bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of different Type Ia SN yields on Milky Way chemical evolution
Authors: Palla Marco
Published: February 2021

We study the effect of different Type Ia SN nucleosynthesis prescriptions on the Milky Way chemical evolution. To this aim, we run detailed one-infall and two-infall chemical evolution models, adopting a large compilation of yield sets corresponding to different white dwarf progenitors (near-Chandrasekar and sub-Chandrasekar) taken from the literature. We adopt a fixed delay time distribution function for Type Ia SNe, in order to avoid degeneracies in the analysis of the different nucleosynthesis channels. We also combine yields for different Type Ia SN progenitors in order to test the contribution to chemical evolution of different Type Ia SN channels. The results of the models are compared with recent LTE and NLTE observational data. We find that ‘classical’ W7 and WDD2 models produce Fe masses and [α/Fe] abundance patterns similar to more recent and physical near-Chandrasekar and sub-Chandrasekar models. For Fe-peak elements, we find that the results strongly depend either on the white dwarf explosion mechanism (deflagration-to-detonation, pure deflagration, double detonation) or on the initial white dwarf conditions (central density, explosion pattern). The comparison of chemical evolution model results with observations suggests that a combination of near-Chandrasekar and sub-Chandrasekar yields is necessary to reproduce the data of V, Cr, Mn and Ni, with different fractions depending on the adopted massive stars stellar yields. This comparison also suggests that NLTE and singly ionized abundances should be definitely preferred when dealing with most of Fe-peak elements at low metallicity.
Magnetorotational core collapse of possible GRB progenitors – III. Three-dimensional models
Authors: Obergaulinger M , Aloy M Á
Published: February 2021

We explore the influence of non-axisymmetric modes on the dynamics of the collapsed core of rotating, magnetized high-mass stars in three-dimensional simulations of a rapidly rotating star with an initial mass of $M_{\rm {\small ZAMS}} = 35 \, \mathrm{M}_{\odot }$ endowed with four different pre-collapse configurations of the magnetic field, ranging from moderate to very strong field strength and including the field predicted by the stellar evolution model. The model with the weakest magnetic field achieves shock revival due to neutrino heating in a gain layer characterized by a large-scale, hydrodynamic m = 1 spiral mode. Later on, the growing magnetic field of the proto neutron star launches weak outflows into the early ejecta. Their orientation follows the evolution of the rotational axis of the proto neutron star, which starts to tilt from the original orientation due to the asymmetric accretion flows impinging on its surface. The models with stronger magnetization generate mildly relativistic, magnetically driven polar outflows propagating over a distance of 104  km within a few $100 \, \textrm {ms}$. These jets are stabilized against disruptive non-axisymmetric instabilities by their fast propagation and by the shear of their toroidal magnetic field. Within the simulation times of around $1 \, \textrm {s}$, the explosions reach moderate energies and the growth of the proto neutron star masses ceases at values substantially below the threshold for black hole formation, which, in combination with the high rotational energies, might suggest a possible later proto-magnetar activity.
Multiwavelength observations of the Galactic X-ray binaries IGR J20155+3827 and Swift J1713.4−4219
Authors: Onori F , Fiocchi M , Masetti N , Rojas A F , Bazzano A , Bassani L , Bird A J
Published: February 2021

In recent years, thanks to the continuous surveys performed by INTEGRAL and Swift satellites, our knowledge of the hard X-ray/soft gamma-ray sky has greatly improved. As a result it is now populated with about 2000 sources, both Galactic and extra-galactic, mainly discovered by IBIS and BAT instruments. Many different follow-up campaigns have been successfully performed by using a multiwavelength approach, shedding light on the nature of a number of these new hard X-ray sources. However, a fraction are still of an unidentified nature. This is mainly due to the lack of lower energy observations, which usually deliver a better constrained position for the sources, and the unavailability of the key observational properties, needed to obtain a proper physical characterization. Here, we report on the classification of two poorly studied Galactic X-ray transients IGR J20155+3827 and Swift J1713.4−4219, for which the combination of new and/or archival X-ray and optical/NIR (near-infrared) observations have allowed us to pinpoint their nature. In particular, thanks to XMM–Newton archival data together with new optical spectroscopic and archival optical/NIR photometric observations, we have been able to classify IGR J20155+3827 as a distant HMXB (high-mass X-ray binaries). The new INTEGRAL and Swift data collected during the 2019 X-ray outburst of Swift J1713.4−4219, in combination with the archival optical/NIR observations, suggest an LMXB (low-mass X-ray binaries) classification for this source.
Comparing turbulence in a Kelvin–Helmholtz instability region across the terrestrial magnetopause
Authors: Quijia Paulina , Fraternale Federico , Stawarz Julia E , Vásconez Christian L , Perri Silvia , Marino Raffaele , Yordanova Emiliya , Sorriso-Valvo Luca
Published: February 2021

