bluuebunny/crossref_metadata_2025 huggingface dataset:
The Immunoproteasome Subunits LMP2, LMP7 and MECL-1 Are Crucial Along the Induction of Cerebral Toxoplasmosis
Authors: French Timothy , Israel Nicole , Düsedau Henning Peter , Tersteegen Anne , Steffen Johannes , Cammann Clemens , Topfstedt Eylin , Dieterich Daniela , Schüler Thomas , Seifert Ulrike , Dunay Ildiko Rita
Published: April 2021

Cell survival and function critically relies on the fine-tuned balance of protein synthesis and degradation. In the steady state, the standard proteasome is sufficient to maintain this proteostasis. However, upon inflammation, the sharp increase in protein production requires additional mechanisms to limit protein-associated cellular stress. Under inflammatory conditions and the release of interferons, the immunoproteasome (IP) is induced to support protein processing and recycling. In antigen-presenting cells constitutively expressing IPs, inflammation-related mechanisms contribute to the formation of MHC class I/II-peptide complexes, which are required for the induction of T cell responses. The control ofToxoplasma gondiiinfection relies on Interferon-γ (IFNγ)-related T cell responses. Whether and how the IP affects the course of anti-parasitic T cell responses along the infection as well as inflammation of the central nervous system is still unknown. To answer this question we used triple knockout (TKO) mice lacking the 3 catalytic subunits of the immunoproteasome (β1i/LMP2, β2i/MECL-1 and β5i/LMP7). Here we show that the numbers of dendritic cells, monocytes and CD8+T cells were reduced inToxoplasma gondii-infected TKO mice. Furthermore, impaired IFNγ, TNF and iNOS production was accompanied by dysregulated chemokine expression and altered immune cell recruitment to the brain. T cell differentiation was altered, apoptosis rates of microglia and monocytes were elevated and STAT3 downstream signaling was diminished. Consequently, anti-parasitic immune responses were impaired in TKO mice leading to elevatedT. gondiiburden and prolonged neuroinflammation. In summary we provide evidence for a critical role of the IP subunits β1i/LMP2, β2i/MECL-1 and β5i/LMP7 for the control of cerebralToxoplasma gondiiinfection and subsequent neuroinflammation.
Coastal Observation Using a Vertical Profiling System at the Southern Coast of Korea
Authors: Park Young-Gyu , Seo Seongbong , Kim Dong Guk , Noh Joocheul , Park Hyuk Min
Published: April 2021

At a coastal station near the southern coast of Korea, the vertical profiles of temperature salinity dissolved oxygen and velocity were obtained using a vertical profiler, Aqualog, every summer from 2016 to 2020. At the site, fishing activity was not allowed, and it was possible to maintain the profiler continuously and stably. It was set to travel every one or 2 h for two to 4 months. Thus, we were able to observe the variations of the water properties from hourly to monthly scales. The sensors were contaminated much less than we expected, and the data could be used without correction at least for our coastal applications. The main phenomena we observed are tides, coastal warming, fresh water, and responses to typhoons. On the daily time scale, the most prominent phenomenon is semi-diurnal tides, with which the thickness and temperature of coastal warm waters changed. The warm water also showed fluctuations between 10 and 15 days. The data also revealed that the tide showed strong seasonality. In summer, when the water is strongly stratified, the tidal current is baroclinic, while in winter, when the water is well mixed, the current is barotropic. Responses to typhoon induced winds were rather complicated. In one case, increase in the upper mixed layer was observed. The thick mixed layer disappeared in about a day due to advection. In another case the upper mixed layer became thinner, while the wind became stronger due the advection of the offshore water. Hydrographic observations conducted every 2 months, of course, or point measurement at a surface buoy could not show such continuous changes. More and more local fishermen are showing interest in oceanographic information, and data from the profiler could be of much use to them.
Reference Values for Five-Repetition Chair Stand Test Among Middle-Aged and Elderly Community-Dwelling Chinese Adults
Authors: Gao Shan-Yan , Xia Yang , Wu Qi-Jun , Chang Qing , Zhao Yu-Hong
Published: April 2021

Background: Previous studies on the five-repetition chair stand test (CS-5) are limited by the representativeness of the sample or the lack of reference equations for CS-5. Defined reference values for CS-5 in a large population are not available for middle-aged and elderly Chinese adults.

Objective: We established age- and sex-stratified reference values for CS-5 times in a large population in China, and to investigate the associations between demographic and anthropometric factors and CS-5 times.

Methods: Analysis of data from the national baseline survey of the China Health and Retirement Longitudinal Study, a nationally representative longitudinal survey that includes 450 urban communities and rural villages within 28 provinces, municipalities, and autonomous regions of China.

Results: Twelve thousand six hundred five of seventeen thousand seven hundred eight participants were included for the reference value analyses. Twelve thousand three hundred out of seventeen thousand seven hundred eight participants were included for the risk factor analyses. Of 12,605 participants, the mean CS-5 time was 10.13 s (SD, 3.32) in men and 11.03 s (SD, 3.54) in women aged 40+ year. The CS-5 times were shorter in men than women of all age categories (P < 0.001). The cut-off points ranged from 5.36 to 9.98 s and from 6.48 to 10.29 s in men and women, respectively. Mean velocity was higher in men than in women (P < 0.001). Age, waist circumference, living in a rural village, and having chronic diseases were positively associated with CS-5 time, whereas male, handgrip strength, currently married, income, and current or ex-drinker were negatively associated with CS-5 time in this population (all P < 0.001).

