bluuebunny/crossref_metadata_2025 huggingface dataset:
No evidence of a generalized potential ‘cost’ of apical dominance for species that have strong apical dominance
Authors: Finley Jenna V , Aarssen Lonnie W
Published: April 2022

When the shoot apical meristem of plants is damaged or removed, fecundity and/or plant growth may suffer (under-compensation), remain unaffected (compensation) or increase (overcompensation). The latter signifies a potential ‘cost’ of apical dominance. Using natural populations of 19 herbaceous angiosperm species with a conspicuously vertical, apically dominant growth form, we removed (clipped) the shoot apical meristem for replicate plants early in the growing season to test for a potential cost of apical dominance. Clipped and unclipped (control) plants had their near neighbours removed, and were harvested after flowering production had finished but before seed dispersal. Dry mass was measured separately for aboveground body size (shoots), leaves, seeds and fruits; and number of leaves, fruits and seeds per plant were counted. We predicted that: (i) our study species (because of their strong apically dominant growth form) would respond to shoot apical meristem removal with greater branching intensity, and thus overcompensation in terms of fecundity and/or biomass; and (ii) overcompensation is particularly enabled for species that produce smaller but more leaves, and hence with a larger bud bank of axillary meristems available for deployment in branching and/or fruit production. Widely variable compensatory capacities were recorded, and with no significant between-species relationship with leaf size or leafing intensity—thus indicating no generalized potential cost of apical dominance. Overall, the results point to species-specific treatment effects on meristem allocation patterns, and suggest importance for effects involving local variation in resource availability, and between-species variation in phenology, life history traits and susceptibility to herbivory.
Rapid X-ray variability in Mkn 421 during a multiwavelength campaign
Authors: Markowitz Alex G , Nalewajko Krzysztof , Bhatta Gopal , Dewangan Gulab C , Chandra Sunil , Dorner Daniela , Schleicher Bernd , Pajdosz-Śmierciak Urszula , Stawarz Łukasz , Zola Staszek , Ostrowski Michał , Carosati Daniele , Krishnan Saikruba , Bachev Rumen , Benítez Erika , Gazeas Kosmas , Hiriart David , Hu Shao-Ming , Larionov Valeri , Marchini Alessandro , Matsumoto Katsura , Nikiforova A A , Pursimo Tapio , Raiteri Claudia M , Reichart Daniel E , Rodriguez Diego , Semkov Evgeni , Strigachev Anton , Sugiura Yuki , Villata Massimo , Webb James R , Arbet-Engels Axel , Baack Dominik , Balbo Matteo , Biland Adrian , Bretz Thomas , Buss Jens , Eisenberger Laura , Elsaesser Dominik , Hildebrand Dorothee , Iotov Roman , Kalenski Adelina , Mannheim Karl , Mitchell Alison , Neise Dominik , Noethe Maximilian , Paravac Aleksander , Rhode Wolfgang , Sliusar Vitalii , Walter Roland
Published: April 2022

