bluuebunny/crossref_metadata_2025 huggingface dataset:
TET2 modulates proliferation and migration of vascular smooth muscle cells via LEMD2/NOX1/NOX4 signaling pathway
Authors: Xie Y L , Qin Y C , Li A H , Yan Z Q , Qiao Z D ,   Shanghai Jiaotong University
Published: October 2021

Background

Ten-eleven translocation 2 (TET2), a widely reported DNA hydroxymethylation enzyme, is involved in active DNA demethylation. TET2 may play an critical role in numerous cellular processes by regulating the level of DNA hydroxymethylation and altering gene expression. TET2 expression was proved to be down-regulated in aorta of spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto rats (WKY) as well as in VSMCs subjected to15% cyclic stretch compared to 5% cyclic stretch. However, whether TET2 regulates vascular smooth muscle cells (VSMCs) proliferation and migration and its underlying mechanisms remains unclear.

Purpose

The present study aims to investigate whether TET2 affects VSMC proliferation and migration and its possible underlying mechanisms.

Methods

TET2 knockdown rat VSMC was established using crispr/Cas9 method. Different expression genes were identified by next generation sequencing (NGS) between TET2 knockdown VSMC and control VSMCs while differentially hydroxymethylated promoter region were identified by hydroxymethylcytosine DNA immunoprecipitation (hMeDIP) sequencing. Expression of mRNA and proteins was detected by qRT-PCR and western blot respectively. The proliferation and migration of VSMCs were assessed by EdU assay, flowcytometry assay, and wound healing assay. LEMD2 overexpression and knockdown stable VSMC lines were established through Lentiviral infection.

Results

The EdU assay and wound healing assay show that knockdown of TET2 enhanced proliferation and migration of VSMCs. NGS identified 123 differentially expressed genes (91 up-regulated and 32 down-regulated) between TET2 knockdown VSMCs and control VSMCs while hMeDIP sequencing identified 166 genes with differentially hydroxymethylated promoter region (68 up-regulated and 98 down-regulated) between TET2 knockdown VSMCs and control VSMCs. Through comparing these sequencing results, we identified a gene named as LEMD2 simultaneously present in both sequencing results. Expression of LEMD2 at mRNA and protein level was significantly increased in TET2 knockdown VSMCs compared to control VSMCs. Then we successfully established LEMD2 overexpression and knockdown stable VSMC lines and found that overexpression of LEMD2 enhanced proliferation and migration of VSMCs while knockdown of LEMD2 inhibited proliferation and migration of VSMCs. Furthermore, overexpression of LEMD2 up-regulated the expression of NOX1 and down-regulated the expression of NOX4 while knockdown of LEMD2 show the opposite effect.

Conclusion

The present study confirmed that TET2 modulates VSMC proliferation and migration via LEMD2/NOX1/NOX4. The ROS level may be involved in VSMC proliferation and migration.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National natural science foundation of China
Omega-3 fatty acids differentially reduced expression of neutrophil degranulation-associated proteins in endothelial cells during IL-6 exposure
Authors: Sherratt S C R , Libby P , Bhatt D L , Dawoud H , Malinski T , Mason R P
Published: October 2021

Background

Neutrophil degranulation contributes to atherogenesis and tissue injury. Mixed omega-3 fatty acid (n3-FA) formulations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have failed to reduce CV events compared to EPA only (REDUCE-IT), but the mechanisms are not understood.

Purpose

The purpose of this study was to compare the effects of EPA and DHA on expression of proteins linked to neutrophil degranulation in the vascular endothelium in vitro.

Methods

Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA or DHA at equimolar levels (10 μM) for 2 h, then challenged with IL-6 at 12 ng/ml for 24 h. Proteomic analysis was performed using LC/MS to measure relative protein expression. Only significant (p<0.05) changes between treatment groups >1-fold were analyzed.

Results

In the Reactome “neutrophil degranulation” pathway, EPA and DHA downregulated 27 and 14 proteins, respectively, (p=9.97E-9 and 5.30E-4, respectively) relative to IL-6 alone. There were 12 protein changes common to both n3-FAs, including heme oxygenase-2 and ferritin light chain. EPA downregulated 15 proteins unlike DHA, including peroxiredoxin-6 and mitogen-activated protein kinase-1 (MAPK1). A combined 21 proteins downregulated by EPA and DHA versus IL-6 were upregulated by IL-6 alone relative to vehicle. EPA also increased expression of Rho-associated protein kinase-1 (ROCK-1), a protein downregulated by IL-6 alone and unaffected by DHA.

Conclusions

EPA and DHA differentially modulated expression of proteins linked to neutrophil degranulation. The distinct effects of EPA on protein expression may contribute to reduced inflammation in vascular injury compared to DHA.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): Amarin Pharma Inc., Elucida Research
Prospective analysis of inflammatory response markers, endothelial dysfunction and hemostasis parameters in COVID-19 associated pneumonia patients with and without type 2 diabetes mellitus
Authors: Petelina T , Musikhina N , Avdeeva K , Leonovich S , Gapon L , Gorbatenko E , Sharoyan Y , Zueva E , Yaroslavskaya E , Gultyaeva E , Kalyuzhnaya E , Shcherbinina A
Published: October 2021

Background

The coronavirus disease 2019 (COVID-19) has spread around the world with high cardiovascular complications and mortality. Patients with heart pathology and diabetes mellitus were at greatest risk. An accurate and timely laboratory diagnosis is a vital step to help manage cardiovascular disease during this pandemic.

