2021

The OH-initiated reaction of ethylbenzene results in major OH addition, and the formed ethylbenzene-OH adducts subsequently react with O2 and NO2, which determine the components of the oxidation products. In this study, nine possible reaction paths of the most stable ethylbenzene-OH adduct, EB-Ortho (2-ethyl-hydroxycyclohexadienyl radical intermediate), with O2 and NO2 were studied using density functional theory and conventional transition state theory. The calculated results showed that ethyl-phenol formed via hydrogen abstraction was the major product of the EB-Ortho reaction with O2 under atmospheric conditions. Peroxy radicals generated from O2 added to EB-Ortho could subsequently react with NO and O2 to produce 5-ethyl-6-oxo-2,4-hexadienal, furan, and ethyl-glyoxal, respectively. However, nitro-ethylbenzene formed from NO2 addition to EB-Ortho was the predominant product of the EB-Ortho reaction with NO2 at room temperature. The total calculated rate constant of the EB-Ortho reaction with O2 and NO2 was 9.57 × 10−16 and 1.78 × 10−11 cm3 molecule−1 s−1, respectively, approximately equivalent to the experimental rate constants of toluene-OH adduct reactions with O2 and NO2. This study might provide a useful theoretical basis for interpreting the oxygen-containing and nitrogen-containing organics in anthropogenic secondary organic aerosol particles.
Targeted RNA-Seq Reveals the M. tuberculosis Transcriptome from an In Vivo Infection Model
Authors: Cornejo-Granados Fernanda , López-Leal Gamaliel , Mata-Espinosa Dulce A. , Barrios-Payán Jorge , Marquina-Castillo Brenda , Equihua-Medina Edgar , Zatarain-Barrón Zyanya L. , Molina-Romero Camilo , Hernández-Pando Rogelio , Ochoa-Leyva Adrian
Published: August 2021

The study of host-pathogen interactions using in vivo models with intracellular pathogens like Mycobacterium tuberculosis (Mtb) entails technical limitations, such as: (i) Selecting an efficient differential lysis system to enrich the pathogen cells; (ii) obtaining sufficient high-quality RNA; and (iii) achieving an efficient rRNA depletion. Thus, some authors had used flow cytometers to separate infected cells or significantly increase the sequencing depth of host–pathogen RNA libraries to observe the pathogens’ gene expression. However, these options carry additional expenses in specialized equipment typically not available for all laboratories. Here, we propose an experimental protocol involving differential cell lysis and a probe-based ribosomal depletion to determine the gene expression of Mtb and its host during in vivo infection. This method increased the number of observed pathogen-expressed genes from 13 using the traditional RNA-seq approach to 702. After eliminating rRNA reads, we observed that 61.59% of Mtb sequences represented 702 genes, while 38.41% represented intergenic regions. Some of the most expressed genes codified for IS1081 (Rv2512c) transposase and eight PE-PGRS members, such as PGRS49 and PGRS50. As expected, a critical percent of the expressed genes codified for secreted proteins essential for infection, such as PE68, lppN, and LpqH. Moreover, three Mtb ncRNAs were highly expressed (small RNA MTS2823, transfer-messenger RNA RF00023, and ribozyme RF00010). Many of the host-expressed genes were related to the inflammation process and the expression of surfactant proteins such as the Sftpa and Sftpc, known to bind Mtb to alveolar macrophages and mi638, a microRNA with no previous associations with pulmonary diseases. The main objective of this study is to present the method, and a general catalog of the Mtb expressed genes at one point of the in vivo infection. We believe our method represents a different approach to the existing ones to study host–pathogen interactions in tuberculosis and other similar intracellular infections, without the necessity of specialized equipment.
Gut Microbiota as a Potential Player in Mn-Induced Neurotoxicity
Authors: Tinkov Alexey A. , Martins Airton C. , Avila Daiana Silva , Gritsenko Victor A. , Skalny Anatoly V. , Santamaria Abel , Lee Eunsook , Bowman Aaron B. , Aschner Michael
Published: August 2021