The properties of turbulence observed within the plasma originating from the magnetosheath and the magnetospheric boundary layer, which have been entrained within vortices driven by the Kelvin–Helmholtz Instability (KHI), are compared. The goal of such a study is to determine similarities and differences between the two different regions. In particular, we study spectra, intermittency and the third-order moment scaling, as well as the distribution of a local energy transfer rate proxy. The analysis is performed using the Magnetospheric Multiscale data from a single satellite that crosses longitudinally the KHI. Two sets of regions, one set containing predominantly magnetosheath plasma and the other containing predominantly magnetospheric plasma, are analysed separately, thus allowing us to explore turbulence properties in two portions of very different plasma samples. Results show that the dynamics in the two regions is different, with the boundary layer plasma presenting a shallower spectra and larger energy transfer rate, indicating an early stage of turbulence. In both regions, the effect of the KHI is evidenced.
A million binaries from Gaia eDR3: sample selection and validation of Gaia parallax uncertainties
Authors: El-Badry Kareem , Rix Hans-Walter , Heintz Tyler M
Published: February 2021

We construct from Gaia eDR3 an extensive catalogue of spatially resolved binary stars within ≈1 kpc of the Sun, with projected separations ranging from a few au to 1 pc. We estimate the probability that each pair is a chance alignment empirically, using the Gaia catalogue itself to calculate the rate of chance alignments as a function of observables. The catalogue contains 1.3 (1.1) million binaries with >90 per cent (>99 per cent) probability of being bound, including 16 000 white dwarf – main-sequence (WD + MS) binaries and 1400 WD + WD binaries. We make the full catalogue publicly available, as well as the queries and code to produce it. We then use this sample to calibrate the published Gaia DR3 parallax uncertainties, making use of the binary components’ near-identical parallaxes. We show that these uncertainties are generally reliable for faint stars (G ≳ 18), but are underestimated significantly for brighter stars. The underestimates are generally $\leq30{{\ \rm per\ cent}}$ for isolated sources with well-behaved astrometry, but are larger (up to ∼80 per cent) for apparently well-behaved sources with a companion within ≲4 arcsec, and much larger for sources with poor astrometric fits. We provide an empirical fitting function to inflate published σϖ values for isolated sources. The public catalogue offers wide ranging follow-up opportunities: from calibrating spectroscopic surveys, to precisely constraining ages of field stars, to the masses and the initial–final mass relation of WDs, to dynamically probing the Galactic tidal field.
The role of resonant plasma instabilities in the evolution of blazar-induced pair beams
Authors: Perry Roy , Lyubarsky Yuri
Published: February 2021

The fate of relativistic pair beams produced in the intergalactic medium by very high energy emission from blazars remains controversial in the literature. The possible role of resonance beam plasma instability has been studied both analytically and numerically but no consensus has been reached. In this paper, we thoroughly analyse the development of this type of instability. This analysis takes into account that a highly relativistic beam loses energy only due to interactions with the plasma waves propagating within the opening angle of the beam (we call them parallel waves), whereas excitation of oblique waves results merely in an angular spreading of the beam, which reduces the instability growth rate. For parallel waves, the growth rate is a few times larger than for oblique ones, so they grow faster than oblique waves and drain energy from the beam before it expands. However, the specific property of extragalactic beams is that they are extraordinarily narrow; the opening angle is only Δθ ∼ 10−6 to 10−5. In this case, the width of the resonance for parallel waves, ∝Δθ2, is too small for them to grow in realistic conditions. We perform both analytical estimates and numerical simulations in the quasi-linear regime. These show that for extragalactic beams, the growth of the waves is incapable of taking a significant portion of the beam’s energy. This type of instability could at best lead to an expansion of the beam by some factor but the beam’s energy remains nearly intact.
Three-dimensional imaging and reconstruction of the whole ovary and testis: a new frontier for the reproductive scientist
Authors: Fiorentino Giulia , Parrilli Annapaola , Garagna Silvia , Zuccotti Maurizio
Published: February 2021

The 3D functional reconstruction of a whole organ or organism down to the single cell level and to the subcellular components and molecules is a major future scientific challenge. The recent convergence of advanced imaging techniques with an impressively increased computing power allowed early attempts to translate and combine 2D images and functional data to obtain in-silico organ 3D models. This review first describes the experimental pipeline required for organ 3D reconstruction: from the collection of 2D serial images obtained with light, confocal, light-sheet microscopy or tomography, followed by their registration, segmentation and subsequent 3D rendering. Then, we summarise the results of investigations performed so far by applying these 3D image analyses to the study of the female and male mammalian gonads. These studies highlight the importance of working towards a 3D in-silico model of the ovary and testis as a tool to gain insights into their biology during the phases of differentiation or adulthood, in normal or pathological conditions. Furthermore, the use of 3D imaging approaches opens to key technical improvements, ranging from image acquisition to optimisation and development of new processing tools, and unfolds novel possibilities for multidisciplinary research.
Anti-CRISPR AcrIF9 functions by inducing the CRISPR–Cas complex to bind DNA non-specifically
Authors: Lu Wang-Ting , Trost Chantel N , Müller-Esparza Hanna , Randau Lennart , Davidson Alan R
Published: February 2021

