bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of phenotypic and WGS drug susceptibility testing in Mycobacterium tuberculosis isolates from the Republic of Korea
Authors: Lee Seung Heon , Ferran Elena , Witney Adam A , Ryu Sungweon , Kang Hyungseok , Storey Nathaniel , McHugh Timothy D , Satta Giovanni
Published: May 2023

Background

WGS has significant potential to help tackle the major public health problem of TB. The Republic of Korea has the third highest rates of TB of all Organisation for Economic Cooperation and Development countries but there has been very limited use of WGS in TB to date.

Objectives

A retrospective comparison of Mycobacterium tuberculosis (MTB) clinical isolates from 2015 to 2017 from two centres in the Republic of Korea using WGS to compare phenotypic drug susceptibility testing (pDST) and WGS drug susceptibility predictions (WGS-DSP).

Methods

Fifty-seven MTB isolates had DNA extracted and were sequenced using the Illumina HiSeq platform. The WGS analysis was performed using bwa mem, bcftools and IQ-Tree; resistance markers were identified using TB profiler. Phenotypic susceptibilities were carried out at the Supranational TB reference laboratory (Korean Institute of Tuberculosis).

Results

For first-line antituberculous drugs concordance for rifampicin, isoniazid, pyrazinamide and ethambutol was 98.25%, 92.98%, 87.72% and 85.96%, respectively. The sensitivity of WGS-DSP compared with pDST for rifampicin, isoniazid, pyrazinamide and ethambutol was 97.30%, 92.11%, 78.95% and 95.65%, respectively. The specificity for these first-line antituberculous drugs was 100%, 94.74%, 92.11% and 79.41%, respectively. The sensitivity and specificity for second-line drugs ranged from 66.67% to 100%, and from 82.98% to 100%, respectively.

Conclusions

This study confirms the potential role for WGS in drug susceptibility prediction, which would reduce turnaround times. However, further larger studies are needed to ensure current databases of drug resistance mutations are reflective of the TB present in the Republic of Korea.
Role of non-coding RNAs in tuberculosis and their potential for clinical applications
Authors: Jumat Mohd Iskandar , Sarmiento Maria E , Acosta Armando , Chin Kai Ling
Published: May 2023

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of mortality due to infectious diseases, only surpassed in 2020 by COVID-19. Despite the development in diagnostics, therapeutics, and evaluation of new vaccines for TB, this infectious disease remains uncontrollable due to the emergence of multidrug-resistant (MDR) and extremely drug-resistant (XDR) TB, among other factors. The development in transcriptomics (RNomics) has enabled the study of gene expression in TB. It is considered that non-coding RNAs (ncRNAs) from host [microRNAs (miRNAs)] and Mtb [small RNAs (sRNAs)] are important elements in TB pathogenesis, immune resistance, and susceptibility. Many studies have shown the importance of host miRNAs in regulating immune response against Mtb via in vitro and in vivo mice models. The bacterial sRNAs play a major role in survival, adaptation, and virulence. Here, we review the characterization and function of host and bacteria ncRNAs in TB and their potential use in clinical applications as diagnostic, prognostic, and therapeutic biomarkers.
Developing and validating a natural language processing algorithm to extract preoperative cannabis use status documentation from unstructured narrative clinical notes
Authors: Sajdeya Ruba , Mardini Mamoun T , Tighe Patrick J , Ison Ronald L , Bai Chen , Jugl Sebastian , Hanzhi Gao , Zandbiglari Kimia , Adiba Farzana I , Winterstein Almut G , Pearson Thomas A , Cook Robert L , Rouhizadeh Masoud
Published: May 2023

Objective

This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) techniques to identify and classify documentation of preoperative cannabis use status.

Materials and Methods

We developed and applied a keyword search strategy to identify documentation of preoperative cannabis use status in clinical documentation within 60 days of surgery. We manually reviewed matching notes to classify each documentation into 8 different categories based on context, time, and certainty of cannabis use documentation. We applied 2 conventional ML and 3 deep learning models against manual annotation. We externally validated our model using the MIMIC-III dataset.

Results

The tested classifiers achieved classification results close to human performance with up to 93% and 94% precision and 95% recall of preoperative cannabis use status documentation. External validation showed consistent results with up to 94% precision and recall.

Discussion

Our NLP model successfully replicated human annotation of preoperative cannabis use documentation, providing a baseline framework for identifying and classifying documentation of cannabis use. We add to NLP methods applied in healthcare for clinical concept extraction and classification, mainly concerning social determinants of health and substance use. Our systematically developed lexicon provides a comprehensive knowledge-based resource covering a wide range of cannabis-related concepts for future NLP applications.

Conclusion

We demonstrated that documentation of preoperative cannabis use status could be accurately identified using an NLP algorithm. This approach can be employed to identify comparison groups based on cannabis exposure for growing research efforts aiming to guide cannabis-related clinical practices and policies.
Reducing False Negatives in Biopsy of Suspicious MRI Findings
Authors: Wang Lilian C , Rao Sandra , Schacht David , Bhole Sonya
Published: May 2023

