bluuebunny/crossref_metadata_2025 huggingface dataset:
Personality traits and polymorphisms of genes coding neurotransmitter receptors or transporters: review of single gene and genome-wide association studies
Authors: Zmorzyński Szymon , Styk Wojciech , Klinkosz Waldemar , Iskra Justyna , Filip Agata Anna
Published: January 2021

Background

The most popular tool used for measuring personality traits is the Five-Factor Model (FFM). It includes neuroticism, extraversion, openness, agreeableness and conscientiousness. Many studies indicated the association of genes encoding neurotransmitter receptors/transporters with personality traits. The relationship connecting polymorphic DNA sequences and FFM features has been described in the case of genes encoding receptors of cannabinoid and dopaminergic systems. Moreover, dopaminergic system receives inputs from other neurotransmitters, like GABAergic or serotoninergic systems.

Methods

We searched PubMed Central (PMC), Science Direct, Scopus, Cochrane Library, Web of Science and EBSCO databases from their inception to November 19, 2020, to identify original studies, as well as peer-reviewed studies examining the FFM and its association with gene polymorphisms affecting the neurotransmitter functions in central nervous system.

Results

Serotonin neurons modulate dopamine function. In gene encoding serotonin transporter protein,SLC6A4, was found polymorphism, which was correlated with openness to experience (in Sweden population), and high scores of neuroticism and low levels of agreeableness (in Caucasian population). The genome-wide association studies (GWASs) found an association of 5q34-q35, 3p24, 3q13 regions with higher scores of neuroticism, extraversion and agreeableness. However, the results for chromosome 3 regions are inconsistent, which was shown in our review paper.

Conclusions

GWASs on polymorphisms are being continued in order to determine and further understand the relationship between the changes in DNA and personality traits.
Low GSTM3 expression is associated with poor disease‐free survival in resected esophageal squamous cell carcinoma
Authors: Yang Fu , Wen Jing , Luo Kongjia , Fu Jianhua
Published: January 2021

Background

Glutathione S-transferase mu 3 (GSTM3) plays a crucial role in tumor progression in various cancers. However, the relationship between GSTM3 expression and the clinical prognosis of esophageal squamous cell carcinoma (ESCC) has not been studied to date. We aimed to characterize the role of GSTM3 in predicting postoperative prognosis of ESCC patients.

Methods

In the retrospective study, GSTM3 mRNA levels in 184 ESCC tissues and matched 43 adjacent nontumorous tissues were measured by quantitative real-time PCR. GSTM3 protein levels in 247 ESCC tissues were measured by immunohistochemistry.

Results

Downregulation of GSTM3 occurred in 62.8 % of primary ESCC tissues compared with their nontumor counterparts. Patients with low GSTM3 expression tended to exhibit an increased rate of poor differentiation in both the mRNA cohort (p = 0.024) and protein cohort (p = 0.004). In the mRNA cohort, low GSTM3 expression was associated with unfavorable 3-year disease-free survival (DFS) (39.2 % vs. 57.4 %) and 5-year DFS (26.8 % vs. 45.1 %) (p = 0.023). The result was confirmed in the protein cohort. Patients with low GSTM3 expression had unfavorable 3-year disease-free survival (DFS) (18.7 % vs. 33.5 %) and 5-year DFS (5.3 % vs. 30.5 %) (p = 0.006). Cox multivariate analysis revealed that GSTM3 expression was an independent prognostic factor.

Conclusions

The findings of the present study provide evidence that GSTM3 may function as a tumor suppressor in ESCC and represents a potential novel prognostic biomarker for disease-free survival for resected ESCC patients.
Intra-fraction displacement of the prostate bed during post-prostatectomy radiotherapy
Authors: Bell Linda J. , Eade Thomas , Hruby George , Bromley Regina , Kneebone Andrew
Published: January 2021

Background

To measure intra-fraction displacement (IFD) in post-prostatectomy patients treated with anisotropic margins and daily soft tissue matching.

Methods

Pre-treatment cone beam computed tomography (CBCT) scans were acquired daily and post-treatment CBCTs for the first week then weekly on 46 patients. The displacement between the scans was calculated retrospectively to measure IFD of the prostate bed (PB). The marginal miss (MM) rate, and the effect of time between imaging was assessed.

Results

A total of 392 post-treatment CBCT’s were reviewed from 46 patients. The absolute mean (95% CI) IFD was 1.5 mm (1.3–1.7 mm) in the AP direction, 1.0 mm (0.9–1.2 mm) SI, 0.8 mm (0.7–0.9 mm) LR, and 2.4 mm (2.2–2.5 mm) 3D displacement. IFD ≥  ± 3 mm and ≥  ± 5 mm was 24.7% and 5.4% respectively. MM of the PB was detected in 33 of 392 post-treatment CBCT (8.4%) and lymph nodes in 6 of 211 post-treatment CBCT images (2.8%). Causes of MM due to IFD included changes in the bladder (87.9%), rectum (66.7%) and buttock muscles (6%). A time ≥ 9 min between the pre and post-treatment CBCT demonstrated that movement ≥ 3 mm and 5 mm increased from 19.2 to 40.5% and 5 to 8.1% respectively.