Phages and other mobile genetic elements express anti-CRISPR proteins (Acrs) to protect their genomes from destruction by CRISPR–Cas systems. Acrs usually block the ability of CRISPR–Cas systems to bind or cleave their nucleic acid substrates. Here, we investigate an unusual Acr, AcrIF9, that induces a gain-of-function to a type I-F CRISPR–Cas (Csy) complex, causing it to bind strongly to DNA that lacks both a PAM sequence and sequence complementarity. We show that specific and non-specific dsDNA compete for the same site on the Csy:AcrIF9 complex with rapid exchange, but specific ssDNA appears to still bind through complementarity to the CRISPR RNA. Induction of non-specific DNA-binding is a shared property of diverse AcrIF9 homologues. Substitution of a conserved positively charged surface on AcrIF9 abrogated non-specific dsDNA-binding of the Csy:AcrIF9 complex, but specific dsDNA binding was maintained. AcrIF9 mutants with impaired non-specific dsDNA binding activity in vitro displayed a reduced ability to inhibit CRISPR–Cas activity in vivo. We conclude that misdirecting the CRISPR–Cas complex to bind non-specific DNA is a key component of the inhibitory mechanism of AcrIF9. This inhibitory mechanism is distinct from a previously characterized anti-CRISPR, AcrIF1, that sterically blocks DNA-binding, even though AcrIF1and AcrIF9 bind to the same site on the Csy complex.
Hypocalcemia and bone mineral changes in hemodialysis patients with low bone mass treated with denosumab: a 2-year observational study
Authors: Hiramatsu Rikako , Ubara Yoshifumi , Sawa Naoki , Sakai Akinori
Published: February 2021

Background

Increases in bone mineral density (BMD) following a single dose of denosumab and increased incidence of denosumab-associated acute hypocalcemia (DAAH) have been reported in chronic kidney disease patients. Little is known about clinical risk factors related to DAAH and the long-term effect of denosumab on BMD in hemodialysis patients.

Methods

An observational noncontrolled study involving 47 hemodialysis patients was conducted to determine the independent risk factors related to percentage changes in serum calcium (Ca) levels associated with denosumab using multivariate regression analysis. Optimal predictive markers for DAAH were explored by receiver operating characteristic analysis. Percentage changes of BMD at the lumbar spine (LS) and femoral neck (FN) at 24 months were investigated.

Results

The incidence of DAAH [serum corrected Ca (cCa) ≤8 mg/dL] following denosumab was 25.5%. Multivariate regression analysis showed that baseline bone alkaline phosphatase was independently related to percentage changes in cCa levels (β = −0.407, P = 0.008). Tartrate-resistant acid phosphatase-5b was found to be the most accurate marker to predict DAAH, with an area under the curve of 0.750 (95% confidence interval 0.546–0.954; P = 0.02), and the optimal cut-off level was 670 mU/mL with sensitivity: 0.727 and specificity: 0.733. BMD significantly increased by 5.9 ± 1.7% (P = 0.01) at LS and 4.2 ± 1.5% (P = 0.04) at FN at 24 months.

Conclusions

In hemodialysis patients, high bone turnover was an independent risk factor for the Ca declines induced by denosumab. Denosumab significantly increased BMD at LS and FN at 24 months.
Systematic review of the nuclear factor erythroid 2-related factor 2 (NRF2) system in human chronic kidney disease: alterations, interventions and relation to morbidity
Authors: Juul-Nielsen Christoffer , Shen Jianlin , Stenvinkel Peter , Scholze Alexandra
Published: February 2021

Background

Nuclear factor erythroid 2-related factor 2 (NRF2) and its effectors NAD(P)H:quinoneoxidoreductase 1 (NQO1) and haem oxygenase 1 (HO-1) are of interest in kidney disease. We therefore reviewed studies about their status in patients with chronic kidney disease (CKD).

Methods

We undertook systematic searches of PubMed and Excerpta Medica dataBASE (EMBASE) databases. Alterations of NRF2, NQO1 and HO-1 in CKD, their responses to interventions and their relation to clinically relevant parameters were reported.

Results

We identified 1373 articles, of which 32 studies met the inclusion criteria. NRF2 levels were decreased in the majority of analyses of CKD patients. Half of the analyses showed a similar or increased NQO1 level versus control, whereas in half of the analyses NQO1 was decreased. Most of the studies reported either an increased or similar HO-1 level in CKD patients compared with controls. For patients with CKD Stages 1–4, studies reported positive correlations to markers of kidney disease severity. Also, positive associations of NQO1/HO-1 levels to inflammation and comorbidities were reported. One-third of the studies showed discordant changes between gene expression and protein level of NRF2 system components. Two-thirds of intervention studies (50% dietary, such as using resistant starch) reported an increase of NRF2, NQO1 or HO-1.

Conclusions

In patients with CKD, NRF2 expression was downregulated, while NQO1 and HO-1 showed varying alterations related to inflammation, comorbidities and severity of kidney damage. Interventions that increased NRF2 system components were described, but their effectiveness and clinical relevance require further clinical studies of high quality. Research on gene expression together with protein analyses is indispensable to understand NRF2 system alterations in CKD.
Associations Between Infant Developmental Delays and Secondhand Smoke Exposure Modified by Maternal Prepregnancy Overweight and Obesity Status
Authors: Wei Chih-Fu , Lin Ching-Chun , Tsai Meng-Shan , Guo Yueliang Leon , Lin Shio-Jean , Liao Hua-Fang , Hsieh Wu-Shiun , Chen Mei-Huei , Chen Pau-Chung
Published: February 2021

Introduction

Secondhand smoke exposure during pregnancy has long been associated with adverse health outcomes in children, but only a few studies have examined its effect modifiers. In this study, we applied effect modification analysis for maternal prepregnancy weight status on detrimental neurodevelopmental effect of secondhand smoke exposure during pregnancy and infancy in a nationwide representative population.