Manganese (Mn) is an essential metal, which at high exposures causes neurotoxic effects and neurodegeneration. The neurotoxic effects of Mn are mediated by neuroinflammation, oxidative and endoplasmic reticulum stress, mitochondrial dysfunction, and other mechanisms. Recent findings have demonstrated the potential impact of Mn overexposure on gut microbiota dysbiosis, which is known to contribute to neurodegeneration via secretion of neuroactive and proinflammatory metabolites. Therefore, in this review, we discuss the existing data on the impact of Mn exposure on gut microbiota biodiversity, bacterial metabolite production, and gut wall permeability regulating systemic levels. Recent data have demonstrated that Mn exposure may affect gut microbiota biodiversity by altering the abundance of Shiegella, Ruminococcus, Dorea, Fusicatenibacter, Roseburia, Parabacteroides, Bacteroidetes, Firmicutes, Ruminococcaceae, Streptococcaceae, and other bacterial phyla. A Mn-induced increase in Bacteroidetes abundance and a reduced Firmicutes/Bacteroidetes ratio may increase lipopolysaccharide levels. Moreover, in addition to increased systemic lipopolysaccharide (LPS) levels, Mn is capable of potentiating LPS neurotoxicity. Due to the high metabolic activity of intestinal microflora, Mn-induced perturbations in gut microbiota result in a significant alteration in the gut metabolome that has the potential to at least partially mediate the biological effects of Mn overexposure. At the same time, a recent study demonstrated that healthy microbiome transplantation alleviates Mn-induced neurotoxicity, which is indicative of the significant role of gut microflora in the cascade of Mn-mediated neurotoxicity. High doses of Mn may cause enterocyte toxicity and affect gut wall integrity through disruption of tight junctions. The resulting increase in gut wall permeability further promotes increased translocation of LPS and neuroactive bacterial metabolites to the systemic blood flow, ultimately gaining access to the brain and leading to neuroinflammation and neurotransmitter imbalance. Therefore, the existing data lead us to hypothesize that gut microbiota should be considered as a potential target of Mn toxicity, although more detailed studies are required to characterize the interplay between Mn exposure and the gut, as well as its role in the pathogenesis of neurodegeneration and other diseases.
Salusin-β in Intermediate Dorsal Motor Nucleus of the Vagus Regulates Sympathetic-Parasympathetic Balance and Blood Pressure
Authors: Wu Lu-Lu , Bo Jin-Hua , Zheng Fen , Zhang Feng , Chen Qi , Li Yue-Hua , Kang Yu-Ming , Zhu Guo-Qing
Published: August 2021

The dorsal motor nucleus of the vagus (DMV) is known to control vagal activity. It is unknown whether the DMV regulates sympathetic activity and whether salusin-β in the DMV contributes to autonomic nervous activity. We investigated the roles of salusin-β in DMV in regulating sympathetic-parasympathetic balance and its underline mechanisms. Microinjections were carried out in the DMV and hypothalamic paraventricular nucleus (PVN) in male adult anesthetized rats. Renal sympathetic nerve activity (RSNA), blood pressure and heart rate were recorded. Immunohistochemistry for salusin-β and reactive oxidative species (ROS) production in the DMV were examined. Salusin-β was expressed in the intermediate DMV (iDMV). Salusin-β in the iDMV not only inhibited RSNA but also enhanced vagal activity and thereby reduced blood pressure and heart rate. The roles of salusin-β in causing vagal activation were mediated by NAD(P)H oxidase-dependent superoxide anion production in the iDMV. The roles of salusin-β in inhibiting RSNA were mediated by not only the NAD(P)H oxidase-originated superoxide anion production in the iDMV but also the γ-aminobutyric acid (GABA)A receptor activation in PVN. Moreover, endogenous salusin-β and ROS production in the iDMV play a tonic role in inhibiting RSNA. These results indicate that salusin-β in the iDMV inhibits sympathetic activity and enhances vagal activity, and thereby reduces blood pressure and heart rate, which are mediated by NAD(P)H oxidase-dependent ROS production in the iDMV. Moreover, GABAA receptor in the PVN mediates the effect of salusin-β on sympathetic inhibition. Endogenous salusin-β and ROS production in the iDMV play a tonic role in inhibiting sympathetic activity.
The Effect of Baseline on Toddler Event-Related Mu-Rhythm Modulation
Authors: Piazza Caterina , Visintin Eleonora , Reni Gianluigi , Montirosso Rosario
Published: August 2021

