bluuebunny/crossref_metadata_2025 huggingface dataset:
Picosecond Q-Switched 1064/532 nm Laser in Tattoo Removal: Our Single Center Experience
Authors: Bennardo Luigi , Cannarozzo Giovanni , Tamburi Federica , Patruno Cataldo , Provenzano Eugenio , Nisticò Steven Paul
Published: October 2021

Background: Tattoo removal is becoming increasingly popular, and Q-switched lasers represent the gold standard in the treatment of this condition. In this study, we report our experience with a new Q-switched picosecond laser device, evaluating its effectiveness and safety. Methods: A total of 34 patients asking for tattoo removal were consecutively enrolled in this open study. The clinicians decided on operating settings based on the Fitzpatrick phototype, the type of tattoo, and the tattoo location. A maximum of seven sessions, with a minimum interval of eight weeks between each session, were performed. At the six month follow-up visit following the last treatment session, patient satisfaction was assessed using a visual analogue scale and two dermatologists evaluated the aesthetic outcome based on pictures taken before and after treatment. Results: A total of 34 patients were included and analyzed: 17 females (50%) and 17 males (50%). The mean patient age was 43.6 ± 11 years. Participants’ Fitzpatrick skin type ranged from II to IV. The mean number of treatment sessions performed was 3.3 ± 2.0 per patient. Over 40% of patients showed complete removal of the tattoo, with most of the patients indicating satisfaction with the treatment. Conclusions: The Q-switched 1064/532 nm laser may be considered the gold standard treatment for tattoo removal. Picosecond pulses seem to guarantee fewer sessions and excellent results when compared to other laser systems in tattoo removal.
Survival of Korean Patients with Malignant Pleural Mesothelioma Compensated for the Asbestos Injury Relief
Authors: Kang Min-Sung , Lee Sung-Soo , Kwon Soon-Chan , Huh Da-An , Lee Yong-Jin
Published: October 2021

Background: The purpose of this study was to identify the epidemiologic characteristics and prognostic factors for malignant pleural mesothelioma in Korea, which are currently insufficient. The data were derived from malignant mesothelioma patients who registered under the Asbestos Injury Relief Act; Methods: A total of 728 patients received compensation from the Asbestos Injury Relief Act due to malignant mesothelioma between 2011 and 2015. Of these, 313 patients (43.0%) with malignant pleural mesothelioma were included in the study. The study variables were sex (male, female), age at diagnosis (<59, 60–69, ≥70), smoking history (yes, no), surgery (yes, no), chemotherapy (yes, no), occupational exposure to asbestos (yes, no), and histological subtype (epithelioid, nonepithelioid); Results: Median survival of mesothelioma was 8.0 months (95% confidence interval: 6.2 to 9.8). The 1-year, 2-year, and 5-year survival rates (%) were 43.5%, 23.6%, and 12.5%, respectively. In multivariate analysis of Cox’s proportional hazards model; sex, age, smoking history, occupational asbestos exposure, and histological subtype were not significant prognostic factors, but surgery and chemotherapy combined was a significant predictor; Conclusions: Although the representativeness of these data is limited, our study estimates the epidemiologic characteristics of malignant pleural mesothelioma. Non-occupational exposure had a similar prognosis to occupational asbestos exposure, and there was no sex difference. In addition, it was found that receiving a combination of surgery and chemotherapy affects the survival rate, but there is a limitation in that factors such as performance status, comorbidities, and stage that contribute to survival are not considered.
Analysis of Fine Crack Images Using Image Processing Technique and High-Resolution Camera
Authors: Jeong Hoseong , Jeong Baekeun , Han Myounghee , Cho Dooyong
Published: October 2021

Visual inspections are performed to investigate cracks in concrete infrastructure. These activities require manpower or equipment such as articulated ladders. Additionally, there are health and safety issues because some structures have low accessibility. To deal with these problems, crack measurement with digital images and digital image processing (DIP) techniques have been adopted in various studies. The objective of this experimental study is to evaluate the optical limit of digital camera lenses as working distance increases. Three different lenses and two digital cameras were used to capture images of lines ranging from 0.1 to 0.5 mm in thickness. As a result of the experiments, it was found that many elements affect width measurement. However, crack width measurement is dependent on the measured pixel values. To accurately measure width, the measured pixel values must be in decimal units, but that is theoretically impossible. According to the results, in the case of 0.3 mm wide or wider cracks, a working distance of 1 m was secured when the focal length was 50 mm, and working distances of 3 m and 4 m were secured when the focal length was 100 mm and 135 mm, respectively. However, for cracks not wider than 0.1 mm, focal lengths of 100 mm and 135 mm showed measurability within 1 m, but a focal length of 50 mm was judged to hardly enable measurement except for certain working positions. Field measurement tests were conducted to verify measurement parameters identified by the results of the indoor experiment. The widths of actual cracks were measured through visual inspection and used for the analysis. From the evaluation, it was confirmed that the number of pixels corresponding to the working distance had a great influence on crack width measurement accuracy when using image processing. Therefore, the optimal distance and measurement guidelines required for the measurement of the size of certain objects was presented for the imaging equipment and optical equipment applied in this study.
Photocatalytic Degradation of Methylene Blue Dye by Electrospun Binary and Ternary Zinc and Titanium Oxide Nanofibers
Authors: Petrovičová Beatrix , Dahrouch Zainab , Triolo Claudia , Pantò Fabiola , Malara Angela , Patanè Salvatore , Allegrini Maria , Santangelo Saveria
Published: October 2021