Conclusions: The comprehensive normative values for CS-5 are essential for enabling clinicians to better evaluate functional performance, determine the appropriate interventional strategy, and promote healthy aging of older adults.
Land-Use System and Forest Floor Explain Prokaryotic Metacommunity Structuring and Spatial Turnover in Amazonian Forest-to-Pasture Conversion Areas
Authors: Rocha Fernando Igne , Ribeiro Thiago Gonçalves , Fontes Marcelo Antoniol , Schwab Stefan , Coelho Marcia Reed Rodrigues , Lumbreras José Francisco , da Motta Paulo Emílio Ferreira , Teixeira Wenceslau Geraldes , Cole James , Borsanelli Ana Carolina , Dutra Iveraldo dos Santos , Howe Adina , de Oliveira Aline Pacobahyba , Jesus Ederson da Conceição
Published: April 2021

Advancing extensive cattle production is a major threat to biodiversity conservation in Amazonia. The dominant vegetation cover has a drastic impact on soil microbial communities, affecting their composition, structure, and ecological services. Herein, we explored relationships between land-use, soil types, and forest floor compartments on the prokaryotic metacommunity structuring in Western Amazonia. Soil samples were taken in sites under high anthropogenic pressure and distributed along a ±800 km gradient. Additionally, the litter and a root layer, characteristic of the forest environment, were sampled. DNA was extracted, and metacommunity composition and structure were assessed through 16S rRNA gene sequencing. Prokaryotic metacommunities in the bulk soil were strongly affected by pH, base and aluminum saturation, Ca + Mg concentration, the sum of bases, and silt percentage, due to land-use management and natural differences among the soil types. Higher alpha, beta, and gamma diversities were observed in sites with higher soil pH and fertility, such as pasture soils or fertile soils of the state of Acre. When taking litter and root layer communities into account, the beta diversity was significantly higher in the forest floor than in pasture bulk soil for all study regions. Our results show that the forest floor’s prokaryotic metacommunity performs a spatial turnover hitherto underestimated to the regional scale of diversity.
Exploring Variances of White Matter Integrity and the Glymphatic System in Simple Febrile Seizures and Epilepsy
Authors: Salimeen Mustafa Salimeen Abdelkareem , Liu Congcong , Li Xianjun , Wang Miaomiao , Singh Martha , Si Shuqing , Li Mengxuan , Cheng Yannan , Wang Xiaoyu , Zhao Huifang , Wu Fan , Zhang Yuli , Tafawa Habib , Pradhan Anuja , Yang Guanyu , Yang Jian
Published: April 2021

Background: Simple febrile seizures (SFS) and epilepsy are common seizures in childhood. However, the mechanism underlying SFS is uncertain, and the presence of obvious variances in white matter (WM) integrity and glymphatic function between SFS and epilepsy remain unclear. Therefore, this study aimed to investigate the differences in WM integrity and glymphatic function between SFS and epilepsy.

Material and Methods: We retrospectively included 26 children with SFS, 33 children with epilepsy, and 28 controls aged 6–60 months who underwent magnetic resonance imaging (MRI). Tract-based spatial statistics (TBSS) were used to compare the diffusion tensor imaging (DTI) metrics of WM among the above-mentioned groups. T2-weighted imaging (T2WI) was used to segment the visible Virchow-Robin space (VRS) through a custom-designed automated method. VRS counts and volume were quantified and compared among the SFS, epilepsy, and control groups. Correlations of the VRS metrics and seizure duration and VRS metrics and the time interval between seizure onset and MRI scan were also investigated.

Results: In comparison with controls, children with SFS showed no significant changes in fractional anisotropy (FA), axial diffusivity (AD), or radial diffusivity (RD) in the WM (P > 0.05). Decreased FA, unchanged AD, and increased RD were observed in the epilepsy group in comparison with the SFS and control groups (P < 0.05). Meanwhile, VRS counts were higher in the SFS and epilepsy groups than in the control group (VRS_SFS, 442.42 ± 74.58, VRS_epilepsy, 629.94 ± 106.55, VRS_control, 354.14 ± 106.58; P < 0.001), and similar results were found for VRS volume (VRS_SFS, 6,228.18 ± 570.74 mm3, VRS_epilepsy, 9,684.84 ± 7,292.66mm3, VRS_control, 4,007.22 ± 118.86 mm3; P < 0.001). However, VRS metrics were lower in the SFS group than in the epilepsy group (P < 0.001). In both SFS and epilepsy, VRS metrics positively correlated with seizure duration and negatively correlated with the course after seizure onset.