Event-related mu-rhythm activity has become a common tool for the investigation of different socio-cognitive processes in pediatric populations. The estimation of the mu-rhythm desynchronization/synchronization (mu-ERD/ERS) in a specific task is usually computed in relation to a baseline condition. In the present study, we investigated the effect that different types of baseline might have on toddler mu-ERD/ERS related to an action observation (AO) and action execution (AE) task. Specifically, we compared mu-ERD/ERS values computed using as a baseline: (1) the observation of a static image (BL1) and (2) a period of stillness (BL2). Our results showed that the majority of the subjects suppressed the mu-rhythm in response to the task and presented a greater mu-ERD for one of the two baselines. In some cases, one of the two baselines was not even able to produce a significant mu-ERD, and the preferred baseline varied among subjects even if most of them were more sensitive to the BL1, thus suggesting that this could be a good baseline to elicit mu-rhythm modulations in toddlers. These results recommended some considerations for the design and analysis of mu-rhythm studies involving pediatric subjects: in particular, the importance of verifying the mu-rhythm activity during baseline, the relevance of single-subject analysis, the possibility of including more than one baseline condition, and caution in the choice of the baseline and in the interpretation of the results of studies investigating mu-rhythm activity in pediatric populations.
Anticipatory Motor Planning and Control of Grasp in Children with Unilateral Spastic Cerebral Palsy
Authors: Gutterman Jennifer , Lee-Miller Trevor , Friel Kathleen M. , Dimitropoulou Katherine , Gordon Andrew M.
Published: August 2021

Children with unilateral spastic cerebral palsy (USCP) have impairments in motor planning, impacting their ability to grasp objects. We examined the planning of digit position and force and the flexibility of the motor system in covarying these during object manipulation. Eleven children with a left hemisphere lesion (LHL), nine children with a right hemisphere lesion (RHL) and nine typically developing children (controls) participated in the study. Participants were instructed to use a precision grip with their dominant/less affected hand to lift and keep an object level, with either a left, centered or right center of mass (COM) location. Digit positions, forces, compensatory torque and object roll where measured. Although children with USCP generated a compensatory torque and modulated digit placement by lift-off, their index finger was either collinear or higher than the thumb, regardless of COM location, leading to larger rolls after lift-off especially for the RHL group. The findings suggest that while the kinetics of grasp control is intact, the kinematics of grasp control is impaired. This study adds to the understanding of the underlying mechanisms of anticipatory planning and control of grasp in children with USCP and may provide insights on how to improve hand function in children with USCP.
The Clinical Utility of Optical Genome Mapping for the Assessment of Genomic Aberrations in Acute Lymphoblastic Leukemia
Authors: Lühmann Jonathan Lukas , Stelter Marie , Wolter Marie , Kater Josephine , Lentes Jana , Bergmann Anke Katharina , Schieck Maximilian , Göhring Gudrun , Möricke Anja , Cario Gunnar , Žaliová Markéta , Schrappe Martin , Schlegelberger Brigitte , Stanulla Martin , Steinemann Doris
Published: August 2021

Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to identify all aberrations relevant for risk stratification. We investigated the feasibility of optical genome mapping (OGM), a DNA-based method, to detect these aberrations in an all-in-one approach. As proof of principle, twelve pediatric ALL samples were analyzed by OGM, and results were validated by comparing OGM data to results obtained from routine diagnostics. All genomic aberrations including translocations (e.g., dic(9;12)), aneuploidies (e.g., high hyperdiploidy) and copy number variations (e.g., IKZF1, PAX5) known from other techniques were also detected by OGM. Moreover, OGM was superior to well-established techniques for resolution of the more complex structure of a translocation t(12;21) and had a higher sensitivity for detection of copy number alterations. Importantly, a new and unknown gene fusion of JAK2 and NPAT due to a translocation t(9;11) was detected. We demonstrate the feasibility of OGM to detect well-established as well as new putative prognostic markers in an all-in-one approach in ALL. We hope that these limited results will be confirmed with testing of more samples in the future.
Cyclin Dependent Kinase-1 (CDK-1) Inhibition as a Novel Therapeutic Strategy against Pancreatic Ductal Adenocarcinoma (PDAC)
Authors: Wijnen Rosa , Pecoraro Camilla , Carbone Daniela , Fiuji Hamid , Avan Amir , Peters Godefridus J. , Giovannetti Elisa , Diana Patrizia
Published: August 2021

