bluuebunny/crossref_metadata_2025 huggingface dataset:
FastRemap: a tool for quickly remapping reads between genome assemblies
Authors: Kim Jeremie S , Firtina Can , Cavlak Meryem Banu , Senol Cali Damla , Alkan Can , Mutlu Onur
Published: August 2022

Motivation

A genome read dataset can be quickly and efficiently remapped from one reference to another similar reference (e.g., between two reference versions or two similar species) using a variety of tools, e.g., the commonly used CrossMap tool. With the explosion of available genomic datasets and references, high-performance remapping tools will be even more important for keeping up with the computational demands of genome assembly and analysis.

Results

We provide FastRemap, a fast and efficient tool for remapping reads between genome assemblies. FastRemap provides up to a 7.82× speedup (6.47×, on average) and uses as low as 61.7% (80.7%, on average) of the peak memory consumption compared to the state-of-the-art remapping tool, CrossMap.

Availability and implementation

FastRemap is written in C++. Source code and user manual are freely available at: github.com/CMU-SAFARI/FastRemap. Docker image available at: https://hub.docker.com/r/alkanlab/fastremap. Also available in Bioconda at: https://anaconda.org/bioconda/fastremap-bio.
Comparative genomics and evolutionary analysis of plant CNGCs
Authors: Baloch Akram Ali , Kakar Kaleem U , Nawaz Zarqa , Mushtaq Muhammad , Abro Asma , Khan Samiullah , Latif Abdul
Published: August 2022

Comparative genomics and computational biology offer powerful research tools for studying evolutionary mechanisms of organisms, and the identification and characterization of conserved/distant genes and gene families. The plant CNGC gene family encodes evolutionary conserved ion channel proteins involved in important signaling pathways and biological functions. The fundamental ideas and standard procedures for genome-wide identification and evolutionary analysis of plant cyclic nucleotide-gated ion channels employing various software, tools, and online servers have been discussed. In particular, this developed method focused on practical procedures involving the comparative analysis of paralogs and orthologs of CNGC genes in different plant species at different levels including phylogenetic analysis, nomenclature and classification, gene structure, molecular protein evolution, and duplication events as mechanisms of gene family expansion and synteny.
CSF biomarkers in patients with epilepsy in Alzheimer’s disease: a nation-wide study
Authors: Banote Rakesh Kumar , Håkansson Samuel , Zetterberg Henrik , Zelano Johan
Published: August 2022

Alzheimer’s disease is the most common neurodegenerative dementia. A subset of Alzheimer’s disease patients develop epilepsy. The risk is higher in young-onset Alzheimer’s disease, but pathophysiological mechanisms remain elusive. The purpose of this study was to assess biomarkers reflecting neurodegeneration in Alzheimer’s disease patients with and without epilepsy. By cross-referencing the largest national laboratory database with Swedish National Patient Register, we could identify CSF biomarker results from 17901 Alzheimer’s disease patients, and compare levels of neurofilament light, glial fibrillary acidic protein, total tau, phosphorylated tau and amyloid beta 42 in patients with (n = 851) and without epilepsy. The concentrations of total tau and phosphorylated tau were higher in Alzheimer’s disease patients with epilepsy than Alzheimer’s disease patients without epilepsy and amyloid beta 42 levels were significantly lower in Alzheimer’s disease patients with epilepsy. No differences in the levels of neurofilament light and glial fibrillary acidic protein were observed. Our study suggests that epilepsy is more common in Alzheimer’s disease patients with more pronounced Alzheimer’s pathology, as determined by the CSF biomarkers. Further studies are needed to investigate the biomarker potential of these CSF markers as predictors of epilepsy course or as indicators of epileptogenesis in Alzheimer’s disease.
Effectiveness of Coronavirus Disease 2019 Vaccines Against Hospitalization and Death in Canada: A Multiprovincial, Test-Negative Design Study
Authors: Nasreen Sharifa , Febriani Yossi , Velásquez García Héctor Alexander , Zhang Geng , Tadrous Mina , Buchan Sarah A , Righolt Christiaan H , Mahmud Salaheddin M , Janjua Naveed Zafar , Krajden Mel , De Serres Gaston , Kwong Jeffrey C
Published: August 2022

Background

A major goal of coronavirus disease 2019 (COVID-19) vaccination is to prevent severe outcomes (hospitalizations and deaths). We estimated the effectiveness of messenger RNA (mRNA) and ChAdOx1 COVID-19 vaccines against severe outcomes in 4 Canadian provinces between December 2020 and September 2021.

Methods

We conducted this multiprovincial, retrospective, test-negative study among community-dwelling adults aged ≥18 years in Ontario, Quebec, British Columbia, and Manitoba using linked provincial databases and a common study protocol. Multivariable logistic regression was used to estimate province-specific vaccine effectiveness against COVID-19 hospitalization and/or death. Estimates were pooled using random-effects models.

