bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexsomnia in Active Duty Military: A Series of Four Cases
Authors: Fernandez Juan D , Soca Rodolfo
Published: April 2021

Sexsomnia is a type of non-rapid eye movement (NREM) parasomnia in which sexual behaviors arise during sleep; these behaviors are varied and can include masturbation, orgasms with or without self-stimulation, sexual vocalizations and talking, and sexual fondling and/or intercourse with the bed partner. The military creates a challenging environment, with sleep deprivation, shift work, and increased psychosocial stress that may predispose service members to an increased risk for all NREM parasomnias, including sexsomnia. Given that sexsomnia is sometimes invoked in sexual assault military lawsuits, it may behoove the military community to understand how this condition usually manifests so that its medicolegal implications can be addressed more clearly. Here, we present the largest case series of sexsomnia to date in active duty military service members, which adds to the limited literature on such cases in the military and to the broader but still growing literature on this rare disorder. We compare and contrast these cases with the available literature to highlight their similarities and differences in addition to commenting on the relevance of these cases in forensic investigations. As none of these cases were involved in legal issues, they could provide useful information about this rare condition in individuals who are less likely to be affected by the biases that are inherent to litigation.
octo-tiger: a new, 3D hydrodynamic code for stellar mergers that uses hpx parallelization
Authors: Marcello Dominic C , Shiber Sagiv , De Marco Orsola , Frank Juhan , Clayton Geoffrey C , Motl Patrick M , Diehl Patrick , Kaiser Hartmut
Published: April 2021

octo-tiger is an astrophysics code to simulate the evolution of self-gravitating and rotating systems of arbitrary geometry based on the fast multipole method, using adaptive mesh refinement. octo-tiger is currently optimized to simulate the merger of well-resolved stars that can be approximated by barotropic structures, such as white dwarfs (WDs) or main-sequence stars. The gravity solver conserves angular momentum to machine precision, thanks to a ‘correction’ algorithm. This code uses hpx parallelization, allowing the overlap of work and communication and leading to excellent scaling properties, allowing for the computation of large problems in reasonable wall-clock times. In this paper, we investigate the code performance and precision by running benchmarking tests. These include simple problems, such as the Sod shock tube, as well as sophisticated, full, WD binary simulations. Results are compared to analytical solutions, when known, and to other grid-based codes such as flash. We also compute the interaction between two WDs from the early mass transfer through to the merger and compare with past simulations of similar systems. We measure octo-tiger’s scaling properties up to a core count of ∼80 000, showing excellent performance for large problems. Finally, we outline the current and planned areas of development aimed at tackling a number of physical phenomena connected to observations of transients.
Long-term measurements of the erosion and accretion of dust deposits on comet 67P/Churyumov–Gerasimenko with the OSIRIS instrument
Authors: Cambianica P , Cremonese G , Fulle M , Simioni E , Naletto G , Pajola M , Lucchetti A , Penasa L , Massironi M , Frattin E , Güttler C , Sierks H , Tubiana C
Published: April 2021

We monitor the seasonal erosion and accretion of dust deposits in the Imhotep, Hatmehit, and Ma’at regions of comet 67P/Churyumov–Gerasimenko with OSIRIS Narrow Angle Camera images. The vertical accuracy of such measurements is 0.2 m and the spatial scale of the images we used is lower than 0.60 m pixel−1. We calculate the height of 21 boulders by applying a tool that allows to measure the shadow length of a boulder projected on the surrounding dust deposit, assuming that any height variation is not due to boulder intrinsic change. Any boulder height variation provides a direct measurement about the thickness variation of the surrounding dust layer due to the occurring erosion and/or accretion. The analysis concerns the period from 2014 August, inbound to perihelion, to 2016 September, outbound. We measured the erosion in the Ma’at region of 0.6 ± 0.2 m from 2014 September 12 to December 2, and an erosion of 0.4 ± 0.3 m from 2014 December 3 to 2015 February 15. Then, we measured a dust deposition of 0.7 ± 0.3 m during the following perihelion phase, until 2016 May–September. This result confirms the link between the erosion of the Southern hemisphere and the fallout in the northern regions. The Imhotep and Hatmehit regions are characterized by a negligible erosion during the inbound orbit, consistent with pebble-made nucleus models predicting no erosion when the temperature of the nucleus surface is Ts < 205 K.
Organic residues in astrophysical ice analogues: Thermal processing of hydrogenated glyoxal ices under interstellar conditions
Authors: Leroux Killian , Guillemin Jean-Claude , Krim Lahouari
Published: April 2021

Organic residues are considered as part of the chemical composition of the interstellar dust grains. They are formed under the extreme conditions of the interstellar medium and play an important role in exobiology. They may contain pre-biotic organic species such as amino acids, constituents of proteins and building blocks of DNA and RNA, key elements of life. By investigating the formation of organic residues in an astrophysical context, many groups have been focusing in the UV irradiation and subsequent warm-up of astrophysical ice analogues. This aims to suggest that organic residues are mainly formed in regions of molecular clouds exposed to UV light or cosmic rays. This study shows an organic residue formation involving glyoxal ice and H atoms. While the hydrogenation of glyoxal at 10 K leads mainly to small molecules such as CO and H2CO and CH3OH, we show that the heating of the hydrogenated ice in the 10–300 K temperature range leads to solid residues whose structure is similar to that of glycolaldehyde but they remain stable in solid phase at 300 K and atmospheric pressure. The analysis of the IR data shows that the organic residues formed through the thermal processing of CHOCHO + H reaction would be a mixture of hydroxypyruvaldehyde and methyl glyoxylate, two solid organics whose formation starts with an H-abstraction from glyoxal to form CHOCO• radical which recombines to •CH2OH and •OCH3 radicals. These latter may be formed and trapped in glyoxal ice as secondary products from H2CO + H secondary reaction.
Interpreting the variation phenomena of B2 1633+382 via the two-component model
Authors: Wang Yi-Fan , Jiang Yun-Guo
Published: April 2021