The role of CDK1 in PDAC onset and development is two-fold. Firstly, since CDK1 activity regulates the G2/M cell cycle checkpoint, overexpression of CDK1 can lead to progression into mitosis even in cells with DNA damage, a potentially tumorigenic process. Secondly, CDK1 overexpression leads to the stimulation of a range of proteins that induce stem cell properties, which can contribute to the development of cancer stem cells (CSCs). CSCs promote tumor-initiation and metastasis and play a crucial role in the development of PDAC. Targeting CDK1 showed promising results for PDAC treatment in different preclinical models, where CDK1 inhibition induced cell cycle arrest in the G2/M phase and led to induction of apoptosis. Next to this, PDAC CSCs are uniquely sensitive to CDK1 inhibition. In addition, targeting of CDK1 has shown potential for combination therapy with both ionizing radiation treatment and conventional chemotherapy, through sensitizing tumor cells and reducing resistance to these treatments. To conclude, CDK1 inhibition induces G2/M cell cycle arrest, stimulates apoptosis, and specifically targets CSCs, which makes it a promising treatment for PDAC. Screening of patients for CDK1 overexpression and further research into combination treatments is essential for optimizing this novel targeted therapy.
Capecitabine in Combination with Endocrine Therapy as Maintenance Therapy after Bevacizumab Plus Paclitaxel Induction Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: KBCSG-TR1214
Authors: Masuda Norikazu , Yoshinami Tetsuhiro , Ikeda Masahiko , Mizutani Makiko , Yamaguchi Miki , Komoike Yoshifumi , Takashima Tsutomu , Yoshidome Katsuhide , Tsurutani Junji , Iwamoto Mitsuhiko , Fujisawa Fumie , Yasojima Hiroyuki , Yamamura Jun , Morishima Hirotaka , Aki Fuminori , Yamada Tomomi , Morita Satoshi , Nakayama Takahiro
Published: August 2021

Optimal treatment strategies for hormone receptor (HR)-positive, HER2-negative advanced and/or metastatic breast cancer (AMBC) remain uncertain. We investigated the clinical usefulness of adding capecitabine to maintenance endocrine therapy after induction chemotherapy and the efficacy of reinduction chemotherapy. Patients who had received bevacizumab–paclitaxel induction therapy and did not have progressive disease (PD) were randomized to maintenance therapy with endocrine therapy alone (group E) or endocrine plus capecitabine (1657 mg/m2/day on days 1–21, q4w) (group EC). In case of PD after maintenance therapy, patients received bevacizumab–paclitaxel reinduction therapy. Ninety patients were randomized. The median progression-free survival (PFS) under maintenance therapy (primary endpoint) was significantly longer in group EC (11.1 {95% CI, 8.0–11.8} months) than in group E (4.3 {3.6–6.0} months) (hazard ratio, 0.53; p < 0.01). At 24 months from the induction therapy start, the overall survival (OS) was significantly longer in group EC than in group E (hazard ratio, 0.41; p = 0.046). No difference was found in the time to failure of strategy (13.9 and 16.6 months in groups E and EC, respectively). Increased capecitabine-associated toxicities in group EC were tolerable. Addition of capecitabine to maintenance endocrine therapy may be a beneficial option after induction chemotherapy for HR-positive, HER2-negative AMBC patients.
NK Cells in Myeloproliferative Neoplasms (MPN)
Authors: Naismith Erin , Steichen Janine , Sopper Sieghart , Wolf Dominik
Published: August 2021

Myeloproliferative neoplasms (MPNs) comprise a heterogenous group of hematologic neoplasms which are divided into Philadelphia positive (Ph+), and Philadelphia negative (Ph−) or classical MPNs. A variety of immunological factors including inflammatory, as well as immunomodulatory processes, closely interact with the disease phenotypes in MPNs. NK cells are important innate immune effectors and substantially contribute to tumor control. Changes to the absolute and proportionate numbers of NK cell, as well as phenotypical and functional alterations are seen in MPNs. In addition to the disease itself, a variety of therapeutic options in MPNs may modify NK cell characteristics. Reports of suppressive effects of MPN treatment strategies on NK cell activity have led to intensive investigations into the respective compounds, to elucidate the possible negative effects of MPN therapy on control of the leukemic clones. We hereby review the available literature on NK cells in Ph+ and Ph− MPNs and summarize today’s knowledge on disease-related alterations in this cell compartment with particular focus on known therapy-associated changes. Furthermore, we critically evaluate conflicting data with possible implications for future projects. We also aim to highlight the relevance of full NK cell functionality for disease control in MPNs and the importance of considering specific changes related to therapy in order to avoid suppressive effects on immune surveillance.
Effective Epoxidation of Fatty Acid Methyl Esters with Hydrogen Peroxide by the Catalytic System H3PW12O40/Quaternary Phosphonium Salts
Authors: Musik Marlena , Janus Ewa , Pełech Robert , Sałaciński Łukasz
Published: August 2021