Results

We included 2 508 296 tested participants, with 31 776 COVID-19 hospitalizations and 5842 deaths. Vaccine effectiveness was 83% after a first dose and 98% after a second dose against both hospitalization and death (separately). Against severe outcomes, effectiveness was 87% (95% confidence interval [CI], 71%–94%) ≥84 days after a first dose of mRNA vaccine, increasing to 98% (95% CI, 96%–99%) ≥112 days after a second dose. Vaccine effectiveness against severe outcomes for ChAdOx1 was 88% (95% CI, 75%–94%) ≥56 days after a first dose, increasing to 97% (95% CI, 91%–99%) ≥56 days after a second dose. Lower 1-dose effectiveness was observed for adults aged ≥80 years and those with comorbidities, but effectiveness became comparable after a second dose. Two doses of vaccines provided very high protection for both homologous and heterologous schedules and against Alpha, Gamma, and Delta variants.

Conclusions

Two doses of mRNA or ChAdOx1 vaccine provide excellent protection against severe outcomes.
Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV)
Authors: Schnittman Samuel R , Lu Michael T , Mayrhofer Thomas , Burdo Tricia H , Fitch Kathleen V , McCallum Sara , Fulda Evelynne S , Zanni Markella V , Foldyna Borek , Malvestutto Carlos , Fichtenbaum Carl J , Aberg Judith A , Bloomfield Gerald S , Overton Edgar T , Currier Judith , Tebas Pablo , Sha Beverly E , Ribaudo Heather J , Flynn Jacqueline M , Douglas Pamela S , Erlandson Kristine M , Grinspoon Steven K
Published: August 2022

Background

Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque.

Methods

The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40–75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry.

Results

Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5.

Conclusions

No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events.

Clinical Trials Registration

NCT02344290.
Bacterial exometabolites influence Chlamydomonas cell cycle and double algal productivity
Authors: Windler Miriam , Stuart Rhona , Deutzmann Joerg S , Mayali Xavier , Navid Ali , D'haeseleer Patrik , Marcu Oana E , Lipton Mary , Nicora Carrie , Spormann Alfred M
Published: August 2022

Algal-bacterial interactions provide clues to algal physiology, but mutualistic interactions are complicated by dynamic exchange. We characterized the response of Chlamydomonas reinhardtii to the presence of a putative alga-benefitting commensal bacterium (Arthrobacter strain ‘P2b’). Co-cultivation promoted chlorophyll content, biomass, average cell size, and number of dividing cells, relative to axenic cultures. Addition of bacterial spent medium (whole, size-fractionated and heat-treated) had similar effects, indicating P2b does not require algal interaction to promote growth. Nutrients and pH were excluded as putative effectors, collectively indicating a commensal interaction mediated by Arthrobacter-released small exometabolite(s). Proteogenomic comparison revealed similar response to co-cultivation and spent media, including differential cell cycle regulation, extensive downregulation of flagellar genes and histones, carbonic anhydrase and RubisCO downregulation, upregulation of some chlorophyll, amino acid and carbohydrate biosynthesis genes, and changes to redox and Fe homeostasis. Further, Arthrobacter protein expression indicated some highly expressed putative secondary metabolites. Together, these results revealed that low molecular weight bacterial metabolites can elicit major physiological changes in algal cell cycle regulation, perhaps through a more productive G1 phase, that lead to substantial increases in photosynthetically-produced biomass. This work illustrates that model commensal interactions can be used to shed light on algal response to stimulating bacteria.
Chromosome-level Genome Assembly of the High-altitude Leopard (Panthera pardus) Sheds Light on Its Environmental Adaptation
Authors: Zhou Chuang , Liu Yi , Zhang Rusong , Zheng Xiaofeng , Zhao Guangqing , Li Fengjun , Liu Wei , Yue Bisong , Yang Nan
Published: August 2022

The leopard (Panthera pardus) has the largest natural distribution from low- to high-altitude areas of any wild felid species, but recent studies have revealed that leopards have disappeared from large areas, probably owing to poaching, a decline of prey species, and habitat degradation. Here, we reported the chromosome-scale genome assembly of the high-altitude leopard (HL) based on nanopore sequencing and high-throughput chromatin conformation capture (Hi-C) technology. Panthera genomes revealed similar repeat composition, and there was an appreciably conserved synteny between HL and the other two Panthera genomes. Divergence time analysis based on the whole genomes revealed that the HL and the low-altitude leopard differentiate from a common ancestor ∼2.2 Ma. Through comparative genomics analyses, we found molecular genetic signatures that may reflect high-altitude adaptation of the HL. Three HL-specific missense mutations were detected in two positively selected genes, that is, ITGA7 (Ala112Gly, Asp113Val, and Gln115Pro) and NOTCH2 (Ala2398Ser), which are likely to be associated with hypoxia adaptation. The chromosome-level genome of the HL provides valuable resources for the investigation of high-altitude adaptation and protection management of the vulnerable leopard.
The Role of the Gut Microbiome in Diet and Exercise Effects on Cognition: A Review of the Intervention Literature
Authors: Koblinsky Noah D , Power Krista A , Middleton Laura , Ferland Guylaine , Anderson Nicole D
Published: August 2022

