bluuebunny/crossref_metadata_2025 huggingface dataset:
Alterations in Glucose Metabolism Due to Decreased Expression of Heterogeneous Nuclear Ribonucleoprotein M in Pancreatic Ductal Adenocarcinoma
Authors: Takino Jun-ichi , Sato Takuma , Hiraishi Isamu , Nagamine Kentaro , Hori Takamitsu
Published: January 2021

The prognosis of pancreatic cancer is considerably worse than that of other cancers, as early detection of pancreatic cancer is difficult and due to its hypovascular environment, which involves low blood flow and a low supply of oxygen and nutrients. Moreover, pancreatic cancer demonstrates a mechanism that allows it to survive in a hypovascular environment. However, the detailed mechanism remains elusive. Recently, it has been reported that heterogeneous ribonuclear protein M (HNRNPM) is a splicing factor associated with malignant tumors. Thus, in this study, we investigated the expression and effects of HNRNPM in pancreatic ductal adenocarcinoma (PDA). We observed that HNRNPM expression, which is highly expressed in pancreatic tissues, was reduced in PDA tissues. Additionally, knockdown of HNRNPM under low-glucose conditions that mimic a hypovascular environment was shown to alter glucose metabolism and prolong cell survival by suppressing glucose consumption. These results suggest that the decreased expression of HNRNPM in PDA may be involved in its adaptation to a hypovascular environment.
Phytochemical Constituents of Citrus hystrix DC. Leaves Attenuate Inflammation via NF-κB Signaling and NLRP3 Inflammasome Activity in Macrophages
Authors: Buakaew Watunyoo , Pankla Sranujit Rungnapa , Noysang Chanai , Thongsri Yordhathai , Potup Pachuen , Nuengchamnong Nitra , Suphrom Nungruthai , Usuwanthim Kanchana
Published: January 2021

Citrus hystrix DC. (CH) is found in many countries in Southeast Asia. This plant has been reported for anti-microbial, anti-cancer and anti-inflammatory bioactivities. However, the anti-inflammatory and anti-inflammasome properties of the leaves remain poorly understood. This study aimed to investigate the effect of CH leaves on NLRP3 and NF-κB signaling pathways. CH leaves were sequentially extracted using hexane, ethyl acetate and 95% ethanol to give three crude extracts. An active compound, lupeol was fractionated from the ethanolic extract using chromatographic techniques, and its structure was identified and confirmed by spectroscopic methods. Anti-inflammatory activities were observed on both lipopolysaccharide-stimulated and NLRP3 adenosine triphosphate-induced macrophages. The release of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). Real-time qRT-polymerase chain reaction (PCR) was used to measure inflammatory-associated gene expression. NF-κB protein expressions were investigated using the immunoblotting technique. The active fraction of ethanolic CH leaves and lupeol significantly reduced the release of pro-inflammatory cytokines and suppressed the expression of both inflammasome genes and NF-κB proteins. The ethanolic extract of CH leaves and lupeol showed potent anti-inflammatory activities by targeting NF-κB and NLRP3 signaling pathways.
From Cell Culture to Organoids-Model Systems for Investigating Prion Strain Characteristics
Authors: Pineau Hailey , Sim Valerie L.
Published: January 2021

Prion diseases are the hallmark protein folding neurodegenerative disease. Their transmissible nature has allowed for the development of many different cellular models of disease where prion propagation and sometimes pathology can be induced. This review examines the range of simple cell cultures to more complex neurospheres, organoid, and organotypic slice cultures that have been used to study prion disease pathogenesis and to test therapeutics. We highlight the advantages and disadvantages of each system, giving special consideration to the importance of strains when choosing a model and when interpreting results, as not all systems propagate all strains, and in some cases, the technique used, or treatment applied, can alter the very strain properties being studied.
Musculoskeletal Features without Ataxia Associated with a Novel de novo Mutation in KCNA1 Impairing the Voltage Sensitivity of Kv1.1 Channel
Authors: Imbrici Paola , Accogli Andrea , Blunck Rikard , Altamura Concetta , Iacomino Michele , D’Adamo Maria Cristina , Allegri Anna , Pedemonte Marina , Brolatti Noemi , Vari Stella , Cataldi Matteo , Capra Valeria , Gustincich Stefano , Zara Federico , Desaphy Jean-Francois , Fiorillo Chiara
Published: January 2021