Purpose

To conduct a prospective analysis of complete blood count parameters, inflammatory response, endothelial dysfunction of arterial wall and hemostasis in groups of patients undergoing COVID-19 associated pneumonia with and without type 2 diabetes mellitus (DM2); to highlight indicators of long-term adverse cardiovascular events.

Methods

The study was carried out within register on one-year cardiac follow-up of patients after COVID-19-associated pneumonia. Patients (n=380) were identified in the period from April to July 2020 according to the data of medical information system of monoinfectious hospital. At the moment, data of the first 65 patients with cardiovascular pathology are obtained. Group 1 included 53 patients without DM2 (mean age 47.83±15.86 years), group 2 consisted of 12 patients with DM2 (61.71±9.12 years). Baseline parameters of complete blood count, biochemistry and hemostasis were assessed on the day of hospitalization. In-depth analysis of laboratory parameters was carried out in 3 months.

Results

In group 1 significant decrease of coagulogram parameters: INR (p=0.004), fibrinogen, APTT, thrombocrit, large platelets level (p<0.0001), CRP level, liver enzymes (p<0.0001), leukocytes (p=0.015), erythrocytes (p=0.006) and increase in hematocrit (p<0.0001) were registered in 3 months compared to baseline data. In group 2 positive dynamics of CRP (p=0.018), platelets (p=0046), APTT (p=0.043) and erythrocytes (p=0.028) were revealed, while CRP concentration remained higher than reference values in 3 months. In group 2 in-depth analysis of biomarkers revealed values exceeding normal levels: hs-CRP (4.72±3.33 mg/L), homocysteine (13.17±7.95 μmol/L), myeloperoxidase (47.6±38.51), NT-proBNP (154.56±127.30 mg/ml), P-selectin (141.29±124.71) TgFb1 (6549.86±1987.87 pg/ml). Correlation analysis detected positive association of homocysteine level with platelets level (p=0.002. R=0.998), myeloperoxidase with fibrinogen (p=0.012. R=0.865).

Conclusion

Three months after COVID-19 elevated levels of inflammatory markers (CRP, hs-CRP, homocysteine), endothelial dysfunction and thrombophilia (large platelets, P-selectin, TgFb1) are indicators of prolonged arterial inflammatory syndrome and increased predisposition to coagulopathy with thrombosis determining a very high risk of developing adverse cardiovascular events in patients with DM2.

Funding Acknowledgement

Type of funding sources: None.
A highly contiguous nuclear genome assembly of the mandarinfish Synchiropus splendidus (Syngnathiformes: Callionymidae)
Authors: Stervander Martin , Cresko William A
Published: October 2021

The fish order Syngnathiformes has been referred to as a collection of misfit fishes, comprising commercially important fish such as red mullets as well as the highly diverse seahorses, pipefishes, and seadragons—the well-known family Syngnathidae, with their unique adaptations including male pregnancy. Another ornate member of this order is the species mandarinfish. No less than two types of chromatophores have been discovered in the spectacularly colored mandarinfish: the cyanophore (producing blue color) and the dichromatic cyano-erythrophore (producing blue and red). The phylogenetic position of mandarinfish in Syngnathiformes, and their promise of additional genetic discoveries beyond the chromatophores, made mandarinfish an appealing target for whole-genome sequencing. We used linked sequences to create synthetic long reads, producing a highly contiguous genome assembly for the mandarinfish. The genome assembly comprises 483 Mbp (longest scaffold 29 Mbp), has an N50 of 12 Mbp, and an L50 of 14 scaffolds. The assembly completeness is also high, with 92.6% complete, 4.4% fragmented, and 2.9% missing out of 4584 BUSCO genes found in ray-finned fishes. Outside the family Syngnathidae, the mandarinfish represents one of the most contiguous syngnathiform genome assemblies to date. The mandarinfish genomic resource will likely serve as a high-quality outgroup to syngnathid fish, and furthermore for research on the genomic underpinnings of the evolution of novel pigmentation.
uS5/Rps2 residues at the 40S ribosome entry channel enhance initiation at suboptimal start codons in vivo
Authors: Dong Jinsheng , Hinnebusch Alan G
Published: October 2021

The eukaryotic 43S pre-initiation complex (PIC) containing Met-tRNAiMet in a ternary complex (TC) with eIF2-GTP scans the mRNA leader for an AUG codon in favorable “Kozak” context. AUG recognition triggers rearrangement of the PIC from an open conformation to a closed state with more tightly bound Met-tRNAiMet. Yeast ribosomal protein uS5/Rps2 is located at the mRNA entry channel of the 40S subunit in the vicinity of mRNA nucleotides downstream from the AUG codon or rRNA residues that communicate with the decoding center, but its participation in start codon recognition was unknown. We found that nonlethal substitutions of conserved Rps2 residues in the entry channel reduce bulk translation initiation and increase discrimination against poor initiation codons. A subset of these substitutions suppress initiation at near-cognate UUG start codons in a yeast mutant with elevated UUG initiation, and also increase discrimination against AUG codons in suboptimal Kozak context, thus resembling previously described substitutions in uS3/Rps3 at the 40S entry channel or initiation factors eIF1 and eIF1A. In contrast, other Rps2 substitutions selectively discriminate against either near-cognate UUG codons, or poor Kozak context of an AUG or UUG start codon. These findings suggest that different Rps2 residues are involved in distinct mechanisms involved in discriminating against different features of poor initiation sites in vivo.
Fast mass lumped multiscale wave propagation modelling
Authors: Geevers Sjoerd , Maier Roland
Published: October 2021