The study of short-term variability properties in AGN jets has the potential to shed light on their particle acceleration and emission mechanisms. We report results from a 4-d coordinated multiwavelength campaign on the highly peaked blazar (HBL) Mkn 421 in 2019 January. We obtained X-ray data from AstroSAT, BVRI photometry with the Whole Earth Blazar Telescope (WEBT), and TeV data from First G-APD Cherenkov Telescope to explore short-term multiwavelength variability in this HBL. The X-ray continuum is rapidly variable on time-scales of tens of ks. Fractional variability amplitude increases with energy across the synchrotron hump, consistent with previous studies; we interpret this observation in the context of a model with multiple cells whose emission spectra contain cutoffs that follow a power-law distribution. We also performed time-averaged and time-resolved (time-scales of 6 ks) spectral fits; a broken power-law model fits all spectra well; time-resolved spectral fitting reveals the usual hardening when brightening behaviour. Intra-X-ray cross-correlations yield evidence for the 0.6–0.8 keV band to likely lead the other bands by an average of 4.6 ± 2.6 ks, but only during the first half of the observation. The source displayed minimal night-to-night variability at all wavebands thus precluding significant interband correlations during our campaign. The broad-band SED is modelled well with a standard one-zone leptonic model, yielding jet parameters consistent with those obtained from previous SEDs of this source.
The extended H i halo of NGC 4945 as seen by MeerKAT
Authors: Ianjamasimanana Roger , Koribalski B S , Józsa Gyula I G , Kamphuis Peter , de Blok W J G , Kleiner Dane , Namumba Brenda , Carignan Claude , Dettmar Ralf-Jürgen , Serra Paolo , Smirnov Oleg M , Thorat Kshitij , Hugo Benjamin V , Ramaila Athanaseus J T , Maina Eric , Maccagni Filippo M , Makhathini Sphesihle , Andati Lexy A L , Molnár Dániel Cs , Perkins Simon , Loi Francesca , Ramatsoku Mpati , Atemkeng Marcellin
Published: April 2022

Observations of the neutral atomic hydrogen (H i) in the nuclear starburst galaxy NGC 4945 with MeerKAT are presented. We find a large amount of halo gas, previously missed by H i observations, accounting for 6.8 per cent of the total H i mass. This is most likely gas blown into the halo by star formation. Our maps go down to a 3σ column density level of 5 × 1018 cm−2. We model the H i distribution using tilted-ring fitting techniques and find a warp on the galaxy’s approaching and receding sides. The H i in the northern side of the galaxy appears to be suppressed. This may be the result of ionization by the starburst activity in the galaxy, as suggested by a previous study. The origin of the warp is unclear but could be due to past interactions or ram pressure stripping. Broad, asymmetric H i absorption lines extending throughout the H i emission velocity channels are present towards the nuclear region of NGC 4945. Such broad lines suggest the existence of a nuclear ring moving at a high circular velocity. This is supported by the clear rotation patterns in the H i absorption velocity field. The asymmetry of the absorption spectra can be caused by outflows or inflows of gas in the nuclear region of NGC 4945. The continuum map shows small extensions on both sides of the galaxy’s major axis that might be signs of outflows resulting from the starburst activity.
Hydrodynamics of warps in the local model of astrophysical discs
Authors: Ogilvie Gordon I
Published: April 2022

We show how the local approximation of astrophysical discs, which is the basis for the well-known model of the shearing box, can be used to study many aspects of the dynamics of warped discs. In the local model, inclination of the orbit of a test particle, with respect to the reference orbit, corresponds to a vertical oscillation of the particle at the orbital frequency. Warping of a disc corresponds to a locally axisymmetric corrugation of the mid-plane of the disc that oscillates vertically at the orbital frequency, while evolution of the warp corresponds to a modulation of the complex amplitude of the vertical oscillation. We derive a conservation law for this amplitude that is the local equivalent of the conservation of angular momentum and therefore governs the evolution of the warp. For length scales that are long compared to the vertical scale height of the disc, the known non-resonant and resonant regimes of warp dynamics, including the diffusive and wave-like regimes of Keplerian discs, occur in the local model in the same way as in a global view of warped discs.
Numerical analysis of processes for the formation of moonlets confining the arcs of Neptune
Authors: Madeira Gustavo , Giuliatti Winter Silvia M
Published: April 2022

The arcs of Neptune – Fraternité, Egalité, Liberté, and Courage – are four incomplete rings immersed in the Adams ring. A recent confinement model for the arcs proposes that the structures are azimuthally confined by four co-orbital moonlets. In this work, we intend to approach some points related to the dynamics of co-orbital moonlets and suggest a model for their formation. We study the equilibrium configurations for 1+N co-orbital satellites under the 42:43 Lindblad resonance with Galatea. We obtained three distinct configurations with 1+3 and 1+4 moonlets able to confine and reproduce the location of the arcs. The moonlets’ formation is analysed by the disruption of an ancient body at a Lagrangian point of a moon. The disruption fragments spread out in horseshoe orbits and collide to form moonlets, which reach an equilibrium configuration due to a non-conservative effect. In such a scenario, the arcs likely formed through a mixture of different processes, with impacts between disruption outcomes and meteoroid impacts with the moonlets being possibilities.
Long-term radio monitoring of the neutron star X-ray binary Swift J1858.6−0814
Authors: Rhodes L , Fender R P , Motta S , van den Eijnden J , Williams D R A , Bright J , Sivakoff G R
Published: April 2022