The KCNA1 gene encodes the α subunit of the voltage-gated Kv1.1 potassium channel that critically regulates neuronal excitability in the central and peripheral nervous systems. Mutations in KCNA1 have been classically associated with episodic ataxia type 1 (EA1), a movement disorder triggered by physical and emotional stress. Additional features variably reported in recent years include epilepsy, myokymia, migraine, paroxysmal dyskinesia, hyperthermia, hypomagnesemia, and cataplexy. Interestingly, a few individuals with neuromyotonia, either isolated or associated with skeletal deformities, have been reported carrying variants in the S2–S3 transmembrane segments of Kv1.1 channels in the absence of any other symptoms. Here, we have identified by whole-exome sequencing a novel de novo variant, T268K, in KCNA1 in a boy displaying recurrent episodes of neuromyotonia, muscle hypertrophy, and skeletal deformities. Through functional analysis in heterologous cells and structural modeling, we show that the mutation, located at the extracellular end of the S3 helix, causes deleterious effects, disrupting Kv1.1 function by altering the voltage dependence of activation and kinetics of deactivation, likely due to abnormal interactions with the voltage sensor in the S4 segment. Our study supports previous evidence suggesting that specific residues within the S2 and S3 segments of Kv1.1 result in a distinctive phenotype with predominant musculoskeletal presentation.
Changes in Prefrontal Cortex–Thalamic Circuitry after Acoustic Trauma
Authors: Barry Kristin M. , Robertson Donald , Mulders Wilhelmina H. A. M.
Published: January 2021

In the adult auditory system, loss of input resulting from peripheral deafferentation is well known to lead to plasticity in the central nervous system, manifested as reorganization of cortical maps and altered activity throughout the central auditory pathways. The auditory system also has strong afferent and efferent connections with cortico-limbic circuitry including the prefrontal cortex and the question arises whether this circuitry is also affected by loss of peripheral input. Recent studies in our laboratory showed that PFC activation can modulate activity of the auditory thalamus or medial geniculate nucleus (MGN) in normal hearing rats. In addition, we have shown in rats that cochlear trauma resulted in altered spontaneous burst firing in MGN. However, whether the PFC influence on MGN is changed after cochlear trauma is unknown. We investigated the effects of electrical stimulation of PFC on single neuron activity in the MGN in anaesthetized Wistar rats 2 weeks after acoustic trauma or sham surgery. Electrical stimulation of PFC showed a variety of effects in MGN neurons both in sham and acoustic trauma groups but inhibitory responses were significantly larger in the acoustic trauma animals. These results suggest an alteration in functional connectivity between PFC and MGN after cochlear trauma. This change may be a compensatory mechanism increasing sensory gating after the development of altered spontaneous activity in MGN, to prevent altered activity reaching the cortex and conscious perception.
Single-Trial Recognition of Video Gamer’s Expertise from Brain Haemodynamic and Facial Emotion Responses
Authors: Andreu-Perez Ana R. , Kiani Mehrin , Andreu-Perez Javier , Reddy Pratusha , Andreu-Abela Jaime , Pinto Maria , Izzetoglu Kurtulus
Published: January 2021

With an increase in consumer demand of video gaming entertainment, the game industry is exploring novel ways of game interaction such as providing direct interfaces between the game and the gamers’ cognitive or affective responses. In this work, gamer’s brain activity has been imaged using functional near infrared spectroscopy (fNIRS) whilst they watch video of a video game (League of Legends) they play. A video of the face of the participants is also recorded for each of a total of 15 trials where a trial is defined as watching a gameplay video. From the data collected, i.e., gamer’s fNIRS data in combination with emotional state estimation from gamer’s facial expressions, the expertise level of the gamers has been decoded per trial in a multi-modal framework comprising of unsupervised deep feature learning and classification by state-of-the-art models. The best tri-class classification accuracy is obtained using a cascade of random convolutional kernel transform (ROCKET) feature extraction method and deep classifier at 91.44%. This is the first work that aims at decoding expertise level of gamers using non-restrictive and portable technologies for brain imaging, and emotional state recognition derived from gamers’ facial expressions. This work has profound implications for novel designs of future human interactions with video games and brain-controlled games.
JAK3 Is Expressed in the Nucleus of Malignant T Cells in Cutaneous T Cell Lymphoma (CTCL)
Authors: Vadivel Chella Krishna , Gluud Maria , Torres-Rusillo Sara , Boding Lasse , Willerslev-Olsen Andreas , Buus Terkild B. , Nielsen Tea Kirkegaard , Persson Jenny L. , Bonefeld Charlotte M. , Geisler Carsten , Krejsgaard Thorbjorn , Fuglsang Anja T. , Odum Niels , Woetmann Anders
Published: January 2021

Perturbation in JAK-STAT signaling has been reported in the pathogenesis of cutaneous T cell lymphoma (CTCL). JAK3 is predominantly associated with the intra-cytoplasmic part of IL-2Rγc located in the plasma membrane of hematopoietic cells. Here we demonstrate that JAK3 is also ectopically expressed in the nucleus of malignant T cells. We detected nuclear JAK3 in various CTCL cell lines and primary malignant T cells from patients with Sézary syndrome, a leukemic variant of CTCL. Nuclear localization of JAK3 was independent of its kinase activity whereas STAT3 had a modest effect on nuclear JAK3 expression. Moreover, JAK3 nuclear localization was only weakly affected by blockage of nuclear export. An inhibitor of the nuclear export protein CRM1, Leptomycin B, induced an increased expression of SOCS3 in the nucleus, but only a weak increase in nuclear JAK3. Importantly, immunoprecipitation experiments indicated that JAK3 interacts with the nuclear protein POLR2A, the catalytic subunit of RNA Polymerase II. Kinase assays showed tyrosine phosphorylation of recombinant human Histone H3 by JAK3 in vitro—an effect which was blocked by the JAK inhibitor (Tofacitinib citrate). In conclusion, we provide the first evidence of nuclear localization of JAK3 in malignant T cells. Our findings suggest that JAK3 may have a cytokine-receptor independent function in the nucleus of malignant T cells, and thus a novel non-canonical role in CTCL.
The Calcitriol/Vitamin D Receptor System Regulates Key Immune Signaling Pathways in Chronic Lymphocytic Leukemia
Authors: Gerousi Marina , Psomopoulos Fotis , Kotta Konstantia , Tsagiopoulou Maria , Stavroyianni Niki , Anagnostopoulos Achilles , Anastasiadis Athanasios , Gkanidou Maria , Kotsianidis Ioannis , Ntoufa Stavroula , Stamatopoulos Kostas
Published: January 2021