In this paper we investigate the use of a mass lumped fully explicit time-stepping scheme for the discretization of the wave equation with underlying material parameters that vary at arbitrarily fine scales. We combine the leapfrog scheme for the temporal discretization with the multiscale technique known as localized orthogonal decomposition (LOD) for the spatial discretization. To speed up the method and to make it fully explicit, a special mass lumping approach is introduced that relies on an appropriate interpolation operator. This operator is also employed in the construction of the LOD and is a key feature of the approach. We prove that the method converges with second order in the energy norm, with a leading constant that does not depend on the scales at which the material parameters vary. We also illustrate the performance of the mass lumped method in a set of numerical experiments.
Severe Acute Respiratory Syndrome Coronavirus 2 Infection Induces Greater T-Cell Responses Compared to Vaccination in Solid Organ Transplant Recipients
Authors: Ferreira Victor H , Marinelli Tina , Ierullo Matthew , Ku Terrance , Hall Victoria G , Majchrzak-Kita Beata , Kulasingam Vathany , Humar Atul , Kumar Deepali
Published: October 2021

T-cell immunity associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination in solid organ transplant recipients (SOTRs) is poorly understood. To address this, we measured T-cell responses in 50 SOTRs with prior SARS-CoV-2 infection. The majority of patients mounted SARS-CoV-2–specific CD4+ T-cell responses against spike (S), nucleocapsid, and membrane proteins; CD8+ T-cell responses were generated to a lesser extent. CD4+ T-cell responses correlated with antibody levels. Severity of disease and mycophenolate dose were moderately associated with lower proportions of antigen-specific T cells. Relative to nontransplant controls, SOTRs had perturbations in both total and antigen-specific T cells, including higher frequencies of total PD-1+ CD4+ T cells. Vaccinated SOTRs (n = 55) mounted significantly lower proportions of S-specific polyfunctional CD4+ T cells after 2 doses, relative to unvaccinated SOTRs with prior coronavirus disease 2019. Together, these results suggest that SOTRs generate robust T-cell responses following natural infection that correlate with disease severity but generate comparatively lower T-cell responses following mRNA vaccination.
Evidence on cataract in low- and middle-income countries: an updated review of reviews using the evidence gap maps approach
Authors: Jolley Emma , Virendrakumar Bhavisha , Pente Vladimir , Baldwin Martin , Mailu Eunice , Schmidt Elena
Published: October 2021

In 2014, Sightsavers developed the first evidence gap map (EGM) to assess the extent and quality of review-level evidence on cataract relevant to low-and middle-income countries. The EGM identified 52 studies across five broad themes. This paper reports the update of the EGM conducted in 2021 and changes to the extent and quality of the evidence base. We updated the EGM using the exact process conducted to develop the original. Searches were run to 14 September 2021, and two independent reviewers selected eligible studies, critically appraised them and extracted data using the Supporting the Use of Research Evidence checklist. A summary quality assessment was shared with the authors for comments. Forty-six new reviews were identified, and the EGM now includes 98 reviews. The new reviews predominantly focus on treatment and risk factors. The overall methodological quality was found to be improved, with 13/46 reporting high confidence in findings. EGMs remain a useful tool for policy-makers to make informed decisions and periodic updates are important to assess changes and to refine the focus for future research. The EGM highlights significant disparity in the topics addressed by reviews, with health system interventions particularly neglected.
Estimating inbreeding depression for growth and reproductive traits using pedigree and genomic methods in Argentinean Brangus cattle
Authors: Forneris Natalia S , Garcia-Baccino Carolina A , Cantet Rodolfo J C , Vitezica Zulma G
Published: October 2021

Inbreeding depression reduces the mean phenotypic value of important traits in livestock populations. The goal of this work was to estimate the level of inbreeding and inbreeding depression for growth and reproductive traits in Argentinean Brangus cattle, in order to obtain a diagnosis and monitor breed management. Data comprised 359,257 (from which 1,990 were genotyped for 40,678 single nucleotide polymorphisms [SNPs]) animals with phenotypic records for at least one of three growth traits: birth weight (BW), weaning weight (WW), and finishing weight (FW). For scrotal circumference (SC), 52,399 phenotypic records (of which 256 had genotype) were available. There were 530,938 animals in pedigree. Three methods to estimate inbreeding coefficients were used. Pedigree-based inbreeding coefficients were estimated accounting for missing parents. Inbreeding coefficients combining genotyped and nongenotyped animal information were also computed from matrix H of the single-step approach. Genomic inbreeding coefficients were estimated using homozygous segments obtained from a Hidden Markov model (HMM) approach. Inbreeding depression was estimated from the regression of the phenotype on inbreeding coefficients in a multiple-trait mixed model framework, either for the whole dataset or for the dataset of genotyped animals. All traits were unfavorably affected by inbreeding depression. A 10% increase in pedigree-based or combined inbreeding would result in a reduction of 0.34 to 0.39 kg in BW, 2.77 to 3.28 kg in WW, and 0.23 cm in SC. For FW, a 10% increase in pedigree-based, genomic, or combined inbreeding would result in a decrease of 8.05 to 11.57 kg. Genomic inbreeding based on the HMM was able to capture inbreeding depression, even in such a compressed genotyped dataset.
Grazing diverse combinations of tanniferous and nontanniferous legumes: implications for foraging behavior, performance, and hair cortisol in beef cattle
Authors: Lagrange Sebastian , MacAdam Jennifer W , Stegelmeier Bryan , Villalba Juan J
Published: October 2021

