bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the functional inflammatory factors involved in therapeutic response to immune checkpoint inhibitors for pan-cancer
Authors: Wu Yanmeizhi , Yu Shan , Qiao Hong
Published: September 2022

Immune checkpoint inhibitors (ICIs) fight tumor progression by activating immune conditions. The inflammatory factors are playing a functional role in programmed death-1 (PD-1) or other immune checkpoints. They are involved in regulating the expression of programmed death ligand-1 (PD-L1), the only predictor recognized by the guidelines in response to ICIs. In addition, abundant components of the tumor microenvironment (TME) all interact with various immune factors contributing to the response to ICIs, including infiltration of various immune cells, extracellular matrix, and fibroblasts. Notably, the occurrence of immune-related adverse events (irAEs) in patients receiving ICIs is increasingly observed in sundry organs. IrAEs are often regarded as an inflammatory factor-mediated positive feedback loop associated with better response to ICIs. It deserves attention because inflammatory factors were observed to be different when targeting different immune checkpoints or in the presence of different irAEs. In the present review, we address the research progresses on regulating inflammatory factors for an intentional controlling anti-cancer response with immune checkpoint inhibitors.
The effect of i-deals on employees’ unethical behavior during the COVID-19 pandemic: The roles of hubristic pride and grandiose narcissism
Authors: Liu Zhihao , Zhang Xiaoyan , Xu Hanzhi , Deng Hui , Li Jiajia , Lan Yuanyuan
Published: September 2022

The COVID-19 pandemic has created enormous challenges for organizations and employees. Due to the effectiveness of idiosyncratic deals (i-deals for short) in management practices, more and more organizations use this human resource management tool to address the challenges posed by the COVID-19 pandemic. However, whether there are potential risks or negative effects of i-deals in the COVID-19 pandemic environment is not very clear. Drawing upon social cognitive theory, we proposed that i-deals may foment focal employees’ unethical behavior by triggering their hubristic pride, and such process may be moderated by their trait of grandiose narcissism. We conducted a survey during the COVID-19 outbreak and tested our hypotheses with 492 samples from Shandong Province, China. Consistent with predictions, we found a positive relationship between i-deals and hubristic pride, which, in turn, increased their unethical behavior. And the relationship between i-deals and unethical behavior was mediated by hubristic pride. Furthermore, grandiose narcissism strengthened the positive relationship between i-deals and hubristic pride, as well as the indirect effect of i-deals on unethical behavior via hubristic pride. Our findings contributed to the literature on i-deals and provided guidance for organizations to address the challenges posed by the COVID-19 pandemic.
The need to be unique and the innovative behavior: The moderating role of supervisor support
Authors: Bekmezci Mustafa , Rehman Wasim Ul , Khurshid Muzammil , Eroğluer Kemal , Trout Inci Yilmazli
Published: September 2022

The purpose of this study is to examine the moderating effect of supervisor support on the relationship between the need to be unique and the innovative behavior. People not only strive to belong to a group but also want to be unique from others and feel exceptional. Individuals’ innovative behavior is one of the things that makes them feel different from other people. Because developing a new idea, supporting this idea, putting this idea into practice, and the positive achievements of this idea distinguish people who exhibit innovative behavior from others. It depends on the behavior of supervisors whether people who break away from typical practices and procedures to feel unique and special continue to act in innovative ways. In this context, it is vitally essential for supervisors to support people who display innovative behavior. The research was conducted on employees working in the education sector in Mersin. We employed the confirmatory factor analysis (CFA) to examine the fitness of the model and moderation was tested. As hypothesized, the need to be unique had a significant and positive effect on innovative behavior. This finding is consistent with existing literature and thus advance knowledge on need to be unique and innovative behavior, particular in education sector. Nonetheless, it has been determined that supervisor support doesn’t have a moderator role on the relationship between the need to be unique and innovative behavior. Although there are some researches in the literature on consumer experiences about the need to be unique and innovative behavior, but literature on education section is sparse and still long way to go to evaluate its’ reflections on the workplace.
Beluga (D. leucas), harbor porpoise (P. phocoena), and killer whale (O. orca) acoustic presence in kotzebue sound, alaska: Silence speaks volumes
Authors: Castellote Manuel , Small Robert J. , Stafford Kathleen M. , Whiting Alex , Frost Kathryn J.
Published: September 2022