It has been proposed that vitamin D may play a role in prevention and treatment of cancer while epidemiological studies have linked vitamin D insufficiency to adverse disease outcomes in various B cell malignancies, including chronic lymphocytic leukemia (CLL). In this study, we sought to obtain deeper biological insight into the role of vitamin D and its receptor (VDR) in the pathophysiology of CLL. To this end, we performed expression analysis of the vitamin D pathway molecules; complemented by RNA-Sequencing analysis in primary CLL cells that were treated in vitro with calcitriol, the biologically active form of vitamin D. In addition, we examined calcitriol effects ex vivo in CLL cells cultured in the presence of microenvironmental signals, namely anti-IgM/CD40L, or co-cultured with the supportive HS-5 cells; and, CLL cells from patients under ibrutinib treatment. Our study reports that the calcitriol/VDR system is functional in CLL regulating signaling pathways critical for cell survival and proliferation, including the TLR and PI3K/AKT pathways. Moreover, calcitriol action is likely independent of the microenvironmental signals in CLL, since it was not significantly affected when combined with anti-IgM/CD40L or in the context of the co-culture system. This finding was also supported by our finding of preserved calcitriol signaling capacity in CLL patients under ibrutinib treatment. Overall, our results indicate a relevant biological role for vitamin D in CLL pathophysiology and allude to the potential clinical utility of vitamin D supplementation in patients with CLL.
Overcoming Challenges for CD3-Bispecific Antibody Therapy in Solid Tumors
Authors: Middelburg Jim , Kemper Kristel , Engelberts Patrick , Labrijn Aran F. , Schuurman Janine , van Hall Thorbald
Published: January 2021

Immunotherapy of cancer with CD3-bispecific antibodies is an approved therapeutic option for some hematological malignancies and is under clinical investigation for solid cancers. However, the treatment of solid tumors faces more pronounced hurdles, such as increased on-target off-tumor toxicities, sparse T-cell infiltration and impaired T-cell quality due to the presence of an immunosuppressive tumor microenvironment, which affect the safety and limit efficacy of CD3-bispecific antibody therapy. In this review, we provide a brief status update of the CD3-bispecific antibody therapy field and identify intrinsic hurdles in solid cancers. Furthermore, we describe potential combinatorial approaches to overcome these challenges in order to generate selective and more effective responses.
Glycerol Hydrogenolysis with In Situ Hydrogen Produced via Methanol Steam Reforming: The Promoting Effect of Pd on a Cu/ZnO/Al2O3 Catalyst
Authors: Liu Yuanqing , Mai Chau T. Q. , Ng Flora T. T.
Published: January 2021

The glycerol hydrogenolysis to produce 1,2-propanediol without using externally supplied hydrogen was investigated using methanol present in crude glycerol to provide in situ hydrogen via its steam reforming reaction. This paper focuses on the promoting effect of Pd on the reactivity of a Cu/Zn/Al2O3 catalyst. Adding 2 wt% Pd onto a Cu/ZnO/Al2O3 catalyst significantly improved the selectivity to 1,2-propanediol from 63.0% to 82.4% and the glycerol conversion from 70.2% to 99.4%. This enhancement on the catalytic activity by Pd is mainly due to the improved hydrogenation of acetol, which is the intermediate formed during the glycerol dehydration. The rapid hydrogenation of acetol can shift the reaction equilibrium of glycerol dehydration forward resulting in a higher glycerol conversion. The improved reducibility of the catalyst by Pd allows the catalyst to be reduced in situ during the reaction preventing any loss of catalyst activity due to any potential oxidation of the catalyst. The catalyst was slightly deactivated when it was firstly recycled resulting in a 5.4% loss of glycerol conversion due to the aggregation of Cu and the deactivation became less noticeable upon further recycling.
Nuclear Pore Complexes Cluster in Dysmorphic Nuclei of Normal and Progeria Cells during Replicative Senescence
Authors: Röhrl Jennifer M. , Arnold Rouven , Djabali Karima
Published: January 2021

