bluuebunny/crossref_metadata_2025 huggingface dataset:
Luteinizing hormone receptor promotes angiogenesis in ovarian endothelial cells ofMacaca fascicularisandHomo sapiens
Authors: Lund Merete , Pearson Andrew C , Sage Megan A G , Duffy Diane M
Published: October 2022

Angiogenesis within the ovarian follicle is an important component of ovulation. New capillary growth is initiated by the ovulatory surge of luteinizing hormone (LH), and angiogenesis is well underway at the time of follicle rupture. LH-stimulated follicular production of vascular growth factors has been shown to promote new capillary formation in the ovulatory follicle. The possibility that LH acts directly on ovarian endothelial cells to promote ovulatory angiogenesis has not been addressed. For these studies, ovaries containing ovulatory follicles were obtained from cynomolgus macaques and used for histological examination of ovarian vascular endothelial cells, and monkey ovarian microvascular endothelial cells (mOMECs) were enriched from ovulatory follicles for in vitro studies. mOMECs expressed LHCGR mRNA and protein, and immunostaining confirmed LHCGR protein in endothelial cells of ovulatory follicles in vivo. Human chorionic gonadotropin (hCG), a ligand for LHCGR, increased mOMEC proliferation, migration and capillary-like sprout formation in vitro. Treatment of mOMECs with hCG increased cAMP, a common intracellular signal generated by LHCGR activation. The cAMP analog dibutyryl cAMP increased mOMEC proliferation in the absence of hCG. Both the protein kinase A (PKA) inhibitor H89 and the phospholipase C (PLC) inhibitor U73122 blocked hCG-stimulated mOMEC proliferation, suggesting that multiple G-proteins may mediate LHCGR action. Human ovarian microvascular endothelial cells (hOMECs) enriched from ovarian aspirates obtained from healthy oocyte donors also expressed LHCGR. hOMECs also migrated and proliferated in response to hCG. Overall, these findings indicate that the LH surge may directly activate ovarian endothelial cells to stimulate angiogenesis of the ovulatory follicle.
Safety, feasibility, and prognostic value of stress perfusion CMR in patients with MR-conditional pacemaker
Authors: Pezel Théo , Lacotte Jérôme , Horvilleur Jérôme , Toupin Solenn , Hovasse Thomas , Unterseeh Thierry , Sanguineti Francesca , Said Mina Ait , Salerno Fiorella , Fiorina Laurent , Manenti Vladimir , Zouaghi Amir , Faradji Alyssa , Nicol Martin , Ah-Sing Tania , Dillinger Jean-Guillaume , Henry Patrick , Garot Philippe , Bousson Valérie , Garot Jérôme
Published: October 2022

Aims

To assess the safety, feasibility, and prognostic value of stress cardiovascular magnetic resonance (CMR) in patients with pacemaker (PM).

Methods and results

Between 2008 and 2021, we conducted a bi-centre longitudinal study with all consecutive patients with MR-conditional PM referred for vasodilator stress CMR at 1.5 T in the Institut Cardiovasculaire Paris Sud and Lariboisiere University Hospital. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction. Cox regression analyses were performed to determine the prognostic value of CMR parameters. The quality of CMR was rated by two observers blinded to clinical details. Of 304 patients who completed the CMR protocol, 273 patients (70% male, mean age 71 ± 9 years) completed the follow-up (median [interquartile range], 7.1 [5.4–7.5] years). Among those, 32 experienced a MACE (11.7%). Stress CMR was well tolerated with no significant change in lead thresholds or pacing parameters. Overall, the image quality was rated good or excellent in 84.9% of segments. Ischaemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 11.71 [95% CI: 4.60–28.2]; and HR: 5.62 [95% CI: 2.02–16.21], both P < 0.001). After adjustment for traditional risk factors, ischaemia and LGE were independent predictors of MACE (HR: 5.08 [95% CI: 2.58–14.0]; and HR: 2.28 [95% CI: 2.05–3.76]; both P < 0.001).

Conclusion

Stress CMR is safe, feasible and has a good discriminative prognostic value in consecutive patients with PM.
YgeA is involved in L- and D-homoserine metabolism in Escherichia coli
Authors: Miyamoto Tetsuya , Saitoh Yasuaki , Katane Masumi , Sekine Masae , Homma Hiroshi
Published: October 2022

Noncanonical D-amino acids are involved in peptidoglycan and biofilm metabolism in bacteria. Previously, we identified amino acid racemases with broad substrate specificity, including YgeA from Escherichia coli, which strongly prefers homoserine as a substrate. In this study, we investigated the functions of this enzyme in vivo. When wild-type and ygeA-deficient E. coli strains were cultured in minimal medium containing D-homoserine, the D-homoserine level was significantly higher in the ygeA-deficient strain than in the wild-type strain, in which it was almost undetectable. Additionally, D-homoserine was detected in YgeA-expressed E. coli cells cultured in minimal medium containing L-homoserine. The growth of the ygeA-deficient strain was significantly impaired in minimal medium with or without supplemental D-homoserine, while L-methionine, L-threonine or L-isoleucine, which are produced via L-homoserine, restored the growth impairment. Furthermore, the wild-type strain formed biofilms significantly more efficiently than the ygeA-deficient strain. Addition of L- or D-homoserine significantly suppressed biofilm formation in the wild-type strain, whereas this addition had no significant effect in the ygeA-deficient strain. Together, these data suggest that YgeA acts as an amino acid racemase and plays a role in L- and D-homoserine metabolism in E. coli.
Mitigating the risk of wind damage at the forest landscape level by using stand neighbourhood and terrain elevation information in forest planning
Authors: Ruotsalainen Roope , Pukkala Timo , Ikonen Veli-Pekka , Packalen Petteri , Peltola Heli
Published: October 2022