Synthetic dyes, dispersed in water, have harmful effects on human health and the environment. In this work, Ti and/or Zn oxide nanofibers (NFs) with engineered architecture and surface were produced via electrospinning followed by calcination. Calcination and subsequent cooling were operated at fast rates to generate porous NFs with capture centers to reduce the recombination rate of the photogenerated charges. After morphological and microstructural characterisation, the NFs were comparatively evaluated as photocatalysts for the removal of methylene blue from water under UV irradiation. The higher band gap and lower crystallinity were responsible for the lower photocatalytic activity of the ternary oxides (ZnTiO3 and Zn2TiO4) towards the degradation of the dye. The optimal loads of the highly performing binary oxides were determined. By using 0.66 mg mL−1 wurtzite ZnO for the discoloration of an aqueous solution with a dye concentration of 15 µM, a higher rate constant (7.94 × 10−2 min−1) than previously reported was obtained. The optimal load for anatase TiO2 was lower (0.33 mg mL−1). The corresponding rate constant (1.12 × 10−1 min−1) exceeds the values reported for the commonly used P25–TiO2 benchmark. The catalyst can be reused twice without any regeneration treatment, with 5.2% and 18.7% activity decrease after the second and third use, respectively.
New Trends in Biosciences
Authors: Ballini Andrea , Di Stasio Dario , Boccaccio Antonio , Contaldo Maria
Published: October 2021

The regulation and evaluation of biosciences are increasing, and this is probably a healthy tendency—at least to a certain extent [...]
Towards Single 2D Image-Level Self-Supervision for 3D Human Pose and Shape Estimation
Authors: Cha Junuk , Saqlain Muhammad , Lee Changhwa , Lee Seongyeong , Lee Seungeun , Kim Donguk , Park Won-Hee , Baek Seungryul
Published: October 2021

Three-dimensional human pose and shape estimation is an important problem in the computer vision community, with numerous applications such as augmented reality, virtual reality, human computer interaction, and so on. However, training accurate 3D human pose and shape estimators based on deep learning approaches requires a large number of images and corresponding 3D ground-truth pose pairs, which are costly to collect. To relieve this constraint, various types of weakly or self-supervised pose estimation approaches have been proposed. Nevertheless, these methods still involve supervision signals, which require effort to collect, such as unpaired large-scale 3D ground truth data, a small subset of 3D labeled data, video priors, and so on. Often, they require installing equipment such as a calibrated multi-camera system to acquire strong multi-view priors. In this paper, we propose a self-supervised learning framework for 3D human pose and shape estimation that does not require other forms of supervision signals while using only single 2D images. Our framework inputs single 2D images, estimates human 3D meshes in the intermediate layers, and is trained to solve four types of self-supervision tasks (i.e., three image manipulation tasks and one neural rendering task) whose ground-truths are all based on the single 2D images themselves. Through experiments, we demonstrate the effectiveness of our approach on 3D human pose benchmark datasets (i.e., Human3.6M, 3DPW, and LSP), where we present the new state-of-the-art among weakly/self-supervised methods.
Platinum Deposited Nitrogen-Doped Vertically Aligned Carbon Nanofibers as Methanol Tolerant Catalyst for Oxygen Reduction Reaction with Improved Durability
Authors: Elangovan Ayyappan , Xu Jiayi , Sekar Archana , Rajendran Sabari , Liu Bin , Li Jun
Published: October 2021

Nitrogen doping in carbon materials can modify the employed carbon material’s electronic and structural properties, which helps in creating a stronger metal-support interaction. In this study, the role of nitrogen doping in improving the durability of Pt catalysts supported on a three-dimensional vertically aligned carbon nanofiber (VACNF) array towards oxygen reduction reaction (ORR) was explored. The nitrogen moieties present in the N-VACNF enhanced the metal-support interaction and contributed to a reduction in the Pt particle size from 3.1 nm to 2.3 nm. The Pt/N-VACNF catalyst showed better durability when compared to Pt/VACNF and Pt/C catalysts with similar Pt loading. DFT calculations validated the increase in the durability of the Pt NPs with an increase in pyridinic N and corroborated the molecular ORR pathway for Pt/N-VACNF. Moreover, the Pt/N-VACNF catalyst was found to have excellent tolerance towards methanol crossover.
Long-Term Variability of Dust Events in Southwestern Iran and Its Relationship with the Drought
Authors: Hamzeh Nasim Hossein , Kaskaoutis Dimitris G. , Rashki Alireza , Mohammadpour Kaveh
Published: October 2021