Conclusions

IFD during PB irradiation was typically small, but was a major contributor to an 8.4% MM rate when using daily soft tissue match and tight anisotropic margins.
Outcome and experience of arthroscopic lateral retinacular release combined with lateral patelloplasty in the management of excessive lateral pressure syndrome
Authors: Wang Cheng-Liang , Chen Ji-Bin , Li Te
Published: January 2021

Background

Only a few studies have described the effect of full arthroscopic surgery in treatment of excessive lateral pressure syndrome (ELPS). Therefore, the purpose of this study was to assess the clinical efficacy and experience of total arthroscopic lateral retinacular (LR) release and lateral patelloplasty for the treatment of ELPS.

Methods

A total of 73 patients (88 knees) with ELPS underwent arthroscopic LR release and lateral patelloplasty. The visual analogue scale (VAS), Kujala score, Lysholm scores, patella medial pushing distance, patellar tilt angle (PTA), and lateral patellofemoral angle (LPFA) were measured and evaluated before and after surgery.

Results

Follow-up ranged from 12 to 36 months with an average of 24 ± 5.8 months. The VAS was significantly lower at the last follow-up than before surgery (P< 0.01). The patella medial pushing distance, Kujala score, Lysholm score, PTA, and LPFA were significantly higher at the last follow-up than before surgery (P< 0.01, respectively). Years and lateral patella Outerbridge classification at the last follow-up have negative correlation with Kujala score, Lysholm score, Patella medial pushing distance, PTA, and LPFA (P< 0.01, respectively) and have positive correlation with VAS (P< 0.01, respectively). Related complications were not reported.

Conclusions

Full arthroscopic LR release combined with lateral patelloplasty in the treatment of ELPS is an effective minimally invasive method, which can effectively correct anomalies of force line and skeleton of patella, relieve pain, and restore knee joint motor function with less complications.
Supportive care needs of patients with rare chronic diseases: multi-method, cross-sectional study
Authors: Depping Miram K. , Uhlenbusch Natalie , von Kodolitsch Yskert , Klose Hans F. E. , Mautner Victor-Felix , Löwe Bernd
Published: January 2021

Background

In the absence of a cure for the majority of rare diseases, the disease management aims to provide optimal supportive care. The goal of this study was to assess supportive care needs in patients with chronic rare diseases.

Methods

Cross-sectional mixed-method study was conducted using validated self-report scales and open-ended questions to assess supportive care needs. Participants affected by rare diseases across Germany were contacted via patient organizations and centers for rare diseases. N = 304 participants with 81 different rare diseases completed the study, 81.6% were female, mean age was 44.2 years (SD = 12.8, range 16–74). The quantitative results regarding supportive care needs were compared to a reference population of patients affected by cancer (N = 888). Main outcomes were unmet supportive care needs of patients with rare diseases, as assessed by the Supportive Care Needs Survey (SNCS-SF34) and an open-ended question on support wishes.

Results

Patients with rare diseases did not feel sufficiently supported with regard to psychological support, health system and information, physical and daily living, patient care and support, and sexuality needs. The unmet supportive care needs were significantly higher in the patient sample with rare diseases compared to the SCNS-SF34 reference sample of patients with cancer. 60% of patients with rare diseases did not feel sufficiently socially supported.

Conclusions

Patients affected by rare diseases have high unmet support needs in all areas studied. Multidisciplinary care, including psychological support and the provision of information regarding the healthcare system, treatment options, disease course and sexuality, might help address these needs.
Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status
Authors: Leoni Chiara , Romeo Domenico Marco , Pelliccioni Michele , Di Già Mariangela , Onesimo Roberta , Giorgio Valentina , Flex Elisabetta , Tedesco Marta , Tartaglia Marco , Rigante Donato , Valassina Antonio , Zampino Giuseppe
Published: January 2021

Background

Costello syndrome (CS)
and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized.

Patients and methods

Herein we reported data on orthopedic findings and functional status of a large sample of CS and CFCS patients. Thirty-four patients (CS = 17 and CFCS = 17) were recruited. Functional and disability evaluations were performed by assessing the 6-min walking test (6MWT) and Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided.

Results

Orthopedic manifestations are highly prevalent in CS and CFCS and overlap in the two disorders. Overall, patients with CS harboring the recurrent HRAS Gly12Ser substitution show a more severe skeletal phenotype compared to patients carrying the Gly12Ala and Gly13Cys variants. Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities. Functional assessment showed that patients with CS and CFCS reached lower values compared to the general population, with CFCS patients displaying the lowest scores.