Aims and Methods

Term singleton mother–infant pairs with nonsmoking mothers were included for main analysis (N = 15 987) from the Taiwan Birth Cohort Study (TBCS), and were further matched with propensity score (n = 5434). We extracted secondhand smoke exposure during pregnancy and infancy, and eight neurodevelopmental milestones from the responses in the baseline visit at 6 months, and 18-month follow-up of TBCS. The associations between secondhand smoke exposure and neurodevelopmental achievement were analyzed with multivariable logistic regression and Cox model. Propensity score weighting and matching were applied for high-versus-low analysis, and relative excess risk due to interaction were used to estimate effect modification.

Results

Higher secondhand smoke exposure was associated with increased likelihood of delayed milestone achievement across gross motor, fine motor, language-related, and social-related domains. The associations in fine motor domains remained observable in propensity score-weighted and -matched models. We identified additive interaction with self-reported maternal overweight and obesity status before pregnancy in milestone development for walking with support, scribbling, and waving goodbye.

Conclusions

Secondhand smoke exposure during pregnancy and infancy were associated with delayed neurodevelopmental milestone achievement at 18 months, and the associations were modified by maternal prepregnancy overweight and obesity status.

Implications

The study results suggested the association between maternal secondhand smoke exposure during pregnancy and infancy and delayed fine motor and language-related milestone achievement at 18 months in multivariable, propensity score weighting, and matching populations. The results of positive effect modifications for maternal prepregnancy overweight and obesity status suggested the importance of concurrent interventions on smoke-free environment and maternal health during pregnancy.
Mental health, reporting bias and economic transitions
Authors: Brown Sarah , Harris Mark N , Srivastava Preety , Taylor Karl
Published: February 2021

Measures of mental health are heavily relied upon to identify at-risk individuals. However, self-reported mental health metrics might be unduly affected by mis-reporting (perhaps stemming from stigma effects). In this article, we consider this phenomenon by focusing upon the mis-reporting of mental health using UK panel data from 1991 to 2018. In separate analyses of males and females, we examine how inaccurate reporting of the General Health Questionnaire (GHQ-12) measure, specifically its sub-components, can adversely affect the distribution of the index. The analysis suggests that individuals typically over report their mental health (especially so for males). The results are then used to adjust the GHQ-12 score to take mis-reporting into account. We then compare the effects of the adjusted/unadjusted GHQ-12 index when modelling a number of important economic transitions. Using the original index typically leads to an underestimate of the effect of poor mental health on transitions into improved economic states, for example, unemployment to employment.
Function of the HYDROXYCINNAMOYL-CoA:SHIKIMATE HYDROXYCINNAMOYL TRANSFERASE is evolutionarily conserved in embryophytes
Authors: Kriegshauser Lucie , Knosp Samuel , Grienenberger Etienne , Tatsumi Kanade , Gütle Desirée D , Sørensen Iben , Herrgott Laurence , Zumsteg Julie , Rose Jocelyn K C , Reski Ralf , Werck-Reichhart Danièle , Renault Hugues
Published: February 2021

The plant phenylpropanoid pathway generates a major class of specialized metabolites and precursors of essential extracellular polymers that initially appeared upon plant terrestrialization. Despite its evolutionary significance, little is known about the complexity and function of this major metabolic pathway in extant bryophytes, which represent the non-vascular stage of embryophyte evolution. Here, we report that the HYDROXYCINNAMOYL-CoA:SHIKIMATE HYDROXYCINNAMOYL TRANSFERASE (HCT) gene, which plays a critical function in the phenylpropanoid pathway during seed plant development, is functionally conserved in Physcomitrium patens (Physcomitrella), in the moss lineage of bryophytes. Phylogenetic analysis indicates that bona fide HCT function emerged in the progenitor of embryophytes. In vitro enzyme assays, moss phenolic pathway reconstitution in yeast and in planta gene inactivation coupled to targeted metabolic profiling, collectively indicate that P. patens HCT (PpHCT), similar to tracheophyte HCT orthologs, uses shikimate as a native acyl acceptor to produce a p-coumaroyl-5-O-shikimate intermediate. Phenotypic and metabolic analyses of loss-of-function mutants show that PpHCT is necessary for the production of caffeate derivatives, including previously reported caffeoyl-threonate esters, and for the formation of an intact cuticle. Deep conservation of HCT function in embryophytes is further suggested by the ability of HCT genes from P. patens and the liverwort Marchantia polymorpha to complement an Arabidopsis thaliana CRISPR/Cas9 hct mutant, and by the presence of phenolic esters of shikimate in representative species of the three bryophyte lineages.
An alternative splicing variant of PtRD26 delays leaf senescence by regulating multiple NAC transcription factors in Populus
Authors: Wang Hou-Ling , Zhang Yi , Wang Ting , Yang Qi , Yang Yanli , Li Ze , Li Bosheng , Wen Xing , Li Wenyang , Yin Weilun , Xia Xinli , Guo Hongwei , Li Zhonghai
Published: February 2021