Dust storms represent a major environmental challenge in the Middle East. The southwest part of Iran is highly affected by dust events transported from neighboring desert regions, mostly from the Iraqi plains and Saudi Arabia, as well as from local dust storms. This study analyzes the spatio-temporal distribution of dust days at five meteorological stations located in southwestern Iran covering a period of 22 years (from 1997 to 2018). Dust codes (06, 07, 30 to 35) from meteorological observations are analyzed at each station, indicating that 84% of the dust events are not of local origin. The average number of dust days maximizes in June and July (188 and 193, respectively), while the dust activity weakens after August. The dust events exhibit large inter-annual variability, with statistically significant increasing trends in all of five stations. Spatial distributions of the aerosol optical depth (AOD), dust loading, and surface dust concentrations from a moderate resolution imaging spectroradiometer (MODIS) and Modern-Era Retrospective analysis for Research and Applications (MERRA-2) retrievals reveal high dust accumulation over southwest Iran and surrounding regions. Furthermore, the spatial distribution of the (MODIS)-AOD trend (%) over southwest Iran indicates a large spatial heterogeneity during 2000–2018 with trends ranging mostly between −9% and 9% (not statistically significant). 2009 was the most active dust year, followed by 2011 and 2008, due to prolonged drought conditions in the fertile crescent and the enhanced dust emissions in the Iraqi plains during this period. In these years, the AOD was much higher than the 19-year average (2000 to 2018), while July 2009 was the dustiest month with about 25–30 dust days in each station. The years with highest dust activity were associated with less precipitation, negative anomalies of the vegetation health index (VHI) and normalized difference vegetation index (NDVI) over the Iraqi plains and southwest Iran, and favorable meteorological dynamics triggering stronger winds.
Climatology of Spread F over Tucumán from Massive Statistical Analysis of Autoscaled Data
Authors: Scotto Carlo , Sabbagh Dario
Published: October 2021

Automatic ionogram interpretation methods developed for real-time ionospheric monitoring can be applied in retrospective studies to analyze large quantities of data. The Autoscala software, implemented for such a purpose, includes a routine for automatic detection of diffused echoes known as spread F, which appear in ionograms due to the presence of ionospheric irregularities along the radio signal path. The main objective of this routine is to reject bad quality ionograms. This new capability was used in a climatological study including a large number of ionograms recorded at the low-latitude ionospheric station of Tucumán (26.9° S, 294.6° E, magnetic latitude 15.5° S, Argentina). The study took into account different levels of geomagnetic and solar activity from 2012 to 2020. The results demonstrate the capability of Autoscala to capture the main signature characteristics of spread F and the temporal evolution of the ionosphere peak heigh hmF2, capturing the post-sunset plasma surge that precedes development of spread F. Maximum occurrence of spread F is observed in local summer, with a tendency to shift before midnight with increasing solar activity. Other new climatological details that emerged from the study are illustrated and briefly discussed, dealing with connection with geomagnetic activity, and morning hmF2 behavior after extremely marked nighttime spread F occurrence.
Objective Calibration of Numerical Weather Prediction Model: Application on Fine Resolution COSMO Model over Switzerland
Authors: Voudouri Antigoni , Avgoustoglou Euripides , Carmona Izthak , Levi Yoav , Bucchignani Edoardo , Kaufmann Pirmin , Bettems Jean-Marie
Published: October 2021

The objective calibration method originally performed on regional climate models is applied to a fine horizontal resolution Numerical Weather Prediction (NWP) model over a mainly continental domain covering the Alpine Arc. The method was implemented on the MeteoSwiss COSMO (consortium for a small-scale modeling) model with a resolution of 0.01° (approximately 1 km). For the model calibration, five tuning parameters of the parameterization schemes affecting turbulence, soil-surface exchange and radiation were chosen. A full year was simulated, with the history of the soil included (hindcast) to find the optimal parameter value. A different year has been used to give an independent assessment of the impact of the optimization process. Although the operational MeteoSwiss model is already a well-tuned configuration, the results showed that a slight model performance gain is obtained by using the Calibration of COSMO (CALMO) methodology.
Polaritons in an Electron Gas—Quasiparticles and Landau Effective Interactions
Authors: Bastarrachea-Magnani Miguel Angel , Thomsen Jannie , Camacho-Guardian Arturo , Bruun Georg M.
Published: October 2021

Two-dimensional semiconductors inside optical microcavities have emerged as a versatile platform to explore new hybrid light–matter quantum states. A strong light–matter coupling leads to the formation of exciton-polaritons, which in turn interact with the surrounding electron gas to form quasiparticles called polaron-polaritons. Here, we develop a general microscopic framework to calculate the properties of these quasiparticles, such as their energy and the interactions between them. From this, we give microscopic expressions for the parameters entering a Landau theory for the polaron-polaritons, which offers a simple yet powerful way to describe such interacting light–matter many-body systems. As an example of the application of our framework, we then use the ladder approximation to explore the properties of the polaron-polaritons. Furthermore, we show that they can be measured in a non-demolition way via the light transmission/reflection spectrum of the system. Finally, we demonstrate that the Landau effective interaction mediated by electron-hole excitations is attractive leading to red shifts of the polaron-polaritons. Our work provides a systematic framework to study exciton-polaritons in electronically doped two-dimensional materials such as novel van der Waals heterostructures.
Low-Energy Elastic Electron Scattering from Helium Atoms
Authors: McEachran Robert P. , Hamilton Kathryn R. , Bartschat Klaus
Published: October 2021