Blazars are variable targets in the sky, whose variation mechanism remains an open question. In this work, we make a comprehensive study of the variation phenomena of the spectral index and polarization degree to deeply understand the variation mechanism of B2 1633+382 (4C 38.41). We use the local cross-correlation function to perform a correlation analysis between multiwavelength light curves. We find that both the γ-ray and the optical V band are correlated with the 15-GHz radio at beyond the 3σ confidence level. Based on the lag analysis, the emitting regions of the γ-ray and optical are located at $14.2_{-2.4}^{+0}$ and $14.2_{-8.3}^{+8.3}$ pc upstream of the core region of the15-GHz radio, and are far away from the broad-line region. The broad lines in the spectrum indicate the existence of an accretion disc component in the radiation. Thus, we consider a two-component model, which includes the relative constant background component and the varying jet component to study the variation behaviours. The Markov Chain Monte Carlo procedure is adopted to study the physical parameters of the jet and the background components. To some extent, the study of normalized residuals indicates that the two-component model fits better than the linear fitting model. The jet with a helical magnetic field is promising for explaining the variation, and the shock-in-jet model is not completely ruled out.
Artificial intelligence and quasar absorption system modelling; application to fundamental constants at high redshift
Authors: Lee Chung-Chi , Webb John K , Carswell R F , Milaković Dinko
Published: April 2021

We have developed a new fully automated Artificial Intelligence (AI)-based method for deriving optimal models of complex absorption systems. The AI structure is built around VPFIT, a well-developed and extensively tested nonlinear least-squares code. The new method forms a sophisticated parallelized system, eliminating human decision-making and hence bias. Here, we describe the workings of such a system and apply it to synthetic spectra, in doing so establishing recommended methodologies for future analyses of Very Large Telescope (VLT) and Extremely Large Telescope (ELT) data. One important result is that modelling line broadening for high-redshift absorption components should include both thermal and turbulent components. Failing to do so means it is easy to derive the wrong model and hence incorrect parameter estimates. One topical application of our method concerns searches for spatial or temporal variations in fundamental constants. This subject is one of the key science drivers for the European Southern Observatory’s ESPRESSO spectrograph on the VLT and for the HIRES spectrograph on the ELT. The quality of new data demands completely objective and reproducible methods. The Monte Carlo aspects of the new method described here reveal that model non-uniqueness can be significant, indicating that it is unrealistic to expect to derive an unambiguous estimate of the fine structure constant α from one or a very small number of measurements. No matter how optimal the modelling method, it is a fundamental requirement to use a large sample of measurements to meaningfully constrain temporal or spatial α variation.
Molecular structure, DNA binding mode, photophysical properties and recommendations for use of SYBR Gold
Authors: Kolbeck Pauline J , Vanderlinden Willem , Gemmecker Gerd , Gebhardt Christian , Lehmann Martin , Lak Aidin , Nicolaus Thomas , Cordes Thorben , Lipfert Jan
Published: April 2021

SYBR Gold is a commonly used and particularly bright fluorescent DNA stain, however, its chemical structure is unknown and its binding mode to DNA remains controversial. Here, we solve the structure of SYBR Gold by NMR and mass spectrometry to be [2-(4-{[diethyl(methyl)ammonio]methyl}phenyl)-6-methoxy-1-methyl-4-{[(2Z)-3-methyl-1,3-benzoxazol-2-ylidene]methyl}quinolin-1-ium] and determine its extinction coefficient. We quantitate SYBR Gold binding to DNA using two complementary approaches. First, we use single-molecule magnetic tweezers (MT) to determine the effects of SYBR Gold binding on DNA length and twist. The MT assay reveals systematic lengthening and unwinding of DNA by 19.1° ± 0.7° per molecule upon binding, consistent with intercalation, similar to the related dye SYBR Green I. We complement the MT data with spectroscopic characterization of SYBR Gold. The data are well described by a global binding model for dye concentrations ≤2.5 μM, with parameters that quantitatively agree with the MT results. The fluorescence increases linearly with the number of intercalated SYBR Gold molecules up to dye concentrations of ∼2.5 μM, where quenching and inner filter effects become relevant. In summary, we provide a mechanistic understanding of DNA-SYBR Gold interactions and present practical guidelines for optimal DNA detection and quantitative DNA sensing applications using SYBR Gold.
Successful Treatment of Chronic Back and Leg Pain With Lower Than Usual Placement of High-Frequency Spinal Cord Stimulation in a Patient With Uncorrected Tethered Cord: Case Report
Authors: Musick Shane , Ferguson Jessalyn , Muizelaar Jan Paul
Published: April 2021

BACKGROUND AND IMPORTANCE

Tethered cord syndrome (TCS) often leads to severe back and leg pain. The typical treatment to stall disease progression is untethering surgery, but this is not always effective for pain. Spinal cord stimulation (SCS) is an efficacious treatment for neuropathic pain. However, it has seldom been utilized in TCS cases. Moreover, with cord elongation, ideal paddle placement is not certain.