A diversity of forages with different types and concentrations of nutrients and plant secondary compounds may lead to complementary relationships that enhance cattle performance and welfare. We determined whether grazing combinations of tanniferous legumes (Lotus corniculatus, birdsfoot trefoil [BFT], Onobrychis viciifolia, sainfoin [SF]), and alfalfa [ALF] (Medicago sativa) influence foraging behavior, performance, and hair cortisol concentration in beef cattle compared with grazing the same legumes as monocultures. Twenty-one pairs of heifers grazed three spatial replications of seven treatments: monocultures of BFT, SF, or ALF, and all possible two- and three-way choices among strips of these legumes: SF-BFT, ALF-BFT, ALF-SF, and ALF-SF-BFT in two periods of 25 d each (adaptation phase + experimental period) during two consecutive years. The lowest incidence of grazing events occurred in the BFT treatment (42.0% of the total scans recorded; P < 0.10), with the rest of the treatments ranging between 47.8% (SF-BFT) and 52.6% (ALF-SF) of the total scans recorded. Heifers selected a varied diet, preferring SF over BFT or ALF in a 46:27:27 ratio for the three-way choice, and in a 70:30 ratio for both two-way choices. Heifers preferred BFT over ALF (62:38 ratio) in a two-way choice. All treatments followed similar daily grazing patterns (P > 0.10), with two major grazing events (1 h after sunrise and 3 h before dark). No differences among treatments were observed for the number of steps taken by heifers on a daily basis, motion index, or the percentage of time heifers spent standing (1,599, 5,356, and 45.3%, respectively; P > 0.10), suggesting that heifers on choice treatments did not invest extra time in walking, searching, or patch switching activities relative to heifers grazing monocultures. Heifers grazing the three-way choice gained more body weight (1.27 kg/d) than the average gains observed for animals grazing in all legume monocultures (1.00 kg/d; P = 0.014) or two-way choices (0.97 kg/d; P = 0.007), suggesting a synergism among pasture species for the treatment with the highest diversity. No differences in hair cortisol concentration were observed among treatments, with values ranging between 1.4 (BFT) and 2.12 ng/g (three-way choice; P > 0.10). Thus, forage diversity has the potential to enhance animal performance without affecting grazing efficiency, likely explained by the spatial arrangement of the forage species presented in the study.
Social Media Public Opinion as Flocks in a Murmuration: Conceptualizing and Measuring Opinion Expression on Social Media
Authors: Zhang Yini , Chen Fan , Rohe Karl
Published: October 2021

We propose a new way of imagining and measuring opinions emerging from social media. As people tend to connect with like-minded others and express opinions in response to current events on social media, social media public opinion is naturally occurring, temporally sensitive, and inherently social. Our framework for measuring social media public opinion first samples targeted nodes from a large social graph and identifies homogeneous, interactive, and stable networks of actors, which we call “flocks,” based on social network structure, and then measures and presents opinions of flocks. We apply this framework to Twitter and provide empirical evidence for flocks being meaningful units of analysis and flock membership predicting opinion expression. Through contextualizing social media public opinion by foregrounding the various homogeneous networks it is embedded in, we highlight the need to go beyond the aggregate-level measurement of social media public opinion and study the social dynamics of opinion expression using social media.
Chalcone-rich extracts from Lonchocarpus cultratus roots present in vitro leishmanicidal and immunomodulatory activity
Authors: Staffen Izabela Virginia , Banhuk Fernanda Weyand , Tomiotto-Pellissier Fernanda , da Silva Bortoleti Bruna Taciane , Pavanelli Wander Rogério , Ayala Thaís Soprani , Menolli Rafael Andrade
Published: October 2021

Objectives

This study aimed to evaluate the in vitro anti-Leishmania activity of chalcone-rich three extracts (LDR, LHR and LMR) from Lonchocarpus cultratus (Vell.) A.M.G. Azevedo & H.C. Lima against L. amazonensis. Also, the immunomodulatory and antioxidant capacity was assessed.

Methods

Successive extraction with hexane, dichloromethane and methanol were performed to obtain LHR, LDR and LMR extracts from L. cultratus roots, which were characterized by 1H NMR. Promastigotes, amastigotes and peritoneal macrophages were exposed to crescent concentrations of the three extracts, and after incubation, the inhibition rates were determined to both types of cells, and morphological analyses were performed on the parasite. The immunomodulatory activity was determined against stimulated macrophages.

Key findings

LDR, LHR and LMR inhibited promastigote cell growth (IC50 0.62 ± 0.3, 0.94 ± 0.5 and 1.28 ± 0.73 µg/ml, respectively) and reduced the number of amastigotes inside macrophages (IC50 1.36 ± 0.14, 1.54 ± 0.26 and 4.09 ± 0.88 µg/ml, respectively). The cytotoxicity against murine macrophages resulted in a CC50 of 13.12 ± 1.92, 92.93 ± 9.1 and >300 µg/ml, resulting in high selectivity index to promastigotes and amastigotes. The extracts also inhibited the nitric oxide secretion in RAW 264.7 macrophages. The antioxidant capacity resulted in a higher scavenger LMR ability.