We reinvestigate a key process in electron-atom collision physics, the elastic scattering of electrons from helium atoms. Specifically, results from a special-purpose relativistic polarized-orbital method, which is designed to treat elastic scattering only, are compared with those from a very extensive, fully ab initio, general-purpose B-spline R-matrix (close-coupling) code.
6G Cognitive Information Theory: A Mailbox Perspective
Authors: Hao Yixue , Miao Yiming , Chen Min , Gharavi Hamid , Leung Victor
Published: October 2021

With the rapid development of 5G communications, enhanced mobile broadband, massive machine type communications and ultra-reliable low latency communications are widely supported. However, a 5G communication system is still based on Shannon’s information theory, while the meaning and value of information itself are not taken into account in the process of transmission. Therefore, it is difficult to meet the requirements of intelligence, customization, and value transmission of 6G networks. In order to solve the above challenges, we propose a 6G mailbox theory, namely a cognitive information carrier to enable distributed algorithm embedding for intelligence networking. Based on Mailbox, a 6G network will form an intelligent agent with self-organization, self-learning, self-adaptation, and continuous evolution capabilities. With the intelligent agent, redundant transmission of data can be reduced while the value transmission of information can be improved. Then, the features of mailbox principle are introduced, including polarity, traceability, dynamics, convergence, figurability, and dependence. Furthermore, key technologies with which value transmission of information can be realized are introduced, including knowledge graph, distributed learning, and blockchain. Finally, we establish a cognitive communication system assisted by deep learning. The experimental results show that, compared with a traditional communication system, our communication system performs less data transmission quantity and error.
Pomacea canaliculata Ampullar Proteome: A Nematode-Based Bio-Pesticide Induces Changes in Metabolic and Stress-Related Pathways
Authors: Boraldi Federica , Lofaro Francesco Demetrio , Bergamini Giulia , Ferrari Agnese , Malagoli Davide
Published: October 2021

Pomacea canaliculata is a freshwater gastropod known for being both a highly invasive species and one of the possible intermediate hosts of the mammalian parasite Angiostrongylus cantonensis. With the aim of providing new information concerning P. canaliculata biology and adaptability, the first proteome of the ampulla, i.e., a small organ associated with the circulatory system and known as a reservoir of nitrogen-containing compounds, was obtained. The ampullar proteome was derived from ampullae of control snails or after exposure to a nematode-based molluscicide, known for killing snails in a dose- and temperature-dependent fashion. Proteome analysis revealed that the composition of connective ampulla walls, cell metabolism and oxidative stress response were affected by the bio-pesticide. Ultrastructural investigations have highlighted the presence of rhogocytes within the ampullar walls, as it has been reported for other organs containing nitrogen storage tissue. Collected data suggested that the ampulla may belong to a network of organs involved in controlling and facing oxidative stress in different situations. The response against the nematode-based molluscicide recalled the response set up during early arousal after aestivation and hibernation, thus encouraging the hypothesis that metabolic pathways and antioxidant defences promoting amphibiousness could also prove useful in facing other challenges stimulating an oxidative stress response, e.g., immune challenges or biocide exposure. Targeting the oxidative stress resistance of P. canaliculata may prove helpful for increasing its susceptibility to bio-pesticides and may help the sustainable control of this pest’s diffusion.
Relationship between Plasma Concentrations of Afatinib and the Onset of Diarrhea in Patients with Non-Small Cell Lung Cancer
Authors: Yokota Hayato , Sato Kazuhiro , Sakamoto Sho , Okuda Yuji , Asano Mariko , Takeda Masahide , Nakayama Katsutoshi , Miura Masatomo
Published: October 2021

We evaluated the area under the plasma concentration–time curve (AUC) of afatinib required to avoid the onset of grade 2 or higher diarrhea. The C0 and AUC0–24 of afatinib were significant higher in patients with grade 2 diarrhea than in those with grade 0–1 diarrhea. The areas under the receiver operator curves were 0.795 with the highest sensitivity (89%) and specificity (74%) at an AUC0–24 threshold of 823.5 ng·h/mL, and 0.754 with the highest sensitivity (89%) and specificity (74%) at a C0 threshold of 28.5 ng/mL. In Kaplan–Meier analysis based on these cut-off AUC0–24 and C0 values, the median time to the incidence of grade 2 diarrhea was 16 days. The predicted AUC0–24 of afatinib from the single point of C6 showed the highest correlation with the measured AUC0–24 (r2 = 0.840); however, a significant correlation between the AUC0–24 and C0 was also observed (r2 = 0.761). C0 could be used as a marker of therapeutic drug monitoring because afatinib C0 was related to AUC0–24. Therefore, afatinib C0 should be monitored on day 8 after beginning therapy, and the daily dose of afatinib should be adjusted as an index with a cut-off value of 28.5 ng/mL.
Predicting the Potential Global Distribution of Amblyomma americanum (Acari: Ixodidae) under Near Current and Future Climatic Conditions, Using the Maximum Entropy Model
Authors: Ma Delong , Lun Xinchang , Li Chao , Zhou Ruobing , Zhao Zhe , Wang Jun , Zhang Qinfeng , Liu Qiyong
Published: October 2021