CLINICAL PRESENTATION

We present the case of a 77-yr-old male with severe chronic lower-back and lower-extremity pain. Magnetic resonance imaging (MRI) showed severe lumbar spine degenerative changes, along with a previously undiagnosed spina bifida and conus medullaris termination at L5. We felt that SCS would be the best treatment avenue for his chief complaint of pain. Due to cord elongation, we trialed lower placement of the high-frequency (HF)-SCS system at T11-T12, which led to 80% improvement in pain symptoms within 1 wk and ability to walk for the first time in a year. At his first follow-up appointment, the patient endorsed 80% to 90% relief of his lower-back and bilateral lower-extremity pain, which improved to 100% relief at 12 mo at last visit.

CONCLUSION

Only 4 other reports were identified in the literature utilizing SCS in TCS cases. Our case adds to the limited body of literature that SCS is an effective therapy for pain in TCS and degenerative spine disease. Only 2 other reports employed lower than usual lead placement. Our case demonstrates that lead placement may need to be changed to accommodate the elongated cord.
Net Drainage as a Novel Metric for Irrigating Drainage Systems in Chronic Subdural Hematoma Management: A Case Report
Authors: Himstead Alexander S , Davies Jordan , Tran Diem Kieu , Vadera Sumeet
Published: April 2021

BACKGROUND AND IMPORTANCE

Chronic subdural hematoma (cSDH) is a common neurosurgical pathology with a projected increase in prevalence as the elderly population grows. Traditional treatment for cSDH involves burr hole drainage or craniotomy with or without a subdural drain. This case describes a novel irrigation and drainage protocol using IRRAflow dual-lumen catheter system that utilizes early irrigation and measurement of the net fluid output to improve postoperative outcomes.

CLINICAL PRESENTATION

A 75-yr-old male presented to the emergency department with 2 wk of progressive dizziness, headache, confusion, and left-sided weakness over the past week. Computed tomography (CT) of the head showed 25-mm-thick, right-sided cSDH with 7 mm of right-to-left midline shift. The patient was taken to the operating room for right-sided craniotomy for subdural hematoma evacuation with placement of IRRAflow irrigating drain in the subdural space. The IRRAflow drain irrigated at 100 cc/h for 23 h with net output consistently greater than irrigation rate. Head CT the following day showed a progressive decrease in subdural collection. The patient was discharged on postoperative day 2 and had complete resolution of his neurological symptoms by postoperative day 11.

CONCLUSION

As cSDHs become more prevalent in the aging population, development of improved management strategies is imperative. This report describes the use of an IRRAflow dual-lumen catheter with a novel protocol consisting of a high rate of irrigation but net fluid output, which led to rapid recovery and resolution of neurological deficits in a patient with a cSDH.
Crossing the Carotid Siphon: Techniques to Facilitate Distal Access in Tortuous Anatomy: 2-Dimensional Operative Video
Authors: Hadley Caroline , Burkhardt Jan-Karl , Johnson Jeremiah N , Kan Peter ,   Endovascular Neurosurgery Research Group, Arthur Adam , Bain Mark , Bendock Bernard , Binning Mandy Jo , Boulos Alan S , Crowley Webster , Fessler Richard , Grande Andrew , Guterman Lee , Hanel Ricardo , Hoit Daniel , Hopkins III L Nelson , Howington Jay , James Robert , Jankowitz Brian , Kan Peter , Khalessi Alex A , Kim Louis , Langer David , Lanzino Giuseppe , Levitt Michael , Levy Elad , Lopes Demetrius , Mack William , Mericle Robert , Mocco J , Ogilvy Chris , Pandey Aditya , Replogle Robert , Riina Howard , Ringer Andrew , Rodriguez Rafael , Saugaveau Eric , Schirmer Clemens , Siddiqui Adnan , Spiotta Alex , Sultan Ali , Tawk Rabih , Thomas Ajith , Turner Raymond , Veznedaroglu Erol , Welch Babu , White Jonathan
Published: April 2021

As capabilities for endovascular treatment of intracranial vascular pathologies continue to expand, the need for access to the distal internal carotid artery with rigid support catheter systems continues to increase. One of the dominant factors limiting this access is patient anatomy, specifically vessel tortuosity. Increased tortuosity of the carotid siphon is a frequently encountered anatomic variant and may complicate endovascular procedures in adults and children.
1,2
Failed attempts to navigate the carotid siphon with a distal access catheter carry a risk of vessel injury and treatment failure. For this reason, techniques that aid in supporting safe advancement of a distal access catheter across a tortuous carotid siphon are essential.
3,4
In this video, we demonstrate 2 ways in which this may be accomplished. The first technique uses a larger diameter microcatheter, such as the AXS Offset catheter (Stryker, Kalamazoo, Michigan), to increase support for the distal access catheter, while the second uses a buddy wire technique to accomplish this increased support. Both of these techniques can help increase the safety of navigating a tortuous carotid siphon and increase the likelihood of successful treatment.

 The procedures shown were performed with the informed consent of the patients.
L5 Vertebral Column Resection for Correction of Severe Lumbar Hyperlordosis and Pelvic Anteversion in an Adolescent With Prior Myelomeningocele Repair and Lumbar Fusion: Case Report
Authors: Lai Christopher S , Cerpa Meghan , Zuckerman Scott L , Menger Richard , Lenke Lawrence G
Published: April 2021

BACKGROUND AND IMPORTANCE

Lumbar hyperlordosis in ambulatory children is an uncommon but potentially problematic spinal deformity, and the operative management has not been comprehensively described.