Conclusion: SFS may not be associated with WM microstructural disruption; however, epilepsy is related to WM alterations. Seizures are associated with glymphatic dysfunction in either SFS or epilepsy.
Circulating Biomarkers for Early Stage Non-Small Cell Lung Carcinoma Detection: Supplementation to Low‐Dose Computed Tomography
Authors: Kan Chin Fung Kelvin , Unis Graham D. , Li Luke Z. , Gunn Susan , Li Li , Soyer H. Peter , Stark Mitchell S.
Published: April 2021

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients’ overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low‐dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.
The Impact of Long Non-Coding RNAs in the Pathogenesis of Hepatocellular Carcinoma
Authors: Ghafouri-Fard Soudeh , Gholipour Mahdi , Hussen Bashdar Mahmud , Taheri Mohammad
Published: April 2021

Hepatocellular carcinoma (HCC) is among the utmost deadly human malignancies. This type of cancer has been associated with several environmental, viral, and lifestyle risk factors. Among the epigenetic factors which contribute in the pathogenesis of HCC is dysregulation of long non-coding RNAs (lncRNAs). These transcripts modulate expression of several tumor suppressor genes and oncogenes and alter the activity of cancer-related signaling axes. Several lncRNAs such as NEAT1, MALAT1, ANRIL, and SNHG1 have been up-regulated in HCC samples. On the other hand, a number of so-called tumor suppressor lncRNAs namely CASS2 and MEG3 are down-regulated in HCC. The interaction between lncRNAs and miRNAs regulate expression of a number of mRNA coding genes which are involved in the pathogenesis of HCC. H19/miR-15b/CDC42, H19/miR-326/TWIST1, NEAT1/miR-485/STAT3, MALAT1/miR-124-3p/Slug, MALAT1/miR-195/EGFR, MALAT1/miR-22/SNAI1, and ANRIL/miR-144/PBX3 axes are among functional axes in the pathobiology of HCC. Some genetic polymorphisms within non-coding regions of the genome have been associated with risk of HCC in certain populations. In the current paper, we describe the recent finding about the impact of lncRNAs in HCC.
Edible Bird’s Nest Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57BL/6J Mice by Restoring the Th17/Treg Cell Balance
Authors: Fan Yaohua , Fan Yanqun , Liu Kunfeng , Lonan Piyanuch , Liao Feng , Huo Yuhang , Zhong Xiaohua , Liang Yueliang , Wang Yaxin , Hou Shaozhen , Lai Xiaoping , Li Geng , Kuang Weihong
Published: April 2021

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) with a complex aetiology that commonly recurs. Most drugs for UC treatment interfere with metabolism and immune responses, often causing some serious adverse reactions. Therefore, the development of alternative treatments, including nutritional supplements and probiotics, have been one of the main areas of current research due to fewer side effect. As both a Chinese medicine and a food, edible bird’s nest (EBN) has high nutritional value. Modern pharmacological studies have shown that it has anti-inflammatory, immunoregulatory, antiviral and neuroprotective effects. In this study, UC was induced with dextran sulfate sodium (DSS) to investigate the protective effect of EBN on colitis mice and the related mechanism. The body weight, faecal morphology and faecal occult blood results of mice were recorded every day from the beginning of the modelling period. After the end of the experiment, the length of the colon was measured, and the colon was collected for histopathological detection, inflammatory factor detection and immunohistochemical detection. Mouse spleens were dissected for flow cytometry. The results showed that in mice with colitis, EBN improved symptoms of colitis, reduced colonic injury, and inhibited the increases in the levels of the pro-inflammatory cytokines IL-1β and TNF-α. The T helper 17 (Th17)/regulatory T (Treg) cell balance was restored by decreasing the expression of IL-17A and IL-6 in intestinal tissues, increasing the expression of TGF-β, and decreasing the number of Th17 cells in each EBN dose group. These findings suggest that EBN has a protective effect on DSS-mediated colitis in mice, mainly by restoring the Th17/Treg cell balance.
Involvement of Nrf2-HO-1/JNK-Erk Signaling Pathways in Aconitine-Induced Developmental Toxicity, Oxidative Stress, and ROS-Mitochondrial Apoptosis in Zebrafish Embryos
Authors: Xia Qing , Gao Shuo , Rapael Gnanamuthu Samuel Rajendran , Zhuang Kaiyan , Song Zhenzhen , Zhang Yun , Wang Xue , Tu Pengfei , Li Jianheng , Liu Kechun
Published: April 2021

Aconitine (AC), one of the bioactive diterpenoid alkaloids extracted from Aconitum plants, is widely used in traditional herbal medicine to treat various diseases. Emerging evidence indicates that AC has attracted great interest for its wide cardiotoxicity and neurotoxicity. However, the toxic effects of AC on embryonic development and its underlying mechanisms remain unclear. Here, a developmental toxicity assay of AC was performed on zebrafish embryos from 4 to 96 h post fertilization (hpf), and its underlying mechanisms were discussed. AC exposure impaired the cardiac, liver, and neurodevelopment. Especially, a high dose of AC (7.27 and 8.23 μM) exposure resulted in malformations at 72 and 96 hpf, including reduced body length, curved body shape, pericardial edema, yolk retention, swim bladder and brain developmental deficiency, and degeneration of dopaminergic neurons. High-concentration AC exposure caused a deficient cardiovascular system with cardiac dysfunctions, increased heart rates at 72 and 96 hpf, and reduced locomotor behavior at 120 hpf. AC treatment significantly increased the ROS level and triggered cell apoptosis in the heart and brain regions of embryos at 96 hpf in 7.27 and 8.23 μM AC treatment zebrafish. Oxidative stress was confirmed by reduced levels of T-SOD activity associated with accumulation of lipid peroxidation in larvae. The expression levels of oxidative stress-related genes (Nrf2, HO-1, Cat, and Sod-1) Erk1/2 and Bcl-2 were significantly downregulated at 96 hpf. The expression pattern of JNK and mitochondrial apoptosis-related genes (Bad, Bax, Cyto C, Casp-9, and Casp-3) was significantly upregulated. Taken together, all these parameters collectively provide the first evidence of AC-induced developmental toxicity in zebrafish embryo/larvae through ROS-medicated mitochondrial apoptosis involving Nrf2/HO-1 and JNK/Erk pathways.
Therapeutic Potential of Bioactive Compounds in Honey for Treating Osteoarthritis
Authors: Martinez-Armenta Carlos , Camacho-Rea María Carmen , Martínez-Nava Gabriela Angélica , Espinosa-Velázquez Rocio , Pineda Carlos , Gomez-Quiroz Luis Enrique , López-Reyes Alberto
Published: April 2021