Six quaternary phosphonium salts (QPSs) in combination with phosphotungstic heteropolyacid, H3PW12O40, were tested in the epoxidation of rapeseed oil fatty acid methyl esters with a hydrogen peroxide aqueous solution. The QPSs consisted of trihexyl(tetradecyl)phosphonium [P6], tributyl-tetradecylphosphonium [P4] or tetraoctylphosphonium [P8] cation and different anions—chloride (Cl−), bromide (Br−), tetrafluoroborate (BF4−), bis(trifluoromethylsulfonyl)amide (NTf2−), bis(2,4,4-trimethyl-pentyl)phosphinate (Phosf−). The influence of the kind of QPS and temperature on the epoxy number, iodine number, glycol content has been determined. The epoxidation was confirmed using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) and elemental analysis CHO. Two QPSs with a trihexyltetradecyphosphonium cation—[P6][Fosf] and [P6][Cl]—were selected as the most effective in the studied epoxidation process. The proposed kinetic model takes into consideration the two reactions, namely, epoxidation and epoxy ring opening involving the formation of hydroxyl groups. The rate constants and activation energies for epoxidation fatty acid methyl esters were determined.
Synthesis, Characterization and Photoelectric Properties of Fe2O3 Incorporated TiO2 Photocatalyst Nanocomposites
Authors: Ali Atif Mossad , Sayed Mahmoud Ahmed , Algarni Hamed , Ganesh Vanga , Aslam Muhd , Ismail Adel Ali , El-Bery Haitham Mohamed
Published: August 2021

In the present work we report the sol-gel synthesis of pure TiO2 and (TiO2)1−x(Fe2O3)x nanocomposites with different Fe2O3 contents (x = 0, 0.1, 0.5, and 1.0 for pure TiO2, Fe2O3 incorporated 0.1, 0.5, and pure Fe2O3 which are denoted as PT, 0.1F, 0.5F, and PF, respectively). The structural, morphological, optical, and surface texture of the prepared nanocomposites were characterized using various techniques. The structural studies confirm the strong influence of Fe2O3 contents on the crystallite sizes and dislocation values. The size of the crystallites was increased by the increase in Fe2O3 contents. The bandgap values elucidated from DRS analysis were decreased from 3.15 eV to 1.91 eV with increasing Fe2O3 contents. The N2-Physorption analysis has confirmed the mesoporous nature of the samples with a comparable specific surface area of 35 m2/g. The photoelectrochemical measurements (CV, CA and EIS) were performed to assess the photoelectric properties of the prepared materials. It was found that the PT samples have the highest catalytic activity and photocurrent response compared to other composites. The reduction in current density was as follows: 2.8, 1.65, 1.5 and 0.9 mA/cm2, while the photocurrent response was ca. 800, 450, 45, 35 µA/cm2 for PT, 0.1F, 0.5F and PF samples, respectively. The EIS results showed that the (TiO2)1−x(Fe2O3)x nanocomposites exhibit lower charge transfer resistance than pure titania and hematite samples.
Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases
Authors: Gonzalez Acera Miguel , Bubeck Marvin , Mascia Fabrizio , Diemand Leonard , Sturm Gregor , Kühl Anja A. , Atreya Raja , Lie Dieter Chichung , Neurath Markus F. , Schumann Michael , Klose Christoph S.N. , Trajanoski Zlatko , Becker Christoph , Patankar Jay V.
Published: August 2021