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disease caused by a mutation in LMNA. A G608G mutation in exon 11 of LMNA is responsible for most HGPS cases, generating a truncated protein called “progerin”. Progerin is permanently farnesylated and accumulates in HGPS cells, causing multiple cellular defects such as nuclear dysmorphism, a thickened lamina, loss of heterochromatin, premature senescence, and clustering of Nuclear Pore Complexes (NPC). To identify the mechanism of NPC clustering in HGPS cells, we evaluated post-mitotic NPC assembly in control and HGPS cells and found no defects. Next, we examined the occurrence of NPC clustering in control and HGPS cells during replicative senescence. We reported that NPC clustering occurs solely in the dysmorphic nuclei of control and HGPS cells. Hence, NPC clustering occurred at a higher frequency in HGPS cells compared to control cells at early passages; however, in late cultures with similar senescence index, NPCs clustering occurred at a similar rate in both control and HGPS. Our results show that progerin does not disrupt post-mitotic reassembly of NPCs. However, NPCs frequently cluster in dysmorphic nuclei with a high progerin content. Additionally, nuclear envelope defects that arise during replicative senescence cause NPC clustering in senescent cells with dysmorphic nuclei.
GRKs and Epac1 Interaction in Cardiac Remodeling and Heart Failure
Authors: Laudette Marion , Formoso Karina , Lezoualc’h Frank
Published: January 2021

β-adrenergic receptors (β-ARs) play a major role in the physiological regulation of cardiac function through signaling routes tightly controlled by G protein-coupled receptor kinases (GRKs). Although the acute stimulation of β-ARs and the subsequent production of cyclic AMP (cAMP) have beneficial effects on cardiac function, chronic stimulation of β-ARs as observed under sympathetic overdrive promotes the development of pathological cardiac remodeling and heart failure (HF), a leading cause of mortality worldwide. This is accompanied by an alteration in cAMP compartmentalization and the activation of the exchange protein directly activated by cAMP 1 (Epac1) signaling. Among downstream signals of β-ARs, compelling evidence indicates that GRK2, GRK5, and Epac1 represent attractive therapeutic targets for cardiac disease. Here, we summarize the pathophysiological roles of GRK2, GRK5, and Epac1 in the heart. We focus on their signalosome and describe how under pathological settings, these proteins can cross-talk and are part of scaffolded nodal signaling systems that contribute to a decreased cardiac function and HF development.
Acknowledgment to Reviewers of Children in 2020
Authors:   Children Editorial Office
Published: January 2021

Peer review is the driving force of journal development, and reviewers are gatekeepers who ensure that Children maintains its standards for the high quality of its published papers [...]
Mechanical Properties of Graphene Oxide Coupled by Multi-Physical Field: Grain Boundaries and Functional Groups
Authors: Xu Xu , Zhang Zeping , Yao Wenjuan
Published: January 2021

Graphene and graphene oxide (GO) usually have grain boundaries (GBs) in the process of synthesis and preparation. Here, we “attach” GBs into GO, a new molecular configuration i.e., polycrystalline graphene oxide (PGO) is proposed. This paper aims to provide an insight into the stability and mechanical properties of PGO by using the molecular dynamics method. For this purpose, the “bottom-up” multi-structure-spatial design performance of PGO and the physical mechanism associated with the spatial structure in mixed dimensions (combination of sp2 and sp3) were studied. Also, the effect of defect coupling (GBs and functional groups) on the mechanical properties was revealed. Our results demonstrate that the existence of the GBs reduces the mechanical properties of PGO and show an “induction” role during the tensile fracture process. The presence of functional groups converts in-plane sp2 carbon atoms into out-of-plane sp3 hybrid carbons, causing uneven stress distribution. Moreover, the mechanical characteristics of PGO are very sensitive to the oxygen content of functional groups, which decrease with the increase of oxygen content. The weakening degree of epoxy groups is slightly greater than that of hydroxyl groups. Finally, we find that the mechanical properties of PGO will fall to the lowest values due to the defect coupling amplification mechanism when the functional groups are distributed at GBs.
Quantifying Waterfowl Numbers: Comparison of Drone and Ground-Based Survey Methods for Surveying Waterfowl on Artificial Waterbodies
Authors: Dundas Shannon J. , Vardanega Molly , O’Brien Patrick , McLeod Steven R.
Published: January 2021

Drones are becoming a common method for surveying wildlife as they offer an aerial perspective of the landscape. For waterbirds in particular, drones can overcome challenges associated with surveying locations not accessible on foot. With the rapid uptake of drone technology for bird surveys, there is a need to compare and calibrate new technologies with existing survey methods. We compared waterfowl counts derived from ground- and drone-based survey methods. We sought to determine if group size and waterbody size influenced the difference between counts of non-nesting waterfowl and if detection of species varied between survey methods. Surveys of waterfowl were carried out at constructed irrigation dams and wastewater treatment ponds throughout the Riverina region of New South Wales (NSW), Australia. Data were analyzed using Bayesian multilevel models (BMLM) with weakly informative priors. Overall, drone-derived counts of waterfowl were greater (+36%) than ground counts using a spotting scope (β_ground= 0.64 [0.62–0.66], (R2 = 0.973)). Ground counts also tended to underestimate the size of groups. Waterbody size had an effect on comparative counts, with ground counts being proportionally less than drone counts (mean = 0.74). The number of species identified in each waterbody type was similar regardless of survey method. Drone-derived counts are more accurate compared to traditional ground counts, but drones do have some drawbacks including initial equipment costs and time-consuming image or photo processing. Future surveys should consider using drones for more accurately surveying waterbirds, especially when large groups of birds are present on larger waterbodies.
A Hybrid Genetic-Hierarchical Algorithm for the Quadratic Assignment Problem
Authors: Misevičius Alfonsas , Verenė Dovilė
Published: January 2021