Dysregulation of joint tissue homeostasis induces articular degenerative changes and musculoskeletal diseases such as osteoarthritis. This pathology represents the first cause of motor disability in individuals over 60 years of age, impacting their quality of life and the costs of health systems. Nowadays, pharmacological treatments for cartilage disease have failed to achieve full tissue regeneration, resulting in a functional loss of the joint; therefore, joint arthroplasty is the gold standard procedure to cure this pathology in severe cases of Osteoarthritis. A different treatment is the use of anti-inflammatory drugs which mitigate pain and inflammation in some degree, but without significant inhibition of disease progression. In this sense, new therapeutic alternatives based on natural compounds have been proposed to delay osteoarthritis progression, particularly those agents that regulate articular homeostasis. Preclinical studies have shown a therapeutic application of honey and its bioactive compounds, ranging from treating wounds, coughs, skin infections, and are also used as a biological stimulant by exerting antioxidant and anti-inflammatory properties. In this article, we reviewed the current medicinal applications of honey with particular emphasis on its use regulating articular homeostasis by inhibiting inflammation and oxidative stress.
Novel 3D Pixel Sensors for the Upgrade of the ATLAS Inner Tracker
Authors: Terzo Stefano , Boscardin Maurizio , Carlotto Juan , Dalla Betta Gian-Franco , Darbo Giovanni , Dorholt Ole , Ficorella Francesco , Gariano Giuseppe , Gemme Claudia , Giannini Giulia , Grinstein Sebastian , Heggelund Andreas , Huiberts Simon , Kok Angela , Koybasi Ozhan , Lapertosa Alessandro , Lauritzen Magne Elk , Manna Maria , Mendicino Roberto , Oide Hideyuki , Pellegrini Giulio , Povoli Marco , Quirion David , Rohne Ole Myren , Ronchin Sabina , Sandaker Heidi , Abdulla Samy Md. Arif , Stugu Bjarne , Vannoli Leonardo
Published: April 2021

The ATLAS experiment will undergo a full replacement of its inner detector to face the challenges posed by the High Luminosity upgrade of the Large Hadron Collider (HL-LHC). The new Inner Tracker (ITk) will have to deal with extreme particle fluences. Due to its superior radiation hardness the 3D silicon sensor technology has been chosen to instrument the innermost pixel layer of ITk, which is the most exposed to radiation damage. Three foundries (CNM, FBK, and SINTEF), have developed and fabricated novel 3D pixel sensors to meet the specifications of the new ITk pixel detector. These are produced in a single-side technology on either Silicon On Insulator (SOI) or Silicon on Silicon (Si-on-Si) bonded wafers by etching both n- and p-type columns from the same side. With respect to previous generations of 3D sensors they feature thinner active substrates and smaller pixel cells of 50 × 50 and 25 × 100 µm2. This paper reviews the main design and technological issues of these novel 3D sensors, and presents their characterization before and after exposure to large radiation doses close to the one expected for the innermost layer of ITk. The performance of pixel modules, where the sensors are interconnected to the recently developed RD53A chip prototype for HL-LHC, has been investigated in the laboratory and at beam tests. The results of these measurements demonstrate the excellent radiation hardness of this new generation of 3D pixel sensors that enabled the project to proceed with the pre-production for the ITk tracker.
Nitrogen Use Efficiency in Sorghum: Exploring Native Variability for Traits Under Variable N-Regimes
Authors: Bollam Srikanth , Romana Kirandeep Kaur , Rayaprolu Laavanya , Vemula Anilkumar , Das Roma Rani , Rathore Abhishek , Gandham Prasad , Chander Girish , Deshpande Santosh P. , Gupta Rajeev
Published: April 2021