We present the results of our long-term radio monitoring campaign at 1.3 GHz (MeerKAT) and 15.5 GHz (Arcminute Microkelvin Imager – Large Array, AMI-LA) for the outburst of the recently discovered neutron star X-ray binary Swift J1858.6−0814. Throughout the outburst, we observe radio emission consistent with a quasi-persistent, self-absorbed jet. In addition, we see two flares at MJD 58427 and 58530. The second flare allows us to place constraints on the magnetic field and minimum energy of the jet at 0.2 G and 5 × 1037 erg, respectively. We use the multifrequency radio data in conjunction with data from Swift-BAT (Burst Alert Telescope) to place Swift J1858.6−0814 on the radio/X-ray correlation. We find that the quasi-simultaneous radio and BAT data make Swift J1858.6−0814 appear to bridge the gap in the radio/X-ray plane between atoll and Z sources. Furthermore, AMI-LA observations made while Swift J1858.6−0814 was in the soft state have allowed us to show that the radio emission during the soft state is quenched by at least a factor of 4.
Six new compact triply eclipsing triples found withTESS
Authors: Rappaport S A , Borkovits T , Gagliano R , Jacobs T L , Kostov V B , Powell B P , Terentev I , Omohundro M , Torres G , Vanderburg A , Mitnyan T , Kristiansen M H , LaCourse D , Schwengeler H M , Kaye T G , Pál A , Pribulla T , Bíró I B , Csányi I , Garai Z , Zasche P , Maxted P F L , Rodriguez J E , Stevens D J
Published: April 2022

In this work, we report the discovery and analysis of six new compact triply eclipsing triple star systems found with the TESS mission: TICs 37743815, 42565581, 54060695, 178010808, 242132789, and 456194776. All of these exhibit distinct third-body eclipses where the inner eclipsing binary (EB) occults the third (‘tertiary’) star, or vice versa. We utilized the TESS photometry, archival photometric data, and available archival spectral energy distribution curves (SED) to solve for the properties of all three stars, as well as many of the orbital elements. We describe in detail our SED fits, search of the archival data for the outer orbital period, and the final global photodynamical analyses. From these analyses, we find that all six systems are coplanar to within 0°−5°, and are viewed nearly edge on (i.e. within a couple of degrees). The outer orbital periods and eccentricities of the six systems are {Pout (days), e}: {68.7, 0.36}, {123, 0.16}, {60.7, 0.01}, {69.0, 0.29}, {41.5, 0.01}, {93.9, 0.29}, respectively, in the order the sources are listed above. The masses of all 12 EB stars were in the range of 0.7–1.8 M⊙ and were situated near the main sequence. By contrast, the masses and radii of the tertiary stars ranged from 1.5 to 2.3 M⊙ and 2.9 to 12 R⊙, respectively. We use this information to estimate the occurrence rate of compact flat triple systems..
Impact of Sex, Sleep, Symptoms of Central Sensitization, and Psychosocial Factors in Adolescents with Chronic Musculoskeletal Pain: An Exploratory Study
Authors: Andias Rosa , Silva Anabela G
Published: April 2022

Objective

This study aimed to explore and compare the associations of psychosocial factors, sleep, and central sensitization with chronic neck, back, limb, and multiregional pain and disability.