Breast MRI is a highly sensitive imaging modality that often detects findings that are occult on mammography and US. Given the overlap in appearance of benign and malignant lesions, an accurate method of tissue sampling for MRI-detected findings is essential. Although MRI-directed US and correlation with mammography can be helpful for some lesions, a correlate is not always found. MRI-guided biopsy is a safe and effective method of tissue sampling for findings seen only on MRI. The unique limitations of this technique, however, contribute to false negatives, which can result in delays in diagnosis and adverse patient outcomes; this is of particular importance as most MRI examinations are performed in the high-risk or preoperative setting. Here, we review strategies to minimize false negatives in biopsy of suspicious MRI findings, including appropriate selection of biopsy modality, use of meticulous MRI-guided biopsy technique, management after target nonvisualization, assessment of adequate lesion sampling, and determination of radiology-pathology concordance. A proposed management algorithm for MRI-guided biopsy results will also be discussed.
Probe-based quantitative PCR and RPA-Cas12a molecular diagnostics for detection of the tomato pest Phthorimaea absoluta (Lepidoptera: Gelechiidae)
Authors: Lewald Kyle M , Song Wenqi , Eweis-LaBolle Daniel , Truong Cindy , Godfrey Kristine E , Chiu Joanna C
Published: May 2023

The tomato pest Phthorimaea absoluta Meyrick is highly invasive but has not yet invaded North America. However, several morphologically similar species are already present, making detection of P. absoluta presence and invasion challenging. We designed a quantitative PCR molecular diagnostic to differentiate P. absoluta, P. operculella (Zeller), or Keiferia lycopersicella (Walsingham) (Lepidoptera: Gelechiidae) DNA. Additionally, we developed an RPA-Cas12a molecular diagnostic that allows for the isothermal detection of P. absoluta DNA, eliminating the need for a thermocycler. The results of the RPA-Cas12a diagnostic can be visualized simply using a UV light source and cell phone camera. We expect these diagnostics to improve quarantine and prevention measures against this serious agricultural threat.
Removing neonicotinoid seed treatments has negligible effects on refuge function and crop protection in transgenic maize targeting western corn rootworm (Coleoptera: Chrysomelidae)
Authors: Bekelja Kyle M , Miller Kathleen M , Kuhar Thomas P , Krupke Christian H , Taylor Sally V
Published: May 2023

Nearly all maize seed sold in the United States includes a neonicotinoid seed treatment (NST), meant to protect seedlings against early-season insect pests. For key pests, including western corn rootworm (Diabrotica virgifera virgifera LeConte) (D.v.v), insecticidal proteins derived from Bacillus thuringiensis (Bt) are expressed in plant tissues as alternatives to soil-applied insecticides. Insect resistance management (IRM) plans use non-Bt “refuges” to encourage survival of Bt-susceptible D.v.v., which maintains susceptible alleles in the population. In non-cotton producing regions, IRM guidelines require a minimum 5% blended refuge for maize expressing more than 1 trait targeting D.v.v. Prior work has shown that 5% blends yield insufficient proportions of refuge beetles to contribute reliably to IRM. Whether NSTs interfere with survivorship of refuge beetles is unknown. Our objective was to determine whether NSTs affect proportions of refuge beetles, and secondarily, to determine whether NSTs provide agronomic advantages over Bt seed alone. To reveal host plant type (i.e., Bt or refuge), we used a stable isotope (15N) to mark refuge plants in plots with 5% seed blends. To assess refuge performance between treatments, we compared proportions of beetles from respective natal hosts. In all site-years, NSTs showed inconsistent effects on proportions of refuge beetles. Treatment comparisons showed inconsistent agronomic benefits of NSTs when combined with Bt traits. Our results demonstrate that NSTs have a negligible impact on refuge performance and reinforces the assertion that 5% blends are serving little benefit for IRM. Plant stand and yield were not improved by NSTs.
The Blessed Tree in the works of Ibn Barrajān of Seville (d. 536/1141)
Authors: Jaffe Sam , Casewit Yousef
Published: May 2023

In his commentary on the Light Verse (Q. 24:35), the Andalusian mystic and Qurʾān exegete Abū al-Ḥakam Ibn Barrajān (d. 1141) presents the blessed tree (al-shajara al-mubāraka) not simply as a terrestrial olive tree in Syria or even as a mystical allegory, but as the ultimate locus of divine disclosure and the highest metaphysical entity in the cosmos that subsumes the world of creation. This article assesses the originality of Ibn Barrajān’s contribution to the heavenly tree motif by examining his unique mystical and exegetical theories informing his ontological reading of the blessed tree, including the concept of the ‘reality upon which creation is created’ and the ‘universal servant’. In addition to analysing the internal logic of Ibn Barrajān’s discourse, this article explores the larger interpretive themes recurrent across exoteric, Sufi, and philosophical interpretations of the Light Verse up to the twelfth century that the author may have had access to in al-Andalus, including the treatises of the Brethren of Purity (Ikhwān al-ṣafā) and Biblical sources. Finally, this article highlights how Ibn Barrajān weaves the Qurʾānic good tree (al-shajara al-ṭayyiba) and the lote tree of the furthest boundary (sidrat al-muntahā) into his overarching understanding of the blessed tree. It also considers how his reading may have contributed to later readings by Ibn ʿArabī (d. 1240) and some of his intellectual heirs.
Patchouli alcohol against renal fibrosis of spontaneously hypertensive rats via Ras/Raf-1/ERK1/2 signalling pathway
Authors: Li Jing , Hu Guanying , Liu Wenxiu , Cao Xiaoyu , Chen Guanru , Peng Fu , Xiaofang Xie , Peng Cheng
Published: May 2023

Objectives

The present study was designed to obverse the protection of patchouli alcohol (PA) ameliorates hypertensive nephropathy in spontaneously hypertensive rats (SHR) and reveals potential mechanism.