Exploring the natural genetic variability and its exploitation for improved Nitrogen Use Efficiency (NUE) in sorghum is one of the primary goals in the modern crop improvement programs. The integrated strategies include high-throughput phenotyping, next generation sequencing (NGS)-based genotyping technologies, and a priori selected candidate gene studies that help understand the detailed physiological and molecular mechanisms underpinning this complex trait. A set of sixty diverse sorghum genotypes was evaluated for different vegetative, reproductive, and yield traits related to NUE in the field (under three N regimes) for two seasons. Significant variations for different yield and related traits under 0 and 50% N confirmed the availability of native genetic variability in sorghum under low N regimes. Sorghum genotypes with distinct genetic background had interestingly similar NUE associated traits. The Genotyping-By-Sequencing based SNPs (>89 K) were used to study the population structure, and phylogenetic groupings identified three distinct groups. The information of grain N and stalk N content of the individuals covered on the phylogenetic groups indicated randomness in the distribution for adaptation under variable N regimes. This study identified promising sorghum genotypes with consistent performance under varying environments, with buffer capacity for yield under low N conditions. We also report better performing genotypes for varied production use—grain, stover, and dual-purpose sorghum having differential adaptation response to NUE traits. Expression profiling of NUE associated genes in shoot and root tissues of contrasting lines (PVK801 and HDW703) grown in varying N conditions revealed interesting outcomes. Root tissues of contrasting lines exhibited differential expression profiles for transporter genes [ammonium transporter (SbAMT), nitrate transporters (SbNRT)]; primary assimilatory (glutamine synthetase (SbGS), glutamate synthase (SbGOGAT[NADH], SbGOGAT[Fd]), assimilatory genes [nitrite reductase (SbNiR[NADH]3)]; and amino acid biosynthesis associated gene [glutamate dehydrogenase (SbGDH)]. Identification and expression profiling of contrasting sorghum genotypes in varying N dosages will provide new information to understand the response of NUE genes toward adaptation to the differential N regimes in sorghum. High NUE genotypes identified from this study could be potential candidates for in-depth molecular analysis and contribute toward the development of N efficient sorghum cultivars.
UPLC-TOF-MS/MS-Based Metabolomics Analysis Reveals Species-Specific Metabolite Compositions in Pitchers of Nepenthes ampullaria, Nepenthes rafflesiana, and Their Hybrid Nepenthes × hookeriana
Authors: Rosli Muhammad Aqil Fitri , Mediani Ahmed , Azizan Kamalrul Azlan , Baharum Syarul Nataqain , Goh Hoe-Han
Published: April 2021

Hybridization is key to the evolution and diversity of plants in nature. Nepenthaceae comprises a family of diverse tropical carnivorous pitcher plant species with extensive hybridization. However, there is no study to date on the metabolite expression of hybrids in this family. We performed a non-targeted metabolomics analysis of the pitchers of twoNepenthesspecies with different dietary habits, namely, the semi-detritivorousN. ampullariaand carnivorousN. rafflesianawith their hybrid (N. ×hookeriana) for a comparative study. The whole-pitcher samples were extracted in methanol:chloroform:water (3:1:1) via sonication-assisted extraction and analyzed using ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS) followed by data analysis to profile chemical compositions. A total of 1,441 metabolite features were profiled from the three species in which 43.3% of features in the hybrid samples were not found in either of its parents. The partial least squares discriminant analysis (PLS-DA) found 324 metabolite features with variable in projection (VIP) values greater than one in which 55 features were statistically significant. This showed that the hybrid is closer toN.rafflesiana, which is consistent to the previous study on gene and protein expressions. A total of 105 metabolites were putatively identified with manual searches using public metabolite databases. Phenols were detected to be the most abundant secondary metabolites due to a high flavonoid content, especially inN. rafflesiana. The most abundant feature 476.3s:449.102 was found to be the most significant VIP for distinguishing between the three species as a chemical marker. This is the first study comparing metabolites in the carnivory organs of differentNepenthesspecies with comprehensive profiling and putative identification. The differential metabolite compositions in the pitchers of different species might have ecological implications with the hybrid showing intermediate phenotype between the parents as well as manifesting unique metabolites. However, there is no clear evidence of metabolites related to the differences in dietary habits between the hybrid and the two parent species.
Genetic Improvement for Resistance to Black Sigatoka in Bananas: A Systematic Review
Authors: Soares Julianna M. S. , Rocha Anelita J. , Nascimento Fernanda S. , Santos Adriadna S. , Miller Robert N. G. , Ferreira Cláudia F. , Haddad Fernando , Amorim Vanusia B. O. , Amorim Edson P.
Published: April 2021

Bananas are an important staple food crop in tropical and subtropical regions in Asia, sub-Saharan Africa, and Central and South America. The plant is affected by numerous diseases, with the fungal leaf disease black Sigatoka, caused by Mycosphaerella fijiensis Morelet [anamorph: Pseudocercospora fijiensis (Morelet) Deighton], considered one of the most economically important phytosanitary problem. Although the development of resistant cultivars is recognized as most effective method for long term control of the disease, the majority of today's cultivars are susceptible. In order to gain insights into this pathosystem, this first systematic literature review on the topic is presented. Utilizing six databases (PubMed Central, Web of Science, Google Academic, Springer, CAPES and Scopus Journals) searches were performed using pre-established inclusion and exclusion criteria. From a total of 3,070 published studies examined, 24 were relevant with regard to the Musa-P. fijiensis pathosystem. Relevant papers highlighted that resistant and susceptible cultivars clearly respond differently to infection by this pathogen. M. acuminata wild diploids such as Calcutta 4 and other diploid cultivars can harbor sources of resistance genes, serving as parentals for the generation of improved diploids and subsequent gene introgression in new cultivars. From the sequenced reference genome of Musa acuminata, although the function of many genes in the genome still require validation, on the basis of transcriptome, proteome and biochemical data, numerous candidate genes and molecules have been identified for further evaluation through genetic transformation and gene editing approaches. Genes identified in the resistance response have included those associated with jasmonic acid and ethylene signaling, transcription factors, phenylpropanoid pathways, antioxidants and pathogenesis-related proteins. Papers in this study also revealed gene-derived markers in Musa applicable for downstream application in marker assisted selection. The information gathered in this review furthers understanding of the immune response in Musa to the pathogen P. fijiensis and is relevant for genetic improvement programs for bananas and plantains for control of black Sigatoka.
An Intrinsic Geometric Constraint on Morphological Stomatal Traits
Authors: Zhang Lirong , Wang Shiping , Yang Xiaoxia , Cui Xiaoyong , Niu Haishan
Published: April 2021

