bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantum versus classical correlations in a double cavity optomechanical system
Authors: Lakhfif Abderrahim , Hidki Abdelkader , El Qars Jamal , Nassik Mostafa
Published: April 2022

In a bipartite quantum state, where the total correlations can be divided into classical and quantum parts, Henderson and Vedral (2001 J. Phys. A: Math. Gen.
34 6899) have conjectured that classical correlations should not be less than quantum ones. Here, we consider two symmetrical states of two driven optomechanical cavities coupled to a squeezed photon source and exposed to Markovian noise and damping. The total and quantum correlations are systematically quantified by quantum mutual information and quantum discord respectively. Interestingly, we analytically demonstrate that classical correlations in the considered two-mode Gaussian states are always superior to quantum ones, whatever the physical and environmental parameters are. Moreover, using experimentally accessible parameters, we show numerically the existence of a domination of classical correlations over quantum ones under various circumstances. Finally, we found that quantum, as well as classical correlations, have similar behaviors under the effect of thermal decoherence, squeezing and optomechanical coupling. Yet, classical correlations are more strong and robust.
Controlled engineering of a vortex-bright soliton dynamics using a constant driving force
Authors: Wang Wenlong
Published: April 2022

A vortex-bright (VB) soliton can precess around a fixed point. Here, we find numerically that the fixed point and the associated precessional orbits can be shifted by applying a constant driving force on the bright component, the displacement is proportional to the force with a minus sign. This robust dynamics is then discussed theoretically by treating the VB soliton as an effective point particle. By appropriately tuning the force, the VB soliton can be guided following an arbitrary trajectory with very weak density modulations, including that it can be repeatedly pinned and released at will. This finding opens a highly flexible and controllable approach of engineering the dynamics of vortical structures in Bose–Einstein condensates.
Spatial and spectral variations of high-order harmonics generated in noble gases
Authors: Iqbal M , Boltaev G S , Abbasi N , Ganeev R A , Alnaser A S
Published: April 2022

We report on the spatial and spectral variation of high-order harmonics generation from noble gases when driven by high-repetition rate femtosecond laser with different peak intensity and polarization states. Ar, Xe, and Kr were chosen for the generation of coherent extreme ultraviolet radiation. We observe that increasing the intensity of the driving pulses (DPs) leads to disappearance of harmonics yield in the on-axis part of the spatial distribution of the harmonics in Xe target, contrary to Ar and Kr. This observation is attributed to the higher ionization potential of the latter gases. Spectral depletion of harmonics generated in Ar and Xe using radially and azimuthally polarized Gaussian–Laguerre two-color DPs is also observed. The significant depletion in the spectral distribution of harmonics is obtained when two-color pump (TCP) scheme is applied. We demonstrate how TCP scheme with azimuthally polarized DPs can be used as a tool to control the spectral distribution of harmonics generated from gas atoms during strong field by utilizing the presence of second harmonic electromagnetic field.
Highly linear capacitive tactile sensor with elastic dome-shaped electrodes
Authors: Ye Jinhua , Chen Kaixuan , Chen Liting , You Zhaoming , Jiang Jinchao , Wu Haibin
Published: April 2022

Capacitive tactile sensors have been widely used for electronic skins and human-machine interfaces due to their high sensitivity, low power consumption, and fast response. Despite great advances in improving the sensitivity of the sensors through structural design or advanced material selection, achieving linear response over a broad detection range for pressure sensing is still a great challenge. Herein, a capacitive tactile sensor with elastic dome-shaped electrode is reported. We find that the elastic dome-shaped electrode can significantly enhance the linear relationship between the effective electrode area of the capacitor and the applied force over a wide range, which endowed the prepared sensor exhibiting excellent linearity (R
2 = 0.999) up to 120 kPa. In addition, the fabricated sensor sample has good stability, quick response, satisfied sensitivity of 0.115 kPa−1 (0–120 kPa), and can be further expanded with a wider sensing range up to 500 kPa. Based on the proposed model, the sensitivity and linear sensing range of the sensor can be designed flexibly for different application. It can provide a simple but powerful strategy to construct high performance flexible pressure sensors in the future.
A graph network model for neural connection prediction and connection strength estimation
Authors: Yuan Ye , Liu Jian , Zhao Peng , Wang Wei , Gu Xiao , Rong Yi , Lai Tinggeng , Chen Yuze , Xin Kuankuan , Niu Xin , Xiang Fengtao , Huo Hong , Li Zhaoyu , Fang Tao
Published: April 2022

Objective. Reconstruction of connectomes at the cellular scale is a prerequisite for understanding the principles of neural circuits. However, due to methodological limits, scientists have reconstructed the connectomes of only a few organisms such as C. elegans, and estimated synaptic strength indirectly according to their size and number. Approach. Here, we propose a graph network model to predict synaptic connections and estimate synaptic strength by using the calcium activity data from C. elegans. Main results. The results show that this model can reliably predict synaptic connections in the neural circuits of C. elegans, and estimate their synaptic strength, which is an intricate and comprehensive reflection of multiple factors such as synaptic type and size, neurotransmitter and receptor type, and even activity dependence. In addition, the excitability or inhibition of synapses can be identified by this model. We also found that chemical synaptic strength is almost linearly positively correlated to electrical synaptic strength, and the influence of one neuron on another is non-linearly correlated with the number between them. This reflects the intrinsic interaction between electrical and chemical synapses. Significance. Our model is expected to provide a more accessible quantitative and data-driven approach for the reconstruction of connectomes in more complex nervous systems, as well as a promising method for accurately estimating synaptic strength.
Tunable multi-bands in twisted double bilayer graphene
Authors: Zhu Yujian , Chen Yiwei , Li Qingxin , Chen Yongdao , Huang Yan , Zhu Wang , An Dongdong , Song Junwei , Gan Qikang , Wang Kaiyuan , Wei Lingnan , Zong Qijun , Watanabe Kenji , Taniguchi Takashi , Wang Haolin , Huang Li , Xian Lede , Sun Liang , Yu Geliang , Wang Lei
Published: April 2022