Methods

One thousand seven hundred thirty (n = 1,730) adolescents responded to an online questionnaire containing questions about sociodemographic data, as well as the Nordic Musculoskeletal Questionnaire; the International Physical Activity Questionnaire; the Functional Disability Inventory; the Depression, Anxiety, and Stress Scale; the Basic Scale on Insomnia Complaints and Quality of Sleep; the Pain Catastrophizing Scale; the Tampa Scale of Kinesiophobia; the Child Self-Efficacy Scale; and the Central Sensitization Inventory. Univariable and multivariable regression analysis were used to assess the associations between these variables and pain and disability.

Results

Groups were categorized into those with neck (n = 54), back (n = 80), upper limb (n = 52), lower limb (n = 109), or multiregional (n = 1,140) pain. Multivariable analysis showed that symptoms of central sensitization increased the odds of neck, back, and multiregional pain; depression, anxiety and stress, and physical activity increased the odds of multiregional pain; and fear of movement increased the odds of lower limb pain. Female gender increased the odds of pain in all groups, except in the lower limb group. Depression, anxiety, and stress also remained associated with disability in neck, back, upper limb, and multiregional pain; poorer sleep remained associated with disability in neck, upper limb, and multiregional pain; catastrophizing remained associated with back and multiregional pain; and fear of movement and symptoms of central sensitization were associated with disability only in multiregional pain.

Conclusions

There are similar but also different variables associated with the presence of pain and disability in the neck, back, limbs, and multiregional pain.
Excitation spectra of heavy baryons in diquark models
Authors: Kumakawa Kento , Jido Daisuke
Published: April 2022

The excitation energy spectra of heavy baryons consisting of a heavy quark and two light quarks are investigated using diquark models in order to examine the nature of the diquark as a constituent of single heavy baryons. We consider two diquark models; in Model A the diquark is treated as a point-like particle, while it has a spatial size in Model B. We determine the masses of scalar and axial vector diquarks by the mass difference of the ground-state charmed baryons and the Λc baryon, while the mass of the ud scalar diquark in the Λc baryon is assumed to be 500 MeV as a reference. The parameters of these models are fixed by the 1p excitation energy of Λc. We find that Model A reproduces well the excitation energy spectra of the charmed and bottomed baryons, although the string tension of the confinement potential in Model A should be half of that of the charmonium, while Model B suggests degeneracy of the 2s and 1d states, which is not seen in the Λc spectrum.
Molecular epidemiological features of SARS-CoV-2 in Japan, 2020–1
Authors: Ode Hirotaka , Nakata Yoshihiro , Nagashima Mami , Hayashi Masaki , Yamazaki Takako , Asakura Hiroyuki , Suzuki Jun , Kubota Mai , Matsuoka Kazuhiro , Matsuda Masakazu , Mori Mikiko , Sugimoto Atsuko , Imahashi Mayumi , Yokomaku Yoshiyuki , Sadamasu Kenji , Iwatani Yasumasa
Published: April 2022

There were five epidemic waves of coronavirus disease 2019 in Japan between 2020 and 2021. It remains unclear how the domestic waves arose and abated. To better understand this, we analyzed the pangenomic sequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and characterized the molecular epidemiological features of the five epidemic waves in Japan. In this study, we performed deep sequencing to determine the pangenomic SARS-CoV-2 sequences of 1,286 samples collected in two cities far from each other, Tokyo Metropolis and Nagoya. Then, the spatiotemporal genetic changes of the obtained sequences were compared with the sequences available in the Global Initiative on Sharing All Influenza Data (GISAID) database. A total of 873 genotypes carrying different sets of mutations were identified in the five epidemic waves. Phylogenetic analysis demonstrated that sharp displacements of lineages and genotypes occurred between consecutive waves over the 2 years. In addition, a wide variety of genotypes were observed in the early half of each wave, whereas a few genotypes were detected across Japan during an entire wave. Phylogenetically, putative descendant genotypes observed late in each wave displayed regional clustering and evolution in Japan. The genetic diversity of SARS-CoV-2 displayed uneven dynamics during each epidemic wave in Japan. Our findings provide an important molecular epidemiological basis to aid in controlling future SARS-CoV-2 epidemics.
Correlation of Kidney Size to Number of Renal Pyramids in the Goat Kidney
Authors: Ashton Leah , Gullekson Russ , Hurley Mary , Olivieri Marion
Published: April 2022