In this paper, we present a hybrid genetic-hierarchical algorithm for the solution of the quadratic assignment problem. The main distinguishing aspect of the proposed algorithm is that this is an innovative hybrid genetic algorithm with the original, hierarchical architecture. In particular, the genetic algorithm is combined with the so-called hierarchical (self-similar) iterated tabu search algorithm, which serves as a powerful local optimizer (local improvement algorithm) of the offspring solutions produced by the crossover operator of the genetic algorithm. The results of the conducted computational experiments demonstrate the promising performance and competitiveness of the proposed algorithm.
Hysteresis-Free Piezoresponse in Thermally Strained Ferroelectric Barium Titanate Films
Authors: Tyunina Marina , Miksovsky Jan , Kocourek Tomas , Dejneka Alexandr
Published: January 2021

Modern technology asks for thin films of sustainable piezoelectrics, whereas electro-mechanical properties of such films are poorly explored and controlled. Here, dynamic and quasi-static polarization, dielectric, and piezoelectric responses were experimentally studied in thin-film stacks of barium titanate sandwiched between electrodes and grown on top of strontium titanate substrate. Accurate piezoelectric characterization was secured by using double beam interferometric technique. All out-of-plane responses were found to be hysteresis-free. Effective piezoelectric coefficient ~50 pm/V and linear strain-voltage characteristic were achieved. The observed behavior was ascribed to field induced out-of-plane polarization, whereas spontaneous polarization is in-plane due to in-plane tensile thermal strain. Hysteresis-free linear piezoresponse was anticipated in thin films on commercial silicon substrates, enabling large thermal strain.
Multiclass ECG Signal Analysis Using Global Average-Based 2-D Convolutional Neural Network Modeling
Authors: Wasimuddin Muhammad , Elleithy Khaled , Abuzneid Abdelshakour , Faezipour Miad , Abuzaghleh Omar
Published: January 2021

Cardiovascular diseases have been reported to be the leading cause of mortality across the globe. Among such diseases, Myocardial Infarction (MI), also known as “heart attack”, is of main interest among researchers, as its early diagnosis can prevent life threatening cardiac conditions and potentially save human lives. Analyzing the Electrocardiogram (ECG) can provide valuable diagnostic information to detect different types of cardiac arrhythmia. Real-time ECG monitoring systems with advanced machine learning methods provide information about the health status in real-time and have improved user’s experience. However, advanced machine learning methods have put a burden on portable and wearable devices due to their high computing requirements. We present an improved, less complex Convolutional Neural Network (CNN)-based classifier model that identifies multiple arrhythmia types using the two-dimensional image of the ECG wave in real-time. The proposed model is presented as a three-layer ECG signal analysis model that can potentially be adopted in real-time portable and wearable monitoring devices. We have designed, implemented, and simulated the proposed CNN network using Matlab. We also present the hardware implementation of the proposed method to validate its adaptability in real-time wearable systems. The European ST-T database recorded with single lead L3 is used to validate the CNN classifier and achieved an accuracy of 99.23%, outperforming most existing solutions.
Influence of the Heating Method on the Efficiency of Biomethane Production from Expired Food Products
Authors: Kazimierowicz Joanna , Zieliński Marcin , Dębowski Marcin
Published: January 2021

The aim of the study was to determine the effect of heating with microwave electromagnetic radiation (EMR) on the efficiency of the methane fermentation (MF) of expired food products (EFP). The research was inspired by the positive effect of EMR on the production of biogas and methane from different organic substrates. The experiment was carried out on a laboratory scale in fully mixed, semi-continuous anaerobic reactors. The technological conditions were as follows: temperature, 35 ± 1 °C; organic load rate (OLR), 2.0 kgVS·m−3∙d−1; and hydraulic retention time (HRT), 40 days. The source of the EMR was a magnetron (electric power, 300 W). There was no statistically significant influence of the use of EMR on the achieved technological effects of MF. The efficiency of biogas production was 710 ± 35 dm3·kgVS−1 in the variant with EMR and 679 ± 26 dm3·kgVS−1 in the variant with convection heating (CH). The methane contents were 63.5 ± 2.4% (EMR) and 62.4 ± 4.0% (CH), and the cumulative methane production after 40 days was 271.2 and 288.6 dm3CH4, respectively.
The Role of Past Suicidal Behavior on Current Suicidality: A Retrospective Study in the Israeli Military
Authors: Shelef Leah , Rabbany Jessica M , Gutierrez Peter M , Kedem Ron , Ben Yehuda Ariel , Mann J. John , Yacobi Assaf
Published: January 2021

