bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of dietary inflammatory index with metabolic syndrome and its components: a systematic review and meta-analysis
Authors: Yi Qian , Li Xue , He Yazhou , Xia Wei , Shao Jing , Ye Zhihong , Song Peige
Published: January 2021

Objective:

Inflammation has been suggested to play an important role in the development and progression of metabolic syndrome (MetS). Dietary inflammatory index (DII), a measurement of inflammatory potential in diets, was suggested to be associated with MetS. The aim of this systematic review and meta-analysis was to establish the associations of DII with MetS and its components based on available observational studies.

Design:

Systematic review and meta-analysis.

Setting:

A comprehensive literature search of studies that assessed the associations between DII and MetS was conducted in PubMed, Medline and Embase, using a combination of search terms relating to DII and MetS.

Participants:

Eighteen articles were eligible, of which fourteen were cross-sectional and four were cohort in design.

Results:

Results from the random effects meta-analysis showed significantly positive associations of higher DII (top v. bottom quartiles) with MetS (OR: 1·23 (95 % CI 1·10, 1·37)), abdominal obesity (OR: 1·15 (95 % CI 1·02, 1·29)), high blood pressure (OR: 1·17 (95 % CI 1·07, 1·29)), hyperglycaemia (OR: 1·18 (95 % CI 1·05, 1·33)) and hypertriacylglycerolaemia (OR: 1·17 (95 % CI 1·07, 1·28)). The effects of summary OR became stronger when analyses were restricted to cohorts, studies that adjudged for covariates (including BMI, physical activity and total energy intake).

Conclusions:

Higher DII, representing pro-inflammatory diet, is associated with higher odds of MetS and its components, except for low HDL-cholesterol. The findings prompt dietary interventions for preventing MetS from the aspect of inflammation.
Digit ratio (2D:4D) and amniotic testosterone and estradiol: an attempted replication of Lutchmaya et al. (2004)
Authors: Richards Gareth , Browne Wendy V. , Constantinescu Mihaela
Published: January 2021

The ratio of length between the second (index) and fourth (ring) fingers (digit ratio or 2D:4D) is frequently employed as a retrospective marker of prenatal sex hormone exposure. Lutchmaya et al. (2004) reported that the ratio of testosterone (T) to estradiol (E) present in second-trimester amniotic fluid was negatively correlated with digit ratios for the right hand (but not the left hand) in a sample of 29 children at 2-year follow-up. This observation is frequently cited as evidence for the measure’s validity but has not been replicated. We therefore present the findings of another study of amniotic T and E that did not find evidence for these effects at 4½-year follow-up. The confidence intervals were large, the direction of correlations observed was generally erratic, and the overall findings question the premise that second-trimester sex hormones affect the development of digit length ratios in humans.
Identifying Suicide and Self-Harm Research Priorities in North West England
Authors: Saini Pooja , Clements Caroline , Gardner Kathryn Jane , Chopra Jennifer , Latham Cameron , Kumar Rohit , Taylor Peter
Published: January 2021

Abstract. Background: Understanding and effectively managing self-harm and suicide require collaborative research between stakeholders focused on shared priorities. Aims: We aimed to develop a consensus about suicide and self-harm research priorities in the North West of England using the Delphi method. Method: Items for the Delphi survey were generated through group discussions at a workshop with 88 stakeholders and subsequent thematic analysis of key themes. A total of 44 participants who were experts-by-experience, researchers, and clinicians based within health services including third-sector organizations completed the Delphi survey. Results: A three-round survey reached consensus on 55 research priority items identifying key priorities in each of the following groups: offenders, children and young people, self-harm in community settings, and crisis care in the community. Limitations: The pool of delegates at the workshop and subsequent self-selection into the Delphi may have introduced bias into the study. Conclusion: The current paper highlights specific actionable priorities were identified in four areas that can be used to inform research efforts and future policy and practice, based on shared areas of perceived importance and concern. Future work is needed to confirm the significance of these priority areas, including the use of evidence synthesis approaches to ascertain the extent to which these priorities have already been investigated and where gaps in understanding remain.
Coseismic Surface Displacement in the 2019 Ridgecrest Earthquakes: Comparison of Field Measurements and Optical Image Correlation Results
Authors: Gold Ryan D , DuRoss Christopher B , Barnhart William D
Published: January 2021

A fundamental topic in earthquake studies is understanding the extent to which fault rupture at the surface is localized on primary fault strands as opposed to distributed tens to hundreds of meters away from primary ruptures through off‐fault deformation (OFD) via a combination of discrete secondary faulting and bulk deformation. The 2019 Ridgecrest, CA Mw6.4 and Mw7.1 earthquakes provide an opportunity to explore this problem via comparison of published field‐based and mostly on‐fault offset measurements, with new lateral displacement measurements made over length scales of hundreds of meters across the primary rupture using WorldView satellite images collected before and after the earthquakes. A mean fit to the field observations underestimates net slip (pixel‐correlation results) by an average of 0.4 m along the Mw6.4 rupture (∼41% of net left‐lateral displacement) and 0.7 m along the Mw7.1 rupture (∼65% of net right‐lateral displacement). We attribute these differences to substantial OFD along the lengths of the Mw6.4 (∼59%) and Mw7.1 (∼35%) ruptures. A maximum fit to the field observations provides an improved match to the pixel correlation results (difference of 0.1–0.2 m or ∼76%–98% of net displacement). OFD may in part depend on displacement magnitude, where locations along the rupture with smaller displacements (<2 m) are characterized by a greater percentage of OFD. Furthermore, OFD increases with rupture zone width, especially at the scale of individual rupture strands (hundreds of meters). These findings contribute to a growing understanding of the important role of OFD in accommodating deformation near the surface.
Equation of State for Fe‐9.0 wt% O up to 246 GPa: Implications for Oxygen in the Earth's Outer Core
Authors: Young G. , Fan Lili , Zhao Bin , Chen Xing , Liu Xun , Huang Haijun
Published: January 2021