Conclusions

These results suggest that L. cultratus extracts have anti-Leishmania potential, are non-toxic, and immunosuppress macrophages in vitro.
Post-kala-azar dermal leishmaniasis due to Leishmania infantum in an HIV-negative patient treated with miltefosine
Authors: Monge-Maillo Begoña , Norman Francesca F , Chamorro-Tojeiro Sandra , Gioia Francesca , Pérez-Molina José-Antonio , Chicharro Carmen , Moreno Javier , López-Vélez Rogelio
Published: October 2021

Post-kala-azar dermal leishmaniasis due to Leishmania infantum in an HIV-negative patient is very infrequent and this case highlights how it can be associated to other types of immunosuppression. Moreover, this case reports an effective therapeutic option with miltefosine, which can be very useful due to the scarce experience reported.
Commission on Human Rights Drafting Committee
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the Drafting Committee (CHR) Draft Outline of International Bill of Rights, 4 June 1947.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR Meeting Summary, 1 June 1949.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR France-Belgium amendment, 18 April 1950.
Commission on Human Rights
Authors: Clooney Amal , Webb Philippa , Nelson Matthew
Published: October 2021

This section presents the CHR France amendment, 9 June 1952.
The effect of dark matter halo shape on bar buckling and boxy/peanut bulges
Authors: Kumar Ankit , Das Mousumi , Kataria Sandeep Kumar
Published: October 2021

It is well established that bars evolve significantly after they form in galaxy discs, often changing shape both in and out of the disc plane. In some cases they may bend or buckle out of the disc plane resulting in the formation of boxy/peanut/x-shape bulges. In this paper we show that the dark matter halo shape affects bar formation and buckling. We have performed N-body simulations of bar buckling in non-spherical dark matter haloes and traced bar evolution for 8 Gyr. We find that bar formation is delayed in oblate haloes, resulting in delayed buckling whereas bars form earlier in prolate haloes leading to earlier buckling. However, the duration of first buckling remains almost comparable. All the models show two buckling events but the most extreme prolate halo exhibits three distinct buckling features. Bars in prolate haloes also show buckling signatures for the longest duration compared to spherical and oblate haloes. Since ongoing buckling events are rarely observed, our study suggests that most barred galaxies may have more oblate or spherical haloes rather than prolate haloes. Our measurement of BPX structures also shows that prolate haloes promote bar thickening and disc heating more than oblate and spherical haloes.
The relativistic parsec-scale jets of the blazars TXS 0506+056 and PKS 0502+049 and their possible association with gamma-ray flares and neutrino production
Authors: Sumida Viktor Y D , Schutzer A de A , Caproni A , Abraham Z
Published: October 2021

The physical nature of the mechanism responsible for the emission of neutrinos in active galactic nuclei (AGNs) has been matter of debate in the literature, with relativistic jets of radio-loud AGNs as possible candidates to be the sources of high-energy neutrinos. The most prominent candidate so far is the blazar TXS 0506+056, which is found to be associated with the neutrino event IceCube-170922A. Furthermore, the IceCube reported an excess of neutrinos towards TXS 0506+056 between September 2014 and March 2015, even though this association needs additional investigation, considering the presence of a nearby gamma-ray source, the quasar PKS 0502+049. Motivated by this, we studied the parsec-scale structures of TXS 0506+056 and PKS 0502+049 through radio interferometry at 8 and 15 GHz. We identified twelve jet components in TXS 0506+056 and seven components in PKS 0502+049. The most reliable jet components show superluminal speeds ranging from 9.5c to 66c in the case of TXS 0506+056, and from 14.3c to 59c for PKS 0502+049, which were used to estimate a lower (upper) limit for the Lorentz factor (jet viewing angle) for both sources. A novel approach using simultaneously the brightness temperature of the core region and the apparent speeds of the jet components allowed us to infer basic jet parameters for TXS 0506+056 at distinct epochs. We also found that the emergence of new jet components coincides with the occurrence of gamma-ray flares. Interestingly, two of these coincidences in the case of PKS 0502+049 and one for TXS 0506+056 seems to be correlated with neutrino events detected by the IceCube Observatory.
Galaxy–galaxy lensing with the DES-CMASS catalogue: measurement and constraints on the galaxy-matter cross-correlation
Authors: Lee S , Troxel M A , Choi A , Elvin-Poole J , Hirata C , Honscheid K , Huff E M , MacCrann N , Ross A J , Eifler T F , Chang C , Miquel R , Omori Y , Prat J , Bernstein G M , Davis C , DeRose J , Gatti M , Rau M M , Samuroff S , Sánchez C , Vielzeuf P , Zuntz J , Aguena M , Allam S , Amon A , Andrade-Oliveira F , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Cawthon R , Conselice C , Costanzi M , da Costa L N , Pereira M E S , De Vicente J , Desai S , Diehl H T , Dietrich J P , Doel P , Everett S , Evrard A E , Ferrero I , Flaugher B , Fosalba P , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Giannantonio T , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hinton S R , Hollowood D L , Hoyle B , Huterer D , James D J , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , March M , Marshall J L , Menanteau F , Mohr J J , Morgan R , Palmese A , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Roodman A , Sanchez E , Scarpine V , Schubnell M , Serrano S , Sevilla-Noarbe I , Sheldon E , Smith M , Suchyta E , Swanson M E C , Tarle G , Thomas D , To C , Varga T N , Weller J ,   (DES Collaboration)
Published: October 2021