During leaf senescence, the final stage of leaf development, nutrients are recycled from leaves to other organs, and therefore proper control of senescence is thus critical for plant fitness. Although substantial progress has been achieved in understanding leaf senescence in annual plants, the molecular factors that control leaf senescence in perennial woody plants are largely unknown. Using RNA sequencing, we obtained a high-resolution temporal profile of gene expression during autumn leaf senescence in poplar (Populus tomentosa). Identification of hub transcription factors (TFs) by co-expression network analysis of genes revealed that senescence-associated NAC family TFs (Sen-NAC TFs) regulate autumn leaf senescence. Age-dependent alternative splicing (AS) caused an intron retention (IR) event in the pre-mRNA encoding PtRD26, a NAC-TF. This produced a truncated protein PtRD26IR, which functions as a dominant-negative regulator of senescence by interacting with multiple hub Sen-NAC TFs, thereby repressing their DNA-binding activities. Functional analysis of senescence-associated splicing factors identified two U2 auxiliary factors that are involved in AS of PtRD26IR. Correspondingly, silencing of these factors decreased PtRD26IR transcript abundance and induced early senescence. We propose that an age-dependent increase of IR splice variants derived from Sen-NAC TFs is a regulatory program to fine tune the molecular mechanisms that regulate leaf senescence in trees.
Magnesium maintains the length of the circadian period in Arabidopsis
Authors: de Melo J Romário F , Gutsch Annelie , Caluwé Thomas De , Leloup Jean-Christophe , Gonze Didier , Hermans Christian , Webb Alex A R , Verbruggen Nathalie
Published: February 2021

The circadian clock coordinates the physiological responses of a biological system to day and night rhythms through complex loops of transcriptional/translational regulation. It can respond to external stimuli and adjust generated circadian oscillations accordingly to maintain an endogenous period close to 24 h. However, the interaction between nutritional status and circadian rhythms in plants is poorly understood. Magnesium (Mg) is essential for numerous biological processes in plants, and its homeostasis is crucial to maintain optimal development and growth. Magnesium deficiency in young Arabidopsis thaliana seedlings increased the period of circadian oscillations of the CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) promoter (pCCA1:LUC) activity and dampened their amplitude under constant light in a dose-dependent manner. Although the circadian period increase caused by Mg deficiency was light dependent, it did not depend on active photosynthesis. Mathematical modeling of the Mg input into the circadian clock reproduced the experimental increase of the circadian period and suggested that Mg is likely to affect global transcription/translation levels rather than a single component of the circadian oscillator. Upon addition of a low dose of cycloheximide to perturb translation, the circadian period increased further under Mg deficiency, which was rescued when sufficient Mg was supplied, supporting the model’s prediction. These findings suggest that sufficient Mg supply is required to support proper timekeeping in plants.
Persistent Post-Mastectomy Pain: The Impact of Regional Anesthesia Among Patients with High vs Low Baseline Catastrophizing
Authors: Zinboonyahgoon Nantthasorn , Patton Megan E , Chen Yun-Yun K , Edwards Rob R , Schreiber Kristin L
Published: February 2021

Background

Persistent post-mastectomy pain (PPMP) varies both in its severity and impact, with psychosocial factors such as catastrophizing conferring greater risk. Preoperative regional anesthesia (RA) is an important nonopioid therapy, but with variable success at preventing PPMP in previous reports. We previously reported that RA was associated with lower acute post-mastectomy pain and opioid use, but more prominently among patients with higher baseline catastrophizing. The current longitudinal investigation at 3, 6, and 12 months postop aimed to detect differential long-term impact of RA on PPMP among patients with high vs low catastrophizing.

Methods

In this prospective observational study, patients (n = 123) completed preoperative psychosocial assessment and underwent mastectomy either with (n = 56) or without (n = 67) preoperative RA. Generalized estimating equation (GEE) regression analysis assessed impact of baseline catastrophizing, RA, and their interaction, on the primary outcome of pain severity index, as well as secondary outcomes including cognitive and emotional impact of pain, and persistent opioid use.

Results

We observed a significant interaction between the effect of catastrophizing and RA on PPMP. Specifically, RA was associated with reduced pain severity and pain impact 3, 6, and 12 months postoperatively, but only among those with high baseline catastrophizing scores. In addition, both RA and lower catastrophizing scores were associated with lower incidence of persistent opioid use.

Conclusions

The efficacy of therapies to prevent PPMP may be importantly influenced by pain-modulatory psychosocial characteristics. These findings underscore the importance of considering individual patient factors when applying preventive treatments, and of including their assessment in future trials.
Radiofrequency Ablation for Chronic Hip Pain: A Comprehensive, Narrative Review
Authors: Cheney Cole W , Ahmadian Amir , Brennick Caroline , Zheng Patricia , Mattie Ryan , McCormick Zachary L , Nagpal Ameet
Published: February 2021

Chronic hip pain can be treated with physical therapy, oral medications, injections, and, definitively, total hip arthroplasty. Enough patients have contraindications to and refractory pain even after total hip arthroplasty, that there is a need to develop alternative managements for this disabling condition. This article examines the state of hip radiofrequency ablation literature including relevant anatomy, patient selection, and treatment outcomes.
Self-reported medicinal plant use by Ghanaian women during pregnancy is associated with poor neonatal health
Authors: Busse Clara E , Wilson Mark L , Bakari Ashura , Moyer Cheryl A
Published: February 2021

Background

More than a third of pregnant women in Africa use medicinal plants (hereafter, ‘herbs’) during pregnancy, yet little is known about herb use among urban African women, or about the potential impact on newborns.

