bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher-order brain regions show shifts in structural covariance in adolescent marmosets
Authors: Quah Shaun K L , McIver Lauren , Bullmore Edward T , Roberts Angela C , Sawiak Stephen J
Published: November 2021

Substantial progress has been made studying morphological changes in brain regions during adolescence, but less is known of network-level changes in their relationship. Here, we compare covariance networks constructed from the correlation of morphometric volumes across 135 brain regions of marmoset monkeys in early adolescence and adulthood. Substantial shifts are identified in the topology of structural covariance networks in the prefrontal cortex (PFC) and temporal lobe. PFC regions become more structurally differentiated and segregated within their own local network, hypothesized to reflect increased specialization after maturation. In contrast, temporal regions show increased inter-hemispheric covariances that may underlie the establishment of distributed networks. Regionally selective coupling of structural and maturational covariance is revealed, with relatively weak coupling in transmodal association areas. The latter may be a consequence of continued maturation within adulthood, but also environmental factors, for example, family size, affecting brain morphology. Advancing our understanding of how morphological relationships within higher-order brain areas mature in adolescence deepens our knowledge of the developing brain’s organizing principles.
Inflammatory Bowel Disease-associated Fatty Liver Disease: the Potential Effect of Biologic Agents
Authors: Papaefthymiou Apostolis , Potamianos Spyros , Goulas Antonis , Doulberis Michael , Kountouras Jannis , Polyzos Stergios A
Published: November 2021

Inflammatory bowel diseases [IBD] exhibit intestinal and systemic manifestations. Nonalcoholic fatty liver disease [NAFLD] is a common co-existing condition, possibly contributing to the cardio-metabolic burden and overall morbidity. Εmerging therapeutic choices of biologic agents have modified the clinical course of IBD; however, their impact on IBD-associated NAFLD has not been extensively evaluated. The prevalence of NAFLD varies among IBD patients, but it appears higher than in the general population in the majority of quality studies. In terms of pathogenetic and risk factors of NAFLD, they may vary with IBD activity. Dysbiosis, mucosal damage, and cytokine release have been implicated in the pathogenesis during the relapses, whereas metabolic risk factors seem to play a dominant role during the remissions of IBD. Considering biologics, although quality data are scarce, agents suppressing tumour necrosis factor may offer potential benefits in IBD-associated NAFLD, whereas anti-integrins do not appear to confer any therapeutic advantage.

In conclusion, IBD-associated NAFLD possibly follows two different patterns, one manifested during the relapses and one during the remissions of IBD. Some, but not all, biologics may benefit NAFLD in patients with IBD. Further mechanistic and prospective cohort studies are warranted to illuminate the effects of various biologics on NAFLD.
Seismic data interpolation using streaming prediction filter in the frequency domain
Authors: Zheng Zhisheng , Liu Yang , Liu Cai
Published: November 2021

Surface conditions and economic factors restrict field geometries, so seismic data acquisition typically obtains field data with irregular spatial distribution, which can adversely affect the subsequent data processing and interpretation. Therefore, data interpolation techniques are used to convert field data into regularly distributed data and reconstruct the missing traces. Recently, the mainstream methods have implemented iterative algorithms to solve data interpolation problems, which require substantial computational resources and restrict their application in high dimensions. In this study, we proposed the f–x and f–x–y streaming prediction filters (SPFs) to reconstruct missing seismic traces without iterations. According to the streaming computation framework, we directly derived an analytic solution to the overdetermined least-squares problem with local smoothness constraints for estimating SPFs in the frequency domain. We introduced different processing paths and filter forms to reduce the interference of missing traces, which can improve the accuracy of filter coefficients. Meanwhile, we utilized a two-step interpolation strategy to guarantee the effective interpolation of the irregularly missing traces. Numerical examples show that the proposed methods effectively recover the missing traces in seismic data when compared with the traditional Fourier Projection Onto Convex Sets method. In particular, the frequency domain SPFs are suitable for high-dimensional seismic data interpolation with the advantages of low computational cost and reasonable non-stationary signal reconstruction.
Smoking and severe illness in hospitalized COVID-19 patients in Japan
Authors: Matsushita Yumi , Yokoyama Tetsuji , Hayakawa Kayoko , Matsunaga Nobuaki , Ohtsu Hiroshi , Saito Sho , Terada Mari , Suzuki Setsuko , Morioka Shinichiro , Kutsuna Satoshi , Mizoue Tetsuya , Hara Hisao , Kimura Akio , Ohmagari Norio
Published: November 2021

Background

The aim of this study was to identify associations between smoking status and the severity of COVID-19, using a large-scale data registry of hospitalized COVID-19 patients in Japan (COVIREGI-JP), and to explore the reasons for the inconsistent results previously reported on this subject.

Methods

The analysis included 17 666 COVID-19 inpatients aged 20–89 years (10 250 men and 7416 women). We graded the severity of COVID-19 (grades 0 to 5) according to the most intensive treatment required during hospitalization. The smoking status of severe grades 3/4/5 (invasive mechanical ventilation/extracorporeal membrane oxygenation/death) and separately of grade 5 (death) were compared with that of grade 0 (no oxygen, reference group) using multiple logistic regression. Results were expressed as odds ratios (OR) and 95% confidence intervals (CI) adjusted for age and other factors considering the potential intermediate effects of comorbidities.