Prior to 1984, belugas (Delphinapterus leucas) were seen in large numbers during spring and summer in Kotzebue Sound, Alaska, and provided an important subsistence resource to coastal residents. Sightings and harvest declined sharply beginning in 1984: the average annual harvest dropped from 84/yr (1977–1983) to 16/yr (1984–2021). To examine the current seasonal and spatial occurrence of belugas in Kotzebue Sound, passive acoustic moorings were deployed in summer 2013 and year-round in 2014–2016. Three moorings were deployed off Cape Krusenstern, northwestern Kotzebue Sound, to monitor cetaceans traveling nearshore. A mooring was also deployed near Chamisso Island, southeastern Kotzebue Sound. We used automatic detectors to process the recordings for echolocation and tonal signals, and all detections were manually validated. Belugas, harbor porpoises (Phocoena), and transient killer whales (Orcinus orca) were detected in both areas, primarily from June to November. Detections extended into early winter for belugas, and sporadic detections were confirmed for porpoises from January to March. Belugas were detected on a total of 20 days, killer whales on 96 days, and porpoises on 179 days. All beluga detections were echolocation signals; the absence of social signals likely reflects an anti-predator response to transient killer whales and possibly to subsistence hunters. Killer whale detections were composed of echolocation signals, limited to very short click trains, double clicks, and single clicks, a known cryptic acoustic behavior used when targeting prey. Killer whales also emitted high frequency whistles (17–51 kHz) providing the first evidence of these types of signals for transients. Our results suggest transient killer whales in predation mode scouting harbor porpoise and beluga habitat, concurrent with belugas in silent anti-predation mode. This anti-predation acoustic behavior by belugas was also evident when killer whales were not present, conveying a continued perception of predation risk for this habitat. The combined natural and anthropogenic predation pressure in Kotzebue Sound could be playing an important role in the continued low occurrence of belugas.
Effects of remnant preservation in anterior cruciate ligament reconstruction: A systematic review and meta-analysis
Authors: Xie Huanyu , Fu Zicai , Zhong Mingjin , Deng Zhenhan , Wang Chen , Sun Yijia , Zhu Weimin
Published: September 2022

Background

Compared with standard anterior cruciate ligament (ACL) reconstruction, it is controversial whether anterior cruciate ligament reconstruction (ACLR) with remnant preservation can lead to better clinical outcomes. We conducted a systematic study and meta-analysis to assess the differences in clinical efficacy between the two.

Method

We searched for clinical randomized controlled studies and cohort studies included in the Cochrane library, PubMed, and Embase from March 2012 to March 2022 in English. The included studies were ACLR with or without remant preservation, and the data were extracted and the quality of the included studies was assessed by two authors, respectively. Revman 5.4 was used for statistical analysis and conclusions were presented.

Result

Ten articles containing a total of 777 patients were finally included. There was no significant difference in postoperative Lachman test [OR = 1.66, 95%CI (0.79, 3.49), P = 0.18 > 0.05], Tegner score [SMD = −0.13, 95%CI (−0.47, 0.22), P = 0.46 > 0.05], synovial coverage rate by second-look arthroscopy [OR = 1.55, 95%CI (0.66, 3.65), P = 0.32 > 0.05], the rate of cyclops lesion [OR = 3.92, 95%CI (0.53, 29.29), P = 0.18 > 0.05], joint range of motion [SMD = 0.27, 95%CI (−0.13, 0.68), P = 0.19 > 0.05] and re-injury rate [OR = 0.57, 95%CI (0.18, 1.74), P = 0.32 > 0.05] between the two groups. There were statistically significant differences in postoperative Lysholm score [SMD = 0.98, 95% CI (0.32, 1.64), P = 0.004 < 0.05], International Knee Documantation Committee grade (IKDC grade) [OR = 2.19, 95%CI (1.03, 4.65), P = 0.04 < 0.05], Pivot shift test [OR = 1.71, 95%CI (1.06, 2.77), P = 0.03 < 0.05], KT1000/2000 arthrometer side-to-side difference [SMD = −0.22, 95%CI (−0.42, −0.03), P = 0.02 < 0.05], operation time [SMD = 11.69, 95%CI (8.85, 14.54), P = 0.00001 < 0.05] and degree of tibial tunnel enlargement [SMD = −0.66, 95%CI (−1.08, −0.23), P = 0.002 < 0.05].

Conclusion

This meta-analysis concluded that remnant preservation significantly had better results in terms of patient functional score (Lysholm, IKDC), knee stability (Pivot shift test, postoperative side-to-side anterior laxity) and tibial tunnel enlargement. In terms of complications (incidence of Cyclops lesions, range of motion, re-injury rate), no significant differences were seen between the two groups. Although many studies concluded that remnant preservation could bring better synovial coverage, this meta-analysis indicated that there is insufficient evidence to support it, possibly due to different remnant preservation procedures.The potential risks associated with longer operation times are also worth considering.
Programmed cell death 1 inhibitor plus chemotherapy vs. chemotherapy in advanced drive-gene-negative non-small-cell lung cancer patients: A real-world study
Authors: Li Ying , Yang Peng , Zhou Xiao , Yang Xuefeng , Wu Shijie
Published: September 2022

Objective

Programmed cell death 1 (PD-1) inhibitor has been in the market in China for several years, which lacks sufficient domestic evidence regarding its application in lung cancer. Thus, this study intended to assess the treatment outcome and tolerance of PD-1 inhibitor plus chemotherapy in advanced, driver-gene-negative, nonsquamous, non-small-cell lung cancer (NSCLC) patients in a real clinical setting.

Methods

This retrospective cohort study analyzed 68 advanced driver-gene-negative nonsquamous NSCLC patients, among which 38 cases received PD-1 inhibitor plus chemotherapy and 30 cases adopted chemotherapy alone. Disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events were reviewed.

Results

Generally, PD-1 inhibitor plus chemotherapy achieved a more satisfying ORR compared with chemotherapy alone (52.6% vs. 30.0%, P = 0.061), while the DCR did not vary between PD-1 inhibitor plus chemotherapy and chemotherapy (84.2% vs. 73.3%, P = 0.271). Patients receiving PD-1 inhibitor plus chemotherapy exhibited favorable PFS (median: 10.1 vs. 7.1 months, P = 0.040) and OS (median: 17.4 vs. 13.9 months, P = 0.049) than patients adopting chemotherapy alone. Additionally, after adjustment using multivariable Cox's analyses, PD-1 inhibitor plus chemotherapy (vs. chemotherapy) could independently realize prolonged PFS (P = 0.020) and OS (P = 0.029). Moreover, the majority of adverse events were manageable; meanwhile, grade 3–4 adverse events included leukopenia (13.2%), neutropenia (13.2%), nausea and vomiting (7.9%), anemia (5.3%), elevated transaminase (5.3%), thrombopenia (2.6%), anorexia (2.6%), peripheral neuropathy (2.6%), and rash (2.6%).