Amblyomma americanum (the lone star tick) is a pathogen vector, mainly from eastern North America, that bites humans. With global integration and climate change, some ticks that are currently confined to a certain place may begin to spread out; some reports have shown that they are undergoing rapid range expansion. The difference in the potential geographic distribution of A. americanum under current and future climatic conditions is dependent on environment variables such as temperature and precipitation, which can affect their survival. In this study, we used a maximum entropy (MaxEnt) model to predict the potential geographic distribution of A. americanum. The MaxEnt model was calibrated at the native range of A. americanum using occurrence data and the current climatic conditions. Seven WorldClim climatic variables were selected by the jackknife method and tested in MaxEnt using different combinations of model feature class functions and regularization multiplier values. The best model was chosen based on the omission rate and the lowest Akaike information criterion. The resulting model was then projected onto the global scale using the current and future climate conditions modeled under four greenhouse gas emission scenarios.
Pharmacological Inhibition of the VCP/Proteasome Axis Rescues Photoreceptor Degeneration in RHOP23H Rat Retinal Explants
Authors: Sen Merve , Kutsyr Oksana , Cao Bowen , Bolz Sylvia , Arango-Gonzalez Blanca , Ueffing Marius
Published: October 2021

Rhodopsin (RHO) misfolding mutations are a common cause of the blinding disease autosomal dominant retinitis pigmentosa (adRP). The most prevalent mutation, RHOP23H, results in its misfolding and retention in the endoplasmic reticulum (ER). Under homeostatic conditions, misfolded proteins are selectively identified, retained at the ER, and cleared via ER-associated degradation (ERAD). Overload of these degradation processes for a prolonged period leads to imbalanced proteostasis and may eventually result in cell death. ERAD of misfolded proteins, such as RHOP23H, includes the subsequent steps of protein recognition, targeting for ERAD, retrotranslocation, and proteasomal degradation. In the present study, we investigated and compared pharmacological modulation of ERAD at these four different major steps. We show that inhibition of the VCP/proteasome activity favors cell survival and suppresses P23H-mediated retinal degeneration in RHOP23H rat retinal explants. We suggest targeting this activity as a therapeutic approach for patients with currently untreatable adRP.
When Order Meets Disorder: Modeling and Function of the Protein Interface in Fuzzy Complexes
Authors: Sacquin-Mora Sophie , Prévost Chantal
Published: October 2021

The degree of proteins structural organization ranges from highly structured, compact folding to intrinsic disorder, where each degree of self-organization corresponds to specific functions: well-organized structural motifs in enzymes offer a proper environment for precisely positioned functional groups to participate in catalytic reactions; at the other end of the self-organization spectrum, intrinsically disordered proteins act as binding hubs via the formation of multiple, transient and often non-specific interactions. This review focusses on cases where structurally organized proteins or domains associate with highly disordered protein chains, leading to the formation of interfaces with varying degrees of fuzziness. We present a review of the computational methods developed to provide us with information on such fuzzy interfaces, and how they integrate experimental information. The discussion focusses on two specific cases, microtubules and homologous recombination nucleoprotein filaments, where a network of intrinsically disordered tails exerts regulatory function in recruiting partner macromolecules, proteins or DNA and tuning the atomic level association. Notably, we show how computational approaches such as molecular dynamics simulations can bring new knowledge to help bridging the gap between experimental analysis, that mostly concerns ensemble properties, and the behavior of individual disordered protein chains that contribute to regulation functions.
Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression
Authors: Molina M. Dolores , Cebrià Francesc
Published: October 2021

Planarians are flatworms capable of whole-body regeneration, able to regrow any missing body part after injury or amputation. The extraordinary regenerative capacity of planarians is based upon the presence in the adult of a large population of somatic pluripotent stem cells. These cells, called neoblasts, offer a unique system to study the process of stem cell specification and differentiation in vivo. In recent years, FACS-based isolation of neoblasts, RNAi functional analyses as well as high-throughput approaches such as single-cell sequencing have allowed a rapid progress in our understanding of many different aspects of neoblast biology. Here, we summarize our current knowledge on the molecular signatures that define planarian neoblasts heterogeneity, which includes a percentage of truly pluripotent stem cells, and guide the commitment of pluripotent neoblasts into lineage-specific progenitor cells, as well as their differentiation into specific planarian cell types.
New-Onset Psoriatic Arthritis under Biologics in Psoriasis Patients: An Increasing Challenge?
Authors: Megna Matteo , Ocampo-Garza Sonia Sofia , Potestio Luca , Fontanella Giuseppina , Gallo Lucia , Cacciapuoti Sara , Ruggiero Angelo , Fabbrocini Gabriella
Published: October 2021

Psoriasis and psoriatic arthritis (PsA) development is sustained by tumor necrosis factor (TNF)α, interleukin (IL)17, and IL23; hence, biologics targeting those cytokines represent useful therapeutic weapons for both conditions. Nevertheless, biologics strongly reduce PsA risk; several studies reported the possibility of new-onset PsA during biologic therapy for psoriasis. The aim of this 1-year prospective study is to evaluate the prevalence of paradoxical PsA in psoriasis patients under biologic therapy and review the existing literature. For each patient, age, sex, psoriasis duration, psoriasis severity, comorbidities, and previous and current psoriasis treatments were collected, and each subject was screened for PsA using the Early ARthritis for Psoriatic patient (EARP) questionnaire every 3 months for 1 year. New-onset PsA was diagnosed in 10 (8.5%) out of 118 patients (three male, 30.0%; mean age 44.5 years) involving every different biologic class (anti-TNF, anti-IL12/23, anti-IL17, and anti-IL23). No significant risk factor for new-onset PsA was identified; no significant difference was found comparing patients who developed PsA and subjects who did not develop PsA regarding psoriasis severity, past/current therapies, and comorbidities. Clinicians must keep in mind the possibility of PsA onset also in patients undergoing biologics so that PsA screening should be strongly recommended at each follow-up.
Capillary Electrophoresis–Mass Spectrometry with Multisegment Injection and In-Capillary Preconcentration for High-Throughput and Sensitive Determination of Therapeutic Decapeptide Triptorelin in Pharmaceutical and Biological Matrices
Authors: Piešťanský Juraj , Čižmárová Ivana , Štefánik Ondrej , Matušková Michaela , Horniaková Andrea , Majerová Petra , Mikuš Peter
Published: October 2021