Conclusions

Orthopedic manifestations appear universal features of CS and CFCS and they can evolve across patients’ life. Longitudinal assessment of disability status by using 6MWT and PODCI could be useful to evaluate the functional impact of orthopedic manifestations on patients’ outcome and help planning a tailored treatment of these comorbidities.
One test for all: whole exome sequencing significantly improves the diagnostic yield in growth retarded patients referred for molecular testing for Silver–Russell syndrome
Authors: Meyer Robert , Begemann Matthias , Hübner Christian Thomas , Dey Daniela , Kuechler Alma , Elgizouli Magdeldin , Schara Ulrike , Ambrozaityte Laima , Burnyte Birute , Schröder Carmen , Kenawy Asmaa , Kroisel Peter , Demuth Stephanie , Fekete Gyorgy , Opladen Thomas , Elbracht Miriam , Eggermann Thomas
Published: January 2021

Background

Silver-Russell syndrome (SRS) is an imprinting disorder which is characterised by severe primordial growth retardation, relative macrocephaly and a typical facial gestalt. The clinical heterogeneity of SRS is reflected by a broad spectrum of molecular changes with hypomethylation in 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat) as the most frequent findings. Monogenetic causes are rare, but a clinical overlap with numerous other disorders has been reported. However, a comprehensive overview on the contribution of mutations in differential diagnostic genes to phenotypes reminiscent to SRS is missing due to the lack of appropriate tests. With the implementation of next generation sequencing (NGS) tools this limitation can now be circumvented.

Main body

We analysed 75 patients referred for molecular testing for SRS by a NGS-based multigene panel, whole exome sequencing (WES), and trio-based WES. In 21/75 patients a disease-causing variant could be identified among them variants in known SRS genes (IGF2, PLAG1, HMGA2). Several patients carried variants in genes which have not yet been considered as differential diagnoses of SRS.

Conclusions

WES approaches significantly increase the diagnostic yield in patients referred for SRS testing. Several of the identified monogenetic disorders have a major impact on clinical management and genetic counseling.
Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
Authors: Huang Kie Kyon , Huang Jiawen , Wu Jeanie Kar Leng , Lee Minghui , Tay Su Ting , Kumar Vikrant , Ramnarayanan Kalpana , Padmanabhan Nisha , Xu Chang , Tan Angie Lay Keng , Chan Charlene , Kappei Dennis , Göke Jonathan , Tan Patrick
Published: January 2021

Background

Deregulated gene expression is a hallmark of cancer; however, most studies to date have analyzed short-read RNA sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (Iso-Seq) and Illumina paired-end short-read RNA sequencing to comprehensively survey the transcriptome of gastric cancer (GC), a leading cause of global cancer mortality.

Results

We performed full-length transcriptome analysis across 10 GC cell lines covering four major GC molecular subtypes (chromosomal unstable, Epstein-Barr positive, genome stable and microsatellite unstable). We identify 60,239 non-redundant full-length transcripts, of which > 66% are novel compared to current transcriptome databases. Novel isoforms are more likely to be cell line and subtype specific, expressed at lower levels with larger number of exons, with longer isoform/coding sequence lengths. Most novel isoforms utilize an alternate first exon, and compared to other alternative splicing categories, are expressed at higher levels and exhibit higher variability. Collectively, we observe alternate promoter usage in 25% of detected genes, with the majority (84.2%) of known/novel promoter pairs exhibiting potential changes in their coding sequences. Mapping these alternate promoters to TCGA GC samples, we identify several cancer-associated isoforms, including novel variants of oncogenes. Tumor-specific transcript isoforms tend to alter protein coding sequences to a larger extent than other isoforms. Analysis of outcome data suggests that novel isoforms may impart additional prognostic information.

Conclusions

Our results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies.
Interleukin (IL)-33 is dispensable for Schistosoma mansoni worm maturation and the maintenance of egg-induced pathology in intestines of infected mice
Authors: Mukendi Jean Pierre Kambala , Nakamura Risa , Uematsu Satoshi , Hamano Shinjiro
Published: January 2021

Background

Schistosomes are trematode worms that dwell in their definitive host’s blood vessels, where females lay eggs that need to be discharged into the environment with host excreta to maintain their life-cycle. Both worms and eggs require type 2 immunity for their maturation and excretion, respectively. However, the immune molecules that orchestrate such immunity remain unclear. Interleukin (IL)-33 is one of the epithelium-derived cytokines that induce type 2 immunity in tissues. The aim of this study was to determine the role of IL-33 in the maturation, reproduction and excretion of Schistosoma mansoni eggs, and in the maintenance of egg-induced pathology in the intestines of mice.