Past suicide attempts are a significant risk factor for future suicidality. Therefore, the present military-based study examined the past suicidal behavior of soldiers who recently made a severe suicide attempt. Our sample consisted of 65 active-duty soldiers (61.5% males), between the ages of 18 and 28 years old (M = 20.4, SD ± 1.3). The inclusion criterion was a recent severe suicide attempt, requiring at least a 24 h hospitalization. This sample was divided into two groups, according to previous suicidal behavior, namely whether their first suicide attempt was before or after enlistment (n = 25; 38.5% and n = 40; 61.5%, respectively). We then examined the lethality and intent of the recent event in regard to this division. Four measures were used to assess the subjects’ suicidal characteristics: the Columbia Suicide Severity Rating Scale, the Self-Harm Behavior Questionnaire, the Suicidal Behaviors Questionnaire-Revised, and the Beck Scale for Suicide Ideation. No significant difference in the severity of the suicide attempts (either actual or potential severity) were found between those who had suicide attempts before enlistment and those who had their first attempt in the service. As a matter of fact, most of the suicide attempts that occurred for the first time during military service had used a violent method (58.3%, n = 21). Finally, using multivariate analyses, we found that current thoughts and behavior, rather than past suicidality, was the strongest predictor for the lethality of suicide attempts.
Application of Portfolio Theory to Healthcare Capacity Management
Authors: Fagefors Carina , Lantz Björn
Published: January 2021

Healthcare systems worldwide are faced with continuously increasing demand for care, while simultaneously experiencing insufficient capacity and unacceptably long patient waiting times. To improve healthcare access and availability, it is thus necessary to improve capacity utilization and increase the efficiency of existing resource usage. For this, variations in healthcare systems must be managed judiciously, and one solution is to apply a capacity pooling approach. A capacity pool is a general, collaborative capacity that can be allocated to parts of the system where the existing workload and demand for capacity are unusually high. In this study, we investigate how basic mean-variance methodology from portfolio theory can be applied as a capacity pooling approach to healthcare systems. A numerical example based on fictitious data is used to illustrate the theoretical value of using a portfolio approach in a capacity pooling context. The example shows that there are opportunities to use capacity more efficiently and increase service levels, given the same capacity, and that a mean-variance analysis could be performed to theoretically dimension the most efficient pooling organization. The study concludes with a discussion regarding the practical usefulness of this methodology in the healthcare context.
New Perspective on Why Women Live Longer Than Men: An Exploration of Power, Gender, Social Determinants, and Capitals
Authors: Baum Fran , Musolino Connie , Gesesew Hailay Abrha , Popay Jennie
Published: January 2021

Background: Women live longer than men, even though many of the recognised social determinants of health are worse for women than men. No existing explanations account fully for these differences in life expectancy, although they do highlight the complexity and interaction of biological, social and health service factors. Methods: this paper is an exploratory explanation of gendered life expectancy difference (GLED) using a novel combination of epidemiological and sociological methods. We present the global picture of GLED. We then utilise a secondary data comparative case analysis offering explanations for GLED in Australia and Ethiopia. We combine a social determinant of health lens with Bourdieu’s concepts of capitals (economic, cultural, symbolic and social). Results: we confirmed continuing GLED in all countries ranging from less than a year to over 11 years. The Australian and Ethiopian cases demonstrated the complex factors underpinning this difference, highlighting similarities and differences in socioeconomic and cultural factors and how they are gendered within and between the countries. Bourdieu’s capitals enabled us to partially explain GLED and to develop a conceptual model of causal pathways. Conclusion: we demonstrate the value of combing a SDH and Bourdieu’s capital lens to investigate GLED. We proposed a theoretical framework to guide future research.
Sleep Characteristics and Mood of Professional Esports Athletes: A Multi-National Study
Authors: Lee Sangha , Bonnar Daniel , Roane Brandy , Gradisar Michael , Dunican Ian C. , Lastella Michele , Maisey Gemma , Suh Sooyeon
Published: January 2021

Esports is becoming increasingly professionalized, yet research on performance management is remarkably lacking. The present study aimed to investigate the sleep and mood of professional esports athletes. Participants were 17 professional esports athletes from South Korea (N = 8), Australia (N = 4), and the United States (N = 5) who played first person shooter games (mean age 20 ± 3.5 years, 100% male). All participants wore a wrist-activity monitor for 7–14 days and completed subjective sleep and mood questionnaires. Participants had a median total sleep time of 6.8 h and a sleep efficiency of 86.4% per night. All participants had significantly delayed sleep patterns (median sleep onset 3:43 a.m. and wake time 11:24 a.m.). Participants had a median sleep onset latency of 20.4 min and prolonged wake after sleep onset of 47.9 min. Korean players had significantly higher depression scores compared to the other groups (p < 0.01) and trained longer per day than the Australian or United States teams (13.4 vs. 4.8 vs. 6.1 h, respectively). Depression scores were strongly correlated with number of awakenings, wake after sleep onset, and daily training time (p < 0.05). As the first pilot sleep study in the esports field, this study indicates that esports athletes show delayed sleep patterns and have prolonged wake after sleep onset. These sleep patterns may be associated with mood (depression) and training time. Sleep interventions designed specifically for esports athletes appear warranted.
Cortisol on Circadian Rhythm and Its Effect on Cardiovascular System
Authors: Mohd Azmi Nor Amira Syahira , Juliana Norsham , Azmani Sahar , Mohd Effendy Nadia , Abu Izuddin Fahmy , Mohd Fahmi Teng Nur Islami , Das Srijit
Published: January 2021