CLINICAL PRESENTATION

We report the case of a 14-yr-old girl presenting with severe progressive lumbar hyperlordosis (−122°) and sagittal imbalance (−6 cm). She had multiple prior surgeries, including myelomeningocele repair at 10 d old, midlumbar meningioma resection at 8 mo old, and posterior lumbar instrumented spinal fusion at 5 yr old. She presented with progressive lumbosacral back pain and intermittent numbness in her left lower extremity, and severe skin contractures over her prior posterior incisions. From an all posterior approach, prior implants and dural scar were removed and then an L5 vertebral column resection (VCR) was performed to disarticulate her lumbar spine from her anteverted pelvis, allowing for slow distraction forces to correct her lumbar hyperlordosis. This was followed by a T7-sacrum fusion using pedicle screws and iliac screws, with autologous bone graft and plastic surgery wound closure. Postoperatively, lumbar lordosis was corrected to −55° and sagittal balance reduced to −0.5 cm. At 10-wk and 14-mo follow-ups, the patient reported resolution of her back pain with no limitations in physical activities. Dramatic improvement was seen in both her preoperative to 14-mo postoperative Oswestry Disability Index (ODI) (54 to 12) and Scoliosis Research Society Scoliosis Research Society (SRS)-22r (54 to 93) scores.

CONCLUSION

This case highlights a rare presentation of severe progressive lumbar hyperlordosis in an ambulatory adolescent after myelomeningocele repair, meningioma resection, and posterior lumbar instrumented spinal fusion with subsequent surgical treatment incorporating important components of both spinal and plastic surgery involvement.
β-Amyrin Synthase1 Controls the Accumulation of the Major Saponins Present in Pea (Pisum sativum)
Authors: Vernoud Vanessa , Lebeigle Ludivine , Munier Jocelyn , Marais Julie , Sanchez Myriam , Pertuit David , Rossin Nadia , Darchy Brigitte , Aubert Grégoire , Le Signor Christine , Berdeaux Olivier , Lacaille-Dubois Marie-Aleth , Thompson Richard
Published: April 2021

The use of pulses as ingredients for the production of food products rich in plant proteins is increasing. However, protein fractions prepared from pea or other pulses contain significant amounts of saponins, glycosylated triterpenes that can impart an undesirable bitter taste when used as an ingredient in foodstuffs. In this article, we describe the identification and characterization of a gene involved in saponin biosynthesis during pea seed development, by screening mutants obtained from two Pisum sativum TILLING (Targeting Induced Local Lesions IN Genomes) populations in two different genetic backgrounds. The mutations studied are located in a gene designated PsBAS1 (β-amyrin synthase1), which is highly expressed in maturing pea seeds and which encodes a protein previously shown to correspond to an active β-amyrin synthase. The first allele is a nonsense mutation, while the second mutation is located in a splice site and gives rise to a mis-spliced transcript encoding a truncated, nonfunctional protein. The homozygous mutant seeds accumulated virtually no saponin without affecting the seed nutritional or physiological quality. Interestingly, BAS1 appears to control saponin accumulation in all other tissues of the plant examined. These lines represent a first step in the development of pea varieties lacking bitterness off-flavors in their seeds. Our work also shows that TILLING populations in different genetic backgrounds represent valuable genetic resources for both crop improvement and functional genomics.
Different DNA-binding specificities of NLP and NIN transcription factors underlie nitrate-induced control of root nodulation
Authors: Nishida Hanna , Nosaki Shohei , Suzuki Takamasa , Ito Momoyo , Miyakawa Takuya , Nomoto Mika , Tada Yasuomi , Miura Kenji , Tanokura Masaru , Kawaguchi Masayoshi , Suzaki Takuya
Published: April 2021

Leguminous plants produce nodules for nitrogen fixation; however, nodule production incurs an energy cost. Therefore, as an adaptive strategy, leguminous plants halt root nodule development when sufficient amounts of nitrogen nutrients, such as nitrate, are present in the environment. Although legume NODULE INCEPTION (NIN)-LIKE PROTEIN (NLP) transcription factors have recently been identified, understanding how nodulation is controlled by nitrate, a fundamental question for nitrate-mediated transcriptional regulation of symbiotic genes, remains elusive. Here, we show that two Lotus japonicus NLPs, NITRATE UNRESPONSIVE SYMBIOSIS 1 (NRSYM1)/LjNLP4 and NRSYM2/LjNLP1, have overlapping functions in the nitrate-induced control of nodulation and act as master regulators for nitrate-dependent gene expression. We further identify candidate target genes of LjNLP4 by combining transcriptome analysis with a DNA affinity purification-seq approach. We then demonstrate that LjNLP4 and LjNIN, a key nodulation-specific regulator and paralog of LjNLP4, have different DNA-binding specificities. Moreover, LjNLP4–LjNIN dimerization underlies LjNLP4-mediated bifunctional transcriptional regulation. These data provide a basic principle for how nitrate controls nodulation through positive and negative regulation of symbiotic genes.
Self-Deception as a Moral Failure
Authors: MacKenzie Jordan
Published: April 2021