The DMASS sample is a photometric sample from the DES Year 1 data set designed to replicate the properties of the CMASS sample from BOSS, in support of a joint analysis of DES and BOSS beyond the small overlapping area. In this paper, we present the measurement of galaxy–galaxy lensing using the DMASS sample as gravitational lenses in the DES Y1 imaging data. We test a number of potential systematics that can bias the galaxy–galaxy lensing signal, including those from shear estimation, photometric redshifts, and observing conditions. After careful systematic tests, we obtain a highly significant detection of the galaxy–galaxy lensing signal, with total S/N = 25.7. With the measured signal, we assess the feasibility of using DMASS as gravitational lenses equivalent to CMASS, by estimating the galaxy-matter cross-correlation coefficient rcc. By jointly fitting the galaxy–galaxy lensing measurement with the galaxy clustering measurement from CMASS, we obtain $r_{\rm cc}=1.09^{+0.12}_{-0.11}$ for the scale cut of $4 \, h^{-1}{\rm \,\,Mpc}$ and $r_{\rm cc}=1.06^{+0.13}_{-0.12}$ for $12 \, h^{-1}{\rm \,\,Mpc}$ in fixed cosmology. By adding the angular galaxy clustering of DMASS, we obtain rcc = 1.06 ± 0.10 for the scale cut of $4 \, h^{-1}{\rm \,\,Mpc}$ and rcc = 1.03 ± 0.11 for $12 \, h^{-1}{\rm \,\,Mpc}$. The resulting values of rcc indicate that the lensing signal of DMASS is statistically consistent with the one that would have been measured if CMASS had populated the DES region within the given statistical uncertainty. The measurement of galaxy–galaxy lensing presented in this paper will serve as part of the data vector for the forthcoming cosmology analysis in preparation.
Developing guidelines for the management of brain tumour related epilepsy
Authors: Vacher Elizabeth , Ruiz Miguel Rodriguez , Rees Jeremy
Published: October 2021

Aims

Brain Tumour Related Epilepsy (BTRE) has a significant impact on Quality of Life with implications for driving, employment and social and domestic activities. Management of BTRE is complex due to the higher incidence of pharmacoresistance and the potential for interaction between anti-cancer therapy and anti-epileptic drugs (AEDs). Neurologists, oncologists, palliative care physicians and clinical nurse specialists treating these patients would benefit from up-to-date clinical guidelines. We aim to review the current evidence to adapt current NICE guidelines for Epilepsy and to outline specific recommendations for the optimal treatment of BTRE, encompassing both primary and metastatic brain tumours.

Method

A comprehensive search of the literature from the past 20 years on BTRE was carried out in three databases: Embase, Medline and EMCARE. A broad search strategy was used and the evidence was evaluated and graded based on the Oxford Centre for Evidence-Based Medicine Levels of Evidence.

Results

All patients with BTRE should be treated with AEDs. There is no proven benefit for the use of prophylactic AEDs, although there are no randomised trials testing newer agents. Seizure frequency varies between 10-40% (Class 2a evidence) in patients with Brain Metastases (BM) and from 30% (high-grade gliomas) to 90% (low-grade gliomas) (Class 2a evidence) in patients with Primary Brain Tumours (PBT). In patients with BM, risk factors include number of BM and melanoma histology (Class 2b evidence). In patients with PBT, risk factors include frontal and temporal location, oligodendroglial histology, IDH mutation and cortical infiltration (Class 2b evidence). There is a low incidence of seizures (13%) after stereotactic radiosurgery for BM (Class 2b evidence). Non-enzyme inducing AEDs are recommended as first line treatment for BTRE, but up to 50% of patients with BTRE due to PBT remain resistant (Class 2b evidence).

Conclusion

The review has highlighted the relative dearth of high quality evidence for the management of BTRE, and provides a framework for further studies aiming to improve seizure control, quality of life, and indications for AEDs.
Initial experience with navigated intraoperative ultrasound for brain tumour surgery
Authors: Nunn Adam , Barua Neil
Published: October 2021

Aims

The use of intraoperative ultrasound (iUS) has been associated with prolonged survival in patients with high grade glioma. However, iUS remains an under-utilised surgical adjunct in many neurosurgical units due to greater familiarity with CT and MR imaging. Navigated intraoperative ultrasound (NiUS) facilitates co-registration of pre-operative MR imaging with iUS, offering a number of advantages over standard neuronavigation. The aim of this study was to describe our initial experiences with NiUS for brain tumour resection in adults.

Method

We prospectively collected data on patient demographics, tumour location and histology, extent of resection and early post-operative outcome in 9 consecutive patients. Brainlab neuronavigation (BrainLab, Germany) and the BK5000 cranial ultrasound probe (BK Medical, Denmark) were used in all cases. We also collected data on surgical intent and the use of surgical adjuncts including neurophysiology monitoring, DTI and 5ALA.

Results

NiUS was used in 9 patients (6 male, 3 female). iUS scans were successfully co-registered in all cases. Histological diagnoses were GBM (7 patients), melanoma (1 patient) and oligodendroglioma (1 patient). NiUS was used in conjunction with the following techniques and adjuncts – awake craniotomy (2), DTI (all cases), neurophysiology monitoring (4 cases) and 5ALA (7 cases). Gross total resection was achieved in 8 patients. The mean operative time was 4 hours and 7 minutes, which is significantly lower than that reported in a recently published series involving intra-operative MRI. No patients suffered any deterioration in neurological status in the early post-operative period.