Interest in the gut–brain axis and its implications for neurodegenerative diseases, such as Alzheimer’s disease and related dementias, is growing. Microbial imbalances in the gastrointestinal tract, which are associated with impaired cognition, may represent a therapeutic target for lowering dementia risk. Multicomponent lifestyle interventions are a promising dementia risk reduction strategy and most often include diet and exercise, behaviors that are also known to modulate the gut microbiome. A better understanding of the role of the gut microbiome in diet and exercise effects on cognition may help to optimize these lifestyle interventions. The purpose of this review is to summarize findings from diet and exercise interventions that have investigated cognitive changes via effects on the microbiome. We aim to discuss the underlying mechanisms, highlight current gaps in the field, and provide new research directions. There is evidence mainly from rodent studies supporting the notion that microbiota changes mediate the effects of diet and exercise on cognition, with potential mechanisms including end-product metabolites and regulation of local and systemic inflammation. The field lacks whole diet and exercise interventions, especially those involving human participants. It is further limited by heterogeneous rodent models, outcome assessments, and the absence of proper mediation analyses. Trials including older adults with dementia risk factors, factorial designs of diet and exercise, and pre and post measures of microbiota, end-product metabolites, and inflammation would help to elucidate and potentially leverage the role of the microbiome in lowering dementia risk through lifestyle modification.
Sexual and Marital Satisfaction in Older Adulthood: Effects of Childhood and Adulthood Violence Exposure
Authors: Kong Jooyoung , Easton Scott D , Zhang Yan
Published: August 2022

Background and Objectives

Guided by the life course perspective and traumagenic dynamics theory, the current study examines (a) the long-term effects of childhood sexual abuse (CSA) and other adverse childhood experiences (ACEs) on older adults’ sexual and marital outcomes, (b) the mediating role of intimate partner violence (IPV) victimization in the association between childhood adversities and sexual and marital satisfaction, and (c) whether gender moderates the mediational association.

Research Design and Methods

We examined 5,391 adults in their early 70s who participated in the 2010–2011 Wisconsin Longitudinal Study. A series of structural equation models was performed to examine the direct and indirect effect of CSA and other ACEs on sexual and marital outcomes in later life.

Results

CSA was directly associated with lower levels of sexual and marital satisfaction in late adulthood. Other ACEs were associated with currently not being married and greater numbers of marriages. Furthermore, other ACEs were significantly associated with low levels of marital satisfaction through IPV victimization. The moderated mediational analysis showed that the negative indirect effect of other ACEs on marital satisfaction via IPV victimization was stronger for women than men.

Discussion and Implications

Using a population-based sample, this is one of the first studies demonstrating that distal life events such as CSA and ACEs can undermine older adults’ sexual and marital health, and revictimization in adulthood may serve as a mechanism for the association. Timely intervention is needed to prevent persistent negative effects of childhood violence.
A re-examination of ellipticity corrections for seismic phases
Authors: Russell Stuart , Rudge John F , Irving Jessica C E , Cottaar Sanne
Published: August 2022

The Earth’s ellipticity of figure has an effect on the traveltimes of seismic waves over teleseismic distances. Tables of ellipticity corrections and coefficients have been used by seismologists for several decades; however, due to the increasing variety and complexity of seismic phases in use, current tables of ellipticity coefficients are now outmoded and incomplete. We present a Python package, EllipticiPy, for the calculation of ellipticity corrections, which removes the dependence on pre-calculated coefficients at discrete source depths and epicentral distances. EllipticiPy also facilitates the calculation of ellipticity corrections on other planetary bodies. When applied to both Earth and Mars, the magnitudes of ellipticity corrections are of the order of single seconds and are significant for some seismic studies on Earth but remain negligible on Mars due to other greater sources of uncertainty.
Influence of shear wave velocity heterogeneity on SH-wave reverberation imaging of the mantle transition zone
Authors: Liu Meichen , Ritsema Jeroen , Chaves Carlos A M
Published: August 2022

Long-period (T > 10 s) shear wave reflections between the surface and reflecting boundaries below seismic stations are useful for studying phase transitions in the mantle transition zone (MTZ) but shear-velocity heterogeneity and finite-frequency effects complicate the interpretation of waveform stacks. We follow up on a recent study by Shearer & Buehler (hereafter SB19) of the top-side shear wave reflection Ssds as a probe for mapping the depths of the 410-km and 660-km discontinuities beneath the USArray. Like SB19, we observe that the recorded Ss410s-S and Ss660s-S traveltime differences are longer at stations in the western United States than in the central-eastern United States. The 410-km and 660-km discontinuities are about 40–50 km deeper beneath the western United States than the central-eastern United States if Ss410s-S and Ss660s-S traveltime differences are transformed to depth using a common-reflection point (CRP) mapping approach based on a 1-D seismic model (PREM in our case). However, the east-to-west deepening of the MTZ disappears in the CRP image if we account for 3-D shear wave velocity variations in the mantle according to global tomography. In addition, from spectral-element method synthetics, we find that ray theory overpredicts the traveltime delays of the reverberations. Undulations of the 410-km and 660-km discontinuities are underestimated when their wavelengths are smaller than the Fresnel zones of the wave reverberations in the MTZ. Therefore, modelling of layering in the upper mantle must be based on 3-D reference structures and accurate calculations of reverberation traveltimes.
An inverse data envelopment analysis model to consider ratio data and preferences of decision-makers
Authors: Mahla Deepak , Agarwal Shivi , Amin Gholam R , Mathur Trilok
Published: August 2022