Wind damage and the bark beetle outbreaks associated with it are major threats to non-declining, long-term wood production in boreal forests. We studied whether the risk of wind damage in a forested landscape could be decreased by using stand neighbourhood information in conjunction with terrain elevation information. A reference management plan minimized the differences in canopy height at stand boundaries and did not utilize information on the topography of the terrain, overlooking the possibility that the risk of windthrow may depend on the elevation of the terrain. Alternative management plans were developed by using four different weighting schemes when minimizing differences in canopy height at stand boundaries: (1) no weight (reference); (2) mean terrain elevation at the stand boundary; (3) deviation of the mean elevation of the boundary from the mean elevation of the terrain within a 100-m radius and (4) multipliers that described the effect of topography on wind speed at the stand boundary. For each management plan, we calculated the total number of at-risk trees and the total area of vulnerable stand edge. These statistics were based on the calculated critical wind speeds needed to uproot trees in stand edge zones. Minimization of the weighted mean of canopy height differences between adjacent stands resulted in homogeneous landscapes in terms of canopy height. Continuous cover management was often preferred instead of rotation management due to smaller canopy height differences between adjacent stands and its economical superiority. The best weighting scheme for calculating the mean canopy height difference between adjacent stands was the deviation between the mean elevation of the boundary and the mean elevation of the terrain within 100 m of the boundary. However, the differences between the weighting schemes were small. It was found that reasonably simple methods, based on a digital terrain model, a stand map, and the canopy heights of stands, could be used in forest planning to minimize the risk of wind damage. Validation against actual wind damages is required to assess the reliability of the results and to further develop the methodology presented.
Fine-Tuning LightGBM Using an Artificial Ecosystem-Based Optimizer for Forest Fire Analysis
Authors: Nguyen Quoc-Huy , Nguyen Huu-Duy , Le Dinh Tan , Bui Quang-Thanh
Published: October 2022

This study’s main objective is to propose a hybrid machine learning model based on a gradient boosting algorithm named LightGBM and an artificial ecosystem-based optimization to improve the accuracy of forest fire susceptibility assessment. Four hundred twenty-six historical forest fires from the NASA portal and thirteen conditional factors including elevation, aspect, slope, curvature, normalized difference vegetation index, normalized difference water index, distance to residence, distance to road, distance to river, temperature, rain, humidity, and wind were used to train the model. The model performance was evaluated and compared with other benchmark models using root mean square error, area under receiver operating characteristics (AUC), and overall accuracy. The results show that the proposed model (AUC = 0.9705) outperforms others, such as Random Forest (AUC = 0.958), AdaBoost (AUC = 0.905), Bagging (AUC = 0.945), and Random Subspace (AUC = 0.938), respectively. The final model was interpreted to better understand the most influential factors of forest fire hazards.
A rapid method for extraction, purification and structure analysis of chondroitin sulfate from six marine tissues
Authors: Wang Yuying , Ahmadi Shokouh , Yu Chengxiao , Zhang Laiming , Hu Xinxin , Ye Xingqian , Chen Shiguo
Published: October 2022

This study was designed to establish a strategy for the extraction, purification, and structure analysis of chondroitin sulfate (CS) in milligram amounts. Crude acidic polysaccharides were extracted from six kinds of marine animals by enzymatic hydrolysis and hexadecylpyridinium chloride precipitation and purified by Q Sepharose Fast Flow strong anion exchange column. The purification of each crude polysaccharide was completed within 1 h. The structure of the polysaccharides, i.e. their chemical characterization, functional group, molecular weight and monosaccharide composition, were analyzed by colorimetry, nuclear magnetic resonace and high-performance liquid chromatogrpahy, respectively. All polysaccharides were identified as CS. The oligosaccharide profile produced by enzyme hydrolysis of polysaccharides was determined by strong anion-exchange high-performance liquid chromatorgraphy. This method can be widely applied to the extraction and characterization of chondroitin sulfate from unknown raw materials, screening high-quality sources of functional polysaccharides, and laying a good foundation for the following study of the structure–function relationship of polysaccharides.
Computational analysis of prodomain cysteines in human TGF-β proteins reveals frequent loss of disulfide-dependent regulation in tumors
Authors: Daly Samantha M , Peraza Ashley , Newfeld Stuart J
Published: October 2022