Methods

This cross-sectional study of 504 women giving birth at an urban government hospital in Kumasi, Ghana (May–July 2018) collected data via chart reviews and maternal interviews. Data were analyzed using conditional logistic regression.

Results

Of 380 singleton births with complete data, 102 mothers (26.84%) reported using herbs during pregnancy and/or delivery. Herb users and non-users did not differ significantly across a range of sociodemographic variables. Controlling for age, education, neonatal birthweight and household running water (socioeconomic status (SES) indicator), herb-using women were twice as likely to have their newborn admitted to the hospital (odds ratio (OR) = 2.05; confidence interval (CI) 95% 1.17, 3.60) and four times as likely to bear a child with a low Apgar score (OR = 4.09; CI 95% 1.66, 10.07) compared with non-users.

Conclusion

Urban-dwelling Ghanaian women from diverse backgrounds use herbs during pregnancy. Maternal herb use was associated with poor neonatal outcomes, regardless of the baby’s birthweight and mother’s age, education or SES, suggesting the importance of educating all women about the possible negative impacts of herb use during pregnancy and delivery.
Incorporating Hierarchical Characters into Phylogenetic Analysis
Authors: Hopkins Melanie J , St. John Katherine
Published: February 2021

Popular optimality criteria for phylogenetic trees focus on sequences of characters that are applicable to all the taxa. As studies grow in breadth, it can be the case that some characters are applicable for a portion of the taxa and inapplicable for others. Past work has explored the limitations of treating inapplicable characters as missing data, noting that this strategy may favor trees where internal nodes are assigned impossible states, where the arrangement of taxa within subclades is unduly influenced by variation in distant parts of the tree, and/or where taxa that otherwise share most primary characters are grouped distantly. Approaches that avoid the first two problems have recently been proposed. Here, we propose an alternative approach which avoids all three problems. We focus on data matrices that use reductive coding of traits, that is, explicitly incorporate the innate hierarchy induced by inapplicability, and as such our approach extend to hierarchical characters, in general. In the spirit of maximum parsimony, the proposed criterion seeks the phylogenetic tree with the minimal changes across any tree branch, but where changes are defined in terms of dissimilarity metrics that weigh the effects of inapplicable characters. The approach can accommodate binary, multistate, ordered, unordered, and polymorphic characters. We give a polynomial-time algorithm, inspired by Fitch’s algorithm, to score trees under a family of dissimilarity metrics, and prove its correctness. We show that the resulting optimality criteria is computationally hard, by reduction to the NP-hardness of the maximum parsimony optimality criteria. We demonstrate our approach using synthetic and empirical data sets and compare the results with other recently proposed methods for choosing optimal phylogenetic trees when the data includes hierarchical characters. [Character optimization, dissimilarity metrics, hierarchical characters, inapplicable data, phylogenetic tree search.]
Genera specific distribution of DEAD-box RNA helicases in cyanobacteria
Authors: Whitford Denise S. , Whitman Brendan T. , Owttrim George W.
Published: February 2021

Although RNA helicases are essentially ubiquitous and perform roles in all stages of RNA metabolism, phylogenetic analysis of the DEAD (Asp-Glu-Ala-Asp)-box RNA helicase family in a single phylum has not been performed. Here, we performed a phylogenetic analysis on DEAD-box helicases from all currently available cyanobacterial genomes, comprising a total of 362 helicase protein sequences from 280 strains. DEAD-box helicases belonging to three distinct clades were observed. Two clades, the CsdA (cold shock DEAD-box A)-like and RhlE (RNA helicase E)-like helicases, cluster with the homologous proteins from

Escherichia coli

. The third clade, the CrhR (cyanobacterial RNA helicase Redox)-like helicases, is unique to cyanobacteria and characterized by a conserved sequence motif in the C-terminal extension. Restricted distribution is observed across cyanobacterial diversity with respect to both helicase type and strain. CrhR-like and CsdA-like helicases essentially never occur together, while RhlE always occurs with either a CrhR-like or CsdA-like helicase. CrhR-like and RhlE-like proteins occurred in filamentous cyanobacteria of the orders

Nostocales

,

Oscillatoriales

and

Synechococcales

. Similarly, CsdA- and RhlE-like proteins are restricted to unicellular cyanobacteria of the genera