In this paper, I defend the view that self-deception is a moral failure. Instead of saying that self-deception is bad because it undermines our moral character or leads to morally deleterious consequences, as has been argued by Butler, Kant, Smith, and others, I argue the distinctive badness of self-deception lies in the tragic relationship that it bears to our own values. On one hand, self-deception is motivated by what we value. On the other hand, it prevents us from valuing those things properly. I argue that we owe it ourselves to take seriously our own values, by striving to properly value them. This gives us both prudential and moral reasons to avoid self-deception.
The Impact of Firearm Legislation on Firearm Deaths, 1991–2017
Authors: Gunn John F , Boxer Paul , Andrews Tracy , Ostermann Michael , Bonne Stephanie L , Gusmano Michael , Sloan-Power Elizabeth , Hohl Bernadette
Published: April 2021

Firearm violence is a major public health concern in the USA with firearm suicide and homicide accounting for the majority of gun deaths. The present work seeks to explore the role of firearm legislation in reducing suicide and homicide rates. Using the State Firearm Law Database (www.statefirearmlaws.org), suicide and homicide rates were compared across the 50 US states from 1991 to 2017. A firearm regulations index was computed to represent the total number of state firearm laws. Generalized estimating equations were used to explore population-level increases or decreases in firearm regulations and their association with state suicide and homicide rates after controlling for several state-level covariates. Even after accounting for several key covariates (US region; time; gun ownership; percent of the state population that was White, Black, below the poverty line and 25 years or older with a bachelor’s degree; incarceration rate, unemployment rate and divorce rate), we found that firearm laws significantly predicted state firearm suicide and homicide rates. States with greater numbers of laws had reduced suicide and homicide rates compared with those with fewer laws. The present findings point to the role of firearm legislation in curbing rates of gun violence across the USA.
On The Schaper Numbers Of Partitions
Authors: Jolliffe Liam , Martin Stuart
Published: April 2021

One of the most useful tools for calculating the decomposition numbers of the symmetric group is Schaper’s sum formula. The utility of this formula for a given Specht module can be improved by knowing the Schaper number of the corresponding partition. Fayers gives a characterization of those partitions whose Schaper number is at least two. In this paper, we shall demonstrate how this knowledge can be used to calculate some decomposition numbers before extending this result with the hope of allowing more decomposition numbers to be calculated in the future. For p = 2 we shall give a complete characterization of partitions whose Schaper number is at least three, and those whose Schaper number at least four. We also present a list of necessary conditions for a partition to have Schaper number at least three for odd primes and a conjecture on the sufficiency of these conditions.
The Strategic Response of Banks to Macroprudential Policies: Evidence from Mortgage Stress Tests in Canada*
Authors: Clark Robert , Li Shaoteng
Published: April 2021

Following the crisis, macroprudential regulations targeting mortgage-market vulnerabilities were widely adopted, their success often relying on the response of financial intermediaries. We provide evidence from Canada suggesting banks may have behaved strategically to limit the effectiveness of recently implemented mortgage stress tests. Before implementation, borrowers had to prove they could make mortgage payments based on the interest rate specified in the contract. The new tests require borrowers to show they can afford payments based on a typically higher qualifying rate, derived from the mode of 5-year rates posted by the six largest banks. The government’s objective was to cool credit markets, but, since many mortgages are government-insured, the big banks’ interests were not aligned. We find evidence of rate manipulation using a difference-in-differences approach comparing changes in spreads for 5-year mortgages with 3-year spreads, unaffected by the policy. The qualifying rates were lowered encouraging continued borrowing, muting the tests’ impact.
Locus Coeruleus Activation Patterns Differentially Modulate Odor Discrimination Learning and Odor Valence in Rats
Authors: Ghosh Abhinaba , Massaeli Faghihe , Power Kyron D , Omoluabi Tamunotonye , Torraville Sarah E , Pritchett Julia B , Sepahvand Tayebeh , Strong Vanessa D , Reinhardt Camila , Chen Xihua , Martin Gerard M , Harley Carolyn W , Yuan Qi
Published: April 2021

The locus coeruleus (LC) produces phasic and tonic firing patterns that are theorized to have distinct functional consequences. However, how different firing modes affect learning and valence encoding of sensory information are unknown. Here, we show bilateral optogenetic activation of rat LC neurons using 10-Hz phasic trains of either 300 ms or 10 s accelerated acquisition of a similar odor discrimination. Similar odor discrimination learning was impaired by noradrenergic blockade in the piriform cortex (PC). However, 10-Hz phasic light-mediated learning facilitation was prevented by a dopaminergic antagonist in the PC, or by ventral tegmental area (VTA) silencing with lidocaine, suggesting a LC–VTA–PC dopamine circuitry involvement. Ten-hertz tonic stimulation did not alter odor discrimination acquisition, and was ineffective in activating VTA DA neurons. For valence encoding, tonic stimulation at 25 Hz induced conditioned odor aversion, whereas 10-Hz phasic stimulations produced an odor preference. Both conditionings were prevented by noradrenergic blockade in the basolateral amygdala (BLA). Cholera Toxin B retro-labeling showed larger engagement of nucleus accumbens-projecting neurons in the BLA with 10-Hz phasic activation, and larger engagement of central amygdala projecting cells with 25-Hz tonic light. These outcomes argue that the LC activation patterns differentially influence both target networks and behavior.
Effects of Double-Stranded RNAs Targeting Fusarium graminearum TRI6 on Fusarium Head Blight and Mycotoxins
Authors: Hao Guixia , McCormick Susan , Vaughan Martha M.
Published: April 2021