The functionally diverse members of the human Transforming Growth Factor-β (TGF-β) family are tightly regulated. TGF-β regulation includes 2 disulfide-dependent mechanisms—dimerization and partner protein binding. The specific cysteines participating in these regulatory mechanisms are known in just 3 of the 33 human TGF-β proteins. Human prodomain alignments revealed that 24 TGF-β prodomains contain conserved cysteines in 2 highly exposed locations. There are 3 in the region of the β8 helix that mediates dimerization near the prodomain carboxy terminus. There are 2 in the Association region that mediates partner protein binding near the prodomain amino terminus. The alignments predict the specific cysteines contributing to disulfide-dependent regulation of 72% of human TGF-β proteins. Database mining then identified 9 conserved prodomain cysteine mutations and their disease phenotypes in 7 TGF-β proteins. Three common adenoma phenotypes for prodomain cysteine mutations suggested 7 new regulatory heterodimer pairs. Two common adenoma phenotypes for prodomain and binding partner cysteine mutations revealed 17 new regulatory interactions. Overall, the analysis of human TGF-β prodomains suggests a significantly expanded scope of disulfide-dependent regulation by heterodimerization and partner protein binding; regulation that is often lost in tumors.
Local magnitude determination for Turkey from two independent seismic networks and a consistent M4 + catalogue
Authors: Rojo Limón G , Ouillon G , Kissling E , Sornette D
Published: October 2022

Turkish seismicity is routinely recorded by two broad-band seismic networks: the Turkish National Seismic Network (AFAD ‘TU’ network) and the Bogazici University Kandilli Observatory And Earthquake Research Institute (KOERI ‘KO’ network). Each of them has over 200 seismic stations distributed across the country. We obtain a new uniform and consistent local magnitude (Ml) scale for Turkey using data from both networks, as well as the M4 + catalogue with Ml values that results from applying said scale to the events that occurred between 2007 and 2016 within the country. We measure the half peak-to-peak amplitude of the vertical component seismograms and estimate the attenuation parameters through an iterative procedure that fits the logarithm of the amplitude as a function of the hypocentral distance, the local magnitude, the station corrections and a constant accounting for possible systematic differences between amplitudes measured on horizontal seismographs and those measured on vertical seismographs. We additionally scale Ml to the moment magnitude measured by an independent source, obtaining a magnitude relationship accounting for attenuation adjustments, as well as differences between maximum horizontal and vertical amplitudes. The estimated Ml formula shows that station corrections from both networks regionally agree, and that non-zero corrections are centred on zero, within −0.48 and 0.46 magnitude units (corresponding to the 2.5 and the 97.5 quantiles). The new M4 + catalogue with consistent Ml values for AFAD and KOERI shows magnitude residuals that cannot be explained by a Gaussian distribution. We also show a very good agreement between our new Ml value and the original Ml values of AFAD and KOERI, with median differences below 0.1 magnitude units.
Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development
Authors: Hale Melissa A , Bates Kameron , Provenzano Marina , Johnson Nicholas E
Published: October 2022

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by expansion of CTG microsatellite repeats within DMPK. The most severe form, congenital myotonic dystrophy (CDM), has symptom onset at birth due to large intergenerational repeat expansions. Despite a common mutation, CDM individuals present with a distinct clinical phenotype and absence of common DM1 symptoms. Given the clinical divergence, it is unknown if the hallmark of DM1 pathology, dysregulation of alternative splicing (AS) due to sequestration of MBNL proteins within toxic CUG repeat RNAs, contributes to disease throughout pediatric development. To evaluate global transcriptomic dysregulation, RNA-seq was performed on 36 CDM skeletal muscle biopsies ages 2 weeks to 16 years, including two longitudinal samples. Fifty DM1 and adult/pediatric controls were also sequenced as comparative groups. Despite a large CTG expansion and shared age of onset, CDM individuals presented with a heterogenous, MBNL-dependent mis-splicing signature. Estimation of intracellular MBNL concentrations from splicing responses of select events correlated with total spliceopathy and revealed a distinct, triphasic pattern of AS dysregulation across pediatric development. CDM infants (< 2 years) possess severe mis-splicing that significantly improves in early childhood (2–8 years) independent of sex or CTG repeat load. Adolescent individuals (8–16 years) stratified into two populations with a full range of global splicing dysregulation. DMPK expression changes correlated with alterations in splicing severity during development. This study reveals the complex dynamics of the CDM muscle transcriptome and provides insights into new therapeutic strategies, timing of therapeutic intervention, and biomarker development.
Singular fourth-order Sturm–Liouville operators and acoustic black holes
Authors: Belinskiy Boris P , Hinton Don B , Nichols Roger A
Published: October 2022

We derive conditions for a one-term fourth-order Sturm–Liouville operator on a finite interval with one singular endpoint to have essential spectrum equal to $[0,\infty )$ or $\varnothing $. Of particular usefulness are Kummer–Liouville transformations which have been a valuable tool in the study of second-order equations. Applications to a mechanical beam with a thickness tapering to zero at one of the endpoints are considered. When the thickness $2h$ satisfies $c_1x^{\nu }\leq h(x)\leq c_2x^{\nu }$, we show that the essential spectrum is empty if and only if $\nu < 2$. As a final application, we consider a tapered beam on a Winkler foundation and derive sufficient conditions on the beam thickness and the foundational rigidity to guarantee the essential spectrum is equal to $[0,\infty )$.
Role of bone biopsy and deep tissue culture for antibiotic stewardship in diabetic foot osteomyelitis
Authors: Hockney Sara M , Steker Danielle , Bhasin Ajay , Krueger Karen M , Williams Janna , Galvin Shannon
Published: October 2022

Objectives

To describe organisms most frequently identified on bone biopsy or deep tissue culture and determine how culture data impacted antibiotic management in patients with diabetic foot osteomyelitis (DFO).