Inverse data envelopment analysis (DEA) determines the optimal level of inputs and/or outputs of decision-making units (DMUs) to reach efficiency targets. This paper presents a new inverse DEA model for determining minimum inputs for working capital management. The proposed model is employed in the Indian textile industry to calculate working capital efficiency. Given the working capital efficiency, the decision maker’s preferences will be estimating the change in inputs when outputs increase. Furthermore, unlike the standard inverse DEA model, this article discusses the inverse DEA model when negative ratio data exist. The DEA model requires additional attention when ratio data are present; therefore, a novel inverse DEA ratio model is proposed. The input targets obtained from the proposed model are less than the standard inverse DEA model. Also, the proposed model is a closer estimate of the production probability set for ratio data.
Anti-cancer mechanisms of action of therapeutic alternating electric fields (tumor treating fields [TTFields])
Authors: Shams Shadi , Patel Chirag B
Published: August 2022

Despite improved survival outcomes across many cancer types, the prognosis remains grim for certain solid organ cancers including glioblastoma and pancreatic cancer. Invariably in these cancers, the control achieved by time-limited interventions such as traditional surgical resection, radiation therapy, and chemotherapy is short-lived. A new form of anti-cancer therapy called therapeutic alternating electric fields (AEFs) or tumor treating fields (TTFields) has been shown, either by itself or in combination with chemotherapy, to have anti-cancer effects that translate to improved survival outcomes in patients. Although the pre-clinical and clinical data are promising, the mechanisms of TTFields are not fully elucidated. Many investigations are underway to better understand how and why TTFields is able to selectively kill cancer cells and impede their proliferation. The purpose of this review is to summarize and discuss the reported mechanisms of action of TTFields from pre-clinical studies (both in vitro and in vivo). An improved understanding of how TTFields works will guide strategies focused on the timing and combination of TTFields with other therapies, to further improve survival outcomes in patients with solid organ cancers.
Force-free magnetic flux ropes: String confinement of super-strong magnetic fields and flare energy release
Authors: Solov'ev A A
Published: August 2022

A new class of force-free solutions for a horizontal magnetic filament with a circular cross-section is found, in which the magnetic field strength on the axis significantly (up to 2–3 orders of magnitude and more) exceeds the strength of the longitudinal external field that keeps the rope from lateral expansion. A weak transverse field leads to a small deviation from the force-free field structure and results in a density deficit and an increase in temperature on the rope axis. The possibility of a flare release of magnetic energy is shown when critical values ​​of the longitudinal electric current density in the filament are reached at which ‘anomalous resistance’ occurs, caused by the development of the current ion-sound plasma instability. It turns out to be much larger than the usual Coulomb resistance. The following values are determined: the scale of the current dissipation region, the electric field strength in it, which significantly exceeds the Dreicer value, and the possible energy of accelerated charged particles (up to hundreds of MeV). The critical density of the longitudinal current at which the plasma turbulence is excited does not depend on the presence of a super-strong field on the flux-rope axis, so that the current density depends only on the electron concentration, temperature, and anomalous conductivity. However, super-strong magnetic fields can manifest themselves in the fact that, in their presence, the excitation of plasma instabilities can occur at sufficiently high electron concentrations. This effect may explain the large number of accelerated particles sometimes observed in solar flares.
Propagating torsional Alfvén waves in thermally active solar plasma
Authors: Belov S A , Vasheghani Farahani S , Molevich N E
Published: August 2022

The aim of this study is to shed light on the effects connected with thermal misbalance due to non-equal cooling and heating rates induced by density and temperature perturbations in solar active regions hosting either propagating torsional or shear Alfvén waves. A description for the non-linear forces connected with Alfvén waves in non-ideal conditions is provided, based on the second-order thin flux tube approximation. This provides insight into the effects of Alfvén-induced motions on the boundary of thin magnetic structures in thermally active plasmas. The equations describing the process of generating longitudinal velocity perturbations, together with density perturbations by non-linear torsional Alfvén waves, are obtained and solved analytically. It is shown that the phase shift (compared with the ideal case) and the amplitude of the induced longitudinal plasma motions against the period of the mother Alfvén wave are greater for shear Alfvén waves compared with torsional Alfvén waves, although following the same pattern. The difference in the influence of thermal misbalance on the induced velocity perturbations is governed by the plasma-β although its effect is stronger for shear waves. It is deduced that for a harmonic Alfvén driver the induced density perturbations are left uninfluenced by the thermal misbalance.
Fragmentation with discontinuous Galerkin schemes: non-linear fragmentation
Authors: Lombart Maxime , Hutchison Mark , Lee Yueh-Ning
Published: August 2022

Small grains play an essential role in astrophysical processes such as chemistry, radiative transfer, and gas/dust dynamics. The population of small grains is mainly maintained by the fragmentation process due to colliding grains. An accurate treatment of dust fragmentation is required in numerical modelling. However, current algorithms for solving fragmentation equation suffer from an overdiffusion in the conditions of 3D simulations. To tackle this challenge, we developed a discontinuous Galerkin scheme to solve efficiently the non-linear fragmentation equation with a limited number of dust bins.
UV to submillimetre luminosity functions of TNG50 galaxies
Authors: Trčka Ana , Baes Maarten , Camps Peter , Kapoor Anand Utsav , Nelson Dylan , Pillepich Annalisa , Barrientos Daniela , Hernquist Lars , Marinacci Federico , Vogelsberger Mark
Published: August 2022