To constrain the amount of oxygen in Earth's outer core, the equation of sate (EoS) for Fe‐9 wt% O (Fe‐9O) was measured up to ∼246 GPa using the dynamic compression technique. The shock velocity and particle velocity relationship can be described by . Using the ideal mixing model, the isothermal equation of state for Fe‐9O at 300 K was fitted to the third‐order Birch‐Murnaghan EoS with bulk modulus  GPa and its pressure derivative . Based on the EoS of Mie‐Grüneisen, the calculated adiabat coincides with our experimental data when its Grüneisen parameters are given by . Using the determined parameters, bulk sound velocities were obtained from the Hugoniot data. By comparing the pressure‐density profiles and sound velocities of Fe‐O system with the preliminary reference Earth model, it was determined that the oxygen‐rich composition does not provide a good match to the observations in the Earth's outer core.
Turbulent Shear Flow Over Large Martian Ripples
Authors: Yizhaq Hezi , Siminovich Arik , Katra Itzhak , Levy Avi , Sullivan Robert , Silverstro Simone , Yakhot Alexander
Published: January 2021

On Mars, large aeolian ripples with wavelengths typically 1–3 m but lacking very coarse sand at crests have been encountered by rovers and observed from orbit. These bedforms have no terrestrial counterpart and several hypotheses for origins have been proposed. This work reports results of Computational Fluid Dynamics (CFD) experiments with ANSYS Fluent under terrestrial and Martian boundary layer conditions, using the k − ω SST turbulence model to evaluate shear stress along a topographic profile of large Martian ripples at different boundary layer wind speeds. Results indicate that, compared with Earth conditions: (1) boundary‐layer flow along large ripples under Martian conditions is less turbulent due to higher kinematic viscosity; (2) reverse‐flow vortex regions from crests at ripple lee flanks are larger; and (3) shear stresses at crests of large ripples are relatively low, so ripple flattening is less likely at high wind speeds. These results indicate Martian ripples formed by the saltation impact splash mechanism should be less constrained by shear stress effects limiting growth of exposed ripple crests, because the low‐density Martian atmosphere applies relatively low wind‐related shear stress to ripple surfaces. Other origins for the large Martian ripples are not excluded, however. On Earth, very large ripples with crests unprotected by very coarse grains do not develop due to higher wind‐related shear stresses.
Subpore‐Scale Trapping Mechanisms Following Imbibition: A Microfluidics Investigation of Surface Roughness Effects
Authors: Sun Zhonghao , Mehmani Ayaz , Torres‐Verdín Carlos
Published: January 2021

Surface roughness is ubiquitous in subsurface formations due to weathering and diagenesis. Yet micromodel studies of porous media have not sufficiently addressed the impact of pore‐wall roughness on multiphase fluid displacement. We investigate the influence of pore‐wall roughness on capillary trapping by implementing surface roughness into glass micromodels and conducting imbibition experiments. Time‐lapse fluorescence microscopy, micromolding in capillaries, and scanning electron microscopy are used to examine flow behavior during spontaneous and forced imbibition experiments with capillary numbers between 10−6 and 10−4. It is found that surface roughness causes interface pinning and irregular displacement fronts within a single pore, promotes latent pore filling following imbibition, enhances snap‐offs, and contributes to interface relaxation. Furthermore, we verify a cooperative effect between corner flow and surface roughness that causes pore filling to occur at over 10 times the channel width ahead of the main bulk front. Consequently, a significant increase in trapped air saturation of up to 60% is observed, especially at lower capillary numbers and narrower pores. Effects of surface roughness also decrease the rate of spontaneous imbibition, which is slower than the prediction from Washburn's equation. Our results emphasize the importance of surface roughness in building conceptual models for capillary trapping when the ratio of surface roughness‐to‐pore size reaches a critical value of about 0.1. Above this critical threshold value, subpore‐scale trapping mechanisms contribute significantly to capillary trapping, which theoretical and numerical models should consider for accurate quantification of fluid‐transport processes.
Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1
Authors: Jang Yongwoo , Kim Woori , Leblanc Pierre , Kim Chun-Hyung , Kim Kwang-Soo
Published: January 2021

Until recently, Nurr1 (NR4A2) was known as an orphan nuclear receptor without a canonical ligand-binding domain, featuring instead a narrow and tight cavity for small molecular ligands to bind. In-depth characterization of its ligand-binding pocket revealed that it is highly dynamic, with its structural conformation changing more than twice on the microsecond-to-millisecond timescale. This observation suggests the possibility that certain ligands are able to squeeze into this narrow space, inducing a conformational change to create an accessible cavity. The cocrystallographic structure of Nurr1 bound to endogenous ligands such as prostaglandin E1/A1 and 5,6-dihydroxyindole contributed to clarifying the crucial roles of Nurr1 and opening new avenues for therapeutic interventions for neurodegenerative and/or inflammatory diseases related to Nurr1. This review introduces novel endogenous and synthetic Nurr1 agonists and discusses their potential effects in Nurr1-related diseases.
High-resolution impedance mapping using electrically activated quantitative phase imaging
Authors: Polonschii Cristina , Gheorghiu Mihaela , David Sorin , Gáspár Szilveszter , Melinte Sorin , Majeed Hassaan , Kandel Mikhail E. , Popescu Gabriel , Gheorghiu Eugen
Published: January 2021