The bandstructure of a material, playing an important role in its electron transport property, is usually governed by the lattice configuration. Materials with a field-effect tunable band, such as bilayer [1] and rhombohedral trilayer graphene [2, 3], are more flexible for electronic applications. Here, on dual-gated twisted double bilayer graphene (TDBG) samples with small twist angle around 1∘, we observe vertical electric-field-tunable bandstructures at multiple moiré fillings with bandgap values continuously varying from zero to tens of mili-electron volts. Moreover, within the first moiré filling on both electron and hole sides, the carrier transport deviates from Fermi liquid behavior, with measured resistivity exhibiting linear temperature dependence between 1.5 K and 50 K. Furthermore, under a vertical magnetic field, the coupling between the two bilayer graphene layers can also be turned on and off by a displacement field. Our results suggest TDBG with small twist angle is a platform for studying the evolution of multiple electric field tunable moiré bands and the resulting emergent correlated electronic phases.
Robust fingerprinting of genomic databases
Authors: Ji Tianxi , Ayday Erman , Yilmaz Emre , Li Pan
Published: April 2022

Motivation

Database fingerprinting has been widely used to discourage unauthorized redistribution of data by providing means to identify the source of data leakages. However, there is no fingerprinting scheme aiming at achieving liability guarantees when sharing genomic databases. Thus, we are motivated to fill in this gap by devising a vanilla fingerprinting scheme specifically for genomic databases. Moreover, since malicious genomic database recipients may compromise the embedded fingerprint (distort the steganographic marks, i.e. the embedded fingerprint bit-string) by launching effective correlation attacks, which leverage the intrinsic correlations among genomic data (e.g. Mendel’s law and linkage disequilibrium), we also augment the vanilla scheme by developing mitigation techniques to achieve robust fingerprinting of genomic databases against correlation attacks.

Results

Via experiments using a real-world genomic database, we first show that correlation attacks against fingerprinting schemes for genomic databases are very powerful. In particular, the correlation attacks can distort more than half of the fingerprint bits by causing a small utility loss (e.g. database accuracy and consistency of SNP–phenotype associations measured via P-values). Next, we experimentally show that the correlation attacks can be effectively mitigated by our proposed mitigation techniques. We validate that the attacker can hardly compromise a large portion of the fingerprint bits even if it pays a higher cost in terms of degradation of the database utility. For example, with around 24% loss in accuracy and 20% loss in the consistency of SNP–phenotype associations, the attacker can only distort about 30% fingerprint bits, which is insufficient for it to avoid being accused. We also show that the proposed mitigation techniques also preserve the utility of the shared genomic databases, e.g. the mitigation techniques only lead to around 3% loss in accuracy.

Availability and implementation

https://github.com/xiutianxi/robust-genomic-fp-github.
Early diagnosis of anastomotic leakage after colorectal cancer surgery using an inflammatory factors-based score system
Authors: Shi Jinyao , Wu Zhouqiao , Wu Xiaolong , Shan Fei , Zhang Yan , Ying Xiangji , Li Ziyu , Ji Jiafu
Published: April 2022

Background

Anastomotic leakage (AL) is a severe complication after colorectal surgery. This study aimed to investigate a method for the early diagnosis of AL after surgical resection by analysing inflammatory factors (IFs) in peritoneal drainage fluid.

Methods

Abdominal drainage fluid of patients with colorectal cancer who underwent resection between April 2017 and April 2018, were prospectively collected in the postoperative interval. Six IFs, including interleukin (IL)-1β, IL-6, IL-10, tumour necrosis factor (TNF)-α, matrix metalloproteinase (MMP)2, and MMP9, in drainage were determined by multiplex immunoassay to investigate AL (in patients undergoing resection and anastomosis) and pelvic collection (in patients undergoing abdominoperineal resection). Sparreboom and colleagues’ prediction model was first evaluated for AL/pelvic collection, followed by a new IF-based score system (AScore) that was developed by a least absolute shrinkage and selection operator (LASSO) regression, for the same outcomes. The model performance was tested for the area under the curve (AUC), sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV).

Results

Out of 123 patients eligible, 119 patients were selected, including 12 patients with AL/pelvic collection. Sparreboom and colleagues’ prediction model was documented with the best diagnostic efficacy on postoperative day 3 (POD3), with an AUC of 0.77. After optimization, AScore on POD3 increased the AUC to 0.83 and on POD1 showed the best diagnostic efficiency, with an AUC of 0.88. Based on the Youden index, the cut-off value of AScore on POD1 was set as −2.46 to stratify patients into low-risk and high-risk groups for AL/pelvic collection. The model showed 90.0 per cent sensitivity, 69.7 per cent specificity, 98.4 per cent NPV, and 25.0 per cent PPV.

Conclusions

The early determination of IFs in abdominal drainage fluid of patients undergoing colorectal surgery could be useful to predict AL or pelvic collection.
Small interfering RNAs in the management of human rheumatoid arthritis
Authors: Gargano Giuseppe , Oliva Francesco , Oliviero Antonio , Maffulli Nicola
Published: April 2022

Background

Rheumatoid arthritis (RA) has unclear pathogenesis, but the molecules that feed its inflammatory state are known. Small interfering RNAs (siRNAs) are useful to identify molecular targets and evaluate the efficacy of specific drugs, and can themselves be used for therapeutic purposes.