Methods

Briefly, the adult spontaneously hypertensive rats (SHR) or Wistar–Kyoto (WKY) rats (half male and half female) were intragastric gavaged or not with PA (80, 40 and 20 mg/kg) for 8 weeks. Body weight, blood pressure (BP), renal weight, renal function and renal morphology were measured. Further, western blotting and immunohistochemical analysis were used to study the underlying mechanism.

Key findings

Compared with the WKY group, plasmatic levels of renin, angiotensin II (Ang-II), transforming growth factor beta 1(TGF-β1), plasminogen activator inhibitor-1(PAI-1), creatinine (Cr), blood urea nitrogen (BUN), renal index, mRNA levels of ERK1/2 and α-SMA were significantly increased in SHR. Histology results showed that renal tubular injury and tubulointerstitial fibrosis occurred in SHR. After administration, SBP of captopril group decreased at each week after administration, especially at 3, 5, 6 7 and 8 weeks (P < 0.05 or P < 0.01). There is no significant effect was assessed in the olive oil group. Decreased plasma Cr, Renin, Ang-II, TGF-β1, PAI-1, SCFAs and Renin, TGF-β1, PAI-1 in renal tissues were observed significantly in captopril (P <0.05 or P < 0.01). Plasma BUN, Ang-II, TGF-β1 and PAI-1 in renal tissues decreased in the olive oil group significantly (P <0.05 or P < 0.01). PA (80, 40 and 20 mg/kg) lowered BP and plasmatic levels of Renin, Ang-II, TGF-β1 and PAI-1. Treatment with PA (40, 20 mg/kg) decreased levels of Cr, BUN and suppressed of activation of pro-fibrosis cytokines including TGF-β1 in kidney. There is no ameliorative change in the olive oil group and the captopril group (P > 0.05) while PA treatment alleviated renal tubular injury and produced dramatic collagen fibre area reductions in mesangial membrane, basement membrane, and renal interstitium obviously (P < 0.05 or P < 0.01). Treatment of SHR with PA-inhibited MFB activation and downregulated mRNA of α-SMA. Treatment with PA suppressed excessive production of the extracellular matrix (ECM) via decreasing Col I, III and FN, downregulating mRNA of tissue inhibitor of TIMP-1 along with upregulating mRNA of MMP-9. The expression of Col III and MMP-9 mRNA-reduced in the captopril group (P < 0.05). In addition, the expression of ERK1/2 and pERK1/2 also reduced in the captopril group significantly (P < 0.05 or P < 0.01). Treatment with PA (20 mg/kg) downregulated proteins expression of Raf-1, ERK1/2 and pERK1/2 and mRNA expression of Ras, Raf-1 and ERK1/2.

Conclusions

Overall, PA restored normal BP, alleviated renal dysfunction and renal fibrosis, possibly by suppressing Ang II and TGF-β1-mediated Ras/Raf-1/ERK1/2 signalling pathway.
Milky pericardial effusion causing tamponade in a neonate after extracorporeal membrane oxygenation cannulation
Authors: Thornhill Rosanne , Fortuna Randall , Canteras Kayla , Raymond Steven L , Khan Faraz A , Radulescu Andrei
Published: May 2023

Cardiac tamponade is a known life-threatening complication of extracorporeal membrane oxygenation (ECMO), often secondary to hemopericardium from major vascular or cardiac perforation. We present the unique case of a neonate with a milky pericardial effusion causing tamponade after ECMO cannulation, managed successfully with pericardial window. Understanding ECMO physiology and its effect on the classic presentation of tamponade is critical and can prevent delays in diagnosis. While hemopericardium is most commonly seen in these cases, findings of a non-bloody, milky effusion should prompt further workup for infection, chylopericardium or total parenteral nutrition-associated pericardial effusion, as the appropriate management can mitigate immediate and potential long-term sequelae.
‘Meeting Together in an Equal and Friendly Manner’: The Workplace Literary Culture of Lancashire Mutual Improvement Societies
Authors: Weiss Lauren
Published: May 2023

This article traces the progress of mutual improvement in the coalfields around Aspull beginning in the 1870s and culminating with the opening of the Garswood Hall Collieries Institute in 1893. It analyses this process in relation to Patrick Joyce’s account of the development of industrial paternalism in Lancashire. It shows how mutual improvement societies were formed primarily on the initiative of individual workers, with some assistance from local religious groups, rather than being employer-led. It also demonstrates how the Aspull Society acted as the starting point for a network of similar societies across the local area. By tracing the careers of a number of individuals closely associated with mutual improvement societies, this article shows that such societies did enable occupational and social mobility, thereby demonstrating the virtues of self-help to workers and employers alike. Next, the article traces the factors which led to the opening of the Garswood Hall Collieries Institute and argues that the formation of the Institute exemplifies the delicate social choreography on which the successful practice of paternalism in an industrial context depended. It demonstrates that local autonomous activity on the part of individual miners was combined with the use of local newspapers and delegations to employers to create the conditions for an appropriate paternalist response in the form of the ‘gift’ of the Institute to the community. The Institute thus became a demonstration of the employers’ fitness to exercise local leadership and a symbol of education as a means of achieving class harmony within the existing social hierarchy. It concludes by observing that in the case of the Garswood Hall Collieries Institute the vision of class harmony which it offered its members nonetheless remained vulnerable to the economic realities of the relationship between capital and labour.
A blue depression in the optical spectra of M dwarfs
Authors: Jones Hugh R A , Pavlenko Yakiv , Lyubchik Yuri , Bessell Mike , Allard Nicole , Pinfield David J
Published: May 2023