Retrieving electrical impedance maps at the nanoscale rapidly via nondestructive inspection with a high signal-to-noise ratio is an unmet need, likely to impact various applications from biomedicine to energy conversion. In this study, we develop a multimodal functional imaging instrument that is characterized by the dual capability of impedance mapping and phase quantitation, high spatial resolution, and low temporal noise. To achieve this, we advance a quantitative phase imaging system, referred to as epi-magnified image spatial spectrum microscopy combined with electrical actuation, to provide complementary maps of the optical path and electrical impedance. We demonstrate our system with high-resolution maps of optical path differences and electrical impedance variations that can distinguish nanosized, semi-transparent, structured coatings involving two materials with relatively similar electrical properties. We map heterogeneous interfaces corresponding to an indium tin oxide layer exposed by holes with diameters as small as ~550 nm in a titanium (dioxide) over-layer deposited on a glass support. We show that electrical modulation during the phase imaging of a macro-electrode is decisive for retrieving electrical impedance distributions with submicron spatial resolution and beyond the limitations of electrode-based technologies (surface or scanning technologies). The findings, which are substantiated by a theoretical model that fits the experimental data very well enable achieving electro-optical maps with high spatial and temporal resolutions. The virtues and limitations of the novel optoelectrochemical method that provides grounds for a wider range of electrically modulated optical methods for measuring the electric field locally are critically discussed.
OCT on a chip aims at high-quality retinal imaging
Authors: Hillmann Dierck
Published: January 2021

Optical coherence tomography (OCT) has become one of the most important techniques in ophthalmic diagnostics, as it is the only way to three-dimensionally visualize morphological changes in the layered structure of the retina at a high resolution. In addition, OCT is applied for countless medical and technical purposes. Recent developments pave the way for small-footprint OCT systems at significantly reduced costs, thereby extending possible use cases. Now, it appears increasingly likely that, in the near future, OCT will find its way into many more industrial and medical applications, including disease monitoring at home.
Interspecies metabolite transfer and aggregate formation in a co-culture of Dehalococcoides and Sulfurospirillum dehalogenating tetrachloroethene to ethene
Authors: Kruse Stefan , Türkowsky Dominique , Birkigt Jan , Matturro Bruna , Franke Steffi , Jehmlich Nico , von Bergen Martin , Westermann Martin , Rossetti Simona , Nijenhuis Ivonne , Adrian Lorenz , Diekert Gabriele , Goris Tobias
Published: January 2021

Microbial communities involving dehalogenating bacteria assist in bioremediation of areas contaminated with halocarbons. To understand molecular interactions between dehalogenating bacteria, we co-cultured Sulfurospirillum multivorans, dechlorinating tetrachloroethene (PCE) to cis−1,2-dichloroethene (cDCE), and Dehalococcoides mccartyi strains BTF08 or 195, dehalogenating PCE to ethene. The co-cultures were cultivated with lactate as electron donor. In co-cultures, the bacterial cells formed aggregates and D. mccartyi established an unusual, barrel-like morphology. An extracellular matrix surrounding bacterial cells in the aggregates enhanced cell-to-cell contact. PCE was dehalogenated to ethene at least three times faster in the co-culture. The dehalogenation was carried out via PceA of S. multivorans, and PteA (a recently described PCE dehalogenase) and VcrA of D. mccartyi BTF08, as supported by protein abundance. The co-culture was not dependent on exogenous hydrogen and acetate, suggesting a syntrophic relationship in which the obligate hydrogen consumer D. mccartyi consumes hydrogen and acetate produced by S. multivorans. The cobamide cofactor of the reductive dehalogenase—mandatory for D. mccartyi—was also produced by S. multivorans. D. mccartyi strain 195 dechlorinated cDCE in the presence of norpseudo-B12 produced by S. multivorans, but D. mccartyi strain BTF08 depended on an exogenous lower cobamide ligand. This observation is important for bioremediation, since cofactor supply in the environment might be a limiting factor for PCE dehalogenation to ethene, described for D. mccartyi exclusively. The findings from this co-culture give new insights into aggregate formation and the physiology of D. mccartyi within a bacterial community.
Clustering suicidal phenotypes and genetic associations with brain-derived neurotrophic factor in patients with substance use disorders
Authors: Icick Romain , Bloch Vanessa , Prince Nathalie , Karsinti Emily , Lépine Jean-Pierre , Laplanche Jean-Louis , Mouly Stéphane , Marie-Claire Cynthia , Brousse Georges , Bellivier Frank , Vorspan Florence
Published: January 2021

Suicide attempts (SA), especially recurrent SA or serious SA, are common in substance use disorders (SUD). However, the genetic component of SA in SUD samples remains unclear. Brain-derived neurotrophic factor (BDNF) alleles and levels have been repeatedly involved in stress-related psychopathology. This investigation uses a within-cases study of BDNF and associated factors in three suicidal phenotypes (‘any’, ‘recurrent’, and ‘serious’) of outpatients seeking treatment for opiate and/or cocaine use disorder. Phenotypic characterization was ascertained using a semi-structured interview. After thorough quality control, 98 SNPs of BDNF and associated factors (the BDNF pathway) were extracted from whole-genome data, leaving 411 patients of Caucasian ancestry, who had reliable data regarding their SA history. Binary and multinomial regression with the three suicidal phenotypes were further performed to adjust for possible confounders, along with hierarchical clustering and compared to controls (N = 2504). Bayesian analyses were conducted to detect pleiotropy across the suicidal phenotypes. Among 154 (37%) ever suicide attempters, 104 (68%) reported at least one serious SA and 96 (57%) two SA or more. The median number of non-tobacco SUDs was three. The BDNF gene remained associated with lifetime SA in SNP-based (rs7934165, rs10835210) and gene-based tests within the clinical sample. rs10835210 clustered with serious SA. Bayesian analysis identified genetic correlation between ‘any’ and ‘serious’ SA regarding rs7934165. Despite limitations, ‘serious’ SA was shown to share both clinical and genetic risk factors of SA—not otherwise specified, suggesting a shared BDNF-related pathophysiology of SA in this population with multiple SUDs.
Targeting autophagy reverses de novo resistance in homologous recombination repair proficient breast cancers to PARP inhibition
Authors: Pai Bellare Ganesh , Saha Bhaskar , Patro Birija Sankar
Published: January 2021