Sources of data

A systematic search of different databases to March 2022 was performed to define the role of siRNAs in RA therapy. Twenty suitable studies were identified.

Areas of agreement

Small interfering RNAs can be useful in the study of inflammatory processes in RA, and identify possible therapeutic targets and drug therapies.

Areas of controversy

Many genes and cytokines participate in the inflammatory process of RA and can be regulated with siRNA. However, it is difficult to determine whether the responses to siRNAs and other drugs studied in human cells in vitro are similar to the responses in vivo.

Growing points

Inflammatory processes can be affected by the gene dysregulation of siRNAs on inflammatory cytokines.

Areas timely for developing research

To date, it is not possible to determine whether the pharmacological response of siRNAs on cells in vitro would be similar to what takes place in vivo for the diseases studied so far.
Theory and Method for Studying How Media Messages Prompt Shared Brain Responses Along the Sensation-to-Cognition Continuum
Authors: Schmälzle Ralf
Published: April 2022

When members of an audience are exposed to the same messages, their brains will, to a certain degree, exhibit similar responses. These similar, and thus shared audience responses constitute the recruitment of sensory, perceptual, and higher-level neurocognitive processes, which occur separately in the brain of each individual, but in a collectively shared fashion across the audience. A method called inter-subject-correlation (ISC) analysis allows to reveal these shared responses. This manuscript introduces a theoretical model of brain function that explains why shared brain responses occur and how they emerge along a gradient from sensation to cognition as individuals process the same message content. This model makes results from ISC-based studies more interpretable from a communication perspective, helps organize the results from existing studies across different subfields, and generates testable predictions. The article discusses how research at the nexus of media, audience research, and neuroscience contributes to and advances communication theory.
The structure–function relationship ofPseudomonas aeruginosain infections and its influence on the microenvironment
Authors: Lichtenberg Mads , Jakobsen Tim Holm , Kühl Michael , Kolpen Mette , Jensen Peter Østrup , Bjarnsholt Thomas
Published: April 2022

Pseudomonas aeruginosa is a human pathogen associated with both acute and chronic infections. While intensively studied, the basic mechanisms enabling the long-term survival of P. aeruginosa in the host, despite massive immune system attack and heavy antimicrobial treatment, remain to be identified. We argue that such infections may represent niche invasions by P. aeruginosa that influence the microenvironment by depleting host-derived substrate and activating the immune response. Bacteria embedded in cell aggregates establish a microenvironmental niche, where they endure the initial host response by slowing down their metabolism. This provides stable, lasting growth conditions with a constant, albeit slow supply of substrate and electron acceptors. Under such stable conditions, P. aeruginosa exhibits distinct adaptive traits, where its gene expression pattern reflects a life exposed to continuous attack by the host immune system and antimicrobials. Here, we review fundamental microenvironmental aspects of chronic P. aeruginosa infections and examine how their structural organization influences their in vivo microenvironment, which in turn affects the interaction of P. aeruginosa biofilm aggregates with the host immune system. We discuss how improving our knowledge about the microenvironmental ecology of P. aeruginosa in chronic infections can be used to combat persistent, hard-to-treat bacterial infections.
Chromosome-Level Genome Assembly of the Hemiparasitic Taxillus chinensis (DC.) Danser
Authors: Fu Jine , Wan Lingyun , Song Lisha , He Lili , Jiang Ni , Long Hairong , Huo Juan , Ji Xiaowen , Hu Fengyun , Wei Shugen , Pan Limei
Published: April 2022

The hemiparasitic Taxillus chinensis (DC.) Danser is a root-parasitizing medicinal plant with photosynthetic ability, which is lost in other parasitic plants. However, the cultivation and medical application of the species are limited by the recalcitrant seeds of the species, and even though the molecular mechanisms underlying this recalcitrance have been investigated using transcriptomic and proteomic methods, genome resources for T. chinensis have yet to be reported. Accordingly, the aim of the present study was to use nanopore, short-read, and high-throughput chromosome conformation capture sequencing to construct a chromosome-level assembly of the T. chinensis genome. The final genome assembly was 521.90 Mb in length, and 496.43 Mb (95.12%) could be grouped into nine chromosomes with contig and scaffold N50 values of 3.80 and 56.90 Mb, respectively. In addition, a total of 33,894 protein-coding genes were predicted, and gene family clustering identified 11 photosystem-related gene families, thereby indicating photosynthetic ability, which is a characteristic of hemiparasitic plants. This chromosome-level genome assembly of T. chinensis provides a valuable genomic resource for elucidating the genetic basis underlying the recalcitrant characteristics of T. chinensis seeds and the evolution of photosynthesis loss in parasitic plants.
On Degenerations of Projective Varieties to Complexity-One T-Varieties
Authors: Kaveh Kiumars , Manon Christopher , Murata Takuya
Published: April 2022