Conclusion

PD-1 inhibitor plus chemotherapy exhibits a better efficacy and equal tolerance compared with chemotherapy alone in advanced driver-gene-negative nonsquamous NSCLC patients.
Effects of Industrial Noise on Physiological Responses
Authors: Masullo Massimiliano , Toma Roxana Adina , Maffei Luigi
Published: September 2022

Noise pollution is one of the most common workplace hazards. Noise exposure may induce auditory and extra-auditory physiological and psychological alterations that affect job performance, safety, comfort, and wellbeing. Recent research showed a connection between frequency components of noise and health outcomes, annoyance, physiological and psychological changes. This study investigated whether and how the activation of different typologies of industrial noises set at three different sound levels induced increases in electrodermal activity (EDA) and the heart rate variations differently. A laboratory listening test was performed for the study, in which 24 subjects were exposed to the activation of different industrial noises: Low Frequency, High Frequency, and Modulated noises at Low, Medium, and High sound levels, while some physiological responses were recorded. The noise stimuli were also evaluated based on a self-report questionnaire. Results show that the EDA variation increases as the Sound Level increases and is higher at HF. In contrast, no relevant changes have been found in RR variation. EDA changes are also related to the perception of the Valence dimension of the noise environment, while RR variations not. The findings of this study emphasized that the changes in EDA depend on the sound levels and frequency content of industrial noise typologies, as well as on the perception of their Valence.
A Formulation of the Industrial Conceptual Design Optimization Problem for Commercial Transport Airplanes
Authors: Takami Hikaru , Obayashi Shigeru
Published: September 2022

A realistic industrial conceptual design optimization problem for commercial transport airplanes was formulated with reasonable fidelity and comprehensiveness by selecting appropriate design parameters, constraints, and objectives, in order to provide a baseline to facilitate research on developing robust and efficient optimization methods for the industrial conceptual design of such airplanes. As a sample problem, a multiobjective simultaneous optimization of the design parameters for two types of civil passenger transport airplanes that constitute a family, with identical wing and tail geometries but different performance specifications, was performed using a genetic algorithm coupled with a constraint-handling technique. The results indicated that a realistic industrial conceptual design optimization of commercial transport airplanes, including simultaneous optimization of family airplanes, could be performed with the formulation. The findings from the sample optimization were also presented.
A Multi-Control Strategy to Achieve Autonomous Field Operation
Authors: Pierre Cyrille , Lenain Roland , Laneurit Jean , Rousseau Vincent
Published: September 2022

Nowadays, there are several methods of controlling a robot depending on the type of agricultural environment in which it operates. In order to perform a complete agricultural task, this paper proposes a switching strategy between several perception/control approaches, allowing us to select the most appropriate one at any given time. This strategy is presented using an electrical tractor and three control approaches we have developed: path tracking, edge following and furrow pursuing. The effectiveness of the proposed development is tested through full-scale experiments in realistic field environments, performing autonomous navigation and weeding operations in an orchard and an open field. The commutation strategy allows us to select behavior depending on the context, with a good robustness with respect to different sizes of crops (maize and bean). The accuracy stays within ten centimeters, allowing us to expect the use of robots to help with the development of agroecological principles.
Can Sequential Images from the Same Object Be Used for Training Machine Learning Models? A Case Study for Detecting Liver Disease by Ultrasound Radiomics
Authors: Sultan Laith R. , Cary Theodore W. , Al-Hasani Maryam , Karmacharya Mrigendra B. , Venkatesh Santosh S. , Assenmacher Charles-Antoine , Radaelli Enrico , Sehgal Chandra M.
Published: September 2022

Machine learning for medical imaging not only requires sufficient amounts of data for training and testing but also that the data be independent. It is common to see highly interdependent data whenever there are inherent correlations between observations. This is especially to be expected for sequential imaging data taken from time series. In this study, we evaluate the use of statistical measures to test the independence of sequential ultrasound image data taken from the same case. A total of 1180 B-mode liver ultrasound images with 5903 regions of interests were analyzed. The ultrasound images were taken from two liver disease groups, fibrosis and steatosis, as well as normal cases. Computer-extracted texture features were then used to train a machine learning (ML) model for computer-aided diagnosis. The experiment resulted in high two-category diagnosis using logistic regression, with AUC of 0.928 and high performance of multicategory classification, using random forest ML, with AUC of 0.917. To evaluate the image region independence for machine learning, Jenson–Shannon (JS) divergence was used. JS distributions showed that images of normal liver were independent from each other, while the images from the two disease pathologies were not independent. To guarantee the generalizability of machine learning models, and to prevent data leakage, multiple frames of image data acquired of the same object should be tested for independence before machine learning. Such tests can be applied to real-world medical image problems to determine if images from the same subject can be used for training.
Lethal Aeromonas veronii Sepsis in the Course of Medicinal Leech Therapy
Authors: Sproll Christoph , Lommen Julian , Balasiu Adriana , Schorn Lara , Kübler Norbert R. , Henrich Birgit , Kram Rainer , Petersdorf Sabine
Published: September 2022