A blue depression is found in the spectra of M dwarfs from 4000 to 4500 Å. This depression shows an increase towards lower temperatures, though it is particularly sensitive to gravity and metallicity. It is the single strongest and most sensitive feature in the optical spectra of M dwarfs. The depression appears as centred on the neutral calcium resonance line at 4227 Å and leads to nearby features being weaker by about two orders of magnitude than predicted. We consider a variety of possible causes for the depression, including temperature, gravity, metallicity, dust, damping constants, and atmospheric stratification. We also consider relevant molecular opacities that might be the cause identifying AlH, SiH, and NaH in the spectral region. However, none of these solutions are satisfactory. In the absence of a more accurate determination of the broadening of the calcium line perturbed by molecular hydrogen, we find a promising empirical fit using a modified Lorentzian line profile for the calcium resonance line. Such fits provide a simplistic line-broadening description for this calcium resonance line and potentially other unmodelled resonance lines in cool high-pressure atmospheres. Thus, we claim that the most plausible cause of the blue depression in the optical spectra of M dwarfs is a lack of appropriate treatment of line broadening for atomic calcium. The broad wings of the calcium resonance line develop at temperatures below about 4000 K and are analogous to the neutral sodium and potassium features, which dominate the red optical spectra of L dwarfs.
The dark side of FIRE: predicting the population of dark matter subhaloes around Milky Way-mass galaxies
Authors: Barry Megan , Wetzel Andrew , Chapman Sierra , Samuel Jenna , Sanderson Robyn , Arora Arpit
Published: May 2023

A variety of observational campaigns seek to test dark matter models by measuring dark matter subhaloes at low masses. Despite their predicted lack of stars, these subhaloes may be detectable through gravitational lensing or via their gravitational perturbations on stellar streams. To set measurable expectations for subhalo populations within Lambda cold dark matter, we examine 11 Milky Way (MW)-mass haloes from the FIRE-2 baryonic simulations, quantifying the counts and orbital fluxes for subhaloes with properties relevant to stellar stream interactions: masses down to $10^{6}\, \text{M}_\odot$, distances ≲50 kpc of the galactic centre, across z = 0 − 1 (tlookback = 0–8 Gyr). We provide fits to our results and their dependence on subhalo mass, distance, and lookback time, for use in (semi)analytical models. A typical MW-mass halo contains ≈16 subhaloes $\gt 10^{7}\, \text{M}_\odot$ (≈1 subhalo $\gt 10^{8}\, \text{M}_\odot$) within 50 kpc at z ≈ 0. We compare our results with dark matter-only versions of the same simulations: because they lack a central galaxy potential, they overpredict subhalo counts by 2–10×, more so at smaller distances. Subhalo counts around a given MW-mass galaxy declined over time, being ≈10× higher at z = 1 than at z ≈ 0. Subhaloes have nearly isotropic orbital velocity distributions at z ≈ 0. Across our simulations, we also identified 4 analogues of Large Magellanic Cloud satellite passages; these analogues enhance subhalo counts by 1.4–2.1 times, significantly increasing the expected subhalo population around the MW today. Our results imply an interaction rate of ∼5 per Gyr for a stream like GD-1, sufficient to make subhalo–stream interactions a promising method of measuring dark subhaloes.
Systematics in asteroseismic modelling: application of a correlated noise model for oscillation frequencies
Authors: Li Tanda , Davies Guy R , Nielsen Martin , Cunha Margarida S , Lyttle Alexander J
Published: May 2023

The detailed modelling of stellar oscillations is a powerful approach to characterizing stars. However, poor treatment of systematics in theoretical models leads to misinterpretations of stars. Here, we propose a more principled statistical treatment for the systematics to be applied to fitting individual mode frequencies with a typical stellar model grid. We introduce a correlated noise model based on a Gaussian process (GP) kernel to describe the systematics given that mode frequency systematics are expected to be highly correlated. We show that tuning the GP kernel can reproduce general features of frequency variations for changing model input physics and fundamental parameters. Fits with the correlated noise model better recover stellar parameters than traditional methods that either ignore the systematics or treat them as uncorrelated noise.
Multiwavelength variability of γ-ray emitting narrow-line Seyfert 1 galaxies
Authors: Yao Su , Komossa S
Published: May 2023

As one of the drivers of feedback in active galactic nuclei (AGNs), the jets launched from supermassive black holes (SMBHs) are important for understanding the co-evolution of SMBHs and their host galaxies. However, the formation of AGN jets is far from clear. The discovery of γ-ray narrow-line Seyfert 1 (NLS1) galaxies during the past two decades has provided us with a new means of studying the link between jets and accretion processes and the formation of jets. Here, we explore the coupling of jet and accretion discs in seven bright γ-ray NLS1 galaxies by studying simultaneous optical/ultraviolet and X-ray observations of these systems taken by Swift. The results show that, except for 1H 0323+342 in which the X-rays are significantly contributed from the accretion disc, the observed X-ray emission of the other sources is dominated by the jet, and accretion process makes little contribution if not absent. Although the origin of the X-ray emission is different, the broad-band spectral shape characterized by αox and the X-ray flux is found to follow the same evolutionary trend in 1H 0323+342, PMN J0948+0022, and PKS 1502+036. For the remaining sources, the trend is not observed or the sampling is not dense enough.
NGC 1436: the making of a lenticular galaxy in the Fornax Cluster
Authors: Loni Alessandro , Serra Paolo , Sarzi Marc , Józsa Gyula I G , Anta Pablo M Galán-de , Zabel Nikki , Kleiner Dane , Maccagni Filippo M , Molnár Daniel , Ramatsoku Mpati , Loi Francesca , Corsini Enrico M , Pisano D J , Kamphuis Peter , Davis Timothy A , de Blok W J G , Dettmar Ralf J , Falcon-Barroso Jesus , Iodice Enrichetta , Lara-López Maritza A , Loubser S Ilani , Morokuma-Matsui Kana , Peletier Reynier , Pinna Francesca , Poci Adriano , Smith Matthew W L , Trager Scott C , van de Ven Glenn
Published: May 2023