Let $R$ be a positively graded finitely generated $\textbf {k}$-domain with Krull dimension $d+1$. We show that there is a homogeneous valuation ${\mathfrak {v}}: R \setminus \{0\} \to {\mathbb {Z}}^d$ of rank $d$ such that the associated graded $\operatorname {gr}_{\mathfrak {v}}(R)$ is finitely generated. This then implies that any polarized $d$-dimensional projective variety $X$ has a flat deformation over ${\mathbb {A}}^1$, with reduced and irreducible fibers, to a polarized projective complexity-one $T$-variety (i.e., a variety with a faithful action of a $(d-1)$-dimensional torus $T$). As an application we conclude that any $d$-dimensional complex smooth projective variety $X$ equipped with an integral Kähler form has a proper $(d-1)$-dimensional Hamiltonian torus action on an open dense subset that extends continuously to all of $X$.
Developing a novel DNA methylation risk score for survival and identification of prognostic gene mutations in endometrial cancer: a study based on TCGA data
Authors: Shen Po-Chien , Wang Ying-Fu , Chang Hao-Chih , Huang Wen-Yen , Lo Cheng-Hsiang , Su Yu-Fu , Yang Jen-Fu , Lin Chun-Shu , Dai Yang-Hong
Published: April 2022

Background

Few studies have focused on DNA methylation in endometrial cancer. The aim of our study is identify its role in endometrial cancer prognosis.

Methods

A publicly available dataset was retrieved from The Cancer Genome Atlas. For validation of expression alteration due to methylation, RNA sequencing data were obtained from other independent cohorts. MethSurv was used to search for candidate CpG probes, which were then filtered by least absolute shrinkage and selection operator Cox regression and multivariate Cox regression analyses to identify final set of CpG probes for overall survival. A methylation-based risk model was developed and receiver operating characteristic analysis with area under curve was used for evaluation. Patients were divided into high- and low-risk groups using an optimal cut-off point. Comprehensive bioinformatic analyses were conducted to identify hub genes, key transcription factors, and enriched cancer-related pathways. Kaplan–Meier curve was used for survival analysis.

Results

A 5-CpG signature score was established. Its predictive value for 5-year overall survival was high, with area under curve of 0.828, 0.835 and 0.816 for the training, testing and entire cohorts. cg27487839 and cg12885678 had strong correlation with their gene expression, XKR6 and PTPRN2, and lower PTPRN2 expression was associated with poorer survival in both The Cancer Genome Atlas and the validation datasets. Low-risk group was associated with significantly better survival. Low-risk group harboured more mutations in hub genes and key transcription factors, and mutations in SP1 and MECP2 represented favourable outcome.

Conclusion

We developed a methylation-based prognostic stratification system for endometrial cancer. Low-risk group was associated with better survival and harboured more mutations in the key regulatory genes.
Population Structure of German Cockroaches (Blattodea: Ectobiidae) in an Urban Environment Based on Single Nucleotide Polymorphisms
Authors: Fan X , Wang C , Bunker D E
Published: April 2022

German cockroaches (Blattella germanica L.) harbor and disperse medically important pathogens and are a source of allergens that impact human health and wellbeing. Management of this pest requires an understanding of their distribution and dispersal. In this study, we collected German cockroaches from three apartment buildings in New Jersey, USA. We identified single-nucleotide polymorphisms (SNPs) from DNA extractions using next generation sequencing. We analyzed the SNPs and characterized cockroach population genetic structure using Fst, principal component, phylogenetic, and STRUCTURE analyses. We found significant differences in German cockroach population structure among the buildings. Within buildings, we found variable population structure that may be evidence for multiple colonization events. This study shows that SNPs derived from next generation sequencing provide a powerful tool for analyzing the genetic population structure of these medically important pests.
Spontaneous splenic rupture from indeterminate dendritic cell proliferation: a case report
Authors: Iqbal Shaikh B , Chittal Abhinandan R , Rao Shiavax J , Lakra Pallavi , Bhansali Deepty , Pyrgos George
Published: April 2022

Spontaneous splenic rupture is a rare and life-threatening phenomenon, usually associated with an underlying infectious, inflammatory, hematological, neoplastic or rheumatologic condition. Indeterminate cell tumor is a rare neoplastic dendritic cell disorder that is poorly understood but shares immunophenotypic markers for Langerhans cells without Birbeck granules. A 73-year-old man presented with upper abdominal pain after an unwitnessed fall. Computed tomography angiography showed splenomegaly and a large ruptured splenic subcapsular hematoma. Intraoperative findings from an emergency laparotomy revealed a large hemoperitoneum and a ruptured spleen. Microscopic sections identified numerous, mostly poorly formed, small nodules classified as a proliferation of indeterminate dendritic cell tumors.
Putting the pea in photoPEAriod
Authors: Chapman Mark A
Published: April 2022

This article comments on:

Williams O, Vander Schoor JK, Butler JB, Ridge S, Sussmilch FC, Hecht VFG, Weller JL. 2022. The genetic architecture of flowering time changes in pea from wild to crop. Journal of Experimental Botany 73,3978–3990.
3D mapping of the Wolf–Rayet nebula M 1-67: clues for post-common envelope evolution in massive stars
Authors: Zavala S , Toalá J A , Santamaría E , Ramos-Larios G , Sabin L , Quino-Mendoza J A , Rubio G , Guerrero M A
Published: April 2022