We apply the radiative transfer (RT) code skirt on a sample of ${\sim } 14\, 000$ low-redshift (z ≤ 0.1) galaxies extracted from the TNG50 simulation to enable an apples-to-apples comparison with observations. The RT procedure is calibrated via comparison of a subsample of TNG50 galaxies with the DustPedia observational sample: we compare several luminosity and colour scaling relations and spectral energy distributions in different specific SFR bins. We consistently derive galaxy luminosity functions for the TNG50 simulation in 14 broad-band filters from UV to submillimetre wavelengths and investigate the effects of the aperture, orientation, radiative transfer recipe, and numerical resolution. We find that, while our TNG50+RT fiducial model agrees well with the observed luminosity functions at the knee (±0.04 dex typical agreement), the TNG50 + RT luminosity functions evaluated within $5\, R_{1/2}$ are generally higher than observed at both the faint and bright ends, by 0.004 (total IR)-0.27 (UKIDSS H) dex and 0.12 (SPIRE250)-0.8 (GALEX FUV) dex, respectively. A change in the aperture does affect the bright end of the luminosity function, easily by up to 1 dex depending on the choice. However, we also find that the galaxy luminosity functions of a worse-resolution run of TNG50 (TNG50-2, with eight times worse mass resolution than TNG50, similar to TNG100) are in better quantitative agreement with observational constraints. Finally, we publicly release the photometry for the TNG50 sample in 53 broad-bands from FUV to submillimetre, in three orientations and four apertures, as well as galaxy spectral energy distributions.
A global test of jet structure and delay time distribution of short-duration gamma-ray bursts
Authors: Luo Jia-Wei , Li Ye , Ai Shunke , Gao He , Zhang Bing
Published: August 2022

The multimessenger joint observations of GW170817 and GRB170817A shed new light on the study of short-duration gamma-ray bursts (SGRBs). Not only did it substantiate the assumption that SGRBs originate from binary neutron star (BNS) mergers, but it also confirms that the jet generated by this type of merger must be structured, hence the observed energy of an SGRB depends on the viewing angle from the observer. However, the precise structure of the jet is still subject to debate. Moreover, whether a single unified jet model can be applied to all SGRBs is not known. Another uncertainty is the delay time-scale of BNS mergers with respect to star-formation history of the Universe. In this paper, we conduct a global test of both delay and jet models of BNS mergers across a wide parameter space with simulated SGRBs. We compare the simulated peak flux, redshift, and luminosity distributions with the observed ones and test the goodness-of-fit for a set of models and parameter combinations. Our simulations suggest that GW170817/GRB 170817A and all SGRBs can be understood within the framework of a universal structured jet viewed at different viewing angles. Furthermore, model invoking a jet plus cocoon structure with a lognormal delay time-scale is most favoured. Some other combinations (e.g. a Gaussian delay with a power-law jet model) are also acceptable. However, the Gaussian delay with Gaussian jet model and the entire set of power-law delay models are disfavoured.
Solar and stellar activity cycles – no synchronization with exoplanets
Authors: Obridko V N , Katsova M M , Sokoloff D D
Published: August 2022

Cyclic activity on the Sun and stars is primarily explained by the generation of the magnetic field by a dynamo mechanism, which converts the energy of the poloidal field into the energy of the toroidal component due to differential rotation . There is, however, an alternative point of view, which explains the field generation by the gravitational influence of the planetary system and, first of all, Jupiter. This hypothesis can be verified by comparing the characteristics of exoplanets with the activity variations on their associated stars. We have performed such a comparison and have drawn a negative conclusion. No relationship between the gravitational influence of the exoplanets and cycle of the host star could be found in any of the cases considered. Moreover, there are reasons to believe that a strong gravitational influence may completely eliminate cyclic variation in stellar activity.
Reasons and risk factors for discontinuation of treatment with any biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: A long-term observational study
Authors: Terabe Kenya , Takahashi Nobunori , Asai Shuji , Hirano Yuji , Kanayama Yasuhide , Yabe Yuichiro , Oguchi Takeshi , Fujibayashi Takayoshi , Ishikawa Hisato , Hanabayashi Masahiro , Hattori Yosuke , Suzuki Mochihito , Kishimoto Kenji , Ohashi Yoshifumi , Imaizumi Takahiro , Imagama Shiro , Kojima Toshihisa
Published: August 2022

Objectives

Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA.

Methods

The study included 564 patients with RA who started bDMARDs treatment before 2008 (<65 years old, n = 413; ≥65, n = 151). The primary outcome was the incidence of bDMARDs discontinuation due to adverse events (AEs). Risk factors were examined using Fine and Gray regression models.

Results

Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3–4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged <65 years, respectively. The subdistribution hazard ratio for discontinuation was significantly higher in the ≥65 group than in the <65 years group (hazard ratio = 3.53, 95% confidence interval = 2.07–6.03). Lack of concomitant treatment with MTX was risk factor for discontinuation in patients ≥65 years. Advanced Steinbrocker class was a risk factor in patients <65 years.