Background

Poly(ADP-ribose) polymerase inhibitors (PARPi) target tumours defective in homologous recombination (HR). Most BRCA-wild-type (WT) HR-proficient breast cancers are intrinsically resistant to PARP inhibitors, e.g., talazoparib. We evaluated the role of autophagy in this de novo resistance and determined the underlying mechanism to overcome this.

Methods

Autophagosome formation and autophagic flux were assessed by evaluating endogenous LC3-II levels and ectopic expression of EGFP-LC3 and mRFP-EGFP-LC3 in breast cancer cells. Autophagy-defective cells were generated by genetic depletion of BECN1, ATG5, p62/SQSTM1 and LAMP1 by using CRISPR-Cas9 double nickase system. The response of PARPi was evaluated in autophagy-proficient and -defective breast cancer cells and in xenograft SCID-mice model.

Results

Pro-survival autophagy was significantly enhanced upon talazoparib treatment in BRCA-WT breast cancer cell lines. Autophagy-deficient cells were hypersensitive to talazoparib. Targeting autophagy synergistically enhanced the therapeutic efficacy of talazoparib in BRCA1-WT breast cancer cells in vitro and in vivo xenograft tumour mouse model. Mechanistically, autophagy inhibition by chloroquine promoted deleterious NHEJ mediated DSB-repair, leading to extensive genomic instability and mitotic catastrophe.

Conclusions

Autophagy confers de novo resistance to PARP inhibitor, talazoparib. Autophagy inhibition improves the therapeutic outcome of PARPi treatment in preclinical mice model, bearing HR-proficient breast tumours, warranting its usage in the clinical settings.
Systemic inflammation scores correlate with survival prognosis in patients with newly diagnosed brain metastases
Authors: Starzer Angelika M. , Steindl Ariane , Mair Maximilian J. , Deischinger Carola , Simonovska Anika , Widhalm Georg , Gatterbauer Brigitte , Dieckmann Karin , Heller Gerwin , Preusser Matthias , Berghoff Anna S.
Published: January 2021

Background

Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer.

Methods

One thousand two hundred and fifty patients with newly diagnosed brain metastases (BM) were identified from the Vienna Brain Metastasis Registry.

Results

PLR and CRP/Alb were higher in patients with progressive extracranial disease and lower in patients with no evidence of extracranial disease. Lower NLR (cut-off = 5.07; 9.3 vs. 5.0 months), LLR (cut-off = 5.76; 10.0 vs. 5.3 months), PLR (cut-off = 335; 8.0 vs. 3.8 months), MLR (cut-off = 0.53; 6.0 vs. 3.5 months) and CRP/Alb (cut-off = 2.93; 8.5 vs. 3.7 months; padj < 0.05) were associated with longer overall survival (OS). In multivariate analysis with graded prognostic assessment (hazard ratio (HR) 1.45; 95% confidence interval (CI): 1.32–1.59; padj = 1.62e − 13), NLR (HR 1.55; 95% CI: 1.38–1.75; padj = 1.92e − 11), LLR (HR 1.57; 95% CI: 1.39–1.77; padj = 1.96e − 11), PLR (HR 1.60; 95% CI: 1.39–1.85; padj = 2.87955e − 9), MLR (HR 1.41; 95% CI: 1.14–1.75; padj = 0.027) and CRP/Alb (HR 1.83; 95% CI: 1.54–2.18; padj = 2.73e − 10) remained independent factors associated with OS at BM diagnosis.

Conclusions

Systemic inflammation, measured by NLR, LLR, PLR, MLR and CRP/Alb, was associated with OS in patients with BM. Further exploration of immune modulating therapies is warranted in the setting of BM.
Tubular Mas receptor mediates lipid-induced kidney injury
Authors: Kong Yonglun , Zhao Xiaoduo , Qiu Miaojuan , Lin Yu , Feng Pinning , Li Suchun , Liang Baien , Zhu Qing , Huang Hui , Li Chunling , Wang Weidong
Published: January 2021