We present a 3D mapping of the Wolf–Rayet (WR) nebula M 1-67 around WR 124. We obtained high-resolution San Pedro Mártir (SPM) Manchester Echelle Spectrograph (MES) observations along 17 long-slit positions covering all morphological features in M 1-67. We are able to unveil the true morphology of M 1-67 and its kinematics by interpreting the SPM MES observations by means of the 3D modelling tool for Astrophysics shape. Our shape model that best reproduces the SPM MES data includes three concentric bipolar structures composed by a hollow ellipsoidal structure and a torus. In addition, the model requires the presence of expanding jets and broken blisters in order to reproduce specific spectral features. Our results are consistent with the idea that M 1-67 and its progenitor star WR 124 have formed through a common envelope scenario that occurred 11.8$^{+4.6}_{-0.8}$ kyr ago. Our bipolar model strongly questions previous suggestions of the presence of a bow shock structure surrounding M 1-67. We interpret that the bright structures detected in the spectra extracted from the central regions are produced by wind compression at the receding region of the innermost structure in M 1-67. Furthermore, WR 124 is moving through a low-density region above the Galactic plane that has negligibly affected the formation history of M 1-67.
Host galaxies of ultrastrong Mg ii absorbers at z ∼ 0.5
Authors: Guha Labanya Kumar , Srianand Raghunathan , Dutta Rajeshwari , Joshi Ravi , Noterdaeme Pasquier , Petitjean Patrick
Published: April 2022

From a sample of 109 candidate ultrastrong Mg ii (USMg ii; having rest equivalent width of Mg ii, W2796 > 3.0 Å) systems at z = 0.4–0.6, we confirm 27 and identify host galaxies of 20 systems based on associated nebular line emission from our SALT observations or from Sloan Digital Sky Survey (SDSS) fiber spectra. The measured impact parameter, [O ii] luminosity, star formation rate, B-band luminosity, and stellar mass are in the ranges 7.3 ≤ D[kpc] ≤ 79, $0.2\le L_{[\mathrm{ O}\,~\small {\rm II}]}[ 10^{41}~\mathrm{ erg} \mathrm{ s}^{-1}]\le 4.5$, 2.59 ≤ SFR[M⊙yr−1] ≤ 33.51, $0.15L_B^{*}\le L_B\le 1.63L_B^{*}$, and 10.21 ≤ log[M*/ M ⊙] ≤ 11.62, respectively. The impact parameters found are larger than that predicted by the W2796 versus D relationship of the general population of Mg ii absorbers. At a given D, USMg ii host galaxies are more luminous and massive compared to typical Mg ii absorbers. However, the measured SFRs are slightly lower than that of main-sequence galaxies with same M⋆ at z ∼ 0.5. We report a correlation between $L_{[\mathrm{ O}\,\small {\rm II}]}$ and W2796 for the full population of Mg ii absorbers, driven mainly by the host galaxies of weak Mg ii absorbers that tend to have low $L_{[\mathrm{ O}\,\small {\rm II}]}$ and large impact parameters. We find at least ∼33 per cent of the USMg ii host galaxies (with a limiting magnitude of mr < 23.6) are isolated and the large W2796 in these cases may originate from gas flows (infall/outflow) in single haloes of massive but not starburst galaxies. We also find galaxy interactions could be responsible for large velocity widths in at least ∼17 per cent cases.
Deep phenotyping: symptom annotation made simple with SAMS
Authors: Steinhaus Robin , Proft Sebastian , Seelow Evelyn , Schalau Tobias , Robinson Peter N , Seelow Dominik
Published: April 2022

Precision medicine needs precise phenotypes. The Human Phenotype Ontology (HPO) uses clinical signs instead of diagnoses and has become the standard annotation for patients’ phenotypes when describing single gene disorders. Use of the HPO beyond human genetics is however still limited. With SAMS (Symptom Annotation Made Simple), we want to bring sign-based phenotyping to routine clinical care, to hospital patients as well as to outpatients. Our web-based application provides access to three widely used annotation systems: HPO, OMIM, Orphanet. Whilst data can be stored in our database, phenotypes can also be imported and exported as Global Alliance for Genomics and Health (GA4GH) Phenopackets without using the database. The web interface can easily be integrated into local databases, e.g. clinical information systems. SAMS offers users to share their data with others, empowering patients to record their own signs and symptoms (or those of their children) and thus provide their doctors with additional information. We think that our approach will lead to better characterised patients which is not only helpful for finding disease mutations but also to better understand the pathophysiology of diseases and to recruit patients for studies and clinical trials. SAMS is freely available at https://www.genecascade.org/SAMS/.
Epigenome editing reveals core DNA methylation for imprinting control in the Dlk1-Dio3 imprinted domain
Authors: Kojima Shin , Shiochi Naoya , Sato Kazuki , Yamaura Mamiko , Ito Toshiaki , Yamamura Nodoka , Goto Naoki , Odamoto Mika , Kobayashi Shin , Kimura Tohru , Sekita Yoichi
Published: April 2022

The Dlk1-Dio3 imprinted domain is controlled by an imprinting control region (ICR) called IG-DMR that is hypomethylated on the maternal allele and hypermethylated on the paternal allele. Although several genetic mutation experiments have shown that IG-DMR is essential for imprinting control of the domain, how DNA methylation itself functions has not been elucidated. Here, we performed both gain and loss of DNA methylation experiments targeting IG-DMR by transiently introducing CRISPR/Cas9 based-targeted DNA methylation editing tools along with one guide RNA into mouse ES cells. Altered DNA methylation, particularly at IG-DMR-Rep, which is a tandem repeat containing ZFP57 methylated DNA-binding protein binding motifs, affected the imprinting state of the whole domain, including DNA methylation, imprinted gene expression, and histone modifications. Moreover, the altered imprinting states were persistent through neuronal differentiation. Our results suggest that the DNA methylation state at IG-DMR-Rep, but not other sites in IG-DMR, is a master element to determine whether the allele behaves as the intrinsic maternal or paternal allele. Meanwhile, this study provides a robust strategy and methodology to study core DNA methylation in cis-regulatory elements, such as ICRs and enhancers.
A systematic dissection of determinants and consequences of snoRNA-guided pseudouridylation of human mRNA
Authors: Nir Ronit , Hoernes Thomas Philipp , Muramatsu Hiromi , Faserl Klaus , Karikó Katalin , Erlacher Matthias David , Sas-Chen Aldema , Schwartz Schraga
Published: April 2022