Cyanobium

and

Synechococcus

. In addition, the unexpected occurrence of RhlE in two

Synechococcus

strains suggests recent acquisition and evolutionary divergence. This study, therefore, raises physiological and evolutionary questions as to why DEAD-box RNA helicases encoded in cyanobacterial lineages display restricted distributions, suggesting niches that require either CrhR or CsdA RNA helicase activity but not both. Extensive conservation of gene synteny surrounding the previously described rimO–crhR operon is also observed, indicating a role in the maintenance of photosynthesis. The analysis provides insights into the evolution, origin and dissemination of sequences within a single gene family to yield divergent functional roles.
BSGatlas: a unified Bacillus subtilis genome and transcriptome annotation atlas with enhanced information access
Authors: Geissler Adrian Sven , Anthon Christian , Alkan Ferhat , González-Tortuero Enrique , Poulsen Line Dahl , Kallehauge Thomas Beuchert , Breüner Anne , Seemann Stefan Ernst , Vinther Jeppe , Gorodkin Jan
Published: February 2021

A large part of our current understanding of gene regulation in Gram-positive bacteria is based on

Bacillus subtilis

, as it is one of the most well studied bacterial model systems. The rapid growth in data concerning its molecular and genomic biology is distributed across multiple annotation resources. Consequently, the interpretation of data from further

B. subtilis

experiments becomes increasingly challenging in both low- and large-scale analyses. Additionally,

B. subtilis

annotation of structured RNA and non-coding RNA (ncRNA), as well as the operon structure, is still lagging behind the annotation of the coding sequences. To address these challenges, we created the

B. subtilis

genome atlas, BSGatlas, which integrates and unifies multiple existing annotation resources. Compared to any of the individual resources, the BSGatlas contains twice as many ncRNAs, while improving the positional annotation for 70 % of the ncRNAs. Furthermore, we combined known transcription start and termination sites with lists of known co-transcribed gene sets to create a comprehensive transcript map. The combination with transcription start/termination site annotations resulted in 717 new sets of co-transcribed genes and 5335 untranslated regions (UTRs). In comparison to existing resources, the number of 5′ and 3′ UTRs increased nearly fivefold, and the number of internal UTRs doubled. The transcript map is organized in 2266 operons, which provides transcriptional annotation for 92 % of all genes in the genome compared to the at most 82 % by previous resources. We predicted an off-target-aware genome-wide library of CRISPR–Cas9 guide RNAs, which we also linked to polycistronic operons. We provide the BSGatlas in multiple forms: as a website (https://rth.dk/resources/bsgatlas/), an annotation hub for display in the UCSC genome browser, supplementary tables and standardized GFF3 format, which can be used in large scale -omics studies. By complementing existing resources, the BSGatlas supports analyses of the

B. subtilis

genome and its molecular biology with respect to not only non-coding genes but also genome-wide transcriptional relationships of all genes.
Bladder Cancer Immunotherapy by BCG is associated with a significantly reduced risk of Alzheimer‘s disease
Authors: Klinger Danielle , Hill Brian L. , Barda Noam , Halperin Eran , Gofrit Ofer N. , Greenblatt Charles L. , Rappoport Nadav , Linial Michal , Bercovier Hervé
Published: February 2021

IMPORTANCE

Despite years of investigation and billions of dollars, there is no cure or even a disease-slowing remedy for Alzheimer’s disease (AD). Most studies thus far have focused on amyloid beta plaques (Aβ) and neurofibrillary tangles as therapeutic targets, and only a few on modulating the associated inflammatory process.

OBJECTIVE

To determine if exposure to Bacillus Calmette–Guérin (BCG) during treatment of non-muscle-invasive bladder cancer (NMIBC) is associated with a lower risk of developing AD.

DESIGN, SETTING AND PARTICIPANTS

Multicenter retrospective study of 12,185 bladder cancer patients including 2301 BCG-treated patients between 2000 and 2019 meeting all inclusion criteria. Data was retrieved from two tertiary hospital systems in Israel and the United States, and the largest Israeli health provider database, with a median follow up of 3.5 to 7 years.

MAIN OUTCOMES AND MEASURES

The primary outcome was time to the first occurrence of AD/Dementia events following a diagnosis of bladder cancer by trans-urethral resection (TURBT) in BCG treated patients, and in bladder cancer patients not receiving BCG (control group).

RESULTS

BCG treatment was associated with a significantly reduced risk of developing AD in bladder cancer patients of ≥75 years following BCG treatment. A competing risk model using Cox Proportional-Hazard (PH) analysis applied to the largest medical records data showed a Hazard Ratio (HR) of 0.726 (95% CI: 0.529 – 0.996, P = 0.0473). The results were duplicated in analyzing NMIBC patients from a tertiary hospital with a HR of 0.416 (95% CI: 0.203 – 0.853, P = 0.017). A reduction in the risk (by 28%) for developing Parkinson’s disease (PD) was also shown in bladder cancer patients subjected to BCG immunotherapy.

CONCLUSIONS AND RELEVANCE

BCG treatment for bladder cancer patients was associated with a significantly reduced risk for developing AD and PD in the elderly population (>75 years), and in NMIBC patients from a tertiary hospital. Prospective studies in elderly inoculated with intradermic BCG should be initiated to evaluate the potential protective effect of BCG against AD and PD.

KEY POINTS

Question

Whether bladder cancer patients treated with BCG immunotherapy have a lower risk to develop AD than bladder cancer patients that do not receive such treatment.

Findings

In a multicenter retrospective study composed of three cohorts covering >12,000 bladder cancer patients, those receiving intravesical BCG immunotherapy had a significantly lower risk of developing AD.