Kidneys are composed of the renal cortex and renal medulla. The renal medulla is arranged into pyramidal‐shaped structures within the renal cortex of the kidney. Humans have an average of seven to eighteen renal pyramids per kidney. Little is known as to why there is such a large range in the average number of renal pyramids in this structure, which is why it would be beneficial to discover if there is a correlation in the size of the kidney and the number of renal pyramids within it. By calculating the mass and volume of each kidney, a relationship between density and number of renal pyramids may be found. Goat kidneys were collected, subjectively examined for dimension, and pyramid number was documented. Preliminary data demonstrates a correlation between kidney size and number of renal pyramids. Ultimately, this information may explain the influence the number of renal pyramids has on overall renal size and function.

Support or Funding Information

Department of Biology and Mathematics of D'Youville College, Buffalo NY
RETINAL NONPERFUSION IN THE EARLY TREATMENT DIABETIC RETINOPATHY STUDY SEVEN FIELDS COMPARED WITH WIDEFIELD FLUORESCEIN ANGIOGRAPHY
Authors: Martin-Gutierrez Maria P. , Vermeirsch Sandra , Chandra Shruti , Agarwal Aditi A. K. , Selvam Senthil , Thottarath Sridevi , Vazquez-Alfageme Clara , Sen Piyali , Sivaprasad Sobha , Hykin Philip G. , Nicholson Luke
Published: April 2022

Background:

In previous landmark studies on central retinal vein occlusion, retinal nonperfusion assessments were obtained using 7-field (7F) angiography. The widespread current use of widefield imaging allows better visualization of the peripheral retina and more comprehensive estimation of the total area of nonperfusion. The relationship between nonperfusion measurement of 7F and widefield angiography (WFA) in central retinal vein occlusion has not been studied. We aim to identify the correlation of retinal nonperfusion measured within the 7F and on WFA in eyes with central retinal vein occlusion.

Methods:

Retinal nonperfusion in participants with central retinal vein occlusion was determined using a 7F Early Treatment Diabetic Retinopathy Study template and the concentric rings method.

Results:

A total of 153 eyes were included. Pearson correlation test showed a near-perfect positive, linear correlation between the nonperfusion found in the 7F and total retinal nonperfusion on WFA (0.985 95% CI [0.793, 0.999]) The regression line equation for nonperfusion on 7F and WFA was y = 37 + 3.2x. Eyes with 0 disk areas (DA), >0 DA to 10 DA and >10 DA of nonperfusion on 7-fields had on average 23 DA 95% CI (19.20, 27.06), 45 DA 95% CI (35.75, 55.18), and 115 DA 95% CI (88.89, 142.05) on widefield respectively.

Conclusion:

There is a positive and linear relationship between nonperfusion measured by 7F and WFA in central retinal vein occlusion with more than 3-times the amount of nonperfusion identified on WFA. Despite <10 DA no areas of nonperfusion on 7F, there is typically at least 35 DA of nonperfusion on WFA whereas eyes with >10 DA of nonperfusion on 7F had at least 88 DA on WFA.
Cerebrospinal Fluid Shunt Infections: A Multicenter Pediatric Study
Authors: McAlpine Alastair , Robinson Joan L. , Barton Michelle , Balamohan Archana , Davies H. Dele , Skar Gwenn , Lefebvre Marie-Astrid , Almadani Ahmed , Freire Dolores , Le Saux Nicole , Bowes Jennifer , Srigley Jocelyn A. , Passarelli Patrick , Bradley John , Khan Sarah , Purewal Rupeena , Viel-Thériault Isabelle , Ranger Adrianna , Hawkes Michael T. ,   for the Paediatric Investigators Collaborative Network on Infections in Canada
Published: April 2022

Background:

Infections complicate 5%–10% of cerebrospinal fluid (CSF) shunts. We aimed to describe the characteristics and contemporary pathogens of shunt infections in children in Canada and the United States.