A patient with oral squamous cell carcinoma (OSCC) underwent complex surgical tumor therapy, including the reconstruction of soft tissues using a radial forearm flap. Due to venous congestion that could only partly be resolved by revision surgery, leech therapy was started on the second postoperative day. The patient developed pneumonia and sepsis and died as a result of septic shock, despite having received targeted broad-spectrum antibiotic therapy since day 5. Aeromonas spp. were cultured from both the patient’s specimens and unused leeches. Biochemical identification and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) yielded inconsistent identification results. Finally, microbiological identification of Aeromonas spp. was performed via 16S rDNA sequencing and use of the basic local alignment search tool (BLAST), and strains from both the patient and the leeches were identified as Aeromonas veronii. Aeromonas spp. strains derived from the patient and leeches and independent laboratory strains were submitted to randomly amplified polymorphic DNA (RAPD) subtyping. RAPD of A. veronii strains from both sources revealed an identical pattern, strongly suggesting the transmission of A. veronii from the leeches to the patient. Physicians should be aware of the potential for severe lethal infections as a fatal side-effect of leech therapy in critically ill patients, which should be addressed using antibiotic prophylaxis.
Effects of Ultraviolet Radiation on Sediment Burial Parameters and Photo-Oxidative Response of the Intertidal Anemone Anthopleura hermaphroditica
Authors: Cubillos Víctor M. , Álvarez Javier A. , Ramírez Eduardo , Cruces Edgardo , Chaparro Oscar R. , Montory Jaime , Spano Carlos A.
Published: September 2022

Anthopleura hermaphroditica is an intertidal anemone that lives semi-buried in soft sediments of estuaries and releases its brooded embryos directly to the benthos, being exposed to potentially detrimental ultraviolet radiation (UVR) levels. In this study, we investigated how experimental radiation (PAR: photosynthetically active radiation; UVA: ultraviolet A radiation; and UVB: ultraviolet B radiation) influences burrowing (time, depth and speed) in adults and juveniles when they were exposed to PAR (P, 400–700 nm), PAR + UVA (PA, 315–700 nm) and PAR + UVA + UVB (PAB, 280–700 nm) experimental treatments. The role of sediment as a physical shield was also assessed by exposing anemones to these radiation treatments with and without sediment, after which lipid peroxidation, protein carbonyls and total antioxidant capacity were quantified. Our results indicate that PAB can induce a faster burial response compared to those anemones exposed only to P. PAB increased oxidative damage, especially in juveniles where oxidative damage levels were several times higher than in adults. Sediment offers protection to adults against P, PA and PAB, as significant differences in their total antioxidant capacity were observed compared to those anemones without sediment. Conversely, the presence or absence of sediment did not influence total antioxidant capacity in juveniles, which may reflect that those anemones have sufficient antioxidant defenses to minimize photooxidative damage due to their reduced tolerance to experimental radiation. Burrowing behavior is a key survival skill for juveniles after they have been released after brooding.
Novel Role of CETP in Macrophages: Reduction of Mitochondrial Oxidants Production and Modulation of Cell Immune-Metabolic Profile
Authors: Dorighello Gabriel G. , Assis Leandro H. P. , Rentz Thiago , Morari Joseane , Santana Monique F. M. , Passarelli Marisa , Ridgway Neale D. , Vercesi Anibal E. , Oliveira Helena C. F.
Published: September 2022

Plasma cholesteryl ester transfer protein (CETP) activity diminishes HDL-cholesterol levels and thus may increase atherosclerosis risk. Experimental evidence suggests CETP may also exhibit anti-inflammatory properties, but local tissue-specific functions of CETP have not yet been clarified. Since oxidative stress and inflammation are major features of atherogenesis, we investigated whether CETP modulates macrophage oxidant production, inflammatory and metabolic profiles. Comparing macrophages from CETP-expressing transgenic mice and non-expressing littermates, we observed that CETP expression reduced mitochondrial superoxide anion production and H2O2 release, increased maximal mitochondrial respiration rates, and induced elongation of the mitochondrial network and expression of fusion-related genes (mitofusin-2 and OPA1). The expression of pro-inflammatory genes and phagocytic activity were diminished in CETP-expressing macrophages. In addition, CETP-expressing macrophages had less unesterified cholesterol under basal conditions and after exposure to oxidized LDL, as well as increased HDL-mediated cholesterol efflux. CETP knockdown in human THP1 cells increased unesterified cholesterol and abolished the effects on mitofusin-2 and TNFα. In summary, the expression of CETP in macrophages modulates mitochondrial structure and function to promote an intracellular antioxidant state and oxidative metabolism, attenuation of pro-inflammatory gene expression, reduced cholesterol accumulation, and phagocytosis. These localized functions of CETP may be relevant for the prevention of atherosclerosis and other inflammatory diseases.
Prunus lusitanica L. Fruits as a Novel Source of Bioactive Compounds with Antioxidant Potential: Exploring the Unknown
Authors: Abraão Ana Santos , Fernandes Nelson , Silva Amélia M. , Domínguez-Perles Raúl , Barros Ana
Published: September 2022