Methods

The morphology of S. mansoni worms and the number of eggs in intestinal tissues were studied at different time points post-infection in S. mansoni-infected IL-33-deficient (IL-33−/−) and wild-type (WT) mice. IL-5 and IL-13 production in the spleens and mesenteric lymph nodes were measured. Tissue histology was performed on the terminal ilea of both infected and non-infected mice.

Results

Worms from IL-33−/− and WT mice did not differ morphologically at 4 and 6 weeks post-infection (wpi). The number of eggs in intestinal tissues of IL-33−/− and WT mice differed only slightly. At 6 wpi, IL-33−/− mice presented impaired type 2 immunity in the intestines, characterized by a decreased production of IL-5 and IL-13 in mesenteric lymph nodes and fewer inflammatory infiltrates with fewer eosinophils in the ilea. There was no difference between IL-33−/− and WT mice in the levels of IL-25 and thymic stromal lymphopoietin (TSLP) in intestinal tissues.

Conclusions

Despite its ability to initiate type 2 immunity in tissues, IL-33 alone seems dispensable for S. mansoni maturation and its absence may not affect much the accumulation of eggs in intestinal tissues. The transient impairment of type 2 immunity observed in the intestines, but not spleens, highlights the importance of IL-33 over IL-25 and TSLP in initiating, but not maintaining, locally-induced type 2 immunity in intestinal tissues during schistosome infection. Further studies are needed to decipher the role of each of these molecules in schistosomiasis and clarify the possible interactions that might exist between them.

Graphical Abstract
The common European mosquitoes Culex pipiens and Aedes albopictus are unable to transmit SARS-CoV-2 after a natural-mimicking challenge with infected blood
Authors: Fortuna Claudia , Montarsi Fabrizio , Severini Francesco , Marsili Giulia , Toma Luciano , Amendola Antonello , Bertola Michela , Michelutti Alice , Ravagnan Silvia , Capelli Gioia , Rezza Giovanni , Di Luca Marco ,   the Working Group
Published: January 2021

Background

On 11 March 2020, the World Health Organisation (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak to be a pandemic. As the mosquito season progressed, the understandable concern that mosquitoes could transmit the virus began to increase among the general public and public health organisations. We have investigated the vector competence ofCulex pipiensandAedes albopictus, the two most common species of vector mosquitoes in Europe, for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the very unusual feeding behaviour ofAe. albopictus, we also evaluated the role of this mosquito in a potential mechanical transmission of the virus.

Methods

For the vector competence study, mosquitoes were allowed to take several infectious blood meals. The mosquitoes were then collected and analysed at 0, 3, 7 and 10 days post-feeding. For the mechanical transmission test,Ae. albopictusfemales were allowed to feed for a short time on a feeder containing infectious blood and then on a feeder containing virus-free blood. Both mosquitoes and blood were tested for viral presence.

Results

Culex pipiensandAe. albopictuswere found not be competent vectors for SARS-CoV-2, andAe. albopictuswas unable to mechanically transmit the virus.

Conclusions

This is the first study to show that the most common species of vector mosquitoes in Europe do not transmit SARS-CoV-2 and thatAe. albopictusis unable to mechanically transmit the virus from a positive host to a healthy host through host-feeding.

Graphical Abstract
Risk factors for lymphatic filariasis and mass drug administration non-participation in Mandalay Region, Myanmar
Authors: Dickson Benjamin F. R. , Graves Patricia M. , Aye Ni Ni , Nwe Thet Wai , Wai Tint , Win San San , Shwe Myint , Douglass Janet , Wood Peter , Wangdi Kinley , McBride William J.
Published: January 2021

Background

Myanmar commenced a lymphatic filariasis (LF) elimination programme in 2000. Whilst the country has made considerable progress since then, a number of districts have demonstrated persistent transmission after many rounds of mass drug administration (MDA). The causes of unsuccessful MDA have been examined elsewhere; however, there remains little information on the factors that contribute in Myanmar.

Methods

We conducted an analysis of factors associated with persistent infection, LF-related hydrocoele and MDA participation in an area with ongoing transmission in 2015. A cross-sectional household survey was undertaken in 24 villages across four townships of Mandalay Region. Participants were screened for circulating filarial antigen (CFA) using immunochromatographic tests and, if positive, for microfilaria by night-time thick blood slide. Individuals 15 year and older were assessed for filariasis morbidity (lymphoedema and, if male, hydrocoele) by ultrasound-assisted clinical examination. A pre-coded questionnaire was used to assess risk factors for LF and for non-participation (never taking MDA). Significant variables identified in univariate analyses were included in separate step-wise multivariate logistic regressions for each outcome.