Fusarium graminearum is the causal agent of Fusarium head blight (FHB), which reduces crop yield and contaminates grains with poisonous trichothecene mycotoxins, including deoxynivalenol (DON). DON functions as an important virulence factor that promotes FHB spread in wheat; therefore, reducing DON production will decrease yield losses to FHB and increase food safety. Recent progress in the topical application of double-stranded RNA (dsRNA) to reduce F. graminearum infection has provided encouraging results. In this study, we designed and synthesized dsRNA targeting the transcription factor TRI6 (TRI6-dsRNA), which is a key regulator of DON biosynthesis. The expression of F. graminearum TRI6 was significantly lower in detached wheat heads treated with TRI6-dsRNA solution compared with the controls. Furthermore, TRI6-dsRNA treatments reduced disease and DON accumulation in inoculated detached wheat heads. Therefore, topical applications of TRI6-dsRNA on wheat heads of intact plants were assessed for their ability to reduce FHB and DON under growth chamber and greenhouse conditions. When wheat heads were treated with TRI6-dsRNA solution in growth chamber conditions, TRI6-dsRNA treatments failed to prevent FHB spread. However, when wheat heads were treated with TRI6-dsRNA solution under greenhouse conditions, FHB and DON were significantly reduced, and infection was restricted to the inoculated floret. In addition, addition of TRI6-dsRNA to toxin induction liquid media had no effect on F. graminearum 15-ADON production. Our study demonstrates that the efficacy of dsRNA applications is strongly dependent on application methods and environmental conditions.
Differential Expression Pattern of Pathogenicity-Related Genes of Ralstonia pseudosolanacearum YQ Responding to Tissue Debris of Casuarina equisetifolia
Authors: Zhou Xiang , Wang Yue , Li Chuqiao , Xu Yuanyou , Su Xiu , Yang Tian , Zhang Xinqi
Published: April 2021

Ralstonia solanacearum species complex (RSSC) contains a group of destructive plant pathogenic bacteria, causing bacterial wilt of >200 species of crops and trees, such as Casuarina equisetifolia, worldwide. RSSC can survive in the soil environment for a long time and start infection after activation by host plants. This study conducted a transcriptome analysis on the expression pattern of the pathogenicity-related genes of a new isolated RSSC strain YQ (Ralstonia pseudosolanacearum phylotype I-16) in response to C. equisetifolia cladophyll (a branch of a stem that resembles and functions as a leaf) and root debris under in vitro culture. The cladophyll debris induced more genes up-regulated than the root debris, including pathogenicity-related genes involved in motility, effectors, type III secretion systems, quorum sensing, and plant cell wall degradation. Besides, many differentially expressed genes were related to transcriptional regulator such as cyclic dimeric guanosine monophosphate. Moreover, the cultures with cladophyll debris induced a faster wilting in bioassays, and the cell swimming was enhanced by cladophyll exudate. C. equisetifolia cladophylls could activate the expression of pathogenicity-related genes of strain YQ and accelerate infection. Our findings suggest that litterfall management in C. equisetifolia forests, or even other plantations, should receive attention to prevent the induction of bacterial wilt disease caused by RSSC.
Bilateral reticular haze and scar involving central cornea
Authors: Moshirfar Majid
Published: April 2021

A 17-year-old girl with a few years' history of declining vision, photophobia, and dry eye symptoms was referred to our clinic. She noted that the vision in the right eye declined significantly over the past several months.

On her last year examination, her uncorrected distance visual acuity (UDVA) was recorded as 20/25 in both eyes with a corrected distance visual acuity (CDVA) of 20/20 in both eyes with minimal refractive error, with a diagnosis of bilateral Salzmann nodular degeneration. The patient was given artificial tears and was encouraged to wear sunglasses.

On examination now, UDVA was 20/70 in the right eye and 20/40 in the left eye. The manifest refraction was −2.00 + 1.25 × 96 in the right eye and −1.00 + 2.00× 34 in the left eye, with a CDVA of 20/50 and 20/30, respectively. Slitlamp examination revealed superficial reticular stromal scar with clear intervening spaces involving the anterior 75 μm of the stromal cornea in the central 6.0 mm optical zone (Figure 1).

JOURNAL/jcrs/04.03/02158034-202104000-00021/figure1/v/2023-08-19T002607Z/r/image-tiff

JOURNAL/jcrs/04.03/02158034-202104000-00021/figure2/v/2023-08-19T002607Z/r/image-tiff

The rest of the anterior and posterior segment examination was completely normal and noncontributory. Anterior segment optical coherence tomography (AS-OCT) revealed subepithelial lesion involving the central aspect of the cornea in the right eye more than that in the left eye (Figure 2). Family history was significant for an older sister with a similar problem who never required medical attention. She also has mild photophobia and dry eye symptoms.