Methods

We retrospectively reviewed patients admitted with a diabetic foot ulcer (DFU) between 3 March 2018 and 31 December 2019 and selected for patients diagnosed with infectious osteomyelitis (OM) of the lower extremity. We stratified patients by whether a bone biopsy or deep tissue culture was obtained and compared rates of antibiotic utilization with chi-squared and Fisher’s exact tests.

Results

Of 305 patients with a DFU, 152 (50%) were clinically diagnosed with DFO. Forty-seven patients received 41 deep tissue cultures and 29 bone biopsy cultures for a total of 70 cultures. Of 45 (64%) positive cultures, 36 (80%) had Gram-positive organisms and 19 (42%) had Gram-negative organisms. MDR organisms were isolated in 7 (15%) patients. Culture data resulted in antibiotic changes in 41 (87%) patients. Therapy was narrowed in 29 (62%) patients and broadened due to inadequate empirical coverage in 4 (9%) patients. Culture data from 18 (40%) patients showed susceptibility to an oral treatment regimen with high bioavailability. There was no significant difference in rates of antibiotic utilization at discharge between patients who underwent bone biopsy or deep tissue culture relative to those who did not (77% versus 75%, P = 0.86), although less MRSA coverage was used (34% versus 50%, P = 0.047).

Conclusions

In patients with DFO, deep tissue and bone biopsy cultures were infrequently obtained but resulted in targeted therapy changes in most patients. Culture data usually allowed for narrowing of antibiotics but revealed inadequate empirical coverage in a subset of patients.
Knowledge, attitudes and practices on antimicrobial resistance among pharmacy personnel and nurses at a tertiary hospital in Ndola, Zambia: implications for antimicrobial stewardship programmes
Authors: Tembo Nanji , Mudenda Steward , Banda Michelo , Chileshe Mwitwa , Matafwali Scott
Published: October 2022

Introduction

Antimicrobial resistance (AMR) is a global public health problem that has led to increased morbidity and mortality, especially in low- and middle-income countries such as Zambia. This study evaluated AMR knowledge, attitudes and practices among pharmacy personnel and nurses at Ndola Teaching Hospital, Zambia’s second-largest hospital.

Methods

A descriptive cross-sectional study was conducted among 263 participants using a structured questionnaire. Data analysis was performed with IBM SPSS version 23.0. All statistical tests were conducted at a 95% confidence level. Univariate analysis was used to determine differences in knowledge, attitudes and practices on AMR between pharmacy personnel and nurses.

Results

Of the 263 participants, 225 (85.6%) were nurses and 38 (14.4%) were pharmacy personnel. Compared with nurses, pharmacy personnel had better knowledge of the spread of resistant bacteria from one person to another (P = 0.001) and the use of antibiotics in livestock as a contributing factor to AMR (P = 0.01). Pharmacy personnel had better attitudes towards AMR as a public health problem (P = 0.001) and the use of antibiotics in livestock as a source of resistant pathogens (P = 001). Lastly, more pharmacy personnel than nurses participated in awareness campaigns (P = 0.029), continued professional development (P = 0.001) and courses on the use of antibiotics and AMR (P = 0.028).

Conclusions

The study showed that most participants had adequate knowledge, a positive attitude and good practices towards AMR. Significant differences in knowledge, attitudes and practices were observed between pharmacy personnel and nurses in AMR, highlighting a need for increased educational programmes for these healthcare personnel.
Terrorism, Media Coverage, and Education: Evidence from al-Shabaab Attacks in Kenya
Authors: Alfano Marco , Görlach Joseph-Simon
Published: October 2022

We relate terrorist attacks to media signal coverage and schooling in Kenya to examine how terrorism alters the demand for education through perceived risks and returns. Exploiting variation in wireless signal coverage and attacks across space and time, we establish that media access reinforces negative effects of terrorism on schooling. Our results are robust to instrumenting both media signal and attacks. We also find that attacks raise self-reported fears for households with media access. Based on these insights, we estimate a simple structural model where heterogeneous households experiencing terrorism form beliefs about risks and returns to education. We allow these beliefs to be affected by media and find that households with media access significantly over-estimate fatality risks.
Doubled-haploid induction generates extensive differential DNA methylation in Arabidopsis
Authors: Piskorz Ewa W , Xu Linhao , Ma Yingrui , Jiang Hua
Published: October 2022