Results

After adjustment for covariates and survey design, being CFA positive was significantly associated with age [odds ratio (OR) 1.03, 95% CI 1.01–1.06), per year], male gender (OR 3.14, 1.27–7.76), elevation (OR 0.96, 0.94–0.99, per metre) and the density of people per household room (OR 1.59, 1.31–1.92). LF-related hydrocoele was associated with age (OR 1.06, 1.03–1.09, per year) and residing in Amarapura Township (OR 8.93, 1.37–58.32). Never taking MDA was associated with male gender [OR 6.89 (2.13–22.28)] and age, particularly in females, with a significant interaction term. Overall, compared to those aged 30–44 years, the proportion never taking MDA was higher in all age groups (OR highest in those < 5 years and > 60 years, ranging from 3.37 to 12.82). Never taking MDA was also associated with residing in Amarapura township (OR 2.48, 1.15–5.31), moving to one’s current village from another (OR 2.62, 1.12–6.11) and ever having declined medication (OR 11.82, 4.25–32.91). Decreased likelihood of never taking MDA was associated with a higher proportion of household members being present during the last MDA round (OR 0.16, 0.03–0.74) and the number visits by the MDA programme (OR 0.69, 0.48–1.00).

Conclusions

These results contribute to the understanding of LF and MDA participation-related risk factors and will assist Myanmar to improve its elimination and morbidity management programmes.

Graphical Abstract
Gene co-expression network analysis of Trypanosoma brucei in tsetse fly vector
Authors: Mwangi Kennedy W. , Macharia Rosaline W. , Bargul Joel L.
Published: January 2021

Background

Trypanosoma bruceispecies are motile protozoan parasites that are cyclically transmitted by tsetse fly (genusGlossina) causing human sleeping sickness and nagana in livestock in sub-Saharan Africa. African trypanosomes display digenetic life cycle stages in the tsetse fly vector and in their mammalian host. Experimental work on insect-stage trypanosomes is challenging because of the difficulty in setting up successfulin vitrocultures. Therefore, there is limited knowledge on the trypanosome biology during its development in the tsetse fly. Consequently, this limits the development of new strategies for blocking parasite transmission in the tsetse fly.

Methods

In this study, RNA-Seq data of insect-stage trypanosomes were used to construct aT. bruceigene co-expression network using the weighted gene co-expression analysis (WGCNA) method. The study identified significant enriched modules for genes that play key roles during the parasite’s development in tsetse fly. Furthermore, potential 3′ untranslated region (UTR) regulatory elements for genes that clustered in the same module were identified using the Finding Informative Regulatory Elements (FIRE) tool.

Results

A fraction of gene modules (12 out of 27 modules) in the constructed network were found to be enriched in functional roles associated with the cell division, protein biosynthesis, mitochondrion, and cell surface. Additionally, 12 hub genes encoding proteins such as RNA-binding protein 6 (RBP6), arginine kinase 1 (AK1),bruceialanine-rich protein (BARP), among others, were identified for the 12 significantly enriched gene modules. In addition, the potential regulatory elements located in the 3′ untranslated regions of genes within the same module were predicted.

Conclusions

The constructed gene co-expression network provides a useful resource for network-based data mining to identify candidate genes for functional studies. This will enhance understanding of the molecular mechanisms that underlie important biological processes during parasite’s development in tsetse fly. Ultimately, these findings will be key in the identification of potential molecular targets for disease control.

Graphical Abstract
MSCR: multidimensional secure clustered routing scheme in hierarchical wireless sensor networks
Authors: Fang Weidong , Zhang Wuxiong , Chen Wei , Liu Jin , Ni Yepeng , Yang Yinxuan
Published: January 2021

For hierarchical wireless sensor network (WSN), the clustered routing protocol can effectively deal with large-scale application requirements, thereby, how to efficiently elect the secure cluster heads becomes very critical. Unfortunately, many current studies only focus on improving security while neglecting energy efficiency and transmission performance. In this paper, a lightweight trust management scheme (LTMS) is proposed based on binomial distribution for defending against the internal attacks. Simultaneously, distance domain, energy domain, security domain and environment domain are considered and introduced to propose a multidimensional secure clustered routing (MSCR) scheme by using dynamic dimension weight in hierarchical WSNs. The simulation results show that LTMS can effectively prevent a malicious node from being elected as a cluster head, and MSCR can achieve a balance between security, transmission performance and energy efficiency under the requirements of environmental applications.
DSSAM: digitally signed secure acknowledgement method for mobile ad hoc network
Authors: Srivastava Ashutosh , Gupta Sachin Kumar , Najim Mohd , Sahu Nitesh , Aggarwal Geetika , Mazumdar Bireshwar Dass
Published: January 2021