Obesity-related kidney diseases are becoming serious health problems worldwide, yet the mechanism by which obesity causes kidney injury is not fully understood. The purpose of current study was to investigate the role of Mas receptor in lipid-induced kidney injury. In mice fed with high-fat diet (HFD), the protein abundance of markers of autophagy, endoplasmic reticulum stress (ER stress) and apoptosis was dramatically increased in the kidney cortex, which was markedly prevented by Mas deletion (Mas−/−) or Mas receptor antagonist A779. Palmitic acid (PA) induced persistently increased autophagy, ER stress, and apoptosis as well as mitochondrial injuries in primary cultured proximal tubular cells from wild type, but not from Mas−/− mice. In human proximal tubular HK2 cells, PA-induced autophagy and ER stress was aggravated by Mas agonists Ang (1–7) or AVE0991, but attenuated by A779 or Mas knockdown. Stimulation of Mas resulted in elevated intracellular calcium levels [Ca2+]i in HK2 cells treated with PA, whereas inhibition or knockdown of Mas decreased [Ca2+]i. Mitochondrial outer membrane located voltage-dependent anion channel (VDAC1) was markedly upregulated in HK2 cells treated with PA, which was associated with impaired mitochondrial morphology and depolarization. These were enhanced by AVE0991 and suppressed by A779 or Mas knockdown. Mas knockdown in HK2 cells prevented impaired interactions among VDAC1, autophagy adaptor P62, and ubiquitin, induced by PA, leading to a potential ubiquitination of VDAC1. In conclusion, Mas receptor-mediated lipid-induced impaired autophagy and ER stress in the kidney, likely contributing to tubular injuries in obesity-related kidney diseases.
3D high-density microelectrode array with optical stimulation and drug delivery for investigating neural circuit dynamics
Authors: Shin Hyogeun , Jeong Sohyeon , Lee Ju-Hyun , Sun Woong , Choi Nakwon , Cho Il-Joo
Published: January 2021

Investigation of neural circuit dynamics is crucial for deciphering the functional connections among regions of the brain and understanding the mechanism of brain dysfunction. Despite the advancements of neural circuit models in vitro, technologies for both precisely monitoring and modulating neural activities within three-dimensional (3D) neural circuit models have yet to be developed. Specifically, no existing 3D microelectrode arrays (MEAs) have integrated capabilities to stimulate surrounding neurons and to monitor the temporal evolution of the formation of a neural network in real time. Herein, we present a 3D high-density multifunctional MEA with optical stimulation and drug delivery for investigating neural circuit dynamics within engineered 3D neural tissues. We demonstrate precise measurements of synaptic latencies in 3D neural networks. We expect our 3D multifunctional MEA to open up opportunities for studies of neural circuits through precise, in vitro investigations of neural circuit dynamics with 3D brain models.
Adenosine modulators and calcium channel blockers as add-on treatment for schizophrenia
Authors: Lintunen Jonne , Lähteenvuo Markku , Tiihonen Jari , Tanskanen Antti , Taipale Heidi
Published: January 2021

Relapses remain common among individuals with schizophrenia indicating a need for improved treatments. Creating a completely new drug molecule is expensive and time consuming, and therefore drug repurposing should be considered. Aim of this study was to investigate the risk of psychiatric rehospitalization associated with use of adenosine modulators (AMs) and calcium channel blockers (CCBs) in schizophrenia. Individuals diagnosed with schizophrenia (N = 61,889) in inpatient care between 1972–2014 in Finland were included. The follow-up lasted from 1996 to 2017. Main exposures were use of AMs (allopurinol and dipyridamole) and CCBs (dihydropyridines, diltiazem, and verapamil). Thiazide diuretics were used as a negative control. Within-individual models in stratified Cox regression were used and adjusted hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Use of AMs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.74, 95% CI 0.65–0.84, P < 0.0001), as well as on the level of individual drugs (allopurinol HR 0.82, 95% CI 0.70–0.97, P = 0.02; dipyridamole HR 0.65, 95% CI 0.55–0.77, P < 0.0001). Use of CCBs was associated with a reduced risk of psychiatric rehospitalization on drug class level (HR 0.81, 95% CI 0.77–0.86, P < 0.0001). From the different CCBs, only exposure to dihydropyridines was associated with a reduced risk (HR 0.79, 95% CI 0.74–0.84, P < 0.0001). No effect was observed for the negative control, thiazide diuretics (HR 0.96, 0.90–1.02, P = 0.20). The effects of dipyridamole and dihydropyridines were more pronounced among younger persons and combination of AMs, and CCBs was associated with a lower risk than either drug class as monotherapy. These results indicate a need for randomized controlled trials of these drugs.
Gene co-expression in the interactome: moving from correlation toward causation via an integrated approach to disease module discovery
Authors: Paci Paola , Fiscon Giulia , Conte Federica , Wang Rui-Sheng , Farina Lorenzo , Loscalzo Joseph
Published: January 2021

In this study, we integrate the outcomes of co-expression network analysis with the human interactome network to predict novel putative disease genes and modules. We first apply the SWItch Miner (SWIM) methodology, which predicts important (switch) genes within the co-expression network that regulate disease state transitions, then map them to the human protein–protein interaction network (PPI, or interactome) to predict novel disease–disease relationships (i.e., a SWIM-informed diseasome). Although the relevance of switch genes to an observed phenotype has been recently assessed, their performance at the system or network level constitutes a new, potentially fascinating territory yet to be explored. Quantifying the interplay between switch genes and human diseases in the interactome network, we found that switch genes associated with specific disorders are closer to each other than to other nodes in the network, and tend to form localized connected subnetworks. These subnetworks overlap between similar diseases and are situated in different neighborhoods for pathologically distinct phenotypes, consistent with the well-known topological proximity property of disease genes. These findings allow us to demonstrate how SWIM-based correlation network analysis can serve as a useful tool for efficient screening of potentially new disease gene associations. When integrated with an interactome-based network analysis, it not only identifies novel candidate disease genes, but also may offer testable hypotheses by which to elucidate the molecular underpinnings of human disease and reveal commonalities between seemingly unrelated diseases.
An epitope-based malaria vaccine targeting the junctional region of circumsporozoite protein
Authors: Jelínková Lucie , Jhun Hugo , Eaton Allison , Petrovsky Nikolai , Zavala Fidel , Chackerian Bryce
Published: January 2021