Results

Among men, former smoking significantly increased the risk of grade 3/4/5 and grade 5, using grade 0 as a reference group, with age- and admission-date-adjusted ORs (95% CI) of 1.51 (1.18–1.93) and 1.65 (1.22–2.24), respectively. An additional adjustment for comorbidities weakened the ORs. Similar results were seen for women. Current smoking did not significantly increase the risk of grade 3/4/5 and grade 5 in either sex.

Conclusions

The severity of COVID-19 was not associated with current or former smoking per se but with the comorbidities caused by smoking. Thus, smoking cessation is likely to be a key factor for preventing smoking-related disease and hence for reducing the risk of severe COVID-19.
Role sharing between minimally invasive oesophagectomy and organ preservation approach for surgically resectable advanced oesophageal cancer
Authors: Matsuda Satoru , Kawakubo Hirofumi , Irino Tomoyuki , Kitagawa Yuko
Published: November 2021

Oesophageal cancer is a dismal disease since it metastasizes widely even from an early stage. In order to improve treatment outcomes, multidisciplinary treatments including surgery, chemotherapy and radiotherapy have been developed. While oesophagectomy is the mainstay in the treatment strategy, it is highly invasive since it requires two to three field approaches. To reduce surgical stress and morbidity, minimally invasive oesophagectomy including thoracoscopy, robotic assisted surgery and mediastinoscopy were introduced. Various clinical trials proved that these techniques decrease the post-operative morbidity rate. Furthermore, with the advancement of multidisciplinary treatment with a higher response rate, the possibility arose for omission of surgical resection in remarkable responders to neoadjuvant therapy. However, in order to safely provide organ preservation without increasing the risk of post-treatment recurrence, an accurate tumour monitoring system is required. Although endoscopy and computed tomography imaging have been a standard, the detection rate of residual tumours after treatment is still unsatisfactory. Utilizing liquid biopsy which could evaluate tumour derivative and host response, an appropriate monitoring system of tumour burden during multidisciplinary treatment can be developed. With the advancement of minimally invasive surgery and multidisciplinary treatment, the treatment strategy needs to be highly individualized based on the tumour biology, patients’ condition and their preferences. Along with the improvement of the tumour monitoring system, appropriate role sharing can be achieved between a minimally invasive surgery and the organ preservation approach.
Analysis of tweets regarding psychological disorders before and during the COVID-19 pandemic: The case of Turkey
Authors: Tankut Ülkü , Esen M Fevzi , Balaban Gülşah
Published: November 2021

This study aimed to examine the effects of the COVID-19 pandemic on Turkish society in relation to obsessive-compulsive disorder, anxiety disorder, and depression via content mining of tweets. Tweets were obtained by searching selected keywords via Twitter application programming interface in Python. The tweets were then filtered for psychopathology-related keywords. The sample consisted of 65,031 publicly available tweets that cover the period between 2 December 2019 and 31 May 2021. Latent Dirichlet allocation, was performed to uncover the latent semantic structures in the tweets. Data transformation and analysis were performed by using open-source R (version 4.0.2). As a result of the analysis, there were statistically significant differences in the total number of tweets, mean number of comments, likes, and retweets per tweet between the pre-pandemic and pandemic periods. From the topic modeling, it was also found that semantic strings of the tweets differed in the pandemic period compared to the pre-pandemic period. Topic analysis of social media shares can provide information on the mental health conditions of individuals and the use of tweet content can contribute to the research of psychopathologies, especially during the pandemic.
Intestinal mycobiome associated with diagnosis of inflammatory bowel disease based on tissue biopsies
Authors: Cimická Jana , Riegert Jan , Kavková Miloslava , Černá Kateřina
Published: November 2021

Analysis of mycobiome from formalin-fixed, paraffin-embedded (FFPE) biopsies should preferentially detect only fungi which are actually present in the intestine wall, in contrast to stool samples, which are limited by the diet composition. Next generation sequencing provides the advantage of analyzing many species from a single sample. Consequently, canonical correspondence analysis divided fungal genera present in FFPE intestinal tissues into three well-defined experimental groups (negative controls - NC, Crohn's disease - CD, ulcerative colitis - UC). Simultaneously, the analysis showed that particular fungal genera are associated with these experimental groups and several fungal genera occurred in all experimental groups equally. Our results also showed a noticeable increase of Ascomycota proportion from NC, through CD to UC. Fungal genera Malassezia, Cladosporium and Toninia occurred in all experimental groups assuming that they are common components of the intestinal mycobiome. Other fungal genera found only in the NC experimental group were non-pathogenic and might bring some benefits. In contrast, CD and UC samples were characterized by an accumulation of genera with inhibitive effects on growth of other fungal genera and the presence of opportunistic pathogens. Furthermore, a decrease in the fungal genus Malassezia in inflammatory tissues was observed; Specifically, the UC experimental group showed a connection between the presence of Candida and seven time's lower amounts of Malassezia (compared to amounts found in NC). The CD experimental group was characterized by the simultaneous presence of Engyodontium album with Lecanicillium, and indicates a possible pathogenic effect of Ramularia in disease development.