Mobile ad hoc network (MANET) is an infrastructure-less, self-motivated, arbitrary, self-configuring, rapidly changing, multi-hop network that is self-possessing wireless bandwidth-conscious links without centrally managed router support. In such a network, wireless media is easy to snoop. It is firm to the surety to access any node, easier to insertion of bad elements or attackers for malicious activities in the network. Therefore, security issues become one of the significant considerations for such kind of networks. The deployment of an effective intrusion detection system is important in order to provide protection against various attacks. In this paper, a Digitally Signed Secure Acknowledgement Method (DSSAM) with the use of the RSA digital signature has been proposed and simulated. Three different parameters are considered, namely secure acknowledgment, node authentication, and packet authentication for study. This article observes the DSSAM performance and compares it with two existing standard methods, namely Watchdog and 2-ACK under standard Dynamic Source Routing (DSR) routing environment. In the end, it is noticed that the rate of detection of malicious behaviour is better in the case of the proposed method. However, associated overheads are high. A trade-off between performance and overhead has been considered.
New type of source extension for a two-dimensional special lattice equation and determinant solutions
Authors: Wang Hong-Yan , Zhu Guo-Qing
Published: January 2021

We present a new type of two-dimensional special lattice equations with self-consistent sources using the source generation procedure. Then we obtain the Grammy-type and Casorati-type determinant solutions of the coupled system. Further, we present the one-soliton and two-soliton solutions.
Pharmacological activation of pyruvate kinase M2 reprograms glycolysis leading to TXNIP depletion and AMPK activation in breast cancer cells
Authors: Almouhanna Fadi , Blagojevic Biljana , Can Suzan , Ghanem Ali , Wölfl Stefan
Published: January 2021

Background

Aerobic glycolysis, discovered by Otto Warburg, is a hallmark of cancer metabolism even though not yet fully understood. The low activity of the cancerous pyruvate kinase isozyme (M2) is thought to play an important role by facilitating the conversion of glycolytic intermediates to other anabolic pathways to support tumors’ high proliferation rate.

Methods

Five breast cancer cell lines representing different molecular subtypes were used in this study where real time measurements of cellular bioenergetics and immunoblotting analysis of energy- and nutrient-sensing pathways were employed to investigate the potential effects of PKM2 allosteric activator (DASA-58) in glucose rewiring.

Results

In this study, we show that DASA-58 can induce pyruvate kinase activity in breast cancer cells without affecting the overall cell survival. The drug is also able to reduce TXNIP levels (an intracellular glucose sensor) probably through depletion of upstream glycolytic metabolites and independent of AMPK and ER signaling. AMPK shows an induction in phosphorylation (T172) in response to treatment an effect that can be potentiated by combining DASA-58 with other metabolic inhibitors.

Conclusions

Altogether, the multifaceted metabolic reprogramming induced by DASA-58 in breast cancer cells increases their susceptibility to other therapeutics suggesting the suitability of the intracellular glucose sensor TXNIP as a marker of PK activity.
Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles
Authors: Nweze Justus Amuche , Mbaoji Florence N. , Li Yan-Ming , Yang Li-Yan , Huang Shu-Shi , Chigor Vincent N. , Eze Emmanuel A. , Pan Li-Xia , Zhang Ting , Yang Deng-Feng
Published: January 2021

Background

Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis.

Main text

We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020.

Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries.

Conclusions

It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.
Mechanisms of change and heterogeneous treatment effects in psychodynamic and cognitive behavioural therapy for patients with depressive disorder: a randomized controlled trial
Authors: Røssberg J. I. , Evensen J. , Dammen T. , Wilberg T. , Klungsøyr O. , Jones M. , Bøen E. , Egeland R. , Breivik R. , Løvgren A. , Ulberg R.
Published: January 2021

Background

Major depressive disorder (MDD) is a prevalent psychiatric condition associated with significant disability, mortality and economic burden. Cognitive behavioral therapy (CBT) and psychodynamic psychotherapy (PDT) are found to be equally effective for patients with depression. However, many patients do not respond sufficiently to either treatment. To offer individualized treatment, we need to know if some patients benefit more from one of the two therapies. At present little is known about what patient characteristics (moderators) may be associated with differential outcomes of CBT and PDT, and through what therapeutic processes and mechanisms (mediators) improvements occur in each therapy mode. Presently only theoretical assumptions, sparsely supported by research findings, describe what potentially moderates and mediates the treatment effects of CBT and PDT. The overall aim of this study is to examine theoretically derived putative moderators and mediators in CBT and PDT and strengthen the evidence base about for whom and how these treatments works in a representative sample of patients with MDD.