A malaria vaccine that elicits long-lasting protection and is suitable for use in endemic areas remains urgently needed. Here, we assessed the immunogenicity and prophylactic efficacy of a vaccine targeting a recently described epitope on the major surface antigen on Plasmodium falciparum sporozoites, circumsporozoite protein (CSP). Using a virus-like particle (VLP)-based vaccine platform technology, we developed a vaccine that targets the junctional region between the N-terminal and central repeat regions of CSP. This region is recognized by monoclonal antibodies, including mAb CIS43, that have been shown to potently prevent liver invasion in animal models. We show that CIS43 VLPs elicit high-titer and long-lived anti-CSP antibody responses in mice and is immunogenic in non-human primates. In mice, vaccine immunogenicity was enhanced by using mixed adjuvant formulations. Immunization with CIS43 VLPs conferred partial protection from malaria infection in a mouse model, and passive transfer of serum from immunized macaques also inhibited parasite liver invasion in the mouse infection model. Our findings demonstrate that a Qβ VLP-based vaccine targeting the CIS43 epitope combined with various adjuvants is highly immunogenic in mice and macaques, elicits long-lasting anti-CSP antibodies, and inhibits parasite infection in a mouse model. Thus, the CIS43 VLP vaccine is a promising pre-erythrocytic malaria vaccine candidate.
Synthesis of nano-fibers containing nano-curcumin in zein corn protein and its physicochemical and biological characteristics
Authors: Fereydouni Narges , Movaffagh Jebrail , Amiri Nafise , Darroudi Susan , Gholoobi Aida , Goodarzi Arash , Hashemzadeh Alireza , Darroudi Majid
Published: January 2021

Curcumin contains many biological activities as a natural bioactive substance, however, its low solubility stands as a huge bioavailability disadvantage. Recently, different methods have been developed for utilizing the tremendous medicinal properties of this material. In this study, an Oil/Water nano-emulsion of curcumin (Nano-CUR) has been woven in zein polymer at three percentages of 5%, 10%, and 15% (v/v). We have investigated the physicochemical properties of nanofibers (NFs) including FESEM, FTIR, tensile strength, encapsulation efficiency, and release profile, as well as biological properties. According to the data, the NFs have been observed to become significantly thinner and more uniformed as the involved percentage of Nano-CUR had been increased from 5 to 15%. It is considerable that the tensile strength can be increased by heightening the existing Nano-CUR from 5% towards 15%. The resultant NFs of zein/Nano-CUR 15% have exhibited higher in vitro release and lower encapsulation efficiency than the other evaluated zein/Nano-CUR NFs. It has been confirmed through the performed viability and antioxidant studies that zein/Nano-CUR 10% NFs are capable of providing the best conditions for cell proliferation. Considering the mentioned facts, this work has suggested that Nano-CUR can be successfully woven in zein NFs and maintain their biological properties.
The 20-million-year old lair of an ambush-predatory worm preserved in northeast Taiwan
Authors: Pan Yu-Yen , Nara Masakazu , Löwemark Ludvig , Miguez-Salas Olmo , Gunnarson Björn , Iizuka Yoshiyuki , Chen Tzu-Tung , Dashtgard Shahin E.
Published: January 2021

The feeding behavior of the giant ambush-predator “Bobbit worm” (Eunice aphroditois) is spectacular. They hide in their burrows until they explode upwards grabbing unsuspecting prey with a snap of their powerful jaws. The still living prey are then pulled into the sediment for consumption. Although predatory polychaetes have existed since the early Paleozoic, their bodies comprise mainly soft tissue, resulting in a very incomplete fossil record, and virtually nothing is known about their burrows and behavior beneath the seafloor. Here we use morphological, sedimentological, and geochemical data from Miocene strata in northeast Taiwan to erect a new ichnogenus,Pennichnus. This trace fossil consists of an up to 2 m long, 2–3 cm in diameter, L-shaped burrow with distinct feather-like structures around the upper shaft. A comparison ofPennichnusto biological analogs strongly suggests that this new ichnogenus is associated with ambush-predatory worms that lived about 20 million years ago.
Study of the effect of band gap and photoluminescence on biological properties of polyaniline/CdS QD nanocomposites based on natural polymer
Authors: Alipour Azita , Mansour Lakouraj Moslem , Tashakkorian Hamed
Published: January 2021

In this work, band gap, photoluminescence and biological properties of new bionanocomposites based on polyaniline (PANi)/hydrolyzed pectin (HPEc)/cadmium sulfide (CdS) QD nanoparticles (NPs) were studied. In order to improve the morphology and properties, CdS NPs were modified with epichlorohydrin to obtain the modified CdS (mCdS). The CdS@HPEc-g-PANi and mCdS@HPEc-g-PANi samples were synthesized via heterogeneous chemical polymerization and characterized by FTIR, 1HNMR, SEM/XRD, EDX/TEM/EDX-mapping and TGA analyses. The objective of this work is the study of physical, optical and cytotoxicity properties of the nanocomposites and comparison between them. The SEM, XRD and TGA images showed that the modification of NPs resulted in homogeneous morphology, increase of crystalline structure and high thermal stability which influenced on physical and biological property. According to UV-DRS analysis, the mCdS@HPEc-g-PANi indicated lower energy gap compared to the CdS@HPEc-g-PANi nancomposite. The presence of conductive polymer and synergy effect between the PANi and CdS caused higher PL intensity in the CdS@HPEc-g-PANi nanocomposite compared to pure CdS. The emission intensity in the mCdS@HPEc-g-PANi nanocomposite was reduced since the organic modifying agent cause reducing emission intensity. The mCdS@HPEc-g-PANi nanocomposite, due to more compatibility of organic agent with cellular walls of biological cells that help to the diffusion of metal CdS NPs into cell tissue indicated more toxicity effect on cell growth.
Dehydration of d-fructose to 5-hydroxymethyl-2-furfural in DMSO using a hydrophilic sulfonated silica catalyst in a process promoted by microwave irradiation
Authors: Barbosa Sandro L. , de S. Freitas Milton , dos Santos Wallans T. P. , Nelson David Lee , Klein Stanlei I. , Clososki Giuliano Cesar , Caires Franco J. , Baroni Adriano C. M. , Wentz Alexandre P.
Published: January 2021