Lay summary

Mycobiome analysis of formalin-fixed and paraffin-embedded biopsies may highlight actual fungal genera composition in the intestinal wall. Interestingly, experimental groups of Crohn's disease and ulcerative colitis clearly differed by structure of their mycobiomes.
On the double-plane plasma lensing
Authors: Er Xinzhong , Wagner Jenny , Mao Shude
Published: November 2021

Plasma lensing is the refraction of low-frequency electromagnetic rays due to cold free electrons in the universe. For sources at a cosmological distance, there is observational evidence of elongated, complex plasma structures along the line of sight requiring a multi-lens-plane description. To investigate the limits of single-plane plasma lensing, we set up a double-plane lens with a projected Gaussian electron density in each lens plane. We compare double-plane scenarios with corresponding effective single-plane configurations. Our results show how double-plane lenses can be distinguished from single-plane lenses by observables, i.e. resolved multiple image positions, relative magnifications, time delays, and pulse shapes. For plasma lensing of fast radio bursts, the observed pulse shape may be dominated by the lensing effect, allowing us to neglect the intrinsic source pulse shape to distinguish different lensing configurations. The time-domain observables turn out to be the most salient features to tell multi- and single-plane lenses apart.
Constraining violations of the weak equivalence principle Using CHIME FRBs
Authors: Sen Kaustubha , Hashimoto Tetsuya , Goto Tomotsugu , Kim Seong Jin , Chen Bo Han , Santos Daryl Joe D , Ho Simon C C , On Alvina Y L , Lu Ting-Yi , Hsiao Tiger Y-Y
Published: November 2021

Einstein’s General relativity (GR) is the basis of modern astronomy and astrophysics. Testing the validity of basic assumptions of GR is important. In this work, we test a possible violation of the weak equivalence principle (WEP), i.e. there might be a time lag between photons of different frequencies caused by the effect of gravitational fields if the speeds of photons are slightly different at different frequencies. We use Fast radio bursts (FRBs), which are astronomical transients with millisecond time-scales detected in the radio frequency range. Being at cosmological distances, accumulated time delay of FRBs can be caused by the plasma in between an FRB source and an observer, and by gravitational fields in the path of the signal. We segregate the delay due to dispersion and gravitational field using the post-Newtonian formalism (PPN) parameter Δγ, which defines the space curvature due to gravity by a unit test mass. We did not detect any time delay from FRBs but obtained tight constraints on the upper limit of Δγ. For FRB20181117C with z = 1.83 ± 0.28 and νobs  = $676.5\, {\rm MHz}$, the best possible constraint is obtained at log(Δγ)  = $-21.58 ^{+0.10}_{-0.12}$ and log(Δγ/rE)  = $-21.75 ^{+0.10}_{-0.14}$, respectively, where rE is the energy ratio of two photons of the same FRB signal. This constraint is about one order of magnitude better than the previous constraint obtained with FRBs, and five orders tighter than any constraint obtained using other cosmological sources.
Constraints on ultra-low-frequency gravitational waves from an eccentric supermassive black hole binary
Authors: Kikunaga Tomonosuke , Hisano Shinnosuke , Kumamoto Hiroki , Takahashi Keitaro
Published: November 2021

Millisecond pulsars with highly stable periods can be considered as very precise clocks and can be used for pulsar timing arrays (PTAs), which attempt to detect nanohertz gravitational waves (GWs) directly. The main sources of nanohertz GWs are supermassive black hole (SMBH) binaries with sub-parsec-scale orbits. On the other hand, an SMBH binary in an earlier phase with a parsec-scale orbit emits ultra-low-frequency ($\lesssim 10^{-9}\, \mathrm{Hz}$) GWs and cannot be detected with the conventional PTA methodology. Such binaries tend to attain high eccentricity, possibly ∼0.9. In this paper, we develop a formalism for extending the constraints on GW amplitudes from single sources obtained by PTAs toward ultra-low frequencies considering the waveform expected from an eccentric SMBH binary. GWs from eccentric binaries are contributed from higher harmonics and therefore have a different waveform to those from circular binaries. Furthermore, we apply our formalism to several hypothetical SMBH binaries at the centre of nearby galaxies, including M87, using the constraints from NANOGrav’s 11-yr data set. For a hypothetical SMBH binary at the centre of M87, the typical upper limit on the mass ratio is 0.16 for an eccentricity of 0.9 and a semimajor axis of a = 1 pc, assuming the binary phase to be the pericentre.
Measurements of the diffuse Galactic synchrotron spectral index and curvature from MeerKLASS pilot data
Authors: Irfan Melis O , Bull Philip , Santos Mario G , Wang Jingying , Grainge Keith , Li Yichao , Carucci Isabella P , Spinelli Marta , Cunnington Steven
Published: November 2021

21 cm intensity mapping experiments are bringing an influx of high spectral resolution observational data in the ∼100 MHz–1 GHz regime. We use pilot 971–1075 MHz data from MeerKAT in single-dish mode, recently used to test the calibration and data reduction scheme of the upcoming MeerKLASS survey, to probe the spectral index of diffuse synchrotron emission below 1 GHz within 145° < α < 180°, −1° < δ < 8°. Through comparisons with data from the OVRO Long Wavelength Array and the Maipu and MU surveys, we find an average spectral index of −2.75 < β < −2.71 between 45 and 1055 MHz. By fitting for spectral curvature with a spectral index of the form $\beta + c \, {\rm {ln}}(\nu / 73~{\rm MHz})$, we measure β = −2.55 ± 0.13 and c = −0.12 ± 0.05 within our target field. Our results are in good agreement (within 1σ) with existing measurements from experiments such as ARCADE2 and EDGES. These results show the calibration accuracy of current data and demonstrate that MeerKLASS will also be capable of achieving a secondary science goal of probing the interstellar medium.
Double-lined spectroscopic binaries in M11
Authors: Kovalev Mikhail , Straumit Ilya
Published: November 2021