Methods

One hundred patients with a diagnosis of MDD will be randomized to either CBT or PDT. Patients will be treated over 28 weeks with either CBT (one weekly session over 16 weeks and three monthly booster sessions) or PDT (one weekly session over 28 weeks). The patients will be evaluated at baseline, during the course of therapy, at the end of therapy, and at follow-up investigations 1 and 3 years post treatment. A large range of patient and observer rated questionnaires (specific preselected putative moderators and mediators) are included.

Discussion

The clinical outcome of this study may better guide clinicians when deciding what kind of treatment any individual patient should be offered. Moreover, the study aims to further our knowledge of what mechanisms lead to symptom improvement and increased psychosocial functioning.

Trial registration

ClinicalTrials.gov Identifier: NCT03022071.
Bats seek refuge in cluttered environment when exposed to white and red lights at night
Authors: Barré Kévin , Kerbiriou Christian , Ing Ros-Kiri , Bas Yves , Azam Clémentine , Le Viol Isabelle , Spoelstra Kamiel
Published: January 2021

Background

Artificial light at night is recognized as an increasing threat to biodiversity. However, information on the way highly mobile taxa such as bats spatially respond to light is limited. Following the hypothesis of a behavioural adaptation to the perceived risks of predation, we hypothesised that bats should avoid lit areas by shifting their flight route to less exposed conditions.

Methods

Using 3D acoustic localization at four experimentally illuminated sites, we studied how the distance to streetlights emitting white and red light affected the Probability of bats Flying Inside the Forest (PFIF) versus along the forest edge.

Results

We show that open-, edge-, and narrow-space foraging bats strongly change flight patterns by increasing PFIF when getting closer to white and red streetlights placed in the forest edge. These behavioural changes occurred mainly on the streetlight side where light was directed.

Conclusions

The results show that bats cope with light exposure by actively seeking refuge in cluttered environment, potentially due to involved predation risks. This is a clear indication that bats make use of landscape structures when reacting to light, and shows the potential of vegetation and streetlight orientation in mitigating effects of light. The study nevertheless calls for preserving darkness as the most efficient way.
Drug supply shortage in Nigeria during COVID-19: efforts and challenges
Authors: Faiva Edward , Hashim Hashim Talib , Ramadhan Mustafa Ahmed , Musa Shingin Kovona , Bchara John , Tuama Yahya Dheyaa , Adebisi Yusuff Adebayo , Kadhim Mustafa Hayder , Essar Mohammad Yasir , Ahmad Shoaib , Lucero-Prisno Don Eliseo
Published: January 2021

The COVID-19 pandemic has resulted in massive disruptions in global supply chains. Nigeria is particularly vulnerable with respect to pharmaceuticals since there is reduced local production and about 70% of the drug supply is imported creating a huge supply–demand disparity particularly in times like COVID-19. Nigeria is in need of huge quantities of quality-assured health commodities to effectively respond to the pandemic. Significant shortages of other essential medicines and medical products across the country could be imminent. Drug scarcity in Nigeria during the COVID-19 pandemic period is because of several accumulated factors, majorly as a result of global lockdown, decreased manufacturing, unaddressed regulatory affairs, poor access to resources by the population, lack of buffer stocks, security instability, and poor funding of the healthcare system. This situation if left unattended, could cause serious drawbacks to the health of the populace as well as the quality of life of Nigerians amid the COVID-19 Pandemic. Appropriate measures should be directed to ensure ethical processes on drug production, importation, pricing, and distribution to avoid such events during unavoidable scenarios, like the COVID-19 pandemic and other public health emergencies.
Multiproxy sedimentological and geochemical analyses across the Lower–Middle Pleistocene boundary: chemostratigraphy and paleoenvironment of the Chiba composite section, central Japan
Authors: Izumi Kentaro , Haneda Yuki , Suganuma Yusuke , Okada Makoto , Kubota Yoshimi , Nishida Naohisa , Kawamata Moto , Matsuzaki Takuya
Published: January 2021