We study the evolutionary path of the Fornax Cluster galaxy NGC 1436, which is known to be currently transitioning from a spiral into a lenticular morphology. This galaxy hosts an inner star-forming disc and an outer quiescent disc, and we analyse data from the MeerKAT Fornax Survey, ALMA, and the Fornax 3D survey to study the interstellar medium and the stellar populations of both disc components. Thanks to the combination of high resolution and sensitivity of the MeerKAT data, we find that the H i is entirely confined within the inner star-forming disc, and that its kinematics is coincident with that of the CO. The cold gas disc is now well settled, which suggests that the galaxy has not been affected by any environmental interactions in the last ∼1 Gyr. The star-formation history derived from the Fornax 3D data shows that both the inner and outer discs experienced a burst of star formation ∼5 Gyr ago, followed by rapid quenching in the outer disc and by slow quenching in the inner disc, which continues forming stars to this day. We claim that NGC 1436 has begun to effectively interact with the cluster environment 5 Gyr ago, when a combination of gravitational and hydrodynamical interactions caused the temporary enhancement of the star-formation rate. Furthermore, due to the weaker gravitational binding H i was stripped from the outer disc, causing its rapid quenching. At the same time, accretion of gas onto the inner disc stopped, causing slow quenching in this region.
A test of invariance of dark matter halo surface density using multiwavelength mock galaxy catalogues
Authors: Gopika K , Desai Shantanu , Paranjape Aseem
Published: May 2023

A large number of observations have shown that the dark matter halo surface density, given by the product of halo core radius and core density, is nearly constant for a diverse suite of galaxies. Although this invariance of the halo surface density is violated at galaxy cluster and group scales, it is still an open question on whether the aforementioned constancy on galactic scales can be explained within Lambda cold dark matter (ΛCDM). For this purpose, we probe the variation of halo surface density as a function of mass using multiwavelength mock galaxy catalogues from ΛCDM simulations, where the adiabatic contraction of dark matter haloes in the presence of baryons has been taken into account. We find that these baryonified ΛCDM haloes were best fitted with a generalized Navarro–Frenk–White profile, and the halo surface density from these haloes has a degeneracy with respect to both the halo mass and the virial concentration. We find that the correlation with mass when averaged over concentration is consistent with a constant halo surface density. However, a power-law dependence as a function of halo mass also cannot be ruled out.
Imprint of magnetic obliquity in apparent spin-down of radio pulsars
Authors: Biryukov Anton , Beskin Gregory
Published: May 2023

Numerical simulations predict that the spin-down rate of a single rotation-powered neutron star depends on the angle α between its spin and magnetic axes as $P\dot{P} \propto \mu ^2 (k_0 + k_1\sin ^2\alpha)$, where P is the star spin period, μ is its magnetic moment, while k0 ∼ k1 ∼ 1. Here, we describe a simple observational test for this prediction based on the comparison of spin-down rates of 50 nearly orthogonal (with α close to 90 deg) and 27 nearly aligned (with α close to 0 deg) pulsars. We found, that the apparent pulsar spin-down is consistent with the theory if assumed, that magnetic moments of orthogonal rotators are systematically larger than those of aligned ones for ∼0.15...0.2 dex. Also, as a by-product of the analysis, we provide yet another constraint on the average braking index of radio pulsars as 1 ≤ n ≤ 4 with formal significance not worse than 99 per cent.
DMPP-3: confirmation of short-period S-type planet(s) in a compact eccentric binary star system, and warnings about long-period RV planet detections
Authors: Stevenson Adam T , Haswell Carole A , Barnes John R , Barstow Joanna K , Ross Zachary O B
Published: May 2023

We present additional HARPS radial velocity observations of the highly eccentric (e ∼ 0.6) binary system DMPP-3AB, which comprises a K0V primary and a low-mass companion at the hydrogen burning limit. The binary has a 507 d orbital period and a 1.2 au semimajor axis. The primary component harbours a known 2.2 M⊕ planet, DMPP-3A b, with a 6.67-d orbit. New HARPS measurements constrain periastron passage for the binary orbit and add further integrity to previously derived solutions for both companion and planet orbits. Gaia astrometry independently confirms the binary orbit and establishes the inclination of the binary is 63.89 ± 0.78°. We performed dynamical simulations that establish that the previously identified ∼800 d RV signal cannot be attributed to an orbiting body. The additional observations, a deviation from strict periodicity, and our new analyses of activity indicators suggest the ∼800 d signal is caused by stellar activity. We conclude that there may be long-period planet ‘detections’ in other systems, which are similar misinterpreted stellar activity artefacts. Without the unusual eccentric binary companion to the planet-hosting star, we could have accepted the ∼800 d signal as a probable planet. Further monitoring of DMPP-3 will reveal which signatures can be used to most efficiently identify these imposters. We also report a threshold detection (0.2 per cent FAP) of a ∼2.26 d periodicity in the RVs, potentially attributed to an Earth-mass S-type planet interior to DMPP-3A b.
One EURO for Uranus: the Elliptical Uranian Relativity Orbiter mission
Authors: Iorio Lorenzo , Girija Athul Pradeepkumar , Durante Daniele
Published: May 2023