A capillary electrophoresis–tandem mass spectrometry method with a multisegment injection and an in-capillary field-enhanced sample stacking for determination of therapeutic peptide triptorelin in pharmaceutical and biological matrices was developed. The CE separation conditions were optimized in order to obtain maximal separation efficiency, analytical signal intensity and stability, and minimal adsorption of the analyzed peptide onto the capillary wall (1 M formic acid—HFo, pH 1.88). The implementation of the field-enhanced sample injection into CE improved the value of limit of detection 50 times while the multisegment injection increased the sample throughput three times in comparison to a conventional CE approach. The proposed method was characterized by favorable performance parameters, such as linearity (r2 ≥ 0.99), limit of detection (5 ng mL−1 in water matrix, 25 ng mL−1 in plasma matrix), precision (relative standard deviation, 1.5–9.4% for intraday and 2.3–11.9% for interday reproducibility), or accuracy (relative errors in the range of 80–109%). The FDA-validated method was successfully applied to the analysis of triptorelin in the commercial drug Diphereline® 0.1 mg (powder for injection) and in spiked human plasma samples. Favorable performance parameters along with proven application potentialities indicate the usefulness of the proposed method for its routine use in drug quality control laboratories and for clinical analysis, such as determination of triptorelin levels in plasma (for pharmacokinetic study).
Computer Simulation of a Surface Charge Nanobiosensor with Internal Signal Integration
Authors: Dyubo Dmitry , Tsybin Oleg Yu.
Published: October 2021

The ionized states of molecular analytes located on solid surfaces require profound investigation and better understanding for applications in the basic sciences in general, and in the design of nanobiosensors, in particular. Such ionized states are induced by the interactions of molecules between them in the analyzed substance and with the target surface. Here, computer simulations using COMSOL Multiphysics software show the effect of surface charge density and distribution on the output generation in a dynamic PIN diode with gate control. This device, having built-in potential barriers, has a unique internal integration of output signal generation. The identified interactions showed the possibility of a new design for implementing a nanobiosensor based on a dynamic PIN diode in a mode with surface charge control.
Decreased Global EEG Synchronization in Amyloid Positive Mild Cognitive Impairment and Alzheimer’s Disease Patients—Relationship to APOE ε4
Authors: Smailovic Una , Johansson Charlotte , Koenig Thomas , Kåreholt Ingemar , Graff Caroline , Jelic Vesna
Published: October 2021

The apolipoprotein E (APOE) ε4 allele is a risk factor for Alzheimer’s disease (AD) that has been linked to changes in brain structure and function as well as to different biological subtypes of the disease. The present study aimed to investigate the association of APOE ε4 genotypes with brain functional impairment, as assessed by quantitative EEG (qEEG) in patients on the AD continuum. The study population included 101 amyloid positive patients diagnosed with mild cognitive impairment (MCI) (n = 50) and AD (n = 51) that underwent resting-state EEG recording and CSF Aβ42 analysis. In total, 31 patients were APOE ε4 non-carriers, 42 were carriers of one, and 28 were carriers of two APOE ε4 alleles. Quantitative EEG analysis included computation of the global field power (GFP) and global field synchronization (GFS) in conventional frequency bands. Amyloid positive patients who were carriers of APOE ε4 allele(s) had significantly higher GFP beta and significantly lower GFS in theta and beta bands compared to APOE ε4 non-carriers. Increased global EEG power in beta band in APOE ε4 carriers may represent a brain functional compensatory mechanism that offsets global EEG slowing in AD patients. Our findings suggest that decreased EEG measures of global synchronization in theta and beta bands reflect brain functional deficits related to the APOE ε4 genotype in patients that are on a biomarker-verified AD continuum.
Reliability of Existing Climate Indices in Assessing the Freeze-Thaw Damage Risk of Internally Insulated Masonry Walls
Authors: Sahyoun Sahar , Ge Hua , Lacasse Michael A. , Defo Maurice
Published: October 2021