We have developed a new method for spectral analysis of binaries. Our method successfully identifies double-lined spectroscopic binary (SB2) candidates from high-resolution Gaia-ESO spectra. Compared to the commonly used cross-correlation function analysis, it works for binaries with rapidly rotating components. We test our method on synthetic and observational spectra of BAFG stars with vsin i from 1 to $330~\, {\rm km}\, {\rm s}^{-1}$ in the open cluster M11. We confirm five previously detected SB2 candidates and find 19 new ones. For three SB2 candidates, we find circular orbits and obtain dynamical mass ratios.
via machinae: Searching for stellar streams using unsupervised machine learning
Authors: Shih David , Buckley Matthew R , Necib Lina , Tamanas John
Published: November 2021

We develop a new machine learning algorithm, via machinae, to identify cold stellar streams in data from the Gaia telescope. via machinae is based on ANODE, a general method that uses conditional density estimation and sideband interpolation to detect local overdensities in the data in a model agnostic way. By applying ANODE to the positions, proper motions, and photometry of stars observed by Gaia, via machinae obtains a collection of those stars deemed most likely to belong to a stellar stream. We further apply an automated line-finding method based on the Hough transform to search for line-like features in patches of the sky. In this paper, we describe the via machinae algorithm in detail and demonstrate our approach on the prominent stream GD-1. Though some parts of the algorithm are tuned to increase sensitivity to cold streams, the via machinae technique itself does not rely on astrophysical assumptions, such as the potential of the Milky Way or stellar isochrones. This flexibility suggests that it may have further applications in identifying other anomalous structures within the Gaia data set, for example debris flow and globular clusters.
A comparison of approximate non-linear Riemann solvers for Relativistic MHD
Authors: Mattia G , Mignone A
Published: November 2021

We compare a particular selection of approximate solutions of the Riemann problem in the context of ideal relativistic magnetohydrodynamics. In particular, we focus on Riemann solvers not requiring a full eigenvector structure. Such solvers recover the solution of the Riemann problem by solving a simplified or reduced set of jump conditions, whose level of complexity depends on the intermediate modes that are included. Five different approaches – namely the HLL, HLLC, HLLD, HLLEM, and GFORCE schemes – are compared in terms of accuracy and robustness against one – and multidimensional standard numerical benchmarks. Our results demonstrate that – for weak or moderate magnetizations – the HLLD Riemann solver yields the most accurate results, followed by HLLC solver(s). The GFORCE approach provides a valid alternative to the HLL solver being less dissipative and equally robust for strongly magnetized environments. Finally, our tests show that the HLLEM Riemann solver is not cost-effective in improving the accuracy of the solution and reducing the numerical dissipation.
Three aspects of the radius-to-frequency mapping in fast radio bursts
Authors: Tong H , Liu J , Wang H G , Yan Z
Published: November 2021

We have explored the radius-to-frequency mapping further in cases of fast radio bursts (FRBs). We present an analytical treatment of Lyutikov (2020, ApJ, 889, 135). We obtain the frequency dependence of the drifting rate and the drifting time-scale. The aberration effect and the twist of the magnetic field lines can result in drifting in both directions. For one FRB, the burst width is larger at a lower frequency, according to the radius-to-frequency mapping. For the FRB population, the magnetic fields of the repeaters might be larger than those of the non-repeaters. Then, according to the radius-to-frequency mapping, the burst widths of the repeaters will be wider than those of the apparent non-repeaters. If a similar window function (or emission cones) as for pulsars and magnetars is also at work in the case of FRBs, then the window function might explain the single or multiple components of FRB profiles. The modelling of the radius-to-frequency mapping is, to some degree, independent of the underlying radio emission mechanism.
Dynamical ejecta of neutron star mergers with nucleonic weak processes I: nucleosynthesis
Authors: Kullmann I , Goriely S , Just O , Ardevol-Pulpillo R , Bauswein A , Janka H-T
Published: November 2021

We present a coherent study of the impact of neutrino interactions on the r-process element nucleosynthesis and the heating rate produced by the radioactive elements synthesized in the dynamical ejecta of neutron star–neutron star (NS–NS) mergers. We have studied the material ejected from four NS–NS merger systems based on hydrodynamical simulations which handle neutrino effects in an elaborate way by including neutrino equilibration with matter in optically thick regions and re-absorption in optically thin regions. We find that the neutron richness of the dynamical ejecta is significantly affected by the neutrinos emitted by the post-merger remnant, in particular when compared to a case neglecting all neutrino interactions. Our nucleosynthesis results show that a solar-like distribution of r-process elements with mass numbers $A \gtrsim 90$ is produced, including a significant enrichment in Sr and a reduced production of actinides compared to simulations without inclusion of the nucleonic weak processes. The composition of the dynamically ejected matter as well as the corresponding rate of radioactive decay heating are found to be rather independent of the system mass asymmetry and the adopted equation of state. This approximate degeneracy in abundance pattern and heating rates can be favourable for extracting the ejecta properties from kilonova observations, at least if the dynamical component dominates the overall ejecta. Part II of this work will study the light curve produced by the dynamical ejecta of our four NS merger models.
Expression Atlas update: gene and protein expression in multiple species
Authors: Moreno Pablo , Fexova Silvie , George Nancy , Manning Jonathan R , Miao Zhichiao , Mohammed Suhaib , Muñoz-Pomer Alfonso , Fullgrabe Anja , Bi Yalan , Bush Natassja , Iqbal Haider , Kumbham Upendra , Solovyev Andrey , Zhao Lingyun , Prakash Ananth , García-Seisdedos David , Kundu Deepti J , Wang Shengbo , Walzer Mathias , Clarke Laura , Osumi-Sutherland David , Tello-Ruiz Marcela Karey , Kumari Sunita , Ware Doreen , Eliasova Jana , Arends Mark J , Nawijn Martijn C , Meyer Kerstin , Burdett Tony , Marioni John , Teichmann Sarah , Vizcaíno Juan Antonio , Brazma Alvis , Papatheodorou Irene
Published: November 2021