Doubled haploids (DHs) fix traits from hybrids in one generation. DH induction includes two changes in ploidy levels typically associated with variation in DNA methylation. However, DNA methylation patterns in DH plants and their biological significance are largely unknown. We generated three DH lines in Arabidopsis thaliana by crossing a haploid inducer with the accession Col-0, thus removing tissue culture and hybridization as a variable. DH induction produced thousands of differentially DNA methylated regions (DMRs), most of which were stochastic. Both haploidization and colchicine-induced genome duplication produced DMRs; the former mainly yielded DMRs at non-CG contexts, whereas the latter affected differential gene body methylation. Spontaneous genome doubling of haploid plants also induced DMRs in greater numbers than self-propagation. Our results provide the first evidence that haploid induction and genome doubling result in differential DNA methylation, offering a novel approach to induce epialleles.
Association of thers3856806Polymorphism in thePPARGGene with Type 2 Diabetes Mellitus: A Meta-Analysis of 11,811 Individuals
Authors: Tiongco Raphael Enrique , Basilio Henry , Camacho Dharleen Ryanne , Ellorin Willie Mae , Sico Clarisse Arianne , Arceo Engracia
Published: October 2022

This study investigated the role of the rs3856806 single nucleotide variant (SNV) on the peroxisome proliferator-activated receptor γ with the development of type 2 diabetes mellitus (T2DM) by conducting a meta-analysis. Relevant studies were searched in PubMed and were selected according to the inclusion criteria. Data were extracted and subjected to analysis using Review Manager 5.4.1. Pooled odds ratios (OR) and 95% confidence intervals (CI) were computed to measure the association of the SNV with T2DM development. Nine studies published in English were retrieved up to October 1, 2021. Homogeneity (I2 = 3%, P = .41) was achieved for the allelic model with significant outcomes (OR: 0.82; 95% CI: 0.76-0.89; P < .00001). Genotypic models also yielded significant associations for the co-dominant, dominant, and recessive models. All genotypic analysis showed homogeneity (I2 = 0-31%, P = .17-0.76) of the pooled outcomes. Our findings suggest that carrying the T allele of the rs3856806 SNV significantly decreases the risk of acquiring T2DM. However, further studies are necessary to support our claims.
Platelet MicroRNA-484 as a Novel Diagnostic Biomarker for Acute Coronary Syndrome
Authors: Masoodi Khabar Parisa , Ghydari Mohamad Esmail , Vazifeh Shiran Nader , Shirazy Mohammadreza , Hamidpour Mohsen
Published: October 2022

Objective

Platelet microRNAs (miRs) have been indicated as a diagnostic biomarker in various diseases, including acute coronary syndrome (ACS). This study aimed to investigate the expression of miR-223-5p, miR-126-5p, miR-484, and miR-130a-3p in individuals with coronary artery disease (CAD).

Methods

Forty subjects with CAD and 13 healthy individuals were under study. The expression of miR-223-5p, miR-126-5p, miR-484, and miR-130a-3p was measured in platelets by quantitative reverse transcription–polymerase chain reaction. The relationship between miRNA expression and various parameters of the subjects was analyzed using analysis of variance and Spearman and t-tests.

Results

The miR-484 expression was significantly upregulated in the ACS subjects (P = .0097). Moreover, miR-484 had diagnostic value for screening subjects with unstable angina vs controls (area under the curve [AUC] = 0.978, 95% confidence interval [CI] 0.92–1, P = .0006) and NSTEMI patients versus controls (AUC = 0.910, 95% CI 0.74–1, P = .005).

Conclusion

The results of this study indicate that the upregulated expression of miR-484 in ACS patients might be used as a diagnostic biomarker in ACS.
Transient Osteoporosis of the Hip: A Case Report of a U.S. Soldier
Authors: Dichiera Robert , Yim Duke
Published: October 2022

Transient osteoporosis of the hip is described as an uncommon, self-limiting condition that typically affects middle-aged men and pregnant women in their third trimester. Transient osteoporosis most commonly affects the hip, but cases have been described in the knee, ankle, and foot. Symptoms include pain, limited range of motion, and antalgic gait. A greater level of awareness of transient osteoporosis of the hip as a differential diagnosis for hip pain will obviate unnecessary, inefficient, or unproductive interventions and treatments. Transient osteoporosis of the hip is a self-limiting disease process that requires only symptomatic treatment such as basic analgesia, physical therapy, and activity modification. On average, recovery is seen within 6-12 months.
Binary black hole merger rates in AGN discs versus nuclear star clusters: loud beats quiet
Authors: Ford K E Saavik , McKernan Barry
Published: October 2022

Galactic nuclei are promising sites for stellar origin black hole (BH) mergers, as part of merger hierarchies in deep potential wells. We show that binary black hole (BBH) merger rates in active galactic nuclei (AGNs) should always exceed merger rates in quiescent galactic nuclei (nuclear star clusters, NSCs) around supermassive black holes (SMBHs) without accretion discs. This is primarily due to average binary lifetimes in AGNs that are significantly shorter than those in NSCs. The lifetime difference comes from rapid hardening of BBHs in AGNs, such that their semimajor axes are smaller than the hard–soft boundary of their parent NSC; this contrasts with the large average lifetime to merger for BBHs in NSCs around SMBHs, due to binary ionization mechanisms. Secondarily, merger rates in AGNs are enhanced by gas-driven binary formation mechanisms. Formation of new BHs in AGN discs is a minor contributor to the rate differences. With the gravitational wave detection of several BBHs with at least one progenitor in the upper mass gap, and signatures of dynamical formation channels in the χeff distribution, we argue that AGNs could contribute $\sim 25{\!-\!}80{{\ \rm per\ cent}}$ of the LIGO–Virgo measured rate of $\sim 24\, \rm {Gpc}^{-3} \rm {yr}^{-1}$.
TRAPUM upper limits on pulsed radio emission for SMC X-ray pulsar J0058−7218
Authors: Carli E , Levin L , Stappers B W , Barr E D , Breton R P , Buchner S , Burgay M , Kramer M , Padmanabh P V , Possenti A , Venkatraman Krishnan V , Behrend J , Champion D J , Chen W , Men Y P
Published: October 2022