The Chiba composite section (CbCS) in the Kokumoto Formation, Kazusa Group, central Japan is a thick and continuous marine succession that straddles the Lower–Middle Pleistocene boundary and the well-recognized Matuyama–Brunhes paleomagnetic polarity boundary. Although recent studies extensively investigated the CbCS, its chemostratigraphy, particularly around the Lower–Middle Pleistocene boundary, is poorly understood. Therefore, in this study, we performed multiproxy sedimentological and geochemical analyses of the CbCS, including the Chiba section, which is the Global Boundary Stratotype Section and Point for defining the base of the Middle Pleistocene Subseries. The aim of these analyses is to establish the high-resolution chemostratigraphy and to reconstruct the paleoenvironments of its sedimentary basin in detail. We used the K/Ti ratio as a broad proxy for the clastic material grain size of the sediments. Although the K/Ti ratio generally varies throughout the studied interval, the K/Ti ratio especially during Marine Isotope Stage (MIS) 19a shows a variation pattern like those of the foraminiferal oxygen isotope (δ18O) records. The records of the C/N ratio of bulk samples and carbon isotope ratio of the organic carbon (δ13Corg) suggest that the organic matter in the CbCS sediments during MIS 19c mostly originated from marine plankton, whereas the organic matter during MIS 18 and 19a was characterized by a mixture of marine plankton and terrestrial plants. These records are clearly indicative of changes in mixing ratio of marine vs. terrestrial organic matter in association with glacial–interglacial cycles from the late MIS 20 to the early MIS 18. In addition, we calculated the mass accumulation rates (MARs) of organic carbon, biogenic carbonate, and terrigenous material for quantitative interpretations on the paleoenvironmental changes. MAR calculations revealed that the contribution of marine organic carbon relative to terrestrial organic carbon increased during MIS 19c, and that the contribution of the terrigenous material relative to biogenic carbonate decreased during MIS 19c. Furthermore, we observed relatively large variations in the total organic carbon and total nitrogen contents during MIS 19a. These variations were probably caused by the relative decrease in bottom-water oxygen level, which is also supported by our trace-fossil data, although it is not certain whether the increase in organic-carbon flux at ~ 760 ka was due to the synchronous increase in biogenic productivity in surface water. Such a relative decrease in bottom-water oxygen level was partly due to the increased ocean stratification because of the northward displacement of the Kuroshio Extension Front.
Farmers’ awareness of the potential of vetiver grass for soil erosion control on Ogbomoso Agricultural Zone farmlands, south-western Nigeria
Authors: Ewetola E. A. , Fanifosi G. E. , Ezekiel A. A. , Adetona A. A. , Oyewole F. M. , Onatoye N. M. , Idowu I. T. , Akinniku A. K.
Published: January 2021

Background

Soil degradation remains a serious threat to agricultural production. With increase downpour due to climate change effect, more farmlands are exposed to erosion. Therefore, ecologically sound strategies for erosion control are indispensable to farmers, to boost agricultural productivity.

Results

A multistage sampling technique was used to select the respondents for this study, and descriptive and inferential statistics were adopted to determine the farmers’ perception of the awareness, adoption and use of vetiver grass technology in controlling erosion in the study area. A total of four hundred valid questionnaires were subjected to analysis and the result shows that most of the farmers (29%) were between the ages of 41 and 50 years and the average age of the respondents stood at 45.5 years, implying that the farmers were in their productive and active age. Most of the respondents were male and married with an average household size of 5.2. Large number (76%) of the respondents had formal education, which the level ranged from primary to post-secondary education. Large proportion of the respondents engaged in private business as secondary occupation with an average income of $84.6 per cropping season. The effectiveness of vetiver grass adoption and use was significantly influenced by age (P < 0.1), gender (P < 0.01), marital status (P < 0.05), level of education (P < 0.01) and income of the respondents (P < 0.05). Most of the respondents within the ages of 41–50 years were aware of the erosion control potentials of vetiver grass and adopted the grass because it was cheap and affordable, easy to cultivate and maintain, and readily available and perceived to possess the potential effectiveness to control erosion.

Conclusion

Stakeholders are enjoined to increase the awareness of the vetiver grass for increased adoption and utilization, as many farmers were ignorant of the vetiver grass technology for erosion control in the study area.
Seismic diffraction separation in the near surface: Detection of high-contrast voids in unconsolidated soils
Authors: Bakhtiari Rad Parsa , Hickey Craig J.
Published: January 2021

Seismic diffractions carry the signature of near-surface high-contrast anomalies and need to be extracted from the data to complement the reflection processing and other geophysical techniques. Because diffractions are often masked by reflections, surface waves, and noise, careful diffraction separation is required as a first step for diffraction imaging. A multiparameter time-imaging method is used to separate near-surface diffractions. The implemented scheme makes use of the wavefront attributes that are reliable fully data-derived processing parameters. To mitigate the effect of strong noise and wavefield interference in near-surface data, our workflow incorporates two wavefront-based parameters, dip angle and coherence, as additional constraints. The output of the diffraction separation is a time trace-based stacked section that provides the basis for further analysis and applications such as time migration. To evaluate the performance of the proposed wavefront-based workflow, it is applied to two challenging field data sets that were collected over small culverts in very near-surface soft soil environments. The results of the proposed constrained workflow and the existing unconstrained approach are presented and compared. The proposed workflow demonstrates superiority over the existing method by attenuating more reflection and noise, leading to improved diffraction separation. The abundance of unmasked diffractions reveals that the very near surface is highly scattering. Time migration is carried out to enhance anomaly detection by focusing the isolated diffractions. Although strong diffractivity is observed at the approximate location of the targets, there are other diffracting zones observed in the final sections that might bring uncertainties for interpretation.