Methods:

Descriptive case series at tertiary care hospitals in Canada (N = 8) and the United States (N = 3) of children up to 18 years of age with CSF shunt infections from July 1, 2013, through June 30, 2019.

Results:

There were 154 children (43% female, median age 2.7 years, 50% premature) with ≥1 CSF shunt infections. Median time between shunt placement and infection was 54 days (interquartile range, 24 days–2.3 years). Common pathogens were coagulase-negative staphylococci (N = 42; 28%), methicillin-susceptible Staphylococcus aureus (N = 24; 16%), methicillin-resistant S. aureus (N = 9; 5.9%), Pseudomonas aeruginosa (N = 9; 5.9%) and other Gram-negative bacilli (N = 14; 9.0%). Significant differences between pathogens were observed, including timing of infection (P = 0.023) and CSF leukocyte count (P = 0.0019); however, differences were not sufficient to reliably predict the causative organism based on the timing of infection or discriminate P. aeruginosa from other pathogens based on clinical features. Empiric antibiotic regimens, which included vancomycin (71%), cefotaxime or ceftriaxone (29%) and antipseudomonal beta-lactams (33%), were discordant with the pathogen isolated in five cases. There was variability between sites in the distribution of pathogens and choice of empiric antibiotics. Nine children died; 4 (44%) deaths were attributed to shunt infection.

Conclusions:

Staphylococci remain the most common cause of CSF shunt infections, although antibiotic resistant Gram-negative bacilli occur and cannot be reliably predicted based on clinical characteristics.
Pediatric Musculoskeletal Coccidioidomycosis in Central California: A Single Center Experience
Authors: Naeem Fouzia , Gerardi Joseph , Gholve Purushottam , Merriott Daniel , Hassan Rida , McCarty James
Published: April 2022

Background:

Published literature on musculoskeletal coccidioidomycosis is sparse and limited to case reports and case series. This is one of the largest case series to describe the clinical presentation, diagnosis, medical and surgical management and outcomes of pediatric musculoskeletal coccidioidomycosis at a tertiary care hospital.

Method:

A retrospective case review was performed on patients ≤ 21 years old who were followed at a tertiary care center with a diagnosis of musculoskeletal coccidioidomycosis from January 1, 2007, to December 31, 2020. Descriptive data are expressed as medians and interquartile range (IQR) for continuous variables or as frequency and percentage for categorical variables. Categorical values were compared using the χ
2 test.

Results:

Forty-one patients were identified. The median age was 12.8 years, and most were male (71%), Latinx (66%) and healthy (71%). Limb swelling (66%), bone pain (54%) and joint pain (46%) were the most common presenting symptoms. Multiple bone involvement was present in 29% while 12% had the joint disease, and craniofacial (n = 10) and metacarpal/metatarsal bones (n=9) were the most commonly involved sites. Elevated Coccidioides complement fixation (CF) titers ≥1:32 were seen in 90% of the patients. Thirty-three patients (81%) required surgical interventions and of these 16 (48%) required additional surgical procedures. Eleven patients (27%) had disease relapse. Children >13 years of age were more likely to have > 1 organ involvement (16 vs. 7, P = 0.04), multiple bone involvement (10 vs. 2, P = 0.004) and maximum Coccidioides CF titers >1:128 (13 vs. 6, P = 0.02).