A strong negative non-linear relationship exists between stomatal density (SD) and size (SS) or length (SL), which is of high importance in gas exchange and plant evolution. However, the cause of this relationship has not been clarified. In geometry, SD has an intrinsic relationship with SS−1 or SL−2, which is defined as a geometric constraint here. We compiled global data to clarify the influence of this geometric constraint on the SD-SS relationship. The log-log scaling slope of the relationship between SD and SS and between SD and SL was not significantly different from −1 and −2, respectively. Although the non-geometric effect drove the SD-SS curve away from the power function with −1, a larger influence of the geometric constraint on SD was found. Therefore, the higher geometric constraint possibly causes the SD-SS relationship to be inevitably non-linear and negative. Compared to pteridophyta and gymnosperms, the geometric constraint was lower for angiosperm species, possibly due to most of them having smaller stomata. The relaxation of the geometric constraint seems to extend the upper range of SD in angiosperm species and hence enable them to exploit a wide range of environments.
Moving Morality Beyond the In-Group: Liberals and Conservatives Show Differences on Group-Framed Moral Foundations and These Differences Mediate the Relationships to Perceived Bias and Threat
Authors: Stewart Brandon D. , Morris David S. M.
Published: April 2021

Moral foundations research suggests that liberals care about moral values related to individual rights such as harm and fairness, while conservatives care about those foundations in addition to caring more about group rights such as loyalty, authority, and purity. However, the question remains about how conservatives and liberals differ in relation to group-level moral principles. We used two versions of the moral foundations questionnaire with the target group being either abstract or specific ingroups or outgroups. Across three studies, we observed that liberals showed more endorsement of Individualizing foundations (Harm and Fairness foundations) with an outgroup target, while conservatives showed more endorsement of Binding foundations (Loyalty, Authority, and Purity foundations) with an ingroup target. This general pattern was found when the framed, target-group was abstract (i.e., ‘ingroups’ and ‘outgroups’ in Study 1) and when target groups were specified about a general British-ingroup and an immigrant-outgroup (Studies 2 and 3). In Studies 2 and 3, both Individualizing-Ingroup Preference and Binding-Ingroup Preference scores predicted more Attitude Bias and more Negative Attitude Bias toward immigrants (Studies 2 and 3), more Implicit Bias (Study 3), and more Perceived Threat from immigrants (Studies 2 and 3). We also demonstrated that increasing liberalism was associated with less Attitude Bias and less Negative Bias toward immigrants (Studies 2 and 3), less Implicit Bias (Study 3), and less Perceived Threat from immigrants (Studies 2 and 3). Outgroup-individualizing foundations and Ingroup-Binding foundations showed different patterns of mediation of these effects.
The Contribution of Learning and Mental Health Variables in First-Year Students' Profiles
Authors: Milienos Fotios S. , Rentzios Christos , Catrysse Leen , Gijbels David , Mastrokoukou Sofia , Longobardi Claudio , Karagiannopoulou Evangelia
Published: April 2021

International studies focus on the successful transition into higher education, which is considered crucial for both the students and the educational institution in the context of students' learning and adjustment in higher education. The aim of the current study was to identify student profiles that include cognitive, metacognitive, and motivational aspects of learning, but also aspects of resilience, emotion dysregulation, and anxiety. The sample consists of 316 Greek undergraduate students (18.7% males and 81.3% females). The results showed four different (meta)-cognitive-emotional learner profiles: the emotionally stable and highly adaptive learner; the emotionally dysregulated and at risk learner; the emotionally dysregulated and highly adaptive learner; the emotionally stable and at risk learner. Emotionally dysregulated and at risk learner has a lower GPA than the emotional stable and highly adaptive learner, the emotionally dysregulated and highly adaptive learner and the emotionally stable and at risk learner.
Context, Development, and Digital Media: Implications for Very Young Adolescents in LMICs
Authors: Magis-Weinberg Lucía , Ballonoff Suleiman Ahna , Dahl Ronald E.
Published: April 2021