Inflammatory bowel diseases (IBD) are characterized by chronic dysregulation of immune homeostasis, epithelial demise, immune cell activation, and microbial translocation. Each of these processes leads to proinflammatory changes via the release of cytokines, damage-associated molecular patterns (DAMPs), and pathogen-associated molecular patterns (PAMPs), respectively. The impact of these noxious agents on the survival and function of the enteric nervous system (ENS) is poorly understood. Here, we show that in contrast to an expected decrease, experimental as well as clinical colitis causes an increase in the transcript levels of enteric neuronal and glial genes. Immunostaining revealed an elevated neuronal innervation of the inflamed regions of the gut mucosa. The increase was seen in models with overt damage to epithelial cells and models of T cell-induced colitis. Transcriptomic data from treatment naïve pediatric IBD patients also confirmed the increase in the neuroglial genes and were replicated on an independent adult IBD dataset. This induction in the neuroglial genes was transient as levels returned to normal upon the induction of remission in both mouse models as well as colitis patients. Our data highlight the dynamic and robust nature of the enteric nervous system in colitis and open novel questions on its regulation.
Using Technology to Assess Bidirectionality between Daily Pain and Physical Activity: The Role of Marginalization during Emerging Adulthood
Authors: Bedree Helen , Miller Steven A. , Buscemi Joanna , Greenley Rachel Neff , Tran Susan T.
Published: August 2021

Emerging adulthood is often overlooked as a developmental time period critical to shaping future health outcomes. Recurrent pain is a commonly experienced health concern within this age group, particularly headaches and low back pain, and early experiences of recurrent pain are related to subsequent chronic pain and disability. Furthermore, adults from marginalized populations report more frequent and severe recurrent pain. Many studies have demonstrated the therapeutic effect of physical activity on pain relief; however, others have demonstrated that physical activity can also exacerbate pain symptoms. Therefore, the current study aimed to (1) assess a bidirectional relationship between reported pain and engagement in physical activity among an emerging adult sample (N = 265) and (2) determine whether sociodemographic factors moderate this relationship. Using longitudinal daily reported pain and ActiGraph monitor data collected over two weeks, a novel dynamic structural equation modeling approach was employed. Results indicated no significant cross-lagged relationships between pain and physical activity, and no significant moderation effects. These findings suggest that a bidirectional relationship does not exist among a diverse college sample of emerging adults even after considering sociodemographic moderators. Excellent retention and few missing data suggest that using accelerometers and daily diaries are feasible methods to collect data in this population. Sample considerations and future analytical approaches are discussed.
“Fitness and Fatness” in Children and Adolescents: An Italian Cross-Sectional Study
Authors: Vandoni Matteo , Calcaterra Valeria , Carnevale Pellino Vittoria , De Silvestri Annalisa , Marin Luca , Zuccotti Gian Vincenzo , Tranfaglia Valeria , Giuriato Matteo , Codella Roberto , Lovecchio Nicola
Published: August 2021

Children with obesity tend to have lower level of physical activity compared to non-obese peers. In fact, sedentary behaviors are prevalent in obese children causing difficulties to perform motor tasks and engaging in sport activities. This, in turn, has direct repercussions on adiposity and related comorbidities. The aim of the study was to investigate several components of fitness and their relationship with the degree of fatness in children. We considered 485 Italian schoolchildren (9.5 ± 1.12 years). BMI and prediction modelling outputs of fat mass were employed as markers of body fatness. Physical fitness (PF) was assessed by the 9-item test battery (explosive power, leg muscle power, arm muscle power, upper body power, coordination, agility, speed and endurance). Differences between groups in the PF tests (p < 0.05) were noted. A similar pattern was reflected in both genders. The relationship between anthropometrics’ characteristics and PF tests showed that weight and fat mass had a high level of correlation with different PF tests. Our findings highlight the importance of investigating the degree of fatness in relation with different components of fitness, in children and adolescents. This combination of proxies may cover an unexpectedly helpful screening of the youth population, for both health and performance.
Evaluating Telehealth Implementation in the Context of Pediatric Chronic Pain Treatment during COVID-19
Authors: Richardson Patricia A. , Parker Delana M. , Chavez Krystal , Birnie Kathryn A. , Krane Elliot J. , Simons Laura E. , Cunningham Natoshia R. , Bhandari Rashmi P.
Published: August 2021