Prunus lusitanica L., also known as Portuguese laurel or locally known as ‘azereiro’, is a rare species with ornamental and ecological value. Only two studies regarding the bioactivity and chemical composition of its leaves were reported to date. Thus, the present study aims to qualitatively and quantitatively evaluate the phenolic profile, through HPLC-PAD-ESI-MS/MS (high-performance liquid chromatography–photodiode array detection–electrospray ionization tandem mass spectrometry), as well as the radical scavenging capacity, through ABTS (2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1 picrylhydrazyl), and the reducing power (FRAP, ferric reducing antioxidant power) assays, of P. lusitanica fruits during a 4-year study. In total, 28 compounds were identified and quantified in the fruits, including 21 hydroxycinnamic acids (60.3%); 2 flavan-3-ols (27.9%), 2 anthocyanins (10.5%), 2 flavonols (1.0%), and 1 secoiridoid (0.3%). High antioxidant capacity was observed, with ABTS values ranging from 7.88 to 10.69 mmol TE (Trolox equivalents)/100 g fw (fresh weight), DPPH values from 5.18 to 8.17 mmol TE/100 g fw, and FRAP values from 8.76 to 11.76 mmol TE/100 g fw. According to these results, it can be concluded that these are rich sources of phenolic compounds with very promising antioxidant capacity and, therefore, with potential applications in the food and/or phytopharmaceutical sectors.
Neuro-Inflammaging and Psychopathological Distress
Authors: Murdaca Giuseppe , Paladin Francesca , Casciaro Marco , Vicario Carmelo Mario , Gangemi Sebastiano , Martino Gabriella
Published: September 2022

Inflammaging is a low degree of chronic and systemic tissue inflammation associated with aging, and is intimately linked to pro-inflammatory mediators. These substances are involved in the pathogenesis of chronic inflammatory diseases and related psychopathological symptoms. When inflammation and aging affect the brain, we use the term neuro-inflammaging. In this review, we focused on the neuro-inflammatory process typical of advanced ages and the related psychopathological symptoms, with particular attention to understanding the immune-pathogenetic mechanisms involved and the potential use of immunomodulatory drugs in the control of clinical psychological signs. Inflammation and CNS were demonstrated being intimately linked in the neuro-inflammatory loop. IL-1, IL-6, TNF-a, COX and PGE are only partially responsible. BBB permeability and the consequent oxidative stress resulting from tissue damage make the rest. Some authors elaborated the “theory of cytokine-induced depression”. Inflammation has a crucial role in the onset symptoms of psychopathological diseases as it is capable of altering the metabolism of biogenic monoamines involved in their pathogenesis. In recent years, NSAIDs as an adjunct therapy in the treatment of relevant psychopathological disorders associated with chronic inflammatory conditions demonstrated their efficacy. Additionally, novel molecules have been studied, such as adalimumab, infliximab, and etanercept showing antidepressant and anxiolytic promising results. However, we are only at the beginning of a new era characterized by the use of biological drugs for the treatment of inflammatory and autoimmune diseases, and this paper aims to stimulate future studies in such a direction.
Eltanexor Effectively Reduces Viability of Glioblastoma and Glioblastoma Stem-Like Cells at Nano-Molar Concentrations and Sensitizes to Radiotherapy and Temozolomide
Authors: Otte Katharina , Zhao Kai , Braun Madita , Neubauer Andreas , Raifer Hartmann , Helmprobst Frederik , Barrera Felipe Ovalle , Nimsky Christopher , Bartsch Jörg W. , Rusch Tillmann
Published: September 2022

Current standard adjuvant therapy of glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to therapy resistance. Thus, novel therapeutic approaches are highly demanded. We tested the therapeutic efficacy of the second-generation XPO1 inhibitor Eltanexor using assays for cell viability and apoptosis in GBM cell lines and GBM stem-like cells. For most GBM-derived cells, IC50 concentrations for Eltanexor were below 100 nM. In correlation with reduced cell viability, apoptosis rates were significantly increased. GBM stem-like cells presented a combinatorial effect of Eltanexor with TMZ on cell viability. Furthermore, pretreatment of GBM cell lines with Eltanexor significantly enhanced radiosensitivity in vitro. To explore the mechanism of apoptosis induction by Eltanexor, TP53-dependent genes were analyzed at the mRNA and protein level. Eltanexor caused induction of TP53-related genes, TP53i3, PUMA, CDKN1A, and PML on both mRNA and protein level. Immunofluorescence of GBM cell lines treated with Eltanexor revealed a strong accumulation of CDKN1A, and, to a lesser extent, of p53 and Tp53i3 in cell nuclei as a plausible mechanism for Eltanexor-induced apoptosis. From these data, we conclude that monotherapy with Eltanexor effectively induces apoptosis in GBM cells and can be combined with current adjuvant therapies to provide a more effective therapy of GBM.
Correction: Pang et al. Canine Mammary Cancer Stem Cells Are Radio- and Chemo- Resistant and Exhibit an Epithelial-Mesenchymal Transition Phenotype. Cancers 2011, 3, 1744–1762
Authors: Pang Lisa Y. , Cervantes-Arias Alejandro , Else Rod W. , Argyle David J.
Published: September 2022

In the original article [...]
Solid-State Synthesis of ZnO/ZnS Photocatalyst with Efficient Organic Pollutant Degradation Performance
Authors: Jin Xuekun , Chen Jianjun , Chen Fengjuan , Duan Haiming , Wang Ziyu , Li Junhua
Published: September 2022