The EMBL-EBI Expression Atlas is an added value knowledge base that enables researchers to answer the question of where (tissue, organism part, developmental stage, cell type) and under which conditions (disease, treatment, gender, etc) a gene or protein of interest is expressed. Expression Atlas brings together data from >4500 expression studies from >65 different species, across different conditions and tissues. It makes these data freely available in an easy to visualise form, after expert curation to accurately represent the intended experimental design, re-analysed via standardised pipelines that rely on open-source community developed tools. Each study's metadata are annotated using ontologies. The data are re-analyzed with the aim of reproducing the original conclusions of the underlying experiments. Expression Atlas is currently divided into Bulk Expression Atlas and Single Cell Expression Atlas. Expression Atlas contains data from differential studies (microarray and bulk RNA-Seq) and baseline studies (bulk RNA-Seq and proteomics), whereas Single Cell Expression Atlas is currently dedicated to Single Cell RNA-Sequencing (scRNA-Seq) studies. The resource has been in continuous development since 2009 and it is available at https://www.ebi.ac.uk/gxa.
Dynamic bulge nucleotides in the KSHV PAN ENE triple helix provide a unique binding platform for small molecule ligands
Authors: Swain Monalisa , Ageeli Abeer A , Kasprzak Wojciech K , Li Mi , Miller Jennifer T , Sztuba-Solinska Joanna , Schneekloth John S , Koirala Deepak , Piccirili Joseph , Fraboni Americo J , Murelli Ryan P , Wlodawer Alexander , Shapiro Bruce A , Baird Nathan , Le Grice Stuart F J
Published: November 2021

Cellular and virus-coded long non-coding (lnc) RNAs support multiple roles related to biological and pathological processes. Several lncRNAs sequester their 3′ termini to evade cellular degradation machinery, thereby supporting disease progression. An intramolecular triplex involving the lncRNA 3′ terminus, the element for nuclear expression (ENE), stabilizes RNA transcripts and promotes persistent function. Therefore, such ENE triplexes, as presented here in Kaposi's sarcoma-associated herpesvirus (KSHV) polyadenylated nuclear (PAN) lncRNA, represent targets for therapeutic development. Towards identifying novel ligands targeting the PAN ENE triplex, we screened a library of immobilized small molecules and identified several triplex-binding chemotypes, the tightest of which exhibits micromolar binding affinity. Combined biophysical, biochemical, and computational strategies localized ligand binding to a platform created near a dinucleotide bulge at the base of the triplex. Crystal structures of apo (3.3 Å) and ligand-soaked (2.5 Å) ENE triplexes, which include a stabilizing basal duplex, indicate significant local structural rearrangements within this dinucleotide bulge. MD simulations and a modified nucleoside analog interference technique corroborate the role of the bulge and the base of the triplex in ligand binding. Together with recently discovered small molecules that reduce nuclear MALAT1 lncRNA levels by engaging its ENE triplex, our data supports the potential of targeting RNA triplexes with small molecules.
Genome-wide mapping of Vibrio cholerae VpsT binding identifies a mechanism for c-di-GMP homeostasis
Authors: Guest Thomas , Haycocks James R J , Warren Gemma Z L , Grainger David C
Published: November 2021

Many bacteria use cyclic dimeric guanosine monophosphate (c-di-GMP) to control changes in lifestyle. The molecule, synthesized by proteins having diguanylate cyclase activity, is often a signal to transition from motile to sedentary behaviour. In Vibrio cholerae, c-di-GMP can exert its effects via the transcription factors VpsT and VpsR. Together, these proteins activate genes needed for V. cholerae to form biofilms. In this work, we have mapped the genome-wide distribution of VpsT in a search for further regulatory roles. We show that VpsT binds 23 loci and recognises a degenerate DNA palindrome having the consensus 5′-W−5R−4[CG]−3Y−2W−1W+1R+2[GC]+3Y+4W+5-3′. Most genes targeted by VpsT encode functions related to motility, biofilm formation, or c-di-GMP metabolism. Most notably, VpsT activates expression of the vpvABC operon that encodes a diguanylate cyclase. This creates a positive feedback loop needed to maintain intracellular levels of c-di-GMP. Mutation of the key VpsT binding site, upstream of vpvABC, severs the loop and c-di-GMP levels fall accordingly. Hence, as well as relaying the c-di-GMP signal, VpsT impacts c-di-GMP homeostasis.
Development of a new ultrasound scoring system to evaluate glandular inflammation in Sjögren’s syndrome: an OMERACT reliability exercise
Authors: Hočevar Alojzija , Bruyn George A , Terslev Lene , De Agustin Juan Jose , MacCarter Daryl , Chrysidis Stavros , Collado Paz , Dejaco Christian , Fana Viktoria , Filippou Georgios , Finzel Stephanie , Gandjbakhch Frederique , Hanova Petra , Hammenfors Daniel , Hernandez-Diaz Cristina , Iagnocco Annamaria , Mortada Mohamed Atia , Inanc Nevsun , Naredo Esperanza , Ohrndorf Sarah , Perko Nejc , Schmidt , Wolfgang A , Tamborrini Giorgio , Tomšič Matija , Chary-Valckenaere Isabelle , Zabotti Alen , Keen Helen I , Pineda Carlos , D’Agostino Maria-Antonietta , Jousse-Joulin Sandrine
Published: November 2021

Objective

The aim of this exercise from the OMERACT Ultrasound subgroup on Sjögren’s syndrome was to develop and assess the reliability of a consensus-based semiquantitative colour Doppler US scoring system for pathologic salivary gland vascularization in patients with primary Sjögren's syndrome (pSS).