Conclusions:

In endemic areas, musculoskeletal coccidioidomycosis causes a substantial disease burden in children and should be considered in the differential diagnosis of those presenting with bone and joint pain or swelling. Early diagnosis and treatment are essential to minimize long-term morbidity and mortality.
Management and Outcome of Febrile Infants ≤60 days, With Emphasis on Infants ≤21 Days Old, in Swedish Pediatric Emergency Departments
Authors: Orfanos Ioannis , Elfving Kristina , Sotoca Fernandez Jorge , Wennlund Lovisa , Weiber Sofia , Eklund Erik A. , Alfvén Tobias
Published: April 2022

Background:

Management of febrile infants ≤60 days of age varies, and the age for routine investigations and antibiotic-treatment is debated. The American Academy of Pediatrics recommended age threshold for lumbar puncture (LP) is 21 days and for blood culture 60 days. We describe management and adverse outcome of febrile infants ≤60 days old, in Sweden.

Methods:

Retrospective cross-sectional study of infants ≤60 days of age with fever without source evaluated in 4 University pediatric emergency departments, between 2014 and 2017. Adverse outcome was defined as delayed-treated invasive bacterial infection (IBI: meningitis or bacteremia).

Results:

We included 1701 infants. In infants ≤21 days old, LP was performed in 16% (95% CI: 12–20) and blood culture in 43% (95% CI: 38–48). Meningitis was diagnosed in 5 (1.3%; 95% CI: 0.4–3.0) and bacteremia in 12 (4.5%; 95% CI: 2.6–7.0) infants. Broad-spectrum antibiotics were not administered to 66% (95% CI: 61–71), of which 2 (0.8%; 95% CI: 0.1–2.8) diagnosed with IBI (1 meningitis and 1 bacteremia). In the 29–60 days age group, blood culture was performed in 21% (95% CI: 19–24), and broad-spectrum antibiotics were not administered to 84% (95% CI: 82–86), with no case of delayed-treated bacteremia.

Conclusions:

The rates of LP, blood culture and broad-spectrum antibiotics were low. Despite that, there were few delayed-treated IBIs, but 2 of the 17 infants ≤21 days of age with IBI were not timely treated, which prompts the need for a safer approach for this age group. Also, the utility of routine blood culture for all febrile infants 29–60 days old could be questioned.
Analysis of non-human primate models for evaluating prion disease therapeutic efficacy
Authors: Mortberg Meredith A , Minikel Eric Vallabh , Vallabh Sonia M
Published: April 2022

Prion disease is a fatal neurodegenerative disease caused by the conformational corruption of the prion protein (PrP), encoded by the prion protein gene (PRNP). While no disease-modifying therapy is currently available, genetic and pharmacological proofs of concept support development of therapies that lower PrP levels in the brain. In light of proposals for clinical testing of such drugs in presymptomatic individuals at risk for genetic prion disease, extensive nonclinical data are likely to be required, with extra attention paid to choice of animal models. Uniquely, the entire prion disease process can be faithfully modeled through transmission of human prions to non-human primates (NHPs), raising the question of whether NHP models should be used to assess therapeutic efficacy. Here we systematically aggregate data from N=527 prion-inoculated animals spanning six decades of research studies. Using this dataset, we assess prion strain, route of administration, endpoint, and passage number to characterize the relationship of tested models to currently prevalent human subtypes of prion disease. We analyze the incubation times observed across diverse models and perform power calculations to assess the practicability of testing prion disease therapeutic efficacy in NHPs. We find that while some models may theoretically be able to support therapeutic efficacy studies, pilot studies would be required to confirm incubation time and attack rate before pivotal studies could be designed, cumulatively requiring several years. The models with the shortest and most tightly distributed incubation times are those with smaller brains and weaker homology to humans. Our findings indicate that it would be challenging to conduct efficacy studies in NHPs in a paradigm that honors the potential advantages of NHPs over other available models, on a timeframe that would not risk unduly delaying patient access to promising drug candidates.
Extraction of Sleep Information from Clinical Notes of Patients with Alzheimer’s Disease Using Natural Language Processing
Authors: Sivarajkumar Sonish , Tam Thomas Yu Chow , Ahamed Mohammad Haneef , Viggiano Samuel , Oniani David , Visweswaran Shyam , Wang Yanshan
Published: April 2022

Objective

Alzheimer’s Disease (AD) is the most common form of dementia in the United States. Sleep is one of the lifestyle-related factors that has been shown critical for optimal cognitive function in old age. However, there is a lack of research studying the association between sleep and AD incidence. A major bottleneck for conducting such research is that the traditional way to acquire sleep information is time-consuming, inefficient, non-scalable, and limited to patients’ subjective experience.