The TRAPUM collaboration has used the MeerKAT telescope to conduct a search for pulsed radio emission from the young Small Magellanic Cloud pulsar J0058−7218 located in the supernova remnant IKT 16, following its discovery in X-rays with XMM–Newton. We report no significant detection of dispersed, pulsed radio emission from this source in three 2-h L-band observations using the core dishes of MeerKAT, setting an upper limit of 7.0 $\mu$Jy on its mean flux density at 1284 MHz. This is nearly seven times deeper than previous radio searches for this pulsar in Parkes L-band observations. This suggests that the radio emission of PSR J0058−7218 is not beamed towards Earth or that PSR J0058−7218 is similar to a handful of Pulsar Wind Nebulae systems that have a very low radio efficiency, such as PSR B0540−6919, the Large Magellanic Cloud Crab pulsar analogue. We have also searched for bright, dispersed, single radio pulses and found no candidates above a fluence of 93 mJy ms at 1284 MHz.
Velocity profiles of matter and biased tracers around voids
Authors: Massara Elena , Percival Will J , Dalal Neal , Nadathur Seshadri , Radinović Slađana , Winther Hans A , Woodfinden Alex
Published: October 2022

The velocity profile of galaxies around voids is a key ingredient for redshift space distortion (RSD) measurements made using the void–galaxy correlation function. In this paper, we use simulations to test whether the velocity profile of the tracers used to find the voids matches the velocity profile of the dark matter around these voids. A mismatch is expected and found in the inner part of voids, where tracers are very sparse. We discuss how this difference is caused by a selection effect where the void centre positions are correlated to the particular realization of the sparse tracers and their spatial distribution. In turn, this then affects the RSD void–galaxy correlation analysis. We show this by evaluating the Jacobian of the real to redshift space mapping using the tracer or matter velocity profile. Differences of the order of 20 per cent in the velocity profile translate into differences of the order of few per cent in the Jacobian. This small discrepancy propagates to the monopole and quadrupole of the void–tracer correlation function, producing modifications of comparable magnitude to those from changes in fσ8 at the level of the statistical uncertainties from current analyses.
Standard self-confinement and extrinsic turbulence models for cosmic ray transport are fundamentally incompatible with observations
Authors: Hopkins Philip F , Squire Jonathan , Butsky Iryna S , Ji Suoqing
Published: October 2022

Models for cosmic ray (CR) dynamics fundamentally depend on the rate of CR scattering from magnetic fluctuations. In the ISM, for CRs with energies ∼MeV-TeV, these fluctuations are usually attributed either to ‘extrinsic turbulence’ (ET) – a cascade from larger scales – or ‘self-confinement’ (SC) – self-generated fluctuations from CR streaming. Using simple analytic arguments and detailed ‘live’ numerical CR transport calculations in galaxy simulations, we show that both of these, in standard form, cannot explain even basic qualitative features of observed CR spectra. For ET, any spectrum that obeys critical balance or features realistic anisotropy, or any spectrum that accounts for finite damping below the dissipation scale, predicts qualitatively incorrect spectral shapes and scalings of B/C and other species. Even if somehow one ignored both anisotropy and damping, observationally required scattering rates disagree with ET predictions by orders of magnitude. For SC, the dependence of driving on CR energy density means that it is nearly impossible to recover observed CR spectral shapes and scalings, and again there is an orders-of-magnitude normalization problem. But more severely, SC solutions with super-Alfvénic streaming are unstable. In live simulations, they revert to either arbitrarily rapid CR escape with zero secondary production, or to bottleneck solutions with far-too-strong CR confinement and secondary production. Resolving these fundamental issues without discarding basic plasma processes requires invoking different drivers for scattering fluctuations. These must act on a broad range of scales with a power spectrum obeying several specific (but plausible) constraints.
Martes martes(Carnivora: Mustelidae)
Authors: Monakhov Vladimir
Published: October 2022

Martes martes (Linnaeus, 1758), commonly called the European pine marten, is a small predator widespread in western Eurasia. In almost all its geographic distribution, it is autochthonous. It is as a secondary consumer but, a predator with omnivorous traits. Martes martes inhabits forests with varied tree compositions, but in recent decades, it has spread to forest-steppe and agricultural areas. It is hunted in some areas, mainly in winter. In some countries during the 20th century, it experienced significant declines in numbers, but at present, it is “Least Concern” (LC) on the International Union for the Conservation of Nature’s Red List of Threatened Species.
Mössbauer-based molecular-level decomposition of the Saccharomyces cerevisiae ironome, and preliminary characterization of isolated nuclei
Authors: Lindahl Paul A , Vali Shaik Waseem
Published: October 2022