RNA can be extensively modified post-transcriptionally with >170 covalent modifications, expanding its functional and structural repertoire. Pseudouridine (Ψ), the most abundant modified nucleoside in rRNA and tRNA, has recently been found within mRNA molecules. It remains unclear whether pseudouridylation of mRNA can be snoRNA-guided, bearing important implications for understanding the physiological target spectrum of snoRNAs and for their potential therapeutic exploitation in genetic diseases. Here, using a massively parallel reporter based strategy we simultaneously interrogate Ψ levels across hundreds of synthetic constructs with predesigned complementarity against endogenous snoRNAs. Our results demonstrate that snoRNA-mediated pseudouridylation can occur on mRNA targets. However, this is typically achieved at relatively low efficiencies, and is constrained by mRNA localization, snoRNA expression levels and the length of the snoRNA:mRNA complementarity stretches. We exploited these insights for the design of snoRNAs targeting pseudouridylation at premature termination codons, which was previously shown to suppress translational termination. However, in this and follow-up experiments in human cells we observe no evidence for significant levels of readthrough of pseudouridylated stop codons. Our study enhances our understanding of the scope, ‘design rules’, constraints and consequences of snoRNA-mediated pseudouridylation.
MEOX2homeobox gene promotes growth of malignant gliomas
Authors: Schönrock Anna , Heinzelmann Elisa , Steffl Bianca , Demirdizen Engin , Narayanan Ashwin , Krunic Damir , Bähr Marion , Park Jong-Whi , Schmidt Claudia , Özduman Koray , Pamir M Necmettin , Wick Wolfgang , Bestvater Felix , Weichenhan Dieter , Plass Christoph , Taranda Julian , Mall Moritz , Turcan Şevin
Published: April 2022

Background

Glioblastoma (GBM) is an aggressive tumor that frequently exhibits gain of chromosome 7, loss of chromosome 10, and aberrantly activated receptor tyrosine kinase signaling pathways. Previously, we identified Mesenchyme Homeobox 2 (MEOX2), a gene located on chromosome 7, as an upregulated transcription factor in GBM. Overexpressed transcription factors can be involved in driving GBM. Here, we aimed to address the role of MEOX2 in GBM.

Methods

Patient-derived GBM tumorspheres were used to constitutively knockdown or overexpress MEOX2 and subjected to in vitro assays including western blot to assess ERK phosphorylation. Cerebral organoid models were used to investigate the role of MEOX2 in growth initiation. Intracranial mouse implantation models were used to assess the tumorigenic potential of MEOX2. RNA-sequencing, ACT-seq, and CUT&Tag were used to identify MEOX2 target genes.

Results

MEOX2 enhanced ERK signaling through a feed-forward mechanism. We identified Ser155 as a putative ERK-dependent phosphorylation site upstream of the homeobox-domain of MEOX2. S155A substitution had a major effect on MEOX2 protein levels and altered its subnuclear localization. MEOX2 overexpression cooperated with p53 and PTEN loss in cerebral organoid models of human malignant gliomas to induce cell proliferation. Using high-throughput genomics, we identified putative transcriptional target genes of MEOX2 in patient-derived GBM tumorsphere models and a fresh frozen GBM tumor.

Conclusions

We identified MEOX2 as an oncogenic transcription regulator in GBM. MEOX2 increases proliferation in cerebral organoid models of GBM and feeds into ERK signaling that represents a core signaling pathway in GBM.
Human capital and welfare
Authors: Bosi Stefano , Camacho Carmen , Desmarchelier David
Published: April 2022

We introduce the Human Development Index (HDI) in a growth model to show that if households cared about human capital, even if infinitesimally, then human capital would increase forever protecting economies indirectly. Here, human capital will have an additional positive effect on social welfare through the quality of individual health and education. In a simple economy with a Cobb–Douglas technology and logarithmic preferences, we provide the explicit trajectories for human capital, consumption, and the HDI, which correspond to the balanced growth path (BGP). Using a two-step maximization strategy, we compute the optimal initial value of the control variable, in this case, the initial optimal labour supply. In other words, we prove the optimality of the BGP. We highlight a HDI crossing property: the propensity to consume has a positive effect on the HDI in the short run, but negative in the long run.
Clinical characteristics and risk factors associated with lymphoma in patients with systemic lupus erythematosus: a nationwide cohort study
Authors: Martín-López María , Galindo Maria , Pego-Reigosa José María , Jiménez Norman , Olivé Marqués Alejandro , Tomero Eva , Freire Mercedes , Martínez-Barrio Julia , Boteanu Alina , Salgado-Perez Eva , Fernández-Nebro Antonio , Calvo Jaime , Menor-Almagro Raul , Rúa-Figueroa Iñigo
Published: April 2022

Objectives

To assess the characteristics and risk of lymphoma in a large cohort of patients with SLE.

Methods

A case–cohort analysis was performed within a dynamic cohort of SLE patients from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Clinical and analytical features were compared between the lymphoma SLE group and the control SLE group using an independent-sample Student’s t-test or Mann–Whitney test for continuous variables and the χ2 test for categorical variables with Fisher’s exact test if necessary. The multivariate analysis was based on a generalized linear model.