The synthesis and secretion of cortisol are controlled by the hypothalamic–pituitary–adrenal axis. Cortisol exhibits a proper 24-h circadian rhythm that affects the brain, the autonomic nervous system, the heart, and the vasculature that prepares the cardiovascular system for optimal function during these anticipated behavioral cycles. A literature search was conducted using databases such as Google Scholar, PubMed, and Scopus. Relevant search terms included “circadian rhythm and cardiovascular”, “cortisol”, “cortisol and acute coronary syndrome”, “cortisol and arrhythmias”, “cortisol and sudden cardiac death”, “cortisol and stroke”, and “cardioprotective agents”. A total of 120 articles were obtained on the basis of the above search. Lower levels of cortisol were seen at the beginning of sleep, while there was a rise towards the end of sleep, with the highest level reached at the moment the individual wakes up. In the present review, we discuss the role of 11β-hydroxysteroid dehydrogenase (11β-HSD1), which is a novel molecular target of interest for treating metabolic syndrome and type-2 diabetes mellitus. 11β-HSD1 is the major determinant of cortisol excess, and its inhibition alleviates metabolic abnormalities. The present review highlights the role of cortisol, which controls the circadian rhythm, and describes its effect on the cardiovascular system. The review provides a platform for future potential cardioprotective therapeutic agents.
Erratum: Yang, X., et al. Isolation, Screening, and Characterization of Antibiotic-Degrading Bacteria for Penicillin V Potassium (PVK) from Soil on a Pig Farm. Int. J. Environ. Res. Public Health 2019, 16, 2166
Authors: Yang Xuanjiang , Li Miao , Guo Panpan , Li Hualong , Hu Zelin , Liu Xianwang , Zhang Qiang
Published: January 2021

The second affiliation of the paper should have been included in our original article [...]
Blue-Light Hazard of Light-Emitting Diodes Assessed with Gaussian Functions
Authors: Bauer Stefan
Published: January 2021

The high blue proportion of phosphor-conversion white-light emitting diodes (pc-LEDs), especially of those with higher correlated color temperatures (CCT), raises concern about photochemically induced retinal damages. Although almost all general lighting service LEDs are safe, other applications exist, like spotlights for theatres or at construction sites, that can pose a severe blue-light hazard (BLH) risk, and their photobiological safety must be assessed. Because of required but challenging radiance measurements, a calculative approach can be supportive for risk assessment. It is the aim of this work to exploit Gaussian functions to study LED parameter variations affecting BLH exposure. Gaussian curve approximations for color LEDs, the BLH action spectrum, and the spectral luminous efficiency for photopic vision enabled analytically solving the BLH efficiency, ηB, and the BLH efficacy of luminous radiation, KB,v. It was found that sigmoidal functions describe the CCT dependence of ηB and KB,v for different color LEDs with equal spectral bandwidth. Regarding pc-LEDs, variations of peak wavelengths, intensities, and bandwidths led to linear or parabolic shaped chromaticity coordinate correlations. ηB and KB,v showed pronounced CCT dependent extrema that might be exploited to reduce BLH. Finally, an experimental test of the presented Gaussian approach yielded its successful applicability for color and pc-LEDs but a minor accuracy for blue and green LEDs.
Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases
Authors: Reiter Russel J. , Sharma Ramaswamy , Rosales-Corral Sergio
Published: January 2021

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.
Effect of Polyhexamethylene Biguanide in Combination with Undecylenamidopropyl Betaine or PslG on Biofilm Clearance
Authors: Zheng Yaqian , Wang Di , Ma Luyan Z.
Published: January 2021