What is your differential diagnosis? What diagnostic test will help you in your diagnosis and clinical decision-making? What is the most likely diagnosis in this case? Do you recommend medical and/or surgical intervention in the right eye, realizing that there has been exacerbation of her ocular condition in the most recent year? What is the long-term prognosis and future plan for a patient with this potential condition?
Neuronal Enhancers are Hotspots For DNA Single-Strand Break Repair
Authors: Wu Wei , Hill Sarah E. , Nathan William J. , Paiano Jacob , Shinoda Kenta , Colon-Mercado Jennifer , Callen Elsa , de Pace Raffaella , Wang Dongpeng , Shih Han-Yu , Coon Steve , Parsadanian Maia , Hanzlikova Hana , McHugh Peter J. , Canela Andres , Caldecott Keith W. , Ward Michael E. , Nussenzweig André
Published: April 2021

Genome stability is essential for all cell types. However, defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons. The neuronal genome is subjected to a constant barrage of endogenous DNA damage due to high levels of oxidative metabolism in the central nervous system. Surprisingly, we know little about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here, we show that neurons, but not other post-mitotic cells, accumulate unexpectedly high numbers of DNA single-strand breaks (SSBs) at specific sites within the genome. These recurrent SSBs are found within enhancers, and trigger DNA repair through recruitment and activation of poly(ADP-ribose) polymerase-1 (PARP1) and XRCC1, the central SSB repair scaffold protein. Notably, deficiencies in PARP1, XRCC1, or DNA polymerase β elevate the localized incorporation of nucleotides, suggesting that the ongoing DNA synthesis at neuronal enhancers involves both short-patch and long-patch SSB repair processes. These data reveal unexpected levels of localized and continuous DNA single-strand breakage in neurons, suggesting an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.
Statins Are Associated with Improved 28-day Mortality in Patients Hospitalized with SARS-CoV-2 Infection
Authors: Memel Zoe N. , Lee Jenny J. , Foulkes Andrea S. , Chung Raymond T. , Thaweethai Tanayott , Bloom Patricia P.
Published: April 2021

Background

Statins may be protective in viral infection and have been proposed as treatment in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.

Objective

We evaluated the effect of statins on mortality in four groups hospitalized with (SARS-CoV-2) infection (continued statin, newly initiated statin, discontinued statin, never on statin).

Design

In a single center cohort study of 1179 patients hospitalized with SARS-CoV-2 infection, the outcome of death, Intensive Care Unit (ICU) admission or hospital discharge was evaluated. Patients’ statin use, laboratory data, and co-morbidities were determined via chart review and electronic health records. Using marginal structural models to account for timing of statin initiation and competing risks, we compared the likelihood of severe outcomes in the four statin exposure groups.

Setting

Academic medical center in the United States

Participants

Patients hospitalized with SARS-CoV-2 infection

Measurements

28-day mortality, ICU admission, or discharge

Results

Among 1179 patients, 360 were never on a statin, 311 were newly initiated on a statin, 466 were continued on a statin, and 42 had a statin discontinued. In this cohort, 154 (13.1%) patients died by 28-days. With marginal structural model analysis, statin use reduced the hazard of 28-day mortality (HR 0.566 [CI 0.372, 0.862], p = 0.008). Both new initiation of statins (HR 0.493 [CI 0.253, 0.963], p=0.038) and continuing statin therapy reduced the hazard of 28-day mortality (HR 0.270 [CI 0.114, 0.637], p=0.003). Sensitivity analysis found that statin use was associated with improved mortality for patients > 65 years, but not for patients 65 years or younger.

Limitation

Observational design

Conclusion

Statin therapy during hospitalization for SARS-CoV-2 infection, including new initiation and continuation of therapy, was associated with reduced short-term mortality.
Raised cardiovascular disease mortality after central nervous system tumour diagnosis: analysis of 171 926 patients from UK and USA
Authors: Jin Kai , Brennan Paul M , Poon Michael TC , Sudlow Cathie LM , Figueroa Jonine D
Published: April 2021

Background

Patients with central nervous system (CNS) tumours have significant morbidity and mortality. Some studies showed CNS tumours patients may be at risk for cardiovascular disease (CVD) mortality. The magnitude of CVD risk among CNS tumours patients has not been comprehensively assessed. If CVD mortality is elevated in this population, there may be a potential for risk reduction to improve outcomes. We examined CVD mortality risk in patients with malignant and non-malignant CNS tumours.

Methods

We conducted analyses using UK (Wales)-based Secure Anonymised Information Linkage (SAIL) for 8,743 CNS tumour patients diagnosed in 2000-2015 (54.9% of whom died), and US-based National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) for 163,183 patients in 2005-2015 (39.6% of whom died). We calculated age-, sex-, and calendar-year-adjusted standardised mortality ratios (SMRs) for CVD death in CNS tumour patients compared to Welsh and US residents. We used multivariable cause-specific Cox regression models to examine factors associated with CVD mortality among CNS tumour patients. We stratified all analyses by malignancy and main histological types.

Results

CVD was the second commonest cause of death for CNS tumour patients in SAIL (UK) and SEER (US) (9.5% & 11.7%, respectively). Patients with CNS tumours had higher CVD mortality than the general population (SAIL SMR=2.64, 95% CI=2.39-2.90, SEER SMR=1.38, 95% CI=1.35-1.42). Malignant CNS tumour patients had over 2-fold higher CVD mortality risk in both US and UK cohorts. SMRs for non-malignant tumours were almost 2-fold higher in SAIL than in SEER (SAIL SMR=2.73, 95% CI=2.46-3.02, SEER 1.30, 95% CI=1.26-1.33). The greatest magnitude of excess CVD mortality risk, particularly from cerebrovascular disease, was substantially greater in patients diagnosed at age younger than 50 years and within the first year after their cancer diagnosis (SAIL SMR=2.98, 95% CI=2.39-3.66; SEER SMR=2.14 95% CI=2.03-2.25). Age, sex, race/ethnicity in USA, deprivation in UK and no surgery were associated with CVD mortality.