This paper evaluates the reliability of the currently used climate-based indices in selecting a moisture reference year (MRY) for the freeze-thaw (FT) damage risk assessment of internally insulated solid brick walls. The evaluation methodology compares the ranking of the years determined by the climate-based indices and response-based indices from simulations, regarded as actual performance. The hygrothermal response of an old brick masonry wall assembly, before and after retrofit, was investigated in two Canadian cities under historical and projected future climates. Results indicated that climate-based indices failed to represent the actual performance. However, among the response-based indices, the freeze-thaw damage risk index (FTDR) showed a better correlation with the climate-based indices. Additionally, results indicated a better correlation between the climatic index (CI), the moisture index (MI), and FTDR in Ottawa; however, in Vancouver, a better fit was found between MI and FTDR. Moreover, the risk of freeze-thaw increased considerably after interior insulation was added under both historical and projected future climates. The risk of FT damage would increase for Ottawa but decrease for Vancouver under a warming climate projected in the future, based on the climate scenario used in this study. Further research is needed to develop a more reliable method for the ranking and the selection of MRYs on the basis of climate-based indices that is suitable for freeze-thaw damage risk assessment.
Effect of Shape, Number, and Location of Openings on Punching Shear Capacity of Flat Slabs
Authors: Yooprasertchai Ekkachai , Tiawilai Yonlada , Wittayawanitchai Theerawee , Angsumalee Jiranuwat , Joyklad Panuwat , Hussain Qudeer
Published: October 2021

Experimental evidence have proved that punching shear capacity of flat slabs deteriorate with the presence of openings located within the critical perimeter around columns. It is understood that this deterioration varies inversely with the distance of openings from column’s face. However, effect of the shape of openings on punching shear capacity is not well known. This study presents experimental results of 14 flat specimens to investigate the effects of the number (2 and 4), shape (circular, square, and rectangular), and location (1 and 4 times of slab’s thickness from column’s face) of openings on punching shear strength. It was found that circular openings had least influence on punching capacity followed by square and rectangular openings, respectively. Further, placing openings at a distance of four times the slab’s thickness from column’s face had minimal impact on punching capacity. Further, increasing the number of openings from 2 to 4 substantially reduced the punching capacity. An effort was made to predict the punching capacities of all specimens using the descriptive equations of ACI 318-19 and Eurocode 2. Mean of the ratio of experimental to analytical results and standard deviation of ACI equations were found to be more accurate than those of Eurocode 2 predictions.
Cellular Therapy Updates in B-Cell Lymphoma: The State of the CAR-T
Authors: Crees Zachary D. , Ghobadi Armin
Published: October 2021

Non-Hodgkin Lymphoma accounts for >460,000 cases and >240,000 deaths globally and >77,000 cases and >20,000 deaths in the U.S. annually, with ~85% of cases being B-cell malignancies. Until recently, patients with relapsed/refractory B-cell lymphoma following standard chemotherapy in combination with anti-CD20 monoclonal antibodies and autologous stem cell transplantation experienced a median overall survival (OS) of <6 months. However, with the approval of four different CD-19 CAR-T therapies between 2017 and 2021, approximately 60–80% of patients receiving CAR-T therapy now achieve an objective response with >3 years median OS. Here, we review the current state of the art of CD19 CAR-T therapies for B-cell lymphomas, focusing on current updates in US FDA-approved products, along with their associated efficacy and toxicities. Lastly, we highlight a selection of promising clinical developments in the field, including various novel strategies to increase CAR-T therapy efficacy while mitigating toxicity.
Prognostic Gene Signature for Squamous Cell Carcinoma with a Higher Risk for Treatment Failure and Accelerated MEK-ERK Pathway Activity
Authors: Feng Bohai , Wang Kai , Herpel Esther , Plath Michaela , Weichert Wilko , Freier Kolja , Zaoui Karim , Hess Jochen
Published: October 2021

Squamous cell carcinoma (SCC) is the most prevalent histological type of human cancer, including head and neck squamous cell carcinoma (HNSCC). However, reliable prognostic gene signatures for SCC and underlying genetic and/or epigenetic principles are still unclear. We identified 37 prognostic candidate genes by best cutoff computation based on survival in a pan-SCC cohort (n = 1334) of The Cancer Genome Atlas (TCGA), whose expression stratified not only the pan-SCC cohort but also independent HNSCC validation cohorts into three distinct prognostic subgroups. The most relevant prognostic genes were prioritized by a Least Absolute Shrinkage and Selection Operator Cox regression model and were used to identify subgroups with high or low risks for unfavorable survival. An integrative analysis of multi-omics data identified FN1, SEMA3A, CDH2, FBN1, COL5A1, and ADAM12 as key nodes in a regulatory network related to the prognostic phenotype. An in-silico drug screen predicted two MEK inhibitors (Trametinib and Selumetinib) as effective compounds for high-risk SCC based on the Cancer Cell Line Encyclopedia, which is supported by a higher p-MEK1/2 immunohistochemical staining of high-risk HNSCC. In conclusion, our data identified a molecular classifier for high-risk HNSCC as well as other SCC patients, who might benefit from treatment with MEK inhibitors.
Molecular Signature Expands the Landscape of Driver Negative Thyroid Cancers
Authors: Bim Larissa Valdemarin , Carneiro Thaise Nayane Ribeiro , Buzatto Vanessa Candiotti , Colozza-Gama Gabriel Avelar , Koyama Fernanda C. , Thomaz Debora Mota Dias , de Jesus Paniza Ana Carolina , Lee Eunjung Alice , Galante Pedro Alexandre Favoretto , Cerutti Janete Maria
Published: October 2021