Telehealth has emerged as a promising healthcare delivery modality due to its ability to ameliorate traditional access-level barriers to treatment. In response to the onset of the novel coronavirus (COVID-19) pandemic, multidisciplinary pain clinics either rapidly built telehealth infrastructure from the ground up or ramped up existing services. As the use of telehealth increases, it is critical to develop data collection frameworks that guide implementation. This applied review provides a theoretically-based approach to capitalize on existing data sources and collect novel data to inform virtually delivered care in the context of pediatric pain care. Reviewed multisource data are (1) healthcare administrative data; (2) electronic chart review; (3) clinical health registries; and (4) stakeholder feedback. Preliminary telehealth data from an interdisciplinary pediatric chronic pain management clinic (PPMC) serving youth ages 8–17 years are presented to illustrate how relevant implementation outcomes can be extracted from multisource data. Multiple implementation outcomes were assessed, including telehealth adoption rates, patient clinical symptoms, and mixed-method patient-report telehealth satisfaction. This manuscript provides an applied roadmap to leverage existing data sources and incorporate stakeholder feedback to guide the implementation of telehealth in pediatric chronic pain settings through and beyond COVID-19. Strengths and limitations of the modeled data collection approach are discussed within the broader context of implementation science.
Complex Differential Diagnosis between Primary Breast Cancer and Breast Metastasis from EGFR-Mutated Lung Adenocarcinoma: Case Report and Literature Review
Authors: Valenza Carmine , Porta Francesca Maria , Rappa Alessandra , Guerini-Rocco Elena , Viale Giuseppe , Barberis Massimo , de Marinis Filippo , Curigliano Giuseppe , Catania Chiara
Published: August 2021

We present a case of a woman with epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma who received gefitinib for 2 years and obtained a partial response. The patient then developed liver metastasis and a breast lesion, displaying high estrogen receptor (ER) expression and harboring the same EGFR mutation. From the radiological studies, it was not possible to make a differential diagnosis between primary breast cancer and breast metastasis from lung cancer. After the removal of the breast nodule, thanks to the clinical history, radiology, and above all, molecular and immunohistochemical investigations, a diagnosis of breast metastasis from lung adenocarcinoma was made. This case emphasizes the importance of a comprehensive clinical, pathological, and molecular analysis in the differential diagnosis between primary breast cancer and metastases from extramammary tumor to guide adequate treatment decision making.
Incorporating Topological and Age Uncertainty into Event-Based Biogeography of Sand Spiders Supports Paleo-Islands in Galapagos and Ancient Connections among Neotropical Dry Forests
Authors: Magalhaes Ivan L. F. , Santos Adalberto J. , Ramírez Martín J.
Published: August 2021

Event-based biogeographic methods, such as dispersal-extinction-cladogenesis, have become increasingly popular for attempting to reconstruct the biogeographic history of organisms. Such methods employ distributional data of sampled species and a dated phylogenetic tree to estimate ancestral distribution ranges. Because the input tree is often a single consensus tree, uncertainty in topology and age estimates are rarely accounted for, even when they may affect the outcome of biogeographic estimates. Even when such uncertainties are taken into account for estimates of ancestral ranges, they are usually ignored when researchers compare competing biogeographic hypotheses. We explore the effect of incorporating this uncertainty in a biogeographic analysis of the 21 species of sand spiders (Sicariidae: Sicarius) from Neotropical xeric biomes, based on a total-evidence phylogeny including a complete sampling of the genus. Using a custom R script, we account for uncertainty in ages and topology by estimating ancestral ranges over a sample of trees from the posterior distribution of a Bayesian analysis, and for uncertainty in biogeographic estimates by using stochastic maps. This approach allows for counting biogeographic events such as dispersal among areas, counting lineages through time per area, and testing biogeographic hypotheses, while not overestimating the confidence in a single topology. Including uncertainty in ages indicates that Sicarius dispersed to the Galapagos Islands when the archipelago was formed by paleo-islands that are now submerged; model comparison strongly favors a scenario where dispersal took place before the current islands emerged. We also investigated past connections among currently disjunct Neotropical dry forests; failing to account for topological uncertainty underestimates possible connections among the Caatinga and Andean dry forests in favor of connections among Caatinga and Caribbean + Mesoamerican dry forests. Additionally, we find that biogeographic models including a founder-event speciation parameter (“+J”) are more prone to suffer from the overconfidence effects of estimating ancestral ranges using a single topology. This effect is alleviated by incorporating topological and age uncertainty while estimating stochastic maps, increasing the similarity in the inference of biogeographic events between models with or without a founder-event speciation parameter. We argue that incorporating phylogenetic uncertainty in biogeographic hypothesis-testing is valuable and should be a commonplace approach in the presence of rogue taxa or wide confidence intervals in age estimates, and especially when using models including founder-event speciation.