Discussion

CVD mortality is high among patients diagnosed with both malignant and non-malignant CNS tumours compared to the general population. Targeted interventions and risk stratification tools might improve survival.
E-cadherinGene Promoter Hyper-methylation in Blood Samples from Breast Cancer Cases
Authors: Ajaz Sadia , Zaidi Sani-e-Zehra , Ali Saleema Mehboob , Siddiqa Aisha , Memon Muhammad Ali
Published: April 2021

In carcinomas, dissemination of cancer cells via blood or lymph circulation constitutes an early event. E-cadherin is a transmembrane calcium dependent adhesion protein. Cellular de-differentiation and plasticity, underlying metastasis, is attributed to the loss of function ofE-cadherin(cdh1) gene. The loss of gene expression may arise from promoter hypermethylation, which has been reported in multiple cancers. In the present pilot project, sixty (60) blood samples were collected from the breast cancer patients at a tertiary care hospital in Karachi, Pakistan. DNA was isolated from the cells circulating in the peripheral blood of the participants. Promoter hypermethylation was investigated through sodium-bisulfite treatment of DNA followed by methylation-specific PCR. In 53.3% of the patients,E-cadheringene promoter hypermethylation was observed. Promoter hypermethylation ofE-cadherinhas been reported in DNA isolated from the tissue specimen. However, to the best of our knowledge this is the first report ofE-cadherinpromoter hypermethylation in cells isolated from the peripheral blood of breast cancer patients from a geographically specific population. The results have important implications in tumour staging and selection of treatment regimens.
Investigating the Impact of Caregiver Transportation Needs on Children’s Response to Behavioral and Mental Health Treatment: A Longitudinal Analysis
Authors: Riley Elizabeth N. , Vsevolozhskaya Olga A. , Zaykin Dmitri V. , Shimshock Stephen M. , Lyons John S.
Published: April 2021

Despite a rich and developing research literature on the relationships between transportation and healthcare outcomes, the impact of unmet transportation needs on children, particularly on their general psychosocial functioning, is less well understood. We hypothesized that caregiver’s transportation needs may be a key point of intervention for child-level health outcomes, such that the resolution of caregiver transportation needs may have an important, downstream impact on other areas of the child’s functioning. We tested this hypothesis in a sample of children (n=4341) served in a large, statewide public behavioral healthcare system. We conducted a retrospective longitudinal analysis of children served in the system between March 2019 and March 2020, using a specialized assessment tool that captures a comprehensive range of psychosocial functioning: the Child and Adolescent Needs and Strengths (CANS; Lyons, 2009) assessment. Linear mixed-effects analyses demonstrated that, if caregivers’ transportation needs were resolved during the episode of care, those children demonstrated greater improvements on both need reduction and strength building across multiple domains than did their peers whose caregivers had unresolved transportation needs. By the end of the episode of care, children whose caregivers had resolved transportation needs were not significantly different than those children whose caregivers never had transportation needs. The resolution of transportation needs may be an important focus for providers working with children with a complex behavioral health, such that the resolution of these transportation needs seems to have a large, positive downstream impact on their overall functioning.
Pharmacogenomics of hypertension in chronic kidney disease: the CKD-PGX study
Authors: Eadon Michael T. , Maddatu Judith , Moe Sharon M. , Sinha Arjun D. , Ferreira Ricardo Melo , Miller Brent W. , Sher S. Jawad , Su Jing , Pratt Victoria M. , Chapman Arlene B. , Skaar Todd S. , Moorthi Ranjani N. ,   for the CKD-PGX investigators
Published: April 2021

Background

Patients with chronic kidney disease (CKD) often have uncontrolled hypertension despite polypharmacy. Pharmacogenomic drug-gene interactions (DGIs) may impact the metabolism or efficacy of antihypertensive agents. We hypothesized that providing a panel of 11 pharmacogenomic predictors of antihypertensive response would improve hypertension control.

Methods

A prospective cohort with CKD and hypertension was followed to assess the effect of pharmacogenomic testing on blood pressure control. The analysis population included 382 hypertensive subjects genotyped for cross-sectional assessment of drug-gene interactions and 335 subjects followed for 1 year to assess systolic (SBP) and diastolic blood pressure (DBP).

Results

Most participants (58.2%) with uncontrolled hypertension had a DGI reducing the efficacy of one or more antihypertensive agents. Subjects with a DGI had 1.88-fold (95% CI 1.2-2.8) higher odds of uncontrolled hypertension as compared to those without a DGI, adjusted for race and CKD grade. CYP2C9 reduced metabolism genotypes were associated with losartan response and uncontrolled hypertension (Odds Ratio 5.2, CI 1.9 -14.7). CYP2D6 intermediate or poor metabolizers had less frequent uncontrolled hypertension compared to normal metabolizers taking metoprolol or carvedilol (OR 0.55, CI 0.3-0.95). In 335 subjects completing 1 year follow-up, SBP (−4.0 mmHg, CI 1.6-6.5) and DBP (−3.3 mmHg, CI 2.0-4.6) were improved. The magnitude of reductions in SBP (−14.8 mmHg, CI 10.3-19.3) and DBP (−8.4 mmHg, CI 5.9-10.9) were greatest in the 90 individuals with uncontrolled hypertension and an actionable genotype.

Conclusions

There is a potential role for the addition of pharmacogenomic testing to optimize antihypertensive regimens in patients with CKD.