Conclusions

Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.
Azathioprine-induced hypersensitivity reaction mimicking sepsis in a patient with systemic lupus erythematosus
Authors: McKenzie Paige L , Chao Yusuf , Pathak Sapna , Kazi Salahuddin
Published: August 2022

A 21-year-old woman with a history of systemic lupus erythematosus presented to the emergency department with acute-onset nausea, vomiting, and fevers. Two weeks prior, she was started on azathioprine 50 mg daily by her outpatient rheumatologist; the dose was up-titrated to 100 mg when repeat blood work showed no drug toxicity. The morning after increasing her dose, she was awoken by recurrent emesis. At presentation, she was febrile, tachycardic, and hypotensive. Her exam showed mild, generalised abdominal tenderness but was otherwise unremarkable. Lab work demonstrated elevated inflammatory markers, elevated liver transaminases, and stable hypocomplementemia. Chest X-ray and computed tomography abdomen/pelvis were unrevealing. She was given intravenous fluids and broad-spectrum antibiotics, and azathioprine was held. A thorough infectious workup returned negative. A flare of her systemic lupus erythematosus was considered but deemed an unlikely explanation of her systemic inflammatory response syndrome. With azathioprine discontinuation, she made a rapid, near-complete recovery within 24 h of admission, suggesting a diagnosis of azathioprine hypersensitivity syndrome. This case exemplifies the difficulty in distinguishing azathioprine hypersensitivity from mimickers such as infection and underlying autoimmune disease flare. Prompt recognition of hypersensitivity can lead to appropriate discontinuation of the drug and prevent future morbidity.
Shift work and cardiovascular strain on working and non-working days
Authors: Stieler L , Hunger B , Seibt R
Published: August 2022

Background

Shift work is often associated with adverse effects on cardiovascular health of employees. Only a few studies address the strain of shift and day workers on non-working days compared to working days.

Aims

This study aims to determine how the cardiovascular strain of hotel and catering industry (HCI) employees who work alternating shifts differs from those working normal day shifts—on both a working day (WD) and a non-working day (ND).

Methods

The sample consisted of 60 alternating shift (morning and afternoon, mean age: 31.5 ± 8.5 years) and 88 day workers (mean age: 35.3 ± 9.4 years). A 24-h ambulatory measurement of blood pressure (BP) and heart rate (HR) on WD and ND with the time phases DAY, SLEEP, and 24-h TOTAL was used to analyse cardiovascular strain. BP status was assessed by self-measurement (36% hypertensives).

Results

The total strain over 24 h was slightly higher on WD than ND (mean BP: 134/79 versus 127/75 mmHg, P = 0.002–0.020; mean HR: 78 versus 75 bpm, P = 0.055). In trend, shift workers had higher systolic BP than day workers during the individual time phases of DAY, SLEEP, and 24-h TOTAL on WD. Known cardiovascular risk factors emerged as critical determinants of cardiovascular strain: older age, male gender, and hypertensive blood pressure status.

Conclusions

The results revealed no clear association between the alternating shift system in HCI and increased cardiovascular strain. The 24-h ambulatory measurement is considered ideal for determining cardiovascular strain in everyday life and under working conditions.
Therapeutic Lumbar Punctures in Human Immunodeficiency Virus–Associated Cryptococcal Meningitis: Should Opening Pressure Direct Management?
Authors: Kagimu Enock , Engen Nicole , Ssebambulidde Kenneth , Kasibante John , Kiiza Tadeo K , Mpoza Edward , Tugume Lillian , Nuwagira Edwin , Nsangi Laura , Williams Darlisha A , Hullsiek Kathy Huppler , Boulware David R , Meya David B , Rhein Joshua , Abassi Mahsa , Musubire Abdu K
Published: August 2022

Background

Increased intracranial pressure (ICP) frequently complicates cryptococcal meningitis. Therapeutic lumbar punctures (LPs) have acute survival benefits in the first week, and we sought to understand the longer-term survival impact of therapeutic LPs.

Methods

We prospectively enrolled human immunodeficiency virus (HIV)–seropositive adults with cryptococcal meningitis from 2013 to 2017 in Uganda. We assessed the association between clinical characteristics, CSF parameters, and 14- and 30-day mortality by baseline ICP. We also assessed 30-day mortality by number of follow-up therapeutic LPs performed within 7 days.

Results

Our analysis included 533 participants. Participants with baseline ICP >350 mm H2O were more likely to have Glasgow Coma Scale (GCS) score <15 (P < .001), seizures (P < .01), and higher quantitative cryptococcal cultures (P < .001), whereas participants with ICP <200 mm H2O were more likely to have baseline sterile CSF cultures (P < .001) and CSF white blood cell count ≥5 cells/µL (P = .02). Thirty-day mortality was higher in participants with baseline ICP >350 mm H2O and ICP <200 mm H2O as compared with baseline ICP 200–350 mm H2O (hazard ratio, 1.55 [95% confidence interval, 1.10–2.19]; P = .02). Among survivors at least 7 days, the 30-day relative mortality was 50% higher among participants who did not receive any additional therapeutic LPs compared to those with ≥1 additional follow-up LP (33% vs 22%; P = .04), irrespective of baseline ICP.