Meaning

Intradermal inoculation of BCG to elderly people should be tested as a potential preventive approach against AD.
Evaluation of saliva self-collection devices for SARS-CoV-2 diagnostics
Authors: Allicock Orchid M. , Petrone Mary E. , Yolda-Carr Devyn , Breban Mallery , Walsh Hannah , Watkins Anne E. , Rothman Jessica E. , Farhadian Shelli F. , Grubaugh Nathan D. , Wyllie Anne L.
Published: February 2021

There is an urgent need to expand testing for SARS-CoV-2 and other respiratory pathogens as the global community struggles to control the COVID-19 pandemic. Current diagnostic methods can be affected by supply chain bottlenecks and require the assistance of medical professionals, impeding the implementation of large-scale testing. Self-collection of saliva may solve these problems, as it can be completed without specialized training and uses generic materials. In this study, we observed thirty individuals who self-collected saliva using four different collection devices and analyzed their feedback. Two of these devices, a funnel and bulb pipette, were used to evaluate at-home saliva collection by 60 individuals. All devices enabled the safe, unsupervised self-collection of saliva. The quantity and quality of the samples received were acceptable for SARS-CoV-2 diagnostic testing, as determined by RNase P detection. Here, we demonstrate inexpensive, generic, buffer free collection devices suitable for unsupervised and home saliva self-collection.
PRINCIPLE trial demonstrates scope for in-pandemic improvement in primary care antibiotic stewardship
Authors: de Lusignan Simon , Joy Mark , Sherlock Julian , Tripathy Manasa , van Hecke Oliver , Gbinigie Oghenekome , Williams John , Butler Christopher , Hobbs FD Richard
Published: February 2021

Background

The Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE) trial has provided in-pandemic evidence of what does not work in the early primary care management of coronavirus-2019 disease (COVID-19). PRINCIPLE’s first finding was that azithromycin and doxycycline were not effective.

Aim

To explore the extent to which azithromycin and doxycycline were being used in-pandemic, and the scope for trial findings impacting on practice.

Design and Setting

We compared crude rates of prescribing and respiratory tract infections (RTI) in 2020, the pandemic year, with 2019, using the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC).

Methods

We used a negative binomial model including age-band, gender, socioeconomic status, and NHS region to compare azithromycin and doxycycline lower respiratory tract infections (LRTI), upper respiratory tract infections (URTI), and influenza-like-illness (ILI) in 2020 with 2019; reporting incident rate ratios (IRR) between years and 95% confidence intervals (95%CI).

Results

Azithromycin prescriptions increased 7% in 2020 compared to 2019, whereas doxycycline decreased by 7%. Concurrently, LRTI and URTI incidence fell by over half (58.3% and 54.4% respectively) while ILI rose slightly (6.4%). The overall percentage of RTI prescribed azithromycin rose by 42.1% between 2019 and 2020, doxycycline increased by 33%.

Our adjusted IRR showed azithromycin prescribing was 22% higher in 2020 (IRR=1.22, 95%CI:1.19-1.26, p<0.0001), for every unit rise in confirmed COVID there was an associated 3% rise in prescription (IRR=1.026, 95%CI 1.024-1.0285, p<0.0001); whereas these measures were static for doxycycline.

Conclusion

PRINCIPLE trial flags scope for improvement in antimicrobial stewardship.
Point-of-care evaluation of a rapid antigen test (CLINITEST® Rapid COVID-19 Antigen Test) for diagnosis of SARS-CoV-2 infection in symptomatic and asymptomatic individuals
Authors: Torres Ignacio , Poujois Sandrine , Albert Eliseo , Álvarez Gabriela , Colomina Javier , Navarro David
Published: February 2021

Rapid antigen assays (RAD) based on lateral flow immunochromatography (LFIC) technology have emerged as a valuable tool for the control of COVID-19 pandemic. Manufacturer□independent, real□world evaluation of these assays is crucial given the considerable heterogeneity reported in their clinical and analytical performances. Here, we report for the first time on the point-of-care performance of the CLINITEST® Rapid COVID-19 Antigen Test (Siemens, Healthineers, Erlangen, Germany) to detect SARS-CoV-2 infection in presumptive COVID-19 cases or asymptomatic close contacts of COVID-19 patients. When compared to RT-PCR, the overall sensitivity of the assay was 80.2 (95% CI, 70.9-87.1) for symptomatic patients sampled (nasopharyngeal specimens) within five days after the onset of symptoms and 60% (95% CI, 40.7-76.6%) for asymptomatic participants. The overall specificity was 100% in both population groups.
Role of Inflammation in Depression and Anxiety: Tests for Disorder Specificity, Linearity and Potential Causality of Association in the UK Biobank
Authors: Ye Zheng , Kappelmann Nils , Moser Sylvain , Smith George Davey , Burgess Stephen , Jones Peter B. , Khandaker Golam M.
Published: February 2021

Background

Concentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.

Methods

Using data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety.

Findings

CRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.

Interpretation

Altered activity of the IL-6/IL-6R pathway could be causally linked to depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.

Funding

MQ (MQDS17/40); Wellcome Trust (201486/Z/16/Z).