To improve the separation efficiency of photogenerated carriers in ZnS, constructing a ZnS-based heterostructure with ZnO is assessed to be an efficient strategy, and a ZnO/ZnS photocatalyst was prepared by a solid-phase approach, and the structure and morphology were systematically studied. The ZnO/ZnS photocatalyst showed excellent photocatalytic properties on methyl orange, rhodamine B and tetracycline under UV light irradiation, indicating that the photocatalyst exhibited efficient broad-spectrum photocatalytic performance. Compared with ZnS, the degradation rates of ZnO/ZnS photocatalysts for methyl orange, rhodamine B and tetracycline under UV light increased from 21%, 9% and 32% to 96%, 94% and 93%, respectively, higher than the reported ZnO/ZnS composites synthesized by a novel wet chemical route, attributing to the improvement of light absorption ability and the effective separation of carriers. In addition, the influence of the sacrificial agent on the reaction system was investigated, and the synergistic mechanism of ZnO and ZnS in the catalytic process was analyzed according to the fluorescence spectra, photocurrent and first-principles calculation results, and a possible catalytic mechanism was put forward.
Synthesis, Characterization, and Solar Photo-Activation of Chitosan-Modified Nickel Magnetite Bio-Composite for Degradation of Recalcitrant Organic Pollutants in Water
Authors: Ara Asmat , Khattak Rozina , Khan Muhammad Sufaid , Begum Bushra , Khan Sanaullah , Han Changseok
Published: September 2022

Photocatalysis is a promising process for decomposing harmful organic pollutants in water. In this study, solar/photocatalytic degradation of two model azo dyes, i.e., methylene blue (MB) and methyl red (MR), in water usinga nanostructured chitosan-modified nickel magnetite (CS-NM) bio-composite was investigated. The CS-NM bio-composite was synthesized through a co-precipitation method and characterized by Fourier transform infrared (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), thermogravimetry (TGA), and UV-Vis spectroscopy. FTIR analysis showed the uniform incorporation and conjugation of nickel magnetite (NM) into the chitosan (CS) polymer matrix. SEM showed that the average particle size was 0.5 μm. The TGA results revealed the good thermal stability of the prepared bio-composite at 300 °C. The point of zero charge was calculated as 7.5. The effect of water quality and process parameters, such as concentration of dyes, catalyst dose, solution pH, and temperatures, was investigated, for application purposes. The solar/CS-NM photocatalysis resulted in 99 and 96% degradation of individual MB and MR (C0 = 50 ppm), respectively, in 90 min. The degradation of MB and MR by solar/CS-NM photocatalysis followed pseudo-first-order kinetics, with observed rate constants (k) of 0.077 and 0.072 min−1, respectively. The CS-NM photocatalyst showed high recyclability, represented by only a 4–6% loss in the photocatalytic efficiency, after four cycles. The results showed that solar/CS-NM photocatalysis is an efficient technique for degrading recalcitrant organic pollutants, such as azo dyes, in water environments.
Long-Term Observational Outcomes after Total Correction of Congenital Heart Disease in Korean Patients with Down Syndrome: A National Cohort Study
Authors: Kwak Ji Hee , Lee Seung Won , Cha Hye Ryeong , Huh June , Kang I-Seok , Jun Tae-Gook , Yang Ji-Hyuk , Han Man Yong , Song Jinyoung
Published: September 2022

Background: In the present study, the population prevalence and postoperative morbidity and mortality in Down syndrome patients who underwent total correction for congenital heart disease were investigated using data from a large national cohort. Methods: Retrospective administrative data from 2,395,966 participants born between 2008 and 2012 were acquired from the National Investigation of Birth Cohort in Korea. Among Down syndrome patients, 58.3% had congenital heart disease and 32.3% underwent total correction. Propensity score matching (maximum 1:1) and stabilized inverse probability treatment weighting (IPTW) were performed for each group (153 Down syndrome patients and 4482 non-Down syndrome patients). Results: T late mortality rate was significantly higher in the Down syndrome group than in the non-Down syndrome group (8.1% vs. 3.8%). No differences were observed in postoperative heart failure and arrhythmias, but pulmonary hypertension was significantly greater in the Down syndrome group than in the non-Down syndrome group (26.9% vs. 7.0%). The length of hospitalization was longer in the Down syndrome group than in the non-Down syndrome group (14 days vs. 11 days; interquartile range (IQR): 10–25 vs. 6–19; p < 0.0001). After total correction, readmission frequency for any reason was minimally but statistically significantly higher in the Down syndrome group compared to the non-Down syndrome group (5 times vs. 5 times; IQR: 3–8 vs. 4–9; p < 0.0001). However, the number of emergency room visits was minimally but significantly lower in the Down syndrome group compared to the non-Down syndrome group (2 visits vs. 2 visits (IQR): 2–7 vs. 1–4; p = 0.016). Conclusions: Down syndrome patients with congenital heart disease undergoing total correction showed pulmonary hypertension after surgery, longer length of hospitalization, frequent hospitalization after surgery, and a higher rate of late mortality.
Vaccine Coverage in Children Younger Than 1 Year of Age during Periods of High Epidemiological Risk: Are We Preparing for New Outbreaks?
Authors: Herdea Valeria , Ghionaru Raluca , Lungu Claudiu N. , Leibovitz Eugene , Diaconescu Smaranda
Published: September 2022