Results

Twenty-one patients with SLE and lymphoma and 3965 non-lymphoma controls with SLE were studied. Most lymphomas were of B cell origin (n = 15/21), with diffuse large B cell lymphoma being the most frequent histological type (8/21, 38.1%). As in the general population, the risk of lymphoma in SLE was higher in male than in female patients and increased with age. In the lymphoma SLE group, bivariate analysis showed a significantly higher percentage of pericarditis, organic brain syndrome, seizures, vasculitis, haemolytic anaemia, splenomegaly, venous thrombosis and mean modified (excluding lymphoma) SLICC/ACR damage index. In contrast, renal involvement, positive anti-dsDNA, and antimalarials ever were less frequent.

Conclusions

In this large multicentre Spanish cohort, we identified characteristics of SLE that are associated with a higher risk of lymphoma. Antimalarials were significantly negatively associated with risk of lymphoma in SLE patients. Nevertheless, further prospective studies are needed to clarify these findings.
PERFORMANCE OF BARC NEUTRON PERSONAL DOSEMETER IN EURADOS INTERCOMPARISON EXERCISE IC2017N – A LESSON LEARNT
Authors: Bakshi A K , Beck Mudit , Shah Pankaj
Published: April 2022

Bhabha Atomic Research Centre (BARC) conducts fast neutron personnel monitoring service to radiation workers involved in reactors, accelerators, spent fuel processing plants, oil-well industries, etc., using CR-39 detector based dosemeter. In this study, performance of the BARC fast neutron personnel dosemeter has been checked through EURADOS intercomparison exercise for simulated workplace neutron fields. The overall performance of the dosemeter in the lower dose equivalent (≤ 5 mSv) was found to be acceptable as per ISO-14146. The performance (ratio of estimated to reference dose equivalent) of the dosemeter in the higher dose equivalent (12 mSv) was found to be in the range of 0.48–0.44 and not satisfactory as per the ISO-14146 criteria for any dosimetry service. Based on this performance, a new imaging system was developed and performance of the dosemeters were improved and found to be acceptable (within ±20%) as per ISO.
In Vitro Pain Assay Using Human iPSC-Derived Sensory Neurons and Microelectrode Array
Authors: Odawara Aoi , Shibata Mikako , Ishibashi Yuto , Nagafuku Nami , Matsuda Naoki , Suzuki Ikuro
Published: April 2022

Drug-induced peripheral neuropathy occurs as an adverse reaction of chemotherapy. However, a highly accurate method for assessing peripheral neuropathy and pain caused by compounds has not been established. The use of human-induced pluripotent stem cell (hiPSC)-derived sensory neurons does not require animal experiments, and it is considered an effective method that can approach extrapolation to humans. In this study, we evaluated the response to pain-related compounds based on neural activities using in vitro microelectrode array (MEA) measurements in hiPSC-derived sensory neurons. Cultured sensory neurons exhibited gene expression of the Nav1.7, TRPV1, TRPA1, and TRPM8 channels, which are typical pain-related channels. Channel-dependent evoked responses were detected using the TRPV1 agonist capsaicin, a TRPA1 agonist, allyl isothiocyanate (AITC), and TRPM8 agonist menthol. In addition, the firing frequency increased with an increase in temperature from 37°C to 46°C, and temperature sensitivity was observed. In addition, the temperature of the peak firing rate differed among individual neurons. Next, we focused on the increase in cold sensitivity, which is a side effect of the anticancer drug oxaliplatin, and evaluated the response to AITC in the presence and absence of oxaliplatin. The response to AITC increased in the presence of oxaliplatin in a concentration-dependent manner, suggesting that the increased cold sensitivity in humans can be reproduced in cultured hiPSC-derived sensory neurons. The in vitro MEA system using hiPSC-derived sensory neurons is an alternative method to animal experiments, and it is anticipated as a method for evaluating peripheral neuropathy and pain induced by compounds.
Neuroblastoma-associated Opsoclonous Myoclonous Ataxia Syndrome: Profile and Outcome Report on 15 Egyptian Patients
Authors: Elzomor Hossam , El Menawi Salma , Elawady Heba , Elkinaai Naglaa , Elshafie Maged , Refaat Amal , Ghareeb Hany , Fawzy Mohamed
Published: April 2022

Opsoclonous myoclonous ataxia syndrome (OMAS) is a rare primarily immune-mediated disease in children. The current study aim was to find out the patterns and outcome of OMAS associated with neuroblastoma (NBL) among Children’s Cancer Hospital—Egypt patients. Data was reviewed for 15 eligible patients enrolled between 2007 and 2016. OMAS treatment included prednisolone and cyclophosphamide with/without intravenous immunoglobulin; NBL treatment was given according to risk-corresponding protocol. Patients’ age ranged from 0.75 to 12 years at presentation with male/female: 1.1/1. Concurrent diagnosis of OMAS and NBL occurred in 6 patients (40%). OMAS preceded NBL within 0.25 to 2 years in 33%, while NBL preceded OMAS within 0.5 to 1.5 years in 27%. Full OMAS picture was present in 10/15 patients, while 20% presented with truncal ataxia and myoclonus, 1 with truncal ataxia and opsoclonus, and 1 had opsoclonus and myoclonus. Median time till improvement of manifestations was 5 months. The 5-year OMAS progression-free survival was 33.3%, where 10 patients needed second-line therapy due to relapse/progression of OMAS. The median time to progression was 28 months measured from OMAS diagnosis. All patients remained alive with NBL 5-year overall survival of 100% and event-free survival of 85.7% for. However, 73% of the patients showed late sequelae ranging from ocular to cognitive, behavioral and motor disorders; rarely seizures and hemolytic anemia.
Role of Electroconvulsive Therapy in Treatment-Resistant Schizophrenia in Forensic Psychiatry
Authors: Seamon Amanda , Groth Cassandra M. , Surya Sandarsh , Rosenquist Peter B.
Published: April 2022