The rapidly expanding universe of information, media, and learning experiences available through digital technology is creating unique opportunities and vulnerabilities for children and adolescents. These issues are particularly salient during the developmental window at the transition from childhood into adolescence. This period of early adolescence is a time of formative social and emotional learning experiences that can shape identity development in both healthy and unhealthy ways. Increasingly, many of these foundational learning experiences are occurring in on-line digital environments. These expanding vulnerabilities and opportunities are being further amplified for young adolescents growing up in low resourced settings around the world. Cultural and contextual factors influence access, use, and appropriation of digital technology. Further, neurobehavioral changes associated with the onset of puberty often coincide with entry into social media and more autonomous use of technology. In low-and-middle-income countries (LMICs), disparities in access, use, and appropriation of digital media can amplify prevailing economic gaps, and compound gender inequalities during early adolescence. In LMICs, adolescents are often the early adopters of mobile technology and social media platforms. While the impact of social media on the well-being, particularly mental health, of young adolescents has been a focus of research in high-income countries (HICs), much less is known about the impacts of social media use on young adolescents in LMICs. In this paper, we review what is known about the interaction between digital media and early adolescent development. We highlight crucial gaps in the evidence in LMICs; and describe some hypotheses and areas for future research to address these compelling issues.
Psychometric Properties of Flourishing Scales From a Comprehensive Well-Being Assessment
Authors: Weziak-Bialowolska Dorota , Bialowolski Piotr , Lee Matthew T. , Chen Ying , VanderWeele Tyler J. , McNeely Eileen
Published: April 2021

In this article, we develop a measure of complete well-being. The framework is derived from the theoretical model of human flourishing understood as a state in which all aspects of a human life are favorable. The approach extends beyond psychological well-being and reflects the World Health Organization definition of health that not only considers the health of body and mind but also embraces the wholeness of the person. The Well-Being Assessment (WBA) is a comprehensive instrument designed to assess holistic well-being in six domains: emotional health, physical health, meaning and purpose, character strengths, social connectedness, and financial security. Although each of these domains is distinct, all of them are nearly universally desired, and all but financial security constitute ends in themselves. Data were collected from a representative sample of working adults. A sample of 276 employees participated in the pilot, 2,370 participated in the first wave and 1,209 in the second wave of the survey. The WBA showed a good fitting (40 items, six factors), satisfactory reliability, test–retest correlation, and convergent/discriminant validity in relation to stability over time and relevant health measures, as well as a good fit to the data that were invariant over time, gender, age, education, and marital status. The instrument can be of use for scientists, practitioners, clinicians, public health officials, and patients. Adoption of more holistic measures of well-being that go beyond psychological well-being may help to shift the focus from health deficiencies to health and well-being promotion.
Psilocybin: From Serendipity to Credibility?
Authors: Rucker James J. , Young Allan H.
Published: April 2021

Psilocybin has a long history of non-medical use and some seem to infer from this that it has therapeutic utility. Early phase clinical trials with psilocybin are encouraging, but suggest only that larger, multicentre trials are required. These are ongoing but will take many years to complete. Meanwhile, retreat centers offering paid experiences with psilocybin truffles have opened in some countries, often using early phase clinical trial data as a basis for bold, public facing claims. This seems unwise. Early phase trials are not designed for their results to be generalized outside the setting they were undertaken in. To do so risks being misleading. Providing what may be seen as an unregulated drug intervention as a paid service is difficult to reconcile with long-held ethical principles underpinning human research and treatment development that were laid down by the 1947 Nuremberg Code and the 1962 Kefauver Harris Amendments. By using psilocybin before it has been properly tested, retreat centers may be undermining their own credibility and the credibility of the wider field.
Multimorbidity and Its Outcomes Among Patients Attending Psychiatric Care Settings: An Observational Study From Odisha, India
Authors: Pati Sanghamitra , Mahapatra Pranab , Dwivedi Rinshu , Athe Ramesh , Sahoo Krushna Chandra , Samal Mousumi , Das Ram Chandra , Hussain Mohammad Akhtar
Published: April 2021

Background: Multimorbidity, the presence of two or more chronic health conditions is linked to premature mortality among psychiatric patients since the presence of one can further complicate the management of either. Little research has focused on the magnitude and effect of multimorbidity among psychiatric patients in low-and middle-income settings. Our study, provides the first ever data on multimorbidity and its outcomes among patients attending psychiatric clinics in Odisha, India. It further explored whether multimorbidity was associated with higher medical expenditure and the interaction effect of psychiatric illness on this association.

Methods: This cross-sectional study included 500 adult patients presenting to the psychiatric clinic of a medical college hospital in Odisha over a period of 6 months (February 2019–July 2019). A validated structured questionnaire, “multimorbidity assessment questionnaire for psychiatric care” (MAQ-PsyC) was used for data collection. We used multinomial logistic model for the effect estimation. Odds ratios (OR) and 95% confidence intervals (CI) for high healthcare utilization and expenditure were calculated by number and pattern of multimorbidity. Data was analyzed by STATA 14.

Results: Half (50%) of the psychiatric outpatients had multimorbidity. The relative probabilities of having one additional condition were 5.3 times (RRR = 5.3; 95% CI: 2.3, 11.9) and multiple morbidities were 6.6 times (RRR = 6.6; 95%CI: 3.3, 13.1) higher for patients in 60+ age group. Healthcare utilization i.e., medication use and physician consultation was significantly higher for psychiatric conditions such as mood disorders, schizophrenia, schizotypal and delusional disorders, and for hypertension, cancer, diabetes, among somatic conditions. Out of pocket expenditure (OOPE) was found to be highest for laboratory investigations, followed by medicines and transport expenditure. Within psychiatric conditions, mood disorders incurred highest OOPE ($93.43) while hypertension was the most leading for OOPE in physical morbidities ($93.43). Psychiatric illnesses had a significant interaction effect on the association between multimorbidity and high medical expenditure (P = 0.001).