Background: According to WHO, infectious disease control can be achieved if the vaccine coverage (VC) exceeds 90%. In recent years there has been a declining trend in VC which could lead to the recurrence of infectious diseases. Objectives: The study analyzed the determinants of VC and of parental decisions regarding immunization in children aged 0–1 year monitored during two high-risk epidemiological periods (the measles epidemic and the COVID-19 pandemic period). Methods: A retrospective observational cohort study-data regarding vaccination of children younger than 1 year of age during the periods January 2019–June 2019 (measles epidemic) and January 2020–June 2020 (COVID-19 pandemic) were analyzed. 2.850 children from 2019 and 2.823 children from 2020 were enrolled. Family physicians interacted with 2840 parents or legal guardians in 2019 and with 2800 parents or legal guardians in 2020, during the infants’ consults providing medical information and answer to their questions and worries regarding their immunization. Data on immunization schedules on the determinants of parents’ decisions regarding vaccination were evaluated. Results: During 2019–2020, VC has followed a declining trend for each type of vaccine included in the Romanian National Immunization Program; the most affected were infants aged 9–12 months during both periods: in 9-month aged infants, the MMR vaccine VC was 67.49% in 2019 vs. 59.04% in 2020 (p < 0.004). In the 12 months aged infants, the MMR VC was 64.29% in 2019 vs. 55.88% in 2020 (p < 0.005). For the Hexavalent vaccine administered at the age of 11 months, the VC was 71.59% in 2019 vs. 62.08% in 2020 (p < 0.001). The determinants of parents’ decisions regarding vaccination included parental hesitance 2019—25% vs. 2020—35%, fear on side effects 2019—32% vs. 2020—45%, vaccination denial 2019—7% vs. 2020—10%. Conclusion: We found a declining trend in the VC in Romania during the epidemic and pandemic periods. The decrease in VC for MMR generated a major risk for new measles outbreaks Permanent awareness educational campaigns regarding infectious disease risk are needed, accompanied by the empowerment of primary care and the emergence of an immunization management program based on national regulatory legislation.
Hypermanganesemia with Dystonia Type 2: A Potentially Treatable Neurodegenerative Disorder: A Case Series in a Tertiary University Hospital
Authors: Alhasan Khalid A. , Alshuaibi Walaa , Hamad Muddathir H. , Salim Suha , Jamjoom Dima Z. , Alhashim Aqeela H. , AlGhamdi Malak Ali , Kentab Amal Y. , Bashiri Fahad A.
Published: September 2022

Importance: Hypermanganesemia with dystonia type 2 is a rare autosomal recessive neurodegenerative disorder characterized by the loss of previously acquired milestones, dystonia, parkinsonian features, a high serum manganese level, and characteristic neuroimaging findings such as bilateral and symmetrically increased T1 and decreased T2/fluid-attenuated inversion recovery signal intensity in the basal ganglia. This condition is secondary to a mutation in the SLC39A14 gene. Objective: To present a series of three cases of hypermanganesemia with dystonia type 2, which was genetically confirmed secondary to a mutation in the SLC39A14 gene, and to describe the treatment and clinical course in these cases. Design: A retrospective case series. Setting: University, Tertiary hospital. Participants: Three unrelated pediatric patients with hypermanganesemia with dystonia type 2, genetically confirmed to be secondary to a mutation in the SLC39A14 gene. Exposures: Chelation therapy using calcium disodium edetate. Main outcome(s) and measure(s): The response to chelation therapy based on clinical improvements in motor and cognition developments. Results: All three patients were started on chelation therapy using calcium disodium edetate, and two of them showed an improvement in their clinical course. The chelation therapy could alter the course of the disease and prevent deterioration in the clinical setting. Conclusions and Relevance: Early diagnosis and intervention with chelating agents, such as calcium disodium edetate, will help change the outcome in patients with hypermanganesemia with dystonia type 2. This finding highlights the importance of early diagnosis and treatment in improving the outcomes of patients with treatable neurodegenerative disorders.
A Critical Review of Radiolysis Issues in Water-Cooled Fission and Fusion Reactors: Part I, Assessment of Radiolysis Models
Authors: Macdonald Digby D. , Engelhardt George R. , Petrov Andrei
Published: September 2022

A critical review is presented on modeling of the radiolysis of the coolant water in nuclear power reactors with emphasis on ITER. The review is presented in two parts: In Part I, we assess previous work in terms of compliance with important chemical principles and conclude that no model proposed to date is completely satisfactory, in this regard. Thus, some reactions that have been proposed in various radiolysis models are not elementary in nature and can be decomposed into two or more elementary reactions, some of which are already included in the models. These reactions must be removed in formulating a viable model. Furthermore, elementary reactions between species of like charge are also commonly included, but they can be discounted upon the basis of Coulombic repulsion under the prevailing conditions (T < 350 °C) and must also be removed. Likewise, it is concluded that the current state of knowledge with respect to radiolytic yields (i.e., G-values) is also unsatisfactory. More work is required to ensure that the yields used in radiolysis models are truly “primary” yields corresponding to a time scale of nanoseconds or less. This is necessary to ensure that the impact of the reactions that occur outside of the spurs (ionizing particle tracks in the medium) are not counted twice. In Part II, the authors review the use of the radiolysis models coupled with electrochemical models to predict the water chemistry, corrosion potential, crack growth rate in Type 304 SS, and accumulated damage in the coolant circuits of boiling water reactors, pressurized water reactors, and the test fusion reactor, ITER. Based on experience with fission reactors, the emphasis should be placed on the control of the electrochemical corrosion potential because it is the parameter that best describes the state of corrosion in coolant circuits.
A Case Series of 39 United States Veterans with Mild Traumatic Brain Injury Treated with Hyperbaric Oxygen Therapy
Authors: Bested Alison C. , Rana Arif M. , Hardigan Patrick , Niyirora Jerome , Cheema Amanpreet , Antony George , Defina Philip A. , Machado Calixto
Published: September 2022