Conclusion

NiUS was rapidly assimilated into our surgical workflow with successful co-registration in all cases. NiUS was used successfully in conjunction with awake craniotomy, neurophysiology monitoring, DTI and 5ALA for both enhancing and non-enhancing tumours. Based on our early experience we offer learning points on patient positioning, set up of equipment and interpretation of iUS. Further studies are required to determine the impact of NiUS on patient outcome.
Strengthening Population Health Perspectives in Physical Therapist Practice Using Epigenetics
Authors: Magnusson Dawn M , Rethorn Zachary D
Published: October 2021

Health starts where we live, learn, work, and play. Population health represents a unifying paradigm for understanding systematic variations in health and related factors, informing integrated action, and reducing health disparities. The pathways connecting social, environmental, and structural factors and various health outcomes have been illuminated by the emergence of epigenetic and epigenomic research, further bolstering the value of population health perspectives in supporting clinical practice, community-based programs, and societal policies. The purpose of this perspective is to consider the placement of epigenetic and epigenomic insights within a population health framework to strengthen the physical therapy profession’s understanding of variations in health, inform integrated action, and further justify our role in reducing health-related disparities.
Relating Cut and Paste Invariants and Tqfts
Authors: Rovi Carmen , Schoenbauer Matthew
Published: October 2021

In this paper, we are concerned with a relation between TQFTs and the cut and paste SKK invariants introduced by Karras, Kreck, Neumann, and Ossa. Cut and paste SKK invariants are functions on the set of smooth manifolds whose values on cut and paste equivalent manifolds differ by an error term depending only on the glueing diffeomorphisms. Here we investigate a surprisingly natural group homomorphism between the group of invertible TQFTs and the group of SKK invariants and describe how these groups fit into an exact sequence. We conclude in particular that all positive real-valued SKK invariants can be realized as restrictions of invertible TQFTs.
Special Repo Rates and the Cross-Section of Bond Prices: The Role of the Special Collateral Risk Premium
Authors: D’Amico Stefania , Pancost N Aaron
Published: October 2021

We price the risky component of specialness spreads—identified by their deviations from the expected auction cycle—within a dynamic term structure model estimated using daily prices of all outstanding Treasury securities and corresponding special collateral (SC) repo rates. This allows us to derive a time-varying SC risk premium that we quantitatively link to various price anomalies, such as the on-the-run premium. The SC risk premium explains about 80% of the on-the-run premium and a substantial share of other Treasury price anomalies, suggesting that unexpected fluctuations in the specialness spreads of recently issued nominal Treasury securities are a common risk factor.
The Macrobiotus ariekammensis species complex provides evidence for parallel evolution of claw elongation in macrobiotid tardigrades
Authors: Stec Daniel , Vončina Katarzyna , Møbjerg Kristensen Reinhardt , Michalczyk Łukasz
Published: October 2021

The recent integrative revision of the family Macrobiotidae demonstrated monophyly of the genus Macrobiotus and its complex, mosaic morphological evolution. Here, we analyse three Macrobiotus populations that exhibit extraordinary claw morphology characterized by elongated primary branches. Two of these populations, from the Arctic, were initially classified as Macrobiotus ariekammensis, but detailed integrative analyses resulted in splitting them into two subspecies: Macrobiotus ariekammensis ariekammensis and Macrobiotus ariekammensis groenlandicus subsp. nov.. The third population was Macrobiotus kirghizicus from Kyrgyzstan. Given the unusual phenotype of the above-mentioned taxa, we tested whether they constitute a distinct lineage in the family Macrobiotidae and could be delineated as a new genus. Although the phylogenetic investigation showed that the three taxa form a monophyletic group, the clade is nested in the genus Macrobiotus. Therefore, despite their morphological distinctiveness, a new genus cannot be established and we group these taxa in the Macrobiotus ariekammensis species complex instead. The complex includes the three above-mentioned taxa and Macrobiotus ramoli, which is included based on morphological characters. Moreover, our results provide evidence for rapid parallel evolution of long claws in macrobiotid tardigrades inhabiting cold and icy environments. Finally, we discuss the validity of the recent suppression of the genus Xerobiotus, which gathers macrobiotids with reduced claws.
Parkland Trauma Index of Mortality: Real-Time Predictive Model for Trauma Patients
Authors: Starr Adam J. , Julka Manjula , Nethi Arun , Watkins John D. , Fairchild Ryan W. , Rinehart Dustin , Park Caroline , Dumas Ryan P. , Box Hayden N. , Cripps Michael W.
Published: October 2021

Objective:

Vital signs and laboratory values are used to guide decisions to use damage control techniques in lieu of early definitive fracture fixation. Previous models attempted to predict mortality risk but have limited utility. There is a need for a dynamic model that captures evolving physiologic changes during a trauma patient's hospital course.

Methods:

The Parkland Trauma Index of Mortality (PTIM) is a machine learning algorithm that uses electronic medical record data to predict mortality within 48 hours during the first 3 days of hospitalization. It updates every hour, recalculating as physiology changes. The model was developed using 1935 trauma patient encounters from 2009 to 2014 and validated on 516 patient encounters from 2015 to 2016. Model performance was evaluated statistically. Data were collected retrospectively on its performance after 1 year of clinical use.