SiO2-SO3H, with a surface area of 115 m2/g, pore volumes of 0.38 cm3g−1 and 1.32 mmol H+/g, was used as a 10% w/w catalyst for the preparation of 5-hydroxymethyl-2-furfural (HMF) from fructose. A conversion of 100% was achieved in a microwave reactor during 10 min at 150 °C in DMSO, with 100% selectivity for HMF, at a molar ratio of fructose: DMSO equal to 1:56. The catalyst could be re-used three times.
Altered structural balance of resting-state networks in autism
Authors: Moradimanesh Z. , Khosrowabadi R. , Eshaghi Gordji M. , Jafari G. R.
Published: January 2021

What makes a network complex, in addition to its size, is the interconnected interactions between elements, disruption of which inevitably results in dysfunction. Likewise, the brain networks’ complexity arises from interactions beyond pair connections, as it is simplistic to assume that in complex networks state of a link is independently determined only according to its two constituting nodes. This is particularly of note in genetically complex brain impairments, such as the autism spectrum disorder (ASD), which has a surprising heterogeneity in manifestations with no clear-cut neuropathology. Accordingly, structural balance theory (SBT) affirms that in real-world signed networks, a link is remarkably influenced by each of its two nodes’ interactions with the third node within a triadic interrelationship. Thus, it is plausible to ask whether ASD is associated with altered structural balance resulting from atypical triadic interactions. In other words, it is the abnormal interplay of positive and negative interactions that matters in ASD, besides and beyond hypo (hyper) pair connectivity. To address this question, we explore triadic interactions based on SBT in the weighted signed resting-state functional magnetic resonance imaging networks of participants with ASD relative to healthy controls (CON). We demonstrate that balanced triads are overrepresented in the ASD and CON networks while unbalanced triads are underrepresented, providing first-time empirical evidence for the strong notion of structural balance on the brain networks. We further analyze the frequency and energy distributions of different triads and suggest an alternative description for the reduced functional integration and segregation in the ASD brain networks. Moreover, results reveal that the scale of change in the whole-brain networks’ energy is more narrow in the ASD networks during development. Last but not least, we observe that energy of the salience network and the default mode network are lower in ASD, which may be a reflection of the difficulty in dynamic switching and flexible behaviors. Altogether, these results provide insight into the atypical structural balance of the ASD brain (sub) networks. It also highlights the potential value of SBT as a new perspective in functional connectivity studies, especially in the case of neurodevelopmental disorders.
Further evidence supporting a potential role for ADH1B in obesity
Authors: Morales Liza D. , Cromack Douglas T. , Tripathy Devjit , Fourcaudot Marcel , Kumar Satish , Curran Joanne E. , Carless Melanie , Göring Harald H. H. , Hu Shirley L. , Lopez-Alvarenga Juan Carlos , Garske Kristina M. , Pajukanta Päivi , Small Kerrin S. , Glastonbury Craig A. , Das Swapan K. , Langefeld Carl , Hanson Robert L. , Hsueh Wen-Chi , Norton Luke , Arya Rector , Mummidi Srinivas , Blangero John , DeFronzo Ralph A. , Duggirala Ravindranath , Jenkinson Christopher P.
Published: January 2021

Insulin is an essential hormone that regulates glucose homeostasis and metabolism. Insulin resistance (IR) arises when tissues fail to respond to insulin, and it leads to serious health problems including Type 2 Diabetes (T2D). Obesity is a major contributor to the development of IR and T2D. We previously showed that gene expression of alcohol dehydrogenase 1B (ADH1B) was inversely correlated with obesity and IR in subcutaneous adipose tissue of Mexican Americans. In the current study, a meta-analysis of the relationship between ADH1B expression and BMI in Mexican Americans, African Americans, Europeans, and Pima Indians verified that BMI was increased with decreased ADH1B expression. Using established human subcutaneous pre-adipocyte cell lines derived from lean (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) donors, we found that ADH1B protein expression increased substantially during differentiation, and overexpression of ADH1B inhibited fatty acid binding protein expression. Mature adipocytes from lean donors expressed ADH1B at higher levels than obese donors. Insulin further induced ADH1B protein expression as well as enzyme activity. Knockdown of ADH1B expression decreased insulin-stimulated glucose uptake. Our findings suggest that ADH1B is involved in the proper development and metabolic activity of adipose tissues and this function is suppressed by obesity.
Whole genomic sequencing based genotyping reveals a specific X3 sublineage restricted to Mexico and related with multidrug resistance
Authors: Jiménez-Ruano Ana Cristina , Madrazo-Moya Carlos Francisco , Cancino-Muñoz Irving , Mejía-Ponce Paulina M. , Licona-Cassani Cuauhtémoc , Comas Iñaki , Muñiz-Salazar Raquel , Zenteno-Cuevas Roberto
Published: January 2021