Importance: The Defense and Veterans Brain Injury Center reported 358,088 mild traumatic brain injury (mTBI) among U.S. service members worldwide between the years 2000 and 2020. Veterans with mTBI have higher rates of Post-Traumatic Stress Disorder (PTSD), depressive disorder, substance use disorder, anxiety disorder, and suicide than their healthy counterparts. Currently, there is no effective treatment for mTBI. Objective: To assess the efficacy of hyperbaric oxygen therapy (HBOT) as a treatment option for mTBI. Design, Setting, Participants: This is a case series of 39 U.S. Veterans diagnosed with mTBI and treated with HBOT. Of these participants, 36 were men and 3 women, and their ages ranged between 28 and 69. The treatment was administered by The 22 Project (a veteran-centered nonprofit organization) using monoplace hyperbaric chambers located in Delray Beach, Florida. Neuroimaging using Single Photon Emission Computer Tomography (SPECT) brain scans performed pre- and post-HBOT were made available for secondary analysis. Nilearn Python Library was utilized to visualize the corresponding neuroimaging data. A two-sided paired t-test in R was used to compare the pre- and post-treatment results. Intervention: A full treatment of HBOT involved 40 sessions. Each session consisted of the administration of 100% oxygen at 1.5 atmospheres for 90 min, twice a day, for 20 days, Mondays to Fridays only. Main Outcome and Measure: Perfusion in the brain’s Brodmann Areas (BA) comparing pre- and post-HBOT using NeuroGam software analysis from brain SPECT scan neuroimaging and multi-symptom self-reports. Results: A comparison between the pre- and post-HBOT brain scans showed significant improvement in the brain perfusion, and the difference was statistically significant (p < 0.001). Separately, participants reported reduced pain, improved mood, and better sleep, an outcome that translated into an average of about 46.6% improvement in the measured symptoms. Conclusions and Relevance: This series demonstrated that HBOT could be a useful treatment for mTBI in U.S. veterans. The participants in the study showed marked improvement in both brain perfusion measured on SPECT scan imaging and measured mTBI symptoms. This is the first study to use brain SPECT scans with quantitative numerical measurements to demonstrate improvement in brain perfusion in veterans with mild TBI treated with HBOT and measured mTBI symptoms. Future research studies are currently being done to validate these important findings.
Clinical Trials of Vitamin Supplements: Are They Meeting the European Medicines Agency Prompt Dissemination Regulation?
Authors: Lampropoulou Maria A. , Grammatikopoulou Maria G. , Theodoridis Xenophon , Katsaridis Savvas , Bobora Despoina , Patsatsi Aikaterini , Haidich Anna-Bettina , Goulis Dimitrios G.
Published: September 2022

Vitamin supplements are over-the-counter medications consumed by the majority of adults. Given that many supplements may be ineffective and/or associated with adverse events, compliance of the registered trials to the European Medicines Agency (EMA) rule for prompt reporting of the results is of crucial importance for consumers’ health. The present retrospective study was designed to evaluate compliance with the European Union (EU) requirement to post the trial results to the EU Clinical Trials Database (EudraCT) and assess the trial characteristics associated with this compliance. Three independent researchers searched the EudraCT for completed trials on vitamin supplements performed on humans. A total of 144 completed trials involving 40,464 participants fulfilled the inclusion criteria. For 45.7% of these, results were due. Trials funded by the industry had approximately quadruple chances of being published, adjusting for their design, masking, comparator, and participant age group. Moreover, trials testing vitamin supplement safety are more likely to report their findings as compared to vitamin efficacy. Many vitamin supplementation trials registered in the EudraCT failed to report their results and adhere to the EMA regulations. Stricter regulations should be imposed concerning trial results reporting to increase transparency and public trust.
Numerical Investigation on Thermal–Hydraulic Performance of a Printed Circuit Heat Exchanger for Liquid Air Energy Storage System
Authors: Liu Hu , Zhang Yankang , Yu Pengfei , Xue Jingwen , Zhang Lei , Che Defu
Published: September 2022

A printed circuit heat exchanger (PCHE) is utilized to cool the compressor inlet air to increase the compression efficiency in a liquid air energy storage and liquid natural gas (LNG) coupled system, which can offer large-scale energy storage with significantly improved exergy efficiency and round-trip efficiency. In this work, the effect of pressure of air, incline angle, and hydraulic diameter on the performance of a compressed air–water PCHE with a semicircle cross-section was studied. The results show that PCHE can realize the intermediate cooling of air compression in the liquid air energy storage system, and the pressure variation of air shows a limited effect on the heat transfer of PCHE; however, the hydraulic diameter and the incline angle both affect the heat transfer and the flow resistance of PCHE, and the best incline angle is 15°.