Recent years have seen increasing interest in sending a mission to Uranus, visited so far only by Voyager 2 in 1986. Elliptical Uranian Relativity Orbiter is a preliminary mission concept investigating the possibility of dynamically measuring the planet’s angular momentum by means of the Lense–Thirring effect affecting a putative Uranian orbiter. It is possible, at least in principle, to separate the relativistic precessions of the orbital inclination to the celestial equator and of the longitude of the ascending node of the spacecraft from its classical rates of the pericentre induced by the multipoles of the planet’s gravity field by adopting an appropriate orbital configuration. For a wide and elliptical $2000\times 100\, 000\, \mathrm{km}$ orbit, the gravitomagnetic signatures amount to tens of milliarcseconds per year, while, for a suitable choice of the initial conditions, the peak-to-peak amplitude of the range-rate shift can reach the level of ≃ 1.5 × 10−3 mm s−1 in a single pericentre passage of a few hours. By lowering the apocentre height to $10\, 000\, \mathrm{km}$, the Lense–Thirring precessions are enhanced to the level of hundreds of milliarcseconds per year. The uncertainties in the orientation of the planetary spin axis and in the inclination are major sources of systematic bias; it turns out that they should be determined with accuracies as good as ≃0.1–1 and ≃1–10 mas, respectively.
Discovery of double Hall pattern associated with collisionless magnetic reconnection in dusty plasmas
Authors: Yang Shu-Di , Wang Liang , Dong Chuanfei
Published: May 2023

Magnetic reconnection is prevalent in magnetized plasmas in space and laboratories. Despite significant investigations on reconnection in electron–ion plasmas, studies of reconnection in magnetized plasmas with negatively charged dust grains are quite sparse. Here, we report the first fully kinetic simulations of collisionless reconnection in a three-species (i.e. electron, proton, and negatively charged dust grain) dusty plasma, through which the discovery of double Hall pattern is made. The double Hall pattern consists of a traditional Hall quadruple current in between the ion and electron diffusion region and a reversed Hall current in between the boundary of the ion and dust diffusion region. The analysis of the reconnection rate is also given. This study may be applicable to explain observations of planetary magnetospheres and the astrophysical objects, and may be realized in the laboratory studies of dusty plasmas.
Non-parametric reconstruction of photon escape fraction from reionization
Authors: Mitra Sourav , Chatterjee Atrideb
Published: May 2023

One of the most crucial yet poorly constrained parameters in modelling the ionizing emissivity is the escape fraction of photons from star-forming galaxies. Several theoretical and observational studies have been conducted over the past few years, but consensus regarding its redshift evolution has yet to be achieved. We present here the first non-parametric reconstruction of this parameter as a function of redshift from a data-driven reionization model using a Gaussian Process Regression method. Our finding suggests a mild redshift evolution of escape fraction with a mean value of $4~{{\ \rm per\ cent}},7~{{\ \rm per\ cent}},\sim 10~{{\ \rm per\ cent}}$ at $z$ = 2, 6, 12. However, a constant escape fraction of $6-10~{{\ \rm per\ cent}}$ at $z$ ≳ 6 is still allowed by current data and also matches other reionization-related observations. With the detection of fainter high-redshift galaxies from upcoming observations of JWST, the approach presented here will be a robust tool to put the most stringent constraint on escape fraction as well as reionization histories.
DNA binding specificity of all four Saccharomyces cerevisiae forkhead transcription factors
Authors: Cooper Brendon H , Dantas Machado Ana Carolina , Gan Yan , Aparicio Oscar M , Rohs Remo
Published: May 2023

Quantifying the nucleotide preferences of DNA binding proteins is essential to understanding how transcription factors (TFs) interact with their targets in the genome. High-throughput in vitro binding assays have been used to identify the inherent DNA binding preferences of TFs in a controlled environment isolated from confounding factors such as genome accessibility, DNA methylation, and TF binding cooperativity. Unfortunately, many of the most common approaches for measuring binding preferences are not sensitive enough for the study of moderate-to-low affinity binding sites, and are unable to detect small-scale differences between closely related homologs. The Forkhead box (FOX) family of TFs is known to play a crucial role in regulating a variety of key processes from proliferation and development to tumor suppression and aging. By using the high-sequencing depth SELEX-seq approach to study all four FOX homologs in Saccharomyces cerevisiae, we have been able to precisely quantify the contribution and importance of nucleotide positions all along an extended binding site. Essential to this process was the alignment of our SELEX-seq reads to a set of candidate core sequences determined using a recently developed tool for the alignment of enriched k-mers and a newly developed approach for the reprioritization of candidate cores.
Hi-TrAC detects active sub-TADs and reveals internal organizations of super-enhancers
Authors: Cao Yaqiang , Liu Shuai , Cui Kairong , Tang Qingsong , Zhao Keji
Published: May 2023