Methods

Using the Delphi method, a colour Doppler semiquantitative scoring system for vascularization of bilateral parotid and submandibular glands was developed and tested in static images and on patients (9 pSS patients and 9 sonographers). Intra-reader and inter-reader reliability of grading the salivary glands were computed by weighted Cohen and Light’s kappa analysis, respectively.

Results

The consensus-based semiquantitative score was: grade 0, no visible vascular signals; grade 1, focal, dispersed vascular signals; grade 2, diffuse vascular signals detected in <50% of the gland; grade 3, diffuse vascular signals in >50% of the gland. In static images, the intra- and inter-reader reliability showed excellent kappa values (95% CI) of 0.90 (0.87, 0.93) and 0.80 (0.74, 0.84), respectively, for all four salivary glands together. In patients, the intra- and inter-reader reliability for all four salivary glands together was kappa = 0.84 (0.73, 0.92) and 0.70 (0.64, 0.76), respectively.

Conclusion

The consensus-based colour Doppler US scoring for the evaluation of salivary gland vascularization in pSS showed a good inter-reader reliability and excellent intra-reader reliability in static images and in patients. The clinical application of the developed scoring system should be tested in clinical settings.
Persistent Use of Prescription Opioids Following Lumbar Spine Surgery
Authors: Holmberg Siril T. , Fredheim Olav M.S. , Skurtveit Svetlana , Salvesen Øyvind O. , Nygaard Øystein P. , Gulati Agnete M. , Solberg Tore K. , Gulati Sasha
Published: November 2021

Study Design.

Prospective pharmacoepidemiological study.

Objective.

To investigate the use of prescription opioids 2 years following degenerative lumbar spine surgery.

Summary of Background Data.

There are limited data providing details to evaluate patterns of opioid use. The number of patients is often limited and data on opioid use following some of the most common surgical procedures are lacking.

Methods.

Data from the Norwegian Registry for Spine Surgery and the Norwegian Prescription Database were linked on an individual level. The primary outcome measure was persistent opioid use the second year after surgery. Functional disability

was measured with the Oswestry disability index (ODI). Study participants were operated between 2007 and 2017.

Results.

Among 32,886 study participants, 2754 (8.4%) met criteria for persistent opioid use the second year after surgery. Among persistent opioid users in the second year after surgery, 64% met the criteria for persistent opioid use the year preceding surgery. Persistent opioid use the year preceding surgery (odds ratio [OR] 31.10, 95% confidence interval [CI] 26.9–36.0, P 
= 0.001), use of high doses of benzodiazepines (OR 1.62, 95% CI 1.30–2.04, P 
= 0.001), and use of high doses of z-hypnotics (OR 1.90, 95% CI 1.58–2.22, P 
= 0.001) the year before surgery were associated with increased risk of persistent opioid use the second year after surgery. A higher ODI score at 1 year was observed in persistent opioid users compared with non-persistent users (41.5 vs. 18.8 points) and there was a significant difference in ODI change (–13.7 points). Patients with persistent opioid use in the year preceding surgery were less likely to achieve a minimal clinically important ODI change at 1 year compared with non-persistent users (37.7% vs. 52.6%, P 
= 0.001).

Conclusion.

Patients with or at risk of developing persistent opioid should be identified and provided counseling and support to taper off opioid treatment.

Level of Evidence: 2
Disc and Vertebral Body Morphology From Birth to Adulthood
Authors: de Reuver Steven , Costa Lorenzo , van Rheenen Hanna , Tabeling Casper S. , Lemans Justin V.C. , Schlösser Tom P.C. , Kruyt Moyo C. , van Stralen Marijn , Castelein René M.
Published: November 2021

Study Design.

Cross-sectional.

Objective.

The aim of this study was to describe the morphology of intervertebral discs and vertebral bodies during growth in asymptomatic children and adolescents.

Summary of Background Data.

Earlier studies demonstrated that spinal growth occurs predominantly in vertebral bodies. This axiom introduced a vertebral-body-focus for unravelling etiological questions and achieve growth-modulation in young spinal deformity patients. Recent studies show the importance of the intervertebral discs in the early phases and possible etiology of pediatric spinal deformities. There is presently a paucity of 3D morphometric data of spinal elements during growth.

Methods.

A database of 298 patients aged 0 to 21 that have received a computed tomography scan for indications not related to the spine was analyzed. Custom made software was used to semi-automatically measure intervertebral disc and vertebral body morphology, corrected for orientation in all 3 planes.

Results.

Vertebral body height increased from birth up to adulthood, from 4-to-14 mm in the cervical, 6 to 20 mm in the thoracic, and 9 to 28 mm in the lumbar spine. This increase was 0.70 mm/year in males, more pronounced than females with 0.62 mm/year (P = 0.001). Lumbar discs increased throughout growth from 4.4 to 9.0 mm, whereas thoracic discs only increased from 3.5 to 4.9 mm at age 4 and remained stable afterwards, similarly for cervical discs. The disc transverse surface area increased greatly and consistently throughout growth. Disc slenderness was stable in the lumbar spine during growth, but decreased in the thoracic and cervical spine. Overall, discs were more slender in females, especially around early adolescence.