Conclusions

Management of increased ICP remains crucial in improving clinical outcomes in cryptococcal meningitis. Guidelines should consider an approach to therapeutic LPs that is not dictated by baseline ICP.
A retrotransposon insertion in MUTL-HOMOLOG 1 affects wild rice seed set and cultivated rice crossover rate
Authors: Liu Kun , Chen Erwang , Gu Zhoulin , Dai Bingxin , Wang Ahong , Zhu Zhou , Feng Qi , Zhou Congcong , Zhu Jingjie , Shangguan Yingying , Wang Yongchun , Li Zhen , Hou Qingqing , Lv Danfeng , Wang Changsheng , Huang Tao , Wang Zixuan , Huang Xuehui , Han Bin
Published: August 2022

Wild rice (Oryza rufipogon) has a lower panicle seed setting rate (PSSR) and gamete fertility than domesticated rice (Oryza sativa), but the genetic mechanisms of this phenomenon remain unknown. Here, we cloned a null allele of OsMLH1, an ortholog of MutL-homolog 1 to yeast and mammals, from wild rice O. rufipogon W1943 and revealed a 5.4-kb retrotransposon insertion in OsMLH1 is responsible for the low PSSR in wild rice. In contrast to the wild-type, a near isogenic line NIL-mlh1 exhibits defective crossover (CO) formation during meiosis, resulting in reduced pollen viability, partial embryo lethality, and low PSSR. Except for the mutant of mismatch repair gene postmeiotic segregation 1 (Ospms1), all other MutL mutants from O. sativa indica subspecies displayed male and female semi-sterility similar to NIL-mlh1, but less severe than those from O. sativa japonica subspecies. MLH1 and MLH3 did not contribute in an additive fashion to fertility. Two types of MutL heterodimers, MLH1-PMS1 and MLH1-MLH3, were identified in rice, but only the latter functions in promoting meiotic CO formation. Compared to japonica varieties, indica cultivars had greater numbers of CO events per meiosis. Our results suggest that low fertility in wild rice may be caused by different gene defects, and indica and japonica subspecies have substantially different CO rates responsible for the discrepancy between the fertility of mlh1 and mlh3 mutants.
The small PPR protein SPR2 interacts with PPR–SMR1 to facilitate the splicing of introns in maize mitochondria
Authors: Cao Shi-Kai , Liu Rui , Wang Miaodi , Sun Feng , Sayyed Aqib , Shi Hong , Wang Xiaomin , Tan Bao-Cai
Published: August 2022

Splicing of plant mitochondrial introns is facilitated by numerous nucleus-encoded protein factors. Although some splicing factors have been identified in plants, the mechanism underlying mitochondrial intron splicing remains largely unclear. In this study, we identified a small P-type pentatricopeptide repeat (PPR) protein containing merely four PPR repeats, small PPR protein 2 (SPR2), which is required for the splicing of more than half of the introns in maize (Zea mays) mitochondria. Null mutations of Spr2 severely impair the splicing of 15 out of the 22 mitochondrial Group II introns, resulting in substantially decreased mature transcripts, which abolished the assembly and activity of mitochondrial complex I. Consequently, embryogenesis and endosperm development were arrested in the spr2 mutants. Yeast two-hybrid, luciferase complementation imaging, bimolecular fluorescence complementation, and semi-in vivo pull-down analyses indicated that SPR2 interacts with small MutS-related domain protein PPR-SMR1, both of which are required for the splicing of 13 introns. In addition, SPR2 and/or PPR-SMR1 interact with other splicing factors, including PPR proteins EMPTY PERICARP16, PPR14, and chloroplast RNA splicing and ribosome maturation (CRM) protein Zm-mCSF1, which participate in the splicing of specific intron(s) of the 13 introns. These results prompt us to propose that SPR2/PPR-SMR1 serves as the core component of a splicing complex and possibly exerts the splicing function through a dynamic interaction with specific substrate recognizing PPR proteins in mitochondria.
New Trigeminal Stimulation Technique with Dorsal Root Ganglion Stimulation Electrode and Maxillary Fixation: Technique Description
Authors: Mansano André Marques , Nouer Frederico Thiago , de Mirando Sergio Luiz , Cheim Junior Adonai Peixoto
Published: August 2022

Background

Trigeminal neuralgia is considered the worst pain a human being can experience. Initial treatment uses anticonvulsant sodium channel blockers, which relieve pain in approximately 70% of patients. In refractory cases, it is possible to perform ablative treatments, decompressive surgeries, and neuromodulatory techniques.

Methods

This report describes the treatment of a patient with refractory trigeminal neuralgia who continued to have a painful clinical presentation after four surgical procedures and three ablative procedures. The patient presented with severe pain (verbal numerical scale between 9 and 10), manifesting an evident suicidal ideation. A dorsal root ganglion (DRG) stimulation electrode was implanted in the trigeminal ganglion through intraoral puncture with maxillary fixation of the electrode, in order to minimize the chances of displacement. The test phase consisted of implanting a quadripolar electrode for DRG stimulation through puncture lateral to the buccal rim in a fluoroscopic coaxial view. The electrode was fixed to the skin and maintained for 5 days, during which the patient remained completely pain free. After the 5-day test period, the definitive stimulation electrode was implanted, this time with intraoral puncture and maxillary electrode fixation.

Results

The patient remains pain free in the 3-month follow-up, with no displacement of the electrode.