The spatial folding of eukaryotic genome plays a key role in genome function. We report here that our recently developed method, Hi-TrAC, which specializes in detecting chromatin loops among accessible genomic regions, can detect active sub-TADs with a median size of 100 kb, most of which harbor one or two cell specifically expressed genes and regulatory elements such as super-enhancers organized into nested interaction domains. These active sub-TADs are characterized by highly enriched histone mark H3K4me1 and chromatin-binding proteins, including Cohesin complex. Deletion of selected sub-TAD boundaries have different impacts, such as decreased chromatin interaction and gene expression within the sub-TADs or compromised insulation between the sub-TADs, depending on the specific chromatin environment. We show that knocking down core subunit of the Cohesin complex using shRNAs in human cells or decreasing the H3K4me1 modification by deleting the H3K4 methyltransferase Mll4 gene in mouse Th17 cells disrupted the sub-TADs structure. Our data also suggest that super-enhancers exist as an equilibrium globule structure, while inaccessible chromatin regions exist as a fractal globule structure. In summary, Hi-TrAC serves as a highly sensitive and inexpensive approach to study dynamic changes of active sub-TADs, providing more explicit insights into delicate genome structures and functions.
Breeze 2.0: an interactive web-tool for visual analysis and comparison of drug response data
Authors: Potdar Swapnil , Ianevski Filipp , Ianevski Aleksandr , Tanoli Ziaurrehman , Wennerberg Krister , Seashore-Ludlow Brinton , Kallioniemi Olli , Östling Päivi , Aittokallio Tero , Saarela Jani
Published: May 2023

Functional precision medicine (fPM) offers an exciting, simplified approach to finding the right applications for existing molecules and enhancing therapeutic potential. Integrative and robust tools ensuring high accuracy and reliability of the results are critical. In response to this need, we previously developed Breeze, a drug screening data analysis pipeline, designed to facilitate quality control, dose-response curve fitting, and data visualization in a user-friendly manner. Here, we describe the latest version of Breeze (release 2.0), which implements an array of advanced data exploration capabilities, providing users with comprehensive post-analysis and interactive visualization options that are essential for minimizing false positive/negative outcomes and ensuring accurate interpretation of drug sensitivity and resistance data. The Breeze 2.0 web-tool also enables integrative analysis and cross-comparison of user-uploaded data with publicly available drug response datasets. The updated version incorporates new drug quantification metrics, supports analysis of both multi-dose and single-dose drug screening data and introduces a redesigned, intuitive user interface. With these enhancements, Breeze 2.0 is anticipated to substantially broaden its potential applications in diverse domains of fPM.
miEAA 2023: updates, new functional microRNA sets and improved enrichment visualizations
Authors: Aparicio-Puerta Ernesto , Hirsch Pascal , Schmartz Georges P , Kern Fabian , Fehlmann Tobias , Keller Andreas
Published: May 2023

MicroRNAs (miRNAs) are small non-coding RNAs that play a critical role in regulating diverse biological processes. Extracting functional insights from a list of miRNAs is challenging, as each miRNA can potentially interact with hundreds of genes. To address this challenge, we developed miEAA, a flexible and comprehensive miRNA enrichment analysis tool based on direct and indirect miRNA annotation. The latest release of miEAA includes a data warehouse of 19 miRNA repositories, covering 10 different organisms and 139 399 functional categories. We have added information on the cellular context of miRNAs, isomiRs, and high-confidence miRNAs to improve the accuracy of the results. We have also improved the representation of aggregated results, including interactive Upset plots to aid users in understanding the interaction among enriched terms or categories. Finally, we demonstrate the functionality of miEAA in the context of ageing and highlight the importance of carefully considering the miRNA input list. MiEAA is free to use and publicly available at https://www.ccb.uni-saarland.de/mieaa/.
Histone chaperone Nap1 dismantles an H2A/H2B dimer from a partially unwrapped nucleosome
Authors: Nagae Fritz , Takada Shoji , Terakawa Tsuyoshi
Published: May 2023

DNA translocases, such as RNA polymerases, inevitably collide with nucleosomes on eukaryotic chromatin. Upon these collisions, histone chaperones are suggested to facilitate nucleosome disassembly and re-assembly. In this study, by performing in vitro transcription assays and molecular simulations, we found that partial unwrapping of a nucleosome by an RNA polymerase dramatically facilitates an H2A/H2B dimer dismantling from the nucleosome by Nucleosome Assembly Protein 1 (Nap1). Furthermore, the results uncovered molecular mechanisms of Nap1 functions in which the highly acidic C-terminal flexible tails of Nap1 contribute to the H2A/H2B binding by associating with the binding interface buried and not accessible to Nap1 globular domains, supporting the penetrating fuzzy binding mechanism seemingly shared across various histone chaperones. These findings have broad implications for the mechanisms by which histone chaperones process nucleosomes upon collisions with translocases in transcription, histone recycling and nucleosomal DNA repair.
MBROLE3: improved functional enrichment of chemical compounds for metabolomics data analysis
Authors: Lopez-Ibañez Javier , Pazos Florencio , Chagoyen Monica
Published: May 2023

MBROLE (Metabolites Biological Role) facilitates the biological interpretation of metabolomics experiments. It performs enrichment analysis of a set of chemical compounds through statistical analysis of annotations from several databases. The original MBROLE server was released in 2011 and, since then, different groups worldwide have used it to analyze metabolomics experiments from a variety of organisms. Here we present the latest version of the system, MBROLE3, accessible at http://csbg.cnb.csic.es/mbrole3. This new version contains updated annotations from previously included databases as well as a wide variety of new functional annotations, such as additional pathway databases and Gene Ontology terms. Of special relevance is the inclusion of a new category of annotations, ‘indirect annotations’, extracted from the scientific literature and from curated chemical-protein associations. The latter allows to analyze enriched annotations of the proteins known to interact with the set of chemical compounds of interest. Results are provided in the form of interactive tables, formatted data to download, and graphical plots.
Early-life undernutrition and depression later in life: a systematic review
Authors: de Souza Julliet Araújo , Pinto Flaydson Clayton Silva , de Souza Sandra Lopes
Published: May 2023

Context

Early adverse experience can have a long-term effect on growth and development and negative repercussions into adulthood. Among the various consequences of undernutrition is depression.