One hundred proteins in Saccharomyces cerevisiae are known to contain iron. These proteins are found mainly in mitochondria, cytosol, nuclei, endoplasmic reticula, and vacuoles. Cells also contain non-proteinaceous low-molecular-mass labile iron pools (LFePs). How each molecular iron species interacts on the cellular or systems’ level is underdeveloped as doing so would require considering the entire iron content of the cell—the ironome. In this paper, Mössbauer (MB) spectroscopy was used to probe the ironome of yeast. MB spectra of whole cells and isolated organelles were predicted by summing the spectral contribution of each iron-containing species in the cell. Simulations required input from published proteomics and microscopy data, as well as from previous spectroscopic and redox characterization of individual iron-containing proteins. Composite simulations were compared to experimentally determined spectra. Simulated MB spectra of non-proteinaceous iron pools in the cell were assumed to account for major differences between simulated and experimental spectra of whole cells and isolated mitochondria and vacuoles. Nuclei were predicted to contain ∼30 μM iron, mostly in the form of [Fe4S4] clusters. This was experimentally confirmed by isolating nuclei from 57Fe-enriched cells and obtaining the first MB spectra of the organelle. This study provides the first semi-quantitative estimate of all concentrations of iron-containing proteins and non-proteinaceous species in yeast, as well as a novel approach to spectroscopically characterizing LFePs.
MiMeDB: the Human Microbial Metabolome Database
Authors: Wishart David S , Oler Eponine , Peters Harrison , Guo AnChi , Girod Sagan , Han Scott , Saha Sukanta , Lui Vicki W , LeVatte Marcia , Gautam Vasuk , Kaddurah-Daouk Rima , Karu Naama
Published: October 2022

The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these ‘omes’ to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.
PDBspheres: a method for finding 3D similarities in local regions in proteins
Authors: Zemla Adam T , Allen Jonathan E , Kirshner Dan , Lightstone Felice C
Published: October 2022

We present a structure-based method for finding and evaluating structural similarities in protein regions relevant to ligand binding. PDBspheres comprises an exhaustive library of protein structure regions (‘spheres’) adjacent to complexed ligands derived from the Protein Data Bank (PDB), along with methods to find and evaluate structural matches between a protein of interest and spheres in the library. PDBspheres uses the LGA (Local–Global Alignment) structure alignment algorithm as the main engine for detecting structural similarities between the protein of interest and template spheres from the library, which currently contains >2 million spheres. To assess confidence in structural matches, an all-atom-based similarity metric takes side chain placement into account. Here, we describe the PDBspheres method, demonstrate its ability to detect and characterize binding sites in protein structures, show how PDBspheres—a strictly structure-based method—performs on a curated dataset of 2528 ligand-bound and ligand-free crystal structures, and use PDBspheres to cluster pockets and assess structural similarities among protein binding sites of 4876 structures in the ‘refined set’ of the PDBbind 2019 dataset.
Prediction of response to lomustine-based chemotherapy in glioma patients at recurrence using MRI and FET PET
Authors: Wollring Michael M , Werner Jan-Michael , Bauer Elena K , Tscherpel Caroline , Ceccon Garry S , Lohmann Philipp , Stoffels Gabriele , Kabbasch Christoph , Goldbrunner Roland , Fink Gereon R , Langen Karl-Josef , Galldiks Norbert
Published: October 2022

Background

We evaluated O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and MRI for early response assessment in recurrent glioma patients treated with lomustine-based chemotherapy.

Methods

Thirty-six adult patients with WHO CNS grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1–3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (not later than two cycles). Tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR >1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. PET parameter thresholds were defined using ROC analyses to predict PFS of ≥6 months and OS of ≥12 months. MRI response assessment was based on RANO criteria. The predictive values of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates.

Results

After treatment initiation, the median follow-up time was 11 months (range, 3–71 months). Relative changes of TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P ≤ .002) and OS (all P ≤ .045). At follow-up, the occurrence of new distant hotspots (n ≥ 1) predicted a worse outcome, with significantly shorter PFS (P = .005) and OS (P < .001). Time-to-peak changes did not predict a significantly longer survival. Multivariate survival analyses revealed that new distant hotspots at follow-up FET PET were most potent in predicting non-response (P < .001; HR, 8.578).

Conclusions

Data suggest that FET PET provides complementary information to RANO criteria for response evaluation of lomustine-based chemotherapy early after treatment initiation.
Law, Coercion and Folk Intuitions
Authors: Miotto Lucas , Almeida Guilherme F C F , Struchiner Noel
Published: October 2022

In discussing whether legal systems are necessarily coercive, legal philosophers usually appeal to thought experiments involving angels or other morally driven beings who need no coercion to organise their social lives. Such appeals have invited criticism. Critics have not only challenged the relevance of such thought experiments to our understanding of legal systems; they have also argued that, contrary to the intuitions of most legal philosophers, the ‘man on the Clapham Omnibus’ would not hold that there is law in a society of angels because the view that law is necessarily coercive ‘enjoys widespread support among laypersons’. This is obviously an empirical claim. Critics, however, never systematically polled the ‘man on the Clapham Omnibus’. We boarded that bus. This article discusses findings from five empirical studies on the relationship between law and coercion.
Black Patients with Metastatic Castrate-Resistant Prostate Cancer Have a Shorter Time Interval Between PSA and Clinical Progression on Novel Hormonal Therapies plus Avelumab
Authors: Hawkins Charlotte (Manogue) , Barata Pedro C , Cotogno Patrick , Davis Gaynelle , Jaeger Ellen , Ledet Elisa , Miller Patrick , Lewis Brian , Sartor Oliver , Layton Jodi
Published: October 2022

Background

Black men are at higher risk for prostate cancer death. Previous studies showed a benefit of different therapies, including immune-based therapy, for Black men with metastatic prostate cancer. We sought to explore the efficacy of the PD-L1 inhibitor avelumab in Black men with metastatic castrate-resistant prostate cancer (mCRPC) progressing after abiraterone or enzalutamide.