Conclusion.

The spine grows predominantly in the vertebral bodies. Thoracic discs increase in height only during the first years, whereas the transverse surface area continues to increase throughout growth, thus discs slenderness decreases. Relatively, female discs remained slenderer around growth-spurt. These measurements may assist future studies on the role of disc morphology in the etiology and treatment of spinal deformity.

Level of Evidence: 4
Turner syndrome with Xp deletions and rare endometrial abnormalities
Authors: Liang Lei , Mei Libin , Shi Yingying , Huang Lingling , Su Zhiying , Zeng Yu , Gao Haijie , He Xuemei , Huang Hui , Huang Yanru , Li Ping , Chen Jing
Published: November 2021

Rationale:

Turner syndrome (TS) is a genetic disorder associated with abnormalities of the X chromosome related to ovarian function, but whether it is associated with endometrial abnormalities is still not clear.

Patient concerns:

We report the case of a 26-year-old Han Chinese woman with TS and Xp11.2 deletion, presenting with short final stature, ovarian hypofunction, unexplained cystic dilatation of the entire endometrium, and endometrial thickening.

Diagnoses:

The patient was diagnosed with chromosome Xp11.2 deletion through cytogenetic analysis and ultrasonic and endometrial pathology.

Interventions:

The patient was treated with conventional in vitro fertilization preimplantation genetic testing for 1 cycle.

Outcomes:

Cytogenetic examination showed karyotype 45, X, del (X) del (p11, 2). Ultrasonic examination showed uneven endometrium thickness and a full-stage cystic dilation echo. After 1 cycle of in vitro fertilization treatment, 4 eggs were obtained without forming an available embryo.

Lessons:

To our knowledge, the present case is the first report of a patient with TS with Xp deletions and ultrasound imaging endometrial abnormalities. Our findings expand the phenotypic spectrum of TS and may provide a reference for other clinicians.
High prevalence of Chlamydia trachomatis infection among women attending STD and gynecology clinics in Jiangsu province, China
Authors: Hu Haiyang , Zhou Ying , Shi Lingen , Lu Jing , Zhang Zhi , Xu Xiaoqin , Huan Xiping , Fu Gengfeng
Published: November 2021

Epidemics of Chlamydia trachomatis (CT) infection among women are major global public health concerns. This study examined the prevalence of CT infection and associated factors among women attending sexually transmitted disease (STD) and gynecology clinics in Jiangsu province, China.

A cross-sectional survey was conducted among women attending STD and gynecology clinics in the province during 2018 to 2019. Socio-demographic and behavioral information were collected through face-to-face questionnaire survey. Cervical swab specimens were collected to test for CT. Chi square tests were used to compare differences in CT prevalence between subgroups of characteristics. Multivariate logistic regression analysis was used to identify factors associated with CT infection.

A total of 2664 participants were enrolled. The prevalence of CT infection was 16.6% (95% confidence interval: 15.0%–18.1%). Of those, CT prevalence among participants from STD clinics (19.4%) and South Jiangsu (18.5%) were higher. Female outpatients who were service personnel (adjusted odds ratio [aOR] = 1.667, P = .004) or farmers (aOR = 1.593, P = .039), lived in South Jiangsu (aOR = 1.796, P = .004), and were from STD clinics (aOR = 1.608, P = .022) were more likely to infect CT.

Our study showed a high prevalence of CT infection among women attending STD and gynecology clinics in Jiangsu province, China. CT screening, surveillance and treatment promotion should therefore be of top priority on the CT prevention agenda.
The application value of contrast-enhanced computed tomography in cervical lymph node metastasis of oral carcinomas
Authors: Zhang Hao , Yang Shou-Kang , Jiang Xiao-Wen , Deng Guo-Lei , Li Kun-Qin , Long Yu-Fang
Published: November 2021

Background:

Oral carcinomas is a concerning condition around the world. Globally, it is the 11th most common form of cancer. Over 90% of oral carcinomas are squamous cell carcinomas. Smoking, tobacco intake, smokeless tobacco (snuff or chewing tobacco), excessive sunlight exposure, alcohol, betel nut consumption, human papillomavirus, and reverse end smoking are the most common causes of oral carcinomas. Oral carcinomas are prone to neck lymph mode metastasis, which has an impact on the prognosis of patients and the five-year survival rate. Thus, precise lymph node metastasis and staging of oral carcinomas are critical. With the development of nuclear medicine and molecular imaging, an increasing number of studies have found that Contrast-Enhanced Computed Tomography (CECT) has high diagnostic value for tumors.

Methods and analyses:

The reviewers will conduct a thorough search for related literature in 6 online databases, including The Cochrane Library, PubMed, WanFang database, Web of Science, Chinese biomedical literature database, and the China National Knowledge Infrastructure. The authors will obtain full text of studies deemed to be eligible to extract and synthesize data. The present systematic review will be reported in accordance with the Preferred Reporting Project (PRISMA-P) of the 2015 System Review and Meta-Analysis Protocol.

Results:

The present systematic analysis will pool the results of individual studies to assess the value of CECT in cervical lymph node metastasis of oral carcinomas.

Conclusion:

The results in the proposed research will determine whether CECT is an efficient diagnostic method for cervical lymph node metastasis of oral carcinomas.