Whole genome sequencing (WGS) has been shown to be superior to traditional procedures of genotyping in tuberculosis (TB), nevertheless, reports of its use in drug resistant TB (DR-TB) isolates circulating in Mexico, are practically unknown. Considering the above the main of this work was to identify and characterize the lineages and genomic transmission clusters present in 67 DR-TB isolates circulating in southeastern Mexico. The results show the presence of three major lineages: L1 (3%), L2 (3%) and L4 (94%), the last one included 16 sublineages. Sublineage 4.1.1.3 (X3) was predominant in 18 (27%) of the isolates, including one genomic cluster, formed by eleven multidrug resistant isolates and sharing the SIT 3278, which seems to be restricted to Mexico. By the use of WGS, it was possible to identify the high prevalence of L4 and a high number of sublineages circulating in the region, also was recognized the presence of a novel X3 sublineage, formed exclusively by multidrug resistant isolates and with restrictive circulation in Mexico for at least the past 17 years.
Multi-omic analysis unveils biological pathways in peripheral immune system associated to minimal hepatic encephalopathy appearance in cirrhotic patients
Authors: Rubio Teresa , Felipo Vicente , Tarazona Sonia , Pastorelli Roberta , Escudero-García Desamparados , Tosca Joan , Urios Amparo , Conesa Ana , Montoliu Carmina
Published: January 2021

Patients with liver cirrhosis may develop minimal hepatic encephalopathy (MHE) which affects their quality of life and life span. It has been proposed that a shift in peripheral inflammation triggers the appearance of MHE. However, the mechanisms involved in this immune system shift remain unknown. In this work we studied the broad molecular changes involved in the induction of MHE with the goal of identifying (1) altered genes and pathways in peripheral blood cells associated to the appearance of MHE, (2) serum metabolites and cytokines with modified levels in MHE patients and (3) MHE-regulated immune response processes related to changes in specific serum molecules. We adopted a multi-omic approach to profile the transcriptome, metabolome and a panel of cytokines of blood samples taken from cirrhotic patients with or without MHE. Transcriptomic analysis supports the hypothesis of alternations in the Th1/Th2 and Th17 lymphocytes cell populations as major drivers of MHE. Cluster analysis of serum molecules resulted in six groups of chemically similar compounds, suggesting that functional modules operate during the induction of MHE. Finally, the multi-omic integrative analysis suggested a relationship between cytokines CCL20, CX3CL1, CXCL13, IL-15, IL-22 and IL-6 with alteration in chemotaxis, as well as a link between long-chain unsaturated phospholipids and the increased fatty acid transport and prostaglandin production. We found altered immune pathways that may collectively contribute to the mild cognitive impairment phenotype in MHE. Our approach is able to combine extracellular and intracellular information, opening new insights to the understanding of the disease.
Scalable synthesis of Cu–Sb–S phases from reactive melts of metal xanthates and effect of cationic manipulation on structural and optical properties
Authors: Alqahtani Tahani , Khan Malik Dilshad , Lewis David J. , Zhong Xiang Li , O’Brien Paul
Published: January 2021

We report a simple, economical and low temperature route for phase-pure synthesis of two distinct phases of Cu–Sb–S, chalcostibite (CuSbS2) and tetrahedrite (Cu12Sb4S13) nanostructures. Both compounds were prepared by the decomposition of a mixture of bis(O-ethylxanthato)copper(II) and tris(O-ethylxanthato)antimony(III), without the use of solvent or capping ligands. By tuning the molar ratio of copper and antimony xanthates, single-phases of either chalcostibite or tetrahedrite were obtained. The tetrahedrite phase exists in a cubic structure, where the Cu and Sb atoms are present in different coordination environments, and tuning of band gap  energy was investigated by the incorporation of multivalent cationic dopants, i.e. by the formation of Zn-doped tetrahedrites Cu12−xZnxSb4S13 (x = 0.25, 0.5, 0.75, 1, 1.2 and 1.5) and the Bi-doped tetrahedrites Cu12Sb4−xBixS13 (x = 0.08, 0.15, 0.25, 0.32, 0.4 and 0.5). Powder  X-ray diffraction (p-XRD) confirms single-phase of cubic tetrahedrite structures for both of the doped series. The only exception was for Cu12Sb4−xBixS13 with x = 0.5, which showed a secondary phase, implying that this value is above the solubility limit of Bi in Cu12Sb4S13 (12%). A linear increase in the lattice parameter a in both Zn- and Bi-doped tetrahedrite samples was observed with increasing dopant concentration. The estimated elemental compositions from EDX data are in line with the stoichiometric ratio expected for the compounds formed. The morphologies of samples were investigated using SEM and TEM, revealing the formation of smaller particle sizes upon  incorporation of  Zn. Incorporation of Zn or Bi into Cu12Sb4S13 led to an increase in band gap energy. The estimated band gap energies of Cu12−xZnxSb4S13 films ranges from 1.49 to 1.6 eV, while the band gaps of Cu12Sb4−xBixS13 films increases from 1.49 to 1.72 eV with increasing x.
An ab initio study of the magnetic properties of strontium hexaferrite
Authors: Tejera-Centeno C. , Gallego S. , Cerdá J. I.
Published: January 2021

The magnetic properties of $${\text{SrFe}}_{12}{\text{O}}_{19}$$

SrFe
12

O
19

, a paradigmatic hexaferrite for permanent magnet applications, have been addressed in detail combining density functional theory including spin–orbit coupling and a Hubbard U term with Monte Carlo simulations. This multiscale approach allows to estimate the Néel temperature of the material from ab initio exchange constants, and to determine the influence of different computational conditions on the magnetic properties by direct comparison versus available experimental data. It is found that the dominant influence arises from the choice of the Hubbard U term, with a value in the 2–3 eV range as the most adequate to quantitatively reproduce the two most relevant magnetic properties of this material, namely: its large perpendicular magnetocrystalline anisotropy and its elevated Néel temperature.