Hospital-acquired infection is a great challenge for clinical treatment due to pathogens’ biofilm formation and their antibiotic resistance. Here, we investigate the effect of antiseptic agent polyhexamethylene biguanide (PHMB) and undecylenamidopropyl betaine (UB) against biofilms of four pathogens that are often found in hospitals, including Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, Gram-positive bacteria Staphylococcus aureus, and pathogenic fungus, Candida albicans. We show that 0.02% PHMB, which is 10-fold lower than the concentration of commercial products, has a strong inhibitory effect on the growth, initial attachment, and biofilm formation of all tested pathogens. PHMB can also disrupt the preformed biofilms of these pathogens. In contrast, 0.1% UB exhibits a mild inhibitory effect on biofilm formation of the four pathogens. This concentration inhibits the growth of S. aureus and C. albicans yet has no growth effect on P. aeruginosa or E. coli. UB only slightly enhances the anti-biofilm efficacy of PHMB on P. aeruginosa biofilms. However, pretreatment with PslG, a glycosyl hydrolase that can efficiently inhibit and disrupt P. aeruginosa biofilm, highly enhances the clearance effect of PHMB on P. aeruginosa biofilms. Meanwhile, PslG can also disassemble the preformed biofilms of the other three pathogens within 30 min to a similar extent as UB treatment for 24 h.
Effects of 6,8-Diprenylgenistein on VEGF-A-Induced Lymphangiogenesis and Lymph Node Metastasis in an Oral Cancer Sentinel Lymph Node Animal Model
Authors: Bae Mun Gyeong , Hwang-Bo Jeon , Lee Dae Young , Lee Youn-Hyung , Chung In Sik
Published: January 2021

Background: The major determining factor of prognosis of oral squamous cell carcinoma is cervical lymph node metastasis. 6,8-Diprenylgenistein (6,8-DG), an isoflavonoid isolated from Cudrania tricuspidata has been reported to have anti-microbial and anti-obesity activities. However, its effects on lymphangiogenesis and lymph node metastasis in oral cancer have not yet been reported. Methods: To investigate the in vitro inhibitory effects of 6,8-DG on VEGF-A-induced lymphangiogenesis, we performed the proliferation, tube formation, and migration assay using human lymphatic microvascular endothelial cells (HLMECs). RT-PCR, Western blot, immunoprecipitation, ELISA and co-immunoprecipitation assays were used to investigate the expression levels of proteins, and mechanism of 6,8-DG. The in vivo inhibitory effects of 6,8-DG were investigated using an oral cancer sentinel lymph node (OCSLN) animal model. Results: 6,8-DG inhibited the proliferation, migration and tube formation of rhVEGF-A treated HLMECs. In addition, the in vivo lymphatic vessel formation stimulated by rhVEGF-A was significantly reduced by 6,8-DG. 6,8-DG inhibited the expression of VEGF-A rather than other lymphangiogenic factors in CoCl2-treated SCCVII cells. 6,8-DG inhibited the expression and activation of VEGFR-2 stimulated by rhVEGF-A in HLMECs. Also, 6,8-DG inhibited the activation of the lymphangiogenesis-related downstream signaling factors such as FAK, PI3K, AKT, p38, and ERK in rhVEGF-A-treated HLMECs. Additionally, 6,8-DG inhibited the expression of the hypoxia-inducible factor (HIF-1α), which is involved in the expression of VEGF-A in CoCl2-treated SCCVII cells, and 6,8-DG inhibited VEGF-A signaling via interruption of the binding of VEGF-A and VEGFR-2 in HLMECs. In the VEGF-A-induced OCSLN animal model, we confirmed that 6,8-DG suppressed tumor-induced lymphangiogenesis and SLN metastasis. Conclusion: These data suggest that 6,8-DG inhibits VEGF-A-induced lymphangiogenesis and lymph node metastasis in vitro and in vivo. Furthermore, the inhibitory effects of 6,8-DG are probably mediated by inhibition of VEGF-A expression in cancer cells and suppression of the VEGF-A/VEGFR-2 signaling pathway in HLMEC. Thus, 6,8-DG could be novel and valuable therapeutic agents for metastasis prevention and treatment of oral cancer.
Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment
Authors: Stasiłowicz Anna , Tomala Anna , Podolak Irma , Cielecka-Piontek Judyta
Published: January 2021

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.
Adsorption of Malachite Green and Alizarin Red S Dyes Using Fe-BTC Metal Organic Framework as Adsorbent
Authors: Delpiano Giulia Rossella , Tocco Davide , Medda Luca , Magner Edmond , Salis Andrea
Published: January 2021

Synthetic organic dyes are widely used in various industrial sectors but are also among the most harmful water pollutants. In the last decade, significant efforts have been made to develop improved materials for the removal of dyes from water, in particular, on nanostructured adsorbent materials. Metal organic frameworks (MOFs) are an attractive class of hybrid nanostructured materials with an extremely wide range of applications including adsorption. In the present work, an iron-based Fe-BTC MOF, prepared according to a rapid, aqueous-based procedure, was used as an adsorbent for the removal of alizarin red S (ARS) and malachite green (MG) dyes from water. The synthesized material was characterized in detail, while the adsorption of the dyes was monitored by UV-Vis spectroscopy. An optimal adsorption pH of 4, likely due to the establishment of favorable interactions between dyes and Fe-BTC, was found. At this pH and at a temperature of 298 K, adsorption equilibrium was reached in less than 30 min following a pseudo-second order kinetics, with k″ of 4.29 × 10−3 and 3.98 × 10−2 g∙mg−1 min−1 for ARS and MG, respectively. The adsorption isotherm followed the Langmuir model with maximal adsorption capacities of 80 mg∙g−1 (ARS) and 177 mg∙g−1 (MG), and KL of 9.30·103 L∙mg−1 (ARS) and 51.56·103 L∙mg−1 (MG).