Thyroid cancer is the most common endocrine malignancy. However, the cytological diagnosis of follicular thyroid carcinoma (FTC), Hürthle cell carcinoma (HCC), and follicular variant of papillary thyroid carcinoma (FVPTC) and their benign counterparts is a challenge for preoperative diagnosis. Nearly 20–30% of biopsied thyroid nodules are classified as having indeterminate risk of malignancy and incur costs to the health care system. Based on that, 120 patients were screened for the main driver mutations previously described in thyroid cancer. Subsequently, 14 mutation-negative cases that are the main source of diagnostic errors (FTC, HCC, or FVPTC) underwent RNA-Sequencing analysis. Somatic variants in candidate driver genes (ECD, NUP98,LRP1B, NCOR1, ATM, SOS1, and SPOP) and fusions were described. NCOR1 and SPOP variants underwent validation. Moreover, expression profiling of driver-negative samples was compared to 16 BRAF V600E, RAS, or PAX8-PPARg positive samples. Negative samples were separated in two clusters, following the expression pattern of the RAS/PAX8-PPARg or BRAF V600E positive samples. Both negative groups showed distinct BRS, ERK, and TDS scores, tumor mutation burden, signaling pathways and immune cell profile. Altogether, here we report novel gene variants and describe cancer-related pathways that might impact preoperative diagnosis and provide insights into thyroid tumor biology.
The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers
Authors: Yang Yiming , Sanders Andrew J. , Dou Q. Ping , Jiang David G. , Li Amber Xinyu , Jiang Wen G.
Published: October 2021

Activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, is a cell adhesion protein that is found in multiple cell types. ALCAM has multiple and diverse roles in various physiological and pathological conditions, including inflammation and cancer. There has been compelling evidence of ALCAM’s prognostic value in solid cancers, indicating that it is a potential therapeutic target. The present article overviews the recent findings and progress in ALCAM and its involvement in cancer, with a primary focus on its clinical connections in cancer and therapeutic values.
Epstein–Barr Virus—Associated Malignancies and Immune Escape: The Role of the Tumor Microenvironment and Tumor Cell Evasion Strategies
Authors: Bauer Marcus , Jasinski-Bergner Simon , Mandelboim Ofer , Wickenhauser Claudia , Seliger Barbara
Published: October 2021

The detailed mechanisms of Epstein–Barr virus (EBV) infection in the initiation and progression of EBV-associated malignancies are not yet completely understood. During the last years, new insights into the mechanisms of malignant transformation of EBV-infected cells including somatic mutations and epigenetic modifications, their impact on the microenvironment and resulting unique immune signatures related to immune system functional status and immune escape strategies have been reported. In this context, there exists increasing evidence that EBV-infected tumor cells can influence the tumor microenvironment to their own benefit by establishing an immune-suppressive surrounding. The identified mechanisms include EBV gene integration and latent expression of EBV-infection-triggered cytokines by tumor and/or bystander cells, e.g., cancer-associated fibroblasts with effects on the composition and spatial distribution of the immune cell subpopulations next to the infected cells, stroma constituents and extracellular vesicles. This review summarizes (i) the typical stages of the viral life cycle and EBV-associated transformation, (ii) strategies to detect EBV genome and activity and to differentiate various latency types, (iii) the role of the tumor microenvironment in EBV-associated malignancies, (iv) the different immune escape mechanisms and (v) their clinical relevance. This gained information will enhance the development of therapies against EBV-mediated diseases to improve patient outcome.
The Roles of Diacylglycerol Kinase α in Cancer Cell Proliferation and Apoptosis
Authors: Sakane Fumio , Hoshino Fumi , Ebina Masayuki , Sakai Hiromichi , Takahashi Daisuke
Published: October 2021

Diacylglycerol (DG) kinase (DGK) phosphorylates DG to generate phosphatidic acid (PA). The α isozyme is activated by Ca2+ through its EF-hand motifs and tyrosine phosphorylation. DGKα is highly expressed in several refractory cancer cells including melanoma, hepatocellular carcinoma, and glioblastoma cells. In melanoma cells, DGKα is an antiapoptotic factor that activates nuclear factor-κB (NF-κB) through the atypical protein kinase C (PKC) ζ-mediated phosphorylation of NF-κB. DGKα acts as an enhancer of proliferative activity through the Raf–MEK–ERK pathway and consequently exacerbates hepatocellular carcinoma progression. In glioblastoma and melanoma cells, DGKα attenuates apoptosis by enhancing the phosphodiesterase (PDE)-4A1–mammalian target of the rapamycin pathway. As PA activates PKCζ, Raf, and PDE, it is likely that PA generated by DGKα plays an important role in the proliferation/antiapoptosis of cancer cells. In addition to cancer cells, DGKα is highly abundant in T cells and induces a nonresponsive state (anergy), which represents the main mechanism by which advanced cancers escape immune action. In T cells, DGKα attenuates the activity of Ras-guanyl nucleotide-releasing protein, which is activated by DG and avoids anergy through DG consumption. Therefore, a DGKα-specific inhibitor is expected to be a dual effective anticancer treatment that inhibits cancer cell proliferation and simultaneously enhances T cell functions. Moreover, the inhibition of DGKα synergistically enhances the anticancer effects of programmed cell death-1/programmed cell death ligand 1 blockade. Taken together, DGKα inhibition provides a promising new treatment strategy for refractory cancers.