Long-term institutionalization of the forensic psychiatry patient population places a psychological burden on patients and family members as well as a financial burden on the health care system at large. Although electroconvulsive therapy is a well-established tool for patients with treatment-resistant schizophrenia, it is infrequently used in the forensic setting. This review serves to demonstrate an example of electroconvulsive therapy in combination with clozapine as a means of reducing length of hospitalization in a forensic psychiatric patient. Furthermore, this review will discuss factors limiting the prescribing of electroconvulsive therapy to this patient population including ethical considerations and availability.
An Examination of Electroconvulsive Therapy and Delivery of Care in Delirious Mania
Authors: Reinfeld Samuel , Yacoub Adeeb
Published: April 2022

Objectives

Delirious mania is a severe life-threatening syndrome, often misdiagnosed, and eminently treatable as a variant of catatonia. Our aim is to provide a comprehensive examination of electroconvulsive therapy (ECT) parameters and clinical features, as well as describe the delivery of care of the patients with delirious mania.

Methods

A retrospective study was conducted of the ECT records at Stony Brook University Hospital from years 2014 to 2021. We characterized demographic and clinical variables, including psychiatric diagnoses and ECT parameters of patients identified with delirious mania.

Results

We identified 8 cases (3 women) of delirious mania with 8 corresponding acute treatment series. The mean age was 43.2 ± 12.6 years (range, 23–59 years). There were a total of 55 sessions performed with an average of 6.9 ± 2.6 (range, 5–13); 45 (82%) were bilateral (bifrontal or bitemporal) and 10 (18%) were right unilateral electrode placement. In 40 (73%) of the sessions, a high-energy stimulus was used (>60%, or 302 millicoulombs). Seizure duration measured on electroencephalogram was 47.4 ± 25.9 seconds (range, 0–143 seconds). Motor seizure duration measured on electromyogram was 32.7 ± 14.9 seconds (range, 0–66 seconds). In 6 cases, ECT was delayed for 10 days, and patients were given inappropriate treatments. High-dose antipsychotics caused worsened aggression and hemodynamic instability requiring physical restraints in 50% of cases.

Conclusions

The clinical presentation of delirious mania remains poorly recognized, and its treatment is often delayed, which may result in negative outcomes. Bilateral ECT with high-energy dosing yielded a rapid remission of symptoms.
Effect of an Educational Video and Information Pamphlet on Knowledge and Attitudes About Electroconvulsive Therapy
Authors: Shin Selina , Ho Joanna , Francis-Taylor Rohan , Wells Karen , Halliday Graeme , Jacek Sarah , Lah Suncica
Published: April 2022

Objective

Electroconvulsive therapy (ECT) is considered an effective, yet underused and stigmatized form of psychiatric treatment. Public misconception can impact informed decision making, and therefore, it is important to educate the community with accurate and realistic representations of modern ECT. The aim of this study was to determine whether exposure to brief information packages developed in Australia leads to changes in attitudes and knowledge about ECT.

Methods

A sample of 100 undergraduate psychology students and 88 volunteers from the general public were randomly allocated to view 1 of 3 resource packages (each containing an information pamphlet and videos totaling ~15 minutes): Concord Centre for Mental Health—Revised, Concord Centre for Mental Health—Original, and a generic information package on depression. Participants' attitudes and knowledge of ECT were assessed before and after psychoeducation using the Questionnaire on Attitudes and Knowledge of ECT (QuAKE).

Results

Participants in the student and general population exposed to either ECT resource package showed significantly improved attitudes and knowledge of ECT compared with participants exposed to generic information about depression and its treatment. A fine-grained analysis of the QuAKE revealed that, although many aspects of knowledge and attitudes improved after exposure to ECT information packages, some remained unchanged.

Conclusions

Brief education through information resources in video and written format can markedly improve attitudes and knowledge toward ECT. Further research is recommended to determine whether the resources contribute to informed decision making of consumers with mental illness, especially those who are candidates for ECT.
Solid forms and β-cyclodextrin complexation of turinabol
Authors: Turza Alexandru , Ulici Adelina , Muresan-Pop Marieta , Borodi Gheorghe
Published: April 2022

4-Chloro-17β-hydroxy-17α-methylandrosta-1,4-dien-3-one (C20H27ClO2), known as turinabol, is a synthetic anabolic–androgenic agent which belongs to the steroid class. Recrystallization from various solvents was performed and the following new solid forms of turinabol were obtained: the hemihydrate (C20H27ClO2·0.5H2O), the anhydrous form (C20H27ClO2), the multicomponent acetic acid hydrate (2C20H27ClO2·C2H4O2·H2O) and the 2,2,2-trifluoroethanol hemisolvate (C20H27ClO2·0.5C2H3F3O). The absolute structures were determined by single-crystal X-ray diffraction. The starting hemihydrate form contains one turinabol molecule in the asymmetric unit, while the others contain two molecules in the asymmetric unit. Structural features were investigated in terms of the conformational analysis of the steroid skeleton rings and intermolecular interactions. The magnitudes, the nature of the crystal structure energies and the intermolecular interactions were also evaluated. Complexation with β-cyclodextrin was performed and the obtained complex was investigated using powder X-ray diffraction, Fourier-transform infrared (FT–IR) spectroscopy and differential thermal analysis/thermogravimetric analysis (DTA/TGA).