Conclusion: Multimorbidity is highly prevalent in psychiatric patients associated with significantly high healthcare utilization and medical expenditure. Such disproportionate effect of psychiatric multimorbidity on healthcare cost and use insinuates the need for stronger financial protection and tailor-made clinical decision making for these vulnerable patient subgroups.
High Throughput Virtual Screening and Molecular Dynamics Simulation for Identifying a Putative Inhibitor of Bacterial CTX-M-15
Authors: Shakil Shazi , Rizvi Syed M. Danish , Greig Nigel H.
Published: April 2021

Background: Multidrug resistant bacteria are a major therapeutic challenge. CTX-M-type enzymes are an important group of class A extended-spectrum β-lactamases (ESBLs). ESBLs are the enzymes that arm bacterial pathogens with drug resistance to an array of antibiotics, notably the advanced-generation cephalosporins. The current need for an effective CTX-M-inhibitor is high. Objective: The aim of the current study was to identify a promising anti-CTX-M-15 ligand whose chemical skeleton could be used as a ‘seed-molecule’ for future drug design against resistant bacteria. Methods: Virtual screening of 5,000,000 test molecules was performed by ‘MCULE Drug Discovery Platform’. ‘ADME analyses’ was performed by ‘SWISS ADME’. TOXICITY CHECKER of MCULE was employed to predict the safety profile of the test molecules. The complex of the ‘Top inhibitor’ with the ‘bacterial CTX-M-15 enzyme’ was subjected to 102.25 ns molecular dynamics simulation. This simulation was run for 3 days on a HP ZR30w workstation. Trajectory analyses were performed by employing the macro ‘md_analyze.mcr’ of YASARA STRUCTURE version 20.12.24.W.64 using AMBER14 force field. YANACONDA macro language was used for complex tasks. Figures, including RMSD and RMSF plots, were generated. Snapshots were acquired after every 250 ps. Finally, two short videos of ‘41 s’ and ‘1 min and 22 s’ duration were recorded. Results: 5-Amino-1-(2H-[1,2,4]triazino[5,6-b]indol-3-yl)-1H-pyrazole-4-carbonitrile, denoted by the MCULE-1352214421-0-56, displayed the most efficient binding with bacterial CTX-M-15 enzyme. This screened molecule significantly interacted with CTX-M-15 via 13 amino acid residues. Notably, nine amino acid residues were found common to avibactam binding (the reference ligand). Trajectory analysis yielded 410 snapshots. The RMSD plot revealed that around 26 ns, equilibrium was achieved and, thereafter, the complex remained reasonably stable. After a duration of 26 ns and onwards until 102.25 ns, the backbone RMSD fluctuations were found to be confined within a range of 0.8–1.4 Å. Conclusion: 5-Amino-1-(2H-[1,2,4]triazino[5,6-b]indol-3-yl)-1H-pyrazole-4-carbonitrile could emerge as a promising seed molecule for CTX-M-15-inhibitor design. It satisfied ADMET features and displayed encouraging ‘simulation results’. Advanced plots obtained by trajectory analyses predicted the stability of the proposed protein-ligand complex. ‘Hands on’ wet laboratory validation is warranted.
Prosthetic Shoulder Joint Infection by Cutibacterium acnes: Does Rifampin Improve Prognosis? A Retrospective, Multicenter, Observational Study
Authors: Vilchez Helem , Escudero-Sanchez Rosa , Fernandez-Sampedro Marta , Murillo Oscar , Auñón Álvaro , Rodríguez-Pardo Dolors , Jover-Sáenz Alfredo , del Toro Mª , Rico Alicia , Falgueras Luis , Praena-Segovia Julia , Guío Laura , Iribarren José , Lora-Tamayo Jaime , Benito Natividad , Morata Laura , Ramirez Antonio , Riera Melchor ,   Study Group on Osteoarticular Infections (GEIO),   the Spanish Network for Research in Infectious Pathology (REIPI)
Published: April 2021

This retrospective, multicenter observational study aimed to describe the outcomes of surgical and medical treatment of C. acnes-related prosthetic joint infection (PJI) and the potential benefit of rifampin-based therapies. Patients with C. acnes-related PJI who were diagnosed and treated between January 2003 and December 2016 were included. We analyzed 44 patients with C. acnes-related PJI (median age, 67.5 years (IQR, 57.3–75.8)); 75% were men. The majority (61.4%) had late chronic infection according to the Tsukayama classification. All patients received surgical treatment, and most antibiotic regimens (43.2%) included β-lactam. Thirty-four patients (87.17%) were cured; five showed relapse. The final outcome (cure vs. relapse) showed a nonsignificant trend toward higher failure frequency among patients with previous prosthesis (OR: 6.89; 95% CI: 0.80–58.90) or prior surgery and infection (OR: 10.67; 95% IC: 1.08–105.28) in the same joint. Patients treated with clindamycin alone had a higher recurrence rate (40.0% vs. 8.8%). Rifampin treatment did not decrease recurrence in patients treated with β-lactams. Prior prosthesis, surgery, or infection in the same joint might be related to recurrence, and rifampin-based combinations do not seem to improve prognosis. Debridement and implant retention appear a safe option for surgical treatment of early PJI.