Methods

This pilot phase II study enrolled self-identified Black patients who developed mCRPC on next-generation hormonal therapies (NHTs) abiraterone acetate or enzalutamide (NCT03770455). Enrolled patients received avelumab 10mg/kg IV every 2 weeks while remaining on the same NHTs. The primary endpoint of our study was ≥ 50% reduction in prostate specific antigen (PSA) at ≥8 weeks.

Results

A total of eight patients were enrolled. The median duration on NHTs prior to enrollment was 364 days (95% CI, 260.9-467.1). The median time to initiate avelumab was 8 days (3-14). With a median follow-up of 196 days, no patients achieved the primary endpoint. The median time to PSA progression was 35 days (95 CI%, 0-94.8) and the median time to radiographic and/or clinical progression was 44 days (95 CI%, 0-118.5). The study was closed prematurely due to safety concerns related to the rapid clinical progression observed in the patients enrolled on study.

Conclusion

In conclusion, the addition of avelumab to NHT did not demonstrate clinical activity in Black men with new mCRPC. The unexpected short interval between PSA and radiographic and/or clinical progression observed in this study has potential clinical implications.

ClinicalTrials.gov Identifier: NCT03770455 (IND number 139559).
Plant biomechanics and resilience to environmental changes are controlled by specific lignin chemistries in each vascular cell type and morphotype
Authors: Ménard Delphine , Blaschek Leonard , Kriechbaum Konstantin , Lee Cheng Choo , Serk Henrik , Zhu Chuantao , Lyubartsev Alexander , Nuoendagula  , Bacsik Zoltán , Bergström Lennart , Mathew Aji , Kajita Shinya , Pesquet Edouard
Published: October 2022

The biopolymer lignin is deposited in the cell walls of vascular cells and is essential for long-distance water conduction and structural support in plants. Different vascular cell types contain distinct and conserved lignin chemistries, each with specific aromatic and aliphatic substitutions. Yet, the biological role of this conserved and specific lignin chemistry in each cell type remains unclear. Here, we investigated the roles of this lignin biochemical specificity for cellular functions by producing single cell analyses for three cell morphotypes of tracheary elements, which all allow sap conduction but differ in their morphology. We determined that specific lignin chemistries accumulate in each cell type. Moreover, lignin accumulated dynamically, increasing in quantity and changing in composition, to alter the cell wall biomechanics during cell maturation. For similar aromatic substitutions, residues with alcohol aliphatic functions increased stiffness whereas aldehydes increased flexibility of the cell wall. Modifying this lignin biochemical specificity and the sequence of its formation impaired the cell wall biomechanics of each morphotype and consequently hindered sap conduction and drought recovery. Together, our results demonstrate that each sap-conducting vascular cell type distinctly controls their lignin biochemistry to adjust their biomechanics and hydraulic properties to face developmental and environmental constraints.
Intensity of Chronic Low Back Pain and Activity Interference: A Daily Diary Study of the Moderating Role of Cognitive Pain Coping Strategies
Authors: Vertsberger Dana , Talmon Anat , Ziadni Maisa , Kong Jiang-Ti , Darnall Beth D , Manber Rachel , Mackey Sean , Gross James J
Published: October 2022

Objective

Chronic low back pain (CLBP) has a significant negative impact on daily functioning, particularly for those with challenges coping adaptively with ongoing pain. However, the dynamics of pain coping in daily life remain understudied. Therefore, we examined the extent to which pain intensity interferes with daily activities, and assessed whether pain coping strategies (as assessed using daily diaries) moderated this link.

Method

We analyzed diary data from a sample of 84 participants with CLBP who completed daily diaries for up to 30 days rating pain intensity, pain interference with daily activities, and their use of pain coping strategies, including pain rumination (i.e., repetitive thinking about the pain and its causes), reappraisal (i.e., evaluating one’s pain less negatively or more positively), and distraction (i.e., diverting attention from the pain). We hypothesized that these coping strategies would moderate the associations between pain and pain interference with daily activities, although in different directions.

Results

Results suggest that pain rumination strengthens the association between pain intensity and pain interference both on the person and day level, while pain reappraisal and distraction weaken this association, at the day and person levels, respectively.

Conclusion

Our findings suggest that those who are more preoccupied with their pain and those who are less likely to reappraise their pain have more pain interference with daily activities. These findings build on prior work on pain coping by using daily diaries and highlight two pain coping strategies that have particular relevance for reducing the impact of CLBP in daily life.