Objective

The present work aimed to evaluate the relationship between early-life undernutrition and depression in adult life.

Data Sources

Data were obtained from the PubMed, SCOPUS, and Web of Science databases in November 2021 and were selected using the systematic bibliographic review manager program State of the Art Through Systematic Review.

Data Extraction

Data were extracted using the State of the Art Through Systematic Review program.

Data Analysis

Of the 559 articles that were identified, 114 were duplicates, and 426 were excluded after inclusion and exclusion criteria were applied to the title and abstract. One other relevant study was included. From the 20 remaining articles, 8 were excluded after the full-text screening. Finally, 12 articles remained for review in the present work. The studies described in these articles investigated humans, rats, or mice, and correlated early-life malnutrition and depression in adulthood as the principal outcome.

Conclusions

Undernutrition in early life and later depression are linked. Furthermore, the knowledge that the risk factors for depression start at the beginning of life points to public health policies starting in intrauterine life and extending throughout childhood and adolescence.
Baltimore Beginnings
Authors: Crease Stephanie Stein
Published: May 2023

William Henry “Chick” Webb was born in 1905 in East Baltimore, a working-class neighborhood. He was the second of four children of William Henry Webb Sr. and Marie Florence Johnson, and their only son. Incorrect data and lack of documentation compound the challenges of researching his and other Black family histories of the time, leaving discrepancies about birth dates and other vital statistics. Webb’s father left the family when Chick was seven years old and died when Chick was thirteen. Chick was raised by his mother and close-knit extended family; his step-grandfather, Clarence Jones, became the steady male presence in his life. When Webb was three or four, he was afflicted with spinal tuberculosis, impacting his growth and leading to his spinal deformity. He was treated by pioneering Black physician Dr. Ralph J. Young. As a child Webb sold newspapers in downtown Baltimore and earned enough to purchase a used drum set. As a young teen, he played for parties and dances, and Clarence Jones helped him carry his drums to events and dance halls.
Scuffling in Heaven
Authors: Crease Stephanie Stein
Published: May 2023

Thanks largely to Eubie Blake and his and Noble Sissle’s 1921 Broadway hit musical Shuffle Along, Baltimore musicians had a good reputation in New York. Chick Webb and his best friend, guitarist Johnny Trueheart, moved there in 1925 and settled in Harlem in the midst of the Harlem Renaissance. They discovered the Rhythm Club in central Harlem, an unofficial union for Black musicians. In nightly jam sessions there and at clubs nearby, they heard the best Black musicians on the New York scene and got exposure in this competitive environment. Webb met Duke Ellington, then leading his Washingtonians at the Kentucky Club in midtown, and started learning the New York “pecking order” to get jobs: jam sessions, rent parties, dancing schools, and nightclubs. The Prohibition era (banning alcohol) led to a network of gangster-owned speakeasies in midtown and in Harlem, attracting white tourists to cabarets like the Cotton Club, Connie’s Inn, and Small’s Paradise, featuring elaborate floor shows and revues with the best Black bands, dancers, and entertainers.
The Reasoning of Constitutional Courts in Europe
Authors: Jakab András
Published: May 2023

This chapter gives an overview of the different types of constitutional reasoning in Europe. Courts interpreting constitutions must deal with the issue of extracting the greatest amount of meaning from a relatively short text. In doing so, courts have developed a set of techniques of interpretation that guides them to a system of concepts (Verfassungsdogmatik), which is more sophisticated than the actual text of their constitutions. The chapter analyses the case-law of national constitutional courts in the European legal space and that of the ECJ and ECtHR. It shows that no specific form of European constitutional reasoning exists. On the contrary, the main trends and characteristics that can be observed in Europe can also be seen worldwide, and the reasoning styles are as diverse in Europe as they are worldwide.
ECJ and ECtHR: Two Senates of Europe’s Constitutional Jurisdiction
Authors: von Bogdandy Armin , Krenn Christoph
Published: May 2023

The goal of this contribution is to develop a concept for Europe’s constitutional jurisdiction, which is essentially exercised by two courts: the European Court of Justice and the European Court of Human Rights. We argue that the two courts can be best described as the ‘two senates’ of Europe’s constitutional jurisdiction. The image of ‘two senates’ expresses the idea that the two courts bear a shared responsibility for the European legal space to which they each contribute in specific ways. The European Court of Justice’s role, as ‘first senate’, is best understood through its contribution to European political unity by fostering and controlling European public authority and ensuring its uniform effect in the European legal space. The European Court of Human Rights, which we consider Europe’s ‘second senate’, aims to entrench a set of basic norms—European human rights—in the European legal space. The contribution employs the concept of ‘two senates’ to trace the genesis of Europe’s constitutional jurisdiction, to conceptualize the differences between the courts’ constitutional work, and to analyse their relationship.