Results:

In the validation data set, PTIM accurately predicted 52 of the sixty-three 12-hour time intervals within 48 hours of mortality, for sensitivity of 82.5% [95% confidence interval (CI), 73.1%–91.9%]. The specificity was 93.6% (95% CI, 92.5%–94.8%), and the positive predictive value (PPV) was 32.5% (95% CI, 25.2%–39.7%). PTIM predicted survival for 1608 time intervals and was incorrect only 11 times, yielding a negative predictive value of 99.3% (95% CI, 98.9%–99.7%). The area under the curve of the receiver operating characteristic curve was 0.94.

During the first year of clinical use, when used in 776 patients, the last PTIM score accurately predicted 20 of the twenty-three 12-hour time intervals within 48 hours of mortality, for sensitivity of 86.9% (95% CI, 73%–100%). The specificity was 94.7% (95% CI, 93%–96%), and the positive predictive value was 33.3% (95% CI, 21.4%–45%). The model predicted survival for 716 time intervals and was incorrect 3 times, yielding a negative predictive value of 99.6% (95% CI, 99.1%–100%). The area under the curve of the receiver operating characteristic curve was 0.97.

Conclusions:

By adapting with the patient's physiologic response to trauma and relying on electronic medical record data alone, the PTIM overcomes many of the limitations of previous models. It may help inform decision-making for trauma patients early in their hospitalization.

Level of Evidence:

Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.
Intravenous thrombolysis for acute ischemic stroke with extended time window
Authors: Jia Xue , Wang Wen , Wu Bo , Sun Xin
Published: October 2021

Background:

Intravenous thrombolysis (IVT) is an effective way for treating acute ischemic stroke (AIS). However, its effects have not been established among AIS patients with unclear stroke symptoms or with stroke onset for >4.5 h.

Methods:

We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Google Scholar databases for randomized controlled trials that compared IVT (IVT group) and placebo or usual care (control group [CG]) in AIS patients with disease onset for >4.5 h. The outcomes of interest included the favorable functional outcome (defined as modified Rankin Scale [mRS] scores 0–1) at 90 days, the functional independence (defined as mRS scores 0–2) at 90 days, proportion of patients with symptomatic intracerebral hemorrhage (sICH) and death at 90 days. We assessed the risk of bias using the Cochrane tool. Pre-specified subgroup analyses were performed by age (≤70 years or >70 years), National Institute of Health Stroke Scale (NIHSS, ≤10 or >10) and time window (4.5–9.0 h or >9.0 h).

Results:

Four trials involving 848 patients were eligible. The risk of bias of included trials was low. Patients in the IVT group were more likely to achieve favorable functional outcomes (45.8% vs. 36.7%; OR 1.48, 95% CI 1.12–1.96) and functional independence (63.8% vs. 55.7%; OR 1.43, 95% CI 1.08–1.90) at 90 days, but had higher risk of sICH (3.0% vs. 0.5%; OR 5.28, 95% CI 1.35–20.68) at 90 days than those in the CG. No significant difference in death at 90 days was found between the two groups (7.0% vs. 4.1%; OR 1.80; 95% CI 0.97–3.34).

Conclusions:

Use of IVT in patients with extended time window may improve their functional outcomes at 90 days, although IVT may induce increased risk of sICH. Care of these patients should well balance the potential benefits and harms of IVT.
Factors relating to bone mineral density in young and middle-aged patients with ankylosing spondylitis
Authors: Wu Xin , Zhong Jia-Yun , Wang Geng , Xu Hu-ji
Published: October 2021

Background:

Ankylosing spondylitis (AS) is a common chronic progressive rheumatic disease. The aim of this study was to explore factors influencing abnormal bone mineral density (BMD) in young and middle-aged patients with AS.

Methods:

From July 2014 to August 2018, hospitalized patients with AS and health examinees in the health examination center of our clinics, ranging in age from 20 to 50 years, were monitored. The BMD of the lumbar spine and femoral neck of AS patients and those of a healthy control group were measured using dual-energy X-ray absorption. The BMDs of AS patients were compared with respect to age, course of disease, iritis, smoking habits, sex, height, weight, body mass index (BMI), medication use, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet volume, platelet count, uric acid (UA), alkaline phosphatase (AKP), and calcium ion levels. Single-nucleotide polymorphisms (SNPs) related to BMD were screened using genome-wide association analysis.

Results:

There was no statistical difference in the proportion of abnormal bone masses between the different body parts. The BMD of all bones in AS patients was lower than that in healthy controls (P < 0.05). Additionally, BMD was correlated with serum calcium and CRP in AS patients (P < 0.05), but not with age, platelet volume, platelet count, ESR, UA, AKP, height, weight, and BMI. The incidence of abnormal bone mass in AS patients was correlated with sex (P < 0.05), but not with medication use, iritis, or smoking. BMD of the lumbar spine in AS patients did not correlate linearly with the course of the disease, but BMD of the femoral neck correlated linearly with the course of the disease (P < 0.05). BMD was correlated with multiple SNPs in patients with AS. Lumbar BMD was correlated with rs7025373 and rs7848078. Femoral head BMD was correlated with 3:102157365, 3:102157417, rs1252202, rs1681355, rs3891857, rs7842614, and rs9870734, suggesting that genetic factors play a role in BMD in patients with AS.

Conclusions:

The proportion of abnormal bone mass in AS patients was higher than that in healthy individuals of the same age. The factors related to BMD in patients with AS are gender, CRP, and blood calcium. The BMD of the femoral neck of AS patients decreases with the course of the disease, but BMD of the lumbar spine is not related to the course of the disease. BMD in AS patients is associated with multiple SNPs.