Conclusions

The DRG electrode may be considered a therapeutic option in patients with severe trigeminal neuralgia. Controlled studies must be performed to determine the efficacy and safety of the method.
Axonal architecture of the mouse inner retina revealed by second harmonic generation
Authors: Meah Arafat , Boodram Vinessia , Bucinca-Cupallari Festa , Lim Hyungsik
Published: August 2022

We describe a novel method for visualizing the network of axons in the unlabeled fresh wholemount retina. The intrinsic radiation of second harmonic generation (SHG) was utilized to visualize single axons of all major retinal neurons, i.e., photoreceptors, horizontal cells, bipolar cells, amacrine cells, and the retinal ganglion cells. The cell types of SHG+ axons were determined using transgenic GFP/YFP mice. New findings were obtained with retinal SHG imaging: Müller cells do not maintain uniformly polarized microtubules in the processes; SHG+ axons of bipolar cells terminate in the inner plexiform layer (IPL) in a subtype-specific manner; a subset of amacrine cells, presumably the axon-bearing types, emits SHG; and the axon-like neurites of amacrine cells provide a cytoskeletal scaffolding for the IPL stratification. To demonstrate the utility, retinal SHG imaging was applied to testing whether the inner retina is preserved in glaucoma, using DBA/2 mice as a model of glaucoma and DBA/2-Gpnmb+ as the nonglaucomatous control. It was found that the morphology of the inner retina was largely intact in glaucoma and the presynaptic compartments to the retinal ganglion cells were uncompromised. It proves retinal SHG imaging as a promising technology for studying the physiological and diseased retinas in 3D.
Alterations of serine racemase expression determine proliferation and differentiation of neuroblastoma cells
Authors: Zhang He , Lu Jinfang , Shang huiping , Chen Juan , Lin Zhengxiu , Liu Yimei , Wang Xianwei , Song Liping , Jiang Xue , Jiang Haiyan , Shi Jiandong , Yan Dongsheng , Wu Shengzhou
Published: August 2022

Although the role of serine racemase (SR) in neuropsychiatric disorders has been extensively studied, its role in cell proliferation and differentiation remains unclear. Deletion of Srr, the encoding gene for SR, has been shown to reduce dendritic arborization and dendritic spine density in the brains of adult mice, whereas increased SR levels have been associated with differentiation in cell cultures. Previously, we demonstrated that valproic acid induces differentiation in the N2A neuroblastoma cell line, and that this differentiation is associated with increased SR expression. These observations suggest that SR may have a role in cell proliferation and differentiation. We herein found that both valproic acid and all‐trans retinoic acid induced N2A differentiation. In contrast, knockdown of SR reduced levels of differentiation, increased N2A proliferation, promoted cell cycle entry, and modulated expression of cell cycle‐related proteins. To further evaluate the effects of SR expression on cell proliferation and differentiation, we used an in vivo model of neuroblastoma in nude mice. N2A cells stably expressing scramble shRNA (Srrwt‐N2A) or specific Srr shRNA (Srrkd‐N2A) were subcutaneously injected into nude mice. The weights and volumes of Srrwt‐N2A‐derived tumors were lower than Srrkd‐N2A‐derived tumors. Furthermore, Srrwt‐N2A‐derived tumors were significantly mitigated by intraperitoneal injection of valproic acid, whereas Srrkd‐N2A‐derived tumors were unaffected. Taken together, our findings demonstrate for the first time that alterations in SR expression determine the transition between proliferation and differentiation in neural progenitor cells. Thus, in addition to its well‐established roles in neuropsychiatric disorders, our study has highlighted a novel role for SR in cell proliferation and differentiation.
Shared Decision-Making in Pancreatic Surgery
Authors: Trobaugh Jennifer , Fuqua Wayne , Folkert Kyra , Khalil Sarah , Shebrain Saad , Munene Gitonga
Published: August 2022

Objective:

The objective of this study is to determine the factors influencing pancreatic surgery patients’ perceptions of the shared decision-making process (SDM).

Background:

Decision-making in pancreatic surgery is complicated by the risk of morbidity and mortality and risk of early recurrence of disease. Improvement in SDM has the potential to improve the receipt of goal- and value-concordant care.

Methods:

This cross-sectional survey included patients who underwent pancreatic surgery. The following components were studied in relation to SDM: modified satisfaction with decision scale (SWD), modified decisional regret scale (DRS), quality of physician and patient interaction, and the impact of quality of life (FACT-Hep). Correlations were computed using Pearson’s correlation score and a regression model.

Results:

The survey completion rate was 72.2% (of 40/55) and the majority (72.5%) of patients underwent pancreaticoduodenectomy. There were significant positive relationships between the SDM measure and (DRS, SWD; r = 0.70, P < 0.001) and responses to questions regarding how well the patient’s actual recovery matched their expectations before treatment (r = 0.62, P < 0.001). The quality of the physician–patient relationship correlated with how well recovery matched expectations (r = 0.53, P = 0.002). SDM measure scores were significant predictors of the decision evaluation measure (R
2(adj) = 0.48, P < 0.001), FACT-Hep (R
2(adj) = 0.15, P < 0.001), and recovery expectations measure (R
2(adj) = 0.37, P < 0.001).

Conclusions:

Improved SDM in pancreatic surgery is associated with more realistic recovery expectations, decreased decisional regret, and improved quality of life.