Ethics and dissemination:

This study will utilize secondary data from pre-published studies. Therefore, an ethical clearance is not required. The research outcomes shall be disseminated in conference reports and peer-reviewed publications.

OSF registration number:

Oct 13, 2021.osf.io/k5nr9. (https://osf.io/k5nr9/).
Efficacy of acupuncture combined with traditional Chinese medicine on chronic prostatitis
Authors: Zheng Xianglong , Yan Zhangren , Wang Wanchun , Mao Wenli , Wang Yuhan , Zhao Yanling , Zhong Zhiying
Published: November 2021

Background:

Chronic prostatitis is a common andrological disease, which brings many troubles to the lives of middle-aged and elderly male patients. With the increase of modern life pressure, the incidence of chronic prostatitis tends to younger, but its etiology and pathogenesis are not fully elucidated. Which seriously affects men's health? Relevant studies have shown that acupuncture combined with traditional Chinese medicine (TCM) has a good effect on the treatment of chronic prostatitis compared with conventional western medicine; however, there is no consistent conclusion at present. The main purpose of this study is to explore whether acupuncture combined with TCM is effective in treating chronic prostatitis.

Methods:

The collection of randomized controlled trials related to acupuncture and TCM for chronic prostatitis will search the following electronic databases, including: PubMed, Web of Science, the Cochrane Database, EMBASE, Chinese National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Weipu. There are 8 electronic databases including the VIP Chinese Science and Technology Periodical Database and the China Biomedical Literature Database. The cure rate and total effective rate are the main indicators, and the recurrence rate and adverse events are the secondary indicators. Meta-analysis using RevMan5.4 provided by Cochrane Collaboration.

Results:

This study will provide the latest evidence of efficacy for the acupuncture combined with TCM in the treatment of chronic prostatitis.

Conclusion:

The effectiveness of acupuncture combined with TCM for chronic prostatitis will be evaluated.

Unique INPLASY number:

INPLASY202130083.
Glucose tolerance in fibromyalgia
Authors: Zetterman Teemu , Markkula Ritva , Kalso Eija
Published: November 2021

Objectives:

Fibromyalgia (FM) patients have an increased risk for glucose metabolism disturbances, and impaired glucose tolerance may be associated with symptom severity. Elevated levels of plasma lactate have been detected in FM patients. Both pyruvate and lactate are produced in glucose metabolism and reflect oxidative metabolism. The objective of our study was to analyse disturbances in glucose, pyruvate, or lactate metabolism in FM patients.

Methods:

We measured plasma levels of glucose, pyruvate, and lactate during an oral glucose tolerance test in 40 non-diabetic, female FM patients and 30 age- and gender-matched healthy controls.

Results:

FM patients showed a higher glycaemic response to the glucose load at 1 hour (F [1,68] = 10.4, P = .006) and 2 hours (F [1,68] = 7.80, P = .02), and higher glucose area under the curve (13.8 [SD 2.92] vs 11.6 [SD 2.31], P < .01), than healthy controls. Group differences were explained by higher body mass index and percentage of smokers among the FM patients. Pyruvate and lactate levels were similar in both groups.

Discussion:

Impaired glucose regulation in FM patients is likely not due to FM itself, but to associated lifestyle factors. Our results highlight the importance of assessing the glucose regulation status and the lifestyle factors affecting glucose regulation in FM patients for prevention or early treatment of diabetes and associated complications.

Trial Registration:

ClinicalTrials.gov (NCT03300635)
Health care costs associated with clinic visits for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania
Authors: Naburi Helga Elineema , Mujinja Phares , Kilewo Charles , Biberfeld Gunnel , Bärnighausen Till , Manji Karim , Lyatuu Goodluck , Urrio Roseline , Zethraeus Niklas , Orsini Nicola , Ekström Anna Mia
Published: November 2021

Early and appropriate antenatal care (ANC) is key for the effectiveness of prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We evaluated the importance of ANC visits and related service costs for women receiving option B+ to prevent mother-to-child transmission (MTCT) of HIV in Tanzania.

A cost analysis from a health care sector perspective was conducted using routine data of 2224 pregnant women newly diagnosed with HIV who gave birth between August 2014 and May 2016 in Dar es Salaam, Tanzania. We evaluated risk of infant HIV infection at 12 weeks postnatally in relation to ANC visits (<4 vs ≥4 visits). Costs for service utilisation were estimated through empirical observations and the World Health Organisation Global Price Reporting Mechanism.

Mean gestational age at first ANC visit was 22 (±7) weeks. The average number of ANC/prevention of MTCT visits among the 2224 pregnant women in our sample was 3.6 (95% confidence interval [CI] 3.6–3.7), and 57.3% made ≥4 visits. At 12 weeks postnatally, 2.7% (95% CI 2.2–3.6) of HIV exposed infants had been infected. The risk of MTCT decreased with the number of ANC visits: 4.8% (95% CI 3.6–6.4) if the mother had <4 visits, and 1.0% (95% CI 0.5–1.7) at ≥4. The adjusted MTCT rates decreased by 51% (odds ratio 0.49, 95% CI 0.31–0.77) for each additional ANC visit made. The potential cost-saving was 2.2 US$ per woman at ≥4 visits (84.8 US$) compared to <4 visits (87.0 US$), mainly due to less defaulter tracing.

Most pregnant women living with HIV in Dar es Salaam initiated ANC late and >40% failed to adhere to the recommended minimum of 4 visits. Improved ANC attendance would likely lead to fewer HIV-infected infants and reduce both short and long-term health care costs due to less spending on defaulter tracing and future treatment costs for the children.