Materials and Methods

A gold standard dataset is created from manual annotation of 570 randomly sampled clinical note documents from the adSLEEP, a corpus of 192,000 de-identified clinical notes of 7,266 AD patients retrieved from the University of Pittsburgh Medical Center (UPMC). We developed a rule-based Natural Language Processing (NLP) algorithm, machine learning models, and Large Language Model(LLM)-based NLP algorithms to automate the extraction of sleep-related concepts, including snoring, napping, sleep problem, bad sleep quality, daytime sleepiness, night wakings, and sleep duration, from the gold standard dataset

Results

Rule-based NLP algorithm achieved the best performance of F1 across all sleep-related concepts. In terms of Positive Predictive Value (PPV), rule-based NLP algorithm achieved 1.00 for daytime sleepiness and sleep duration, machine learning models: 0.95 and for napping, 0.86 for bad sleep quality and 0.90 for snoring; and LLAMA2 with finetuning achieved PPV of 0.93 for Night Wakings, 0.89 for sleep problem, and 1.00 for sleep duration.

Discussion

Although sleep information is infrequently documented in the clinical notes, the proposed rule-based NLP algorithm and LLM-based NLP algorithms still achieved promising results. In comparison, the machine learning-based approaches didn’t achieve good results, which is due to the small size of sleep information in the training data.

Conclusion

The results show that the rule-based NLP algorithm consistently achieved the best performance for all sleep concepts. This study focused on the clinical notes of patients with AD, but could be extended to general sleep information extraction for other diseases.
Cannabis potential effects to prevent or attenuate SARS-COV2 contagion
Authors: Herrera-Gómez Paula M. , Echeverri-Cataño Luis F. , Giraldo S , Ruiz Colorado- Y , Vélez van Meerbeke Alberto
Published: April 2022

Medical cannabis has gained an exponential interest in recent years. Therapeutic targets have been broadened from specific applications over pain control, chemotherapy side effects, treatment-resistant epilepsies and multiple sclerosis, among others. Several in vitro and animal studies, along with few human controlled studies, suggest cannabinoids have a potential therapeutic role over medical conditions comporting inflammatory mechanisms. Given the tremendous world-wide impact of the COVID-19 pandemic, research efforts are converging towards the use of cannabinoids to attenuate severe or fatal forms of the disease. The present survey aims to explore possible correlations between cannabis use, either recreational or medical, over the presence of SARS-COV-2 contagion, along with the symptom’s severity. 4026 surveys were collected via electronic form. Results suggest a relation between any type of cannabis use and a lower risk of SARS-COV-2 contagion (p=0,004; OR=0,689, IC95% 0,534-0,889). Despite several methodological limitations, the present survey steps up the urge to expand our understanding on cannabinoids potential use on human controlled studies, that can better arm us in the fight against the current COVID-19 pandemic.
What (if anything) is going on? Examining longitudinal associations between social media use and mental ill-health among young people
Authors: Kelly Yvonne , Xue Baowen , Booker Cara , Sacker Amanda , Lacey Rebecca , Ploubidis George , Patalay Praveetha
Published: April 2022

Objectives

In mid-adolescence, to 1) examine cyclical associations between social media use and mental ill health by investigating longitudinal and bidirectional associations, dose response relationships, and changes in social media use and in mental health; 2) assess potential interaction effects between social media use and mental health with pre-existing early life vulnerabilities.

Methods

Longitudinal data on 12,114 participants from the Millennium Cohort Study on social media use, depressive symptoms, self-harm and early life risk factors were used.

Results

We found little support for the existence of cyclical relationships between social media use and mental health. Where detected, effect sizes were small. Dose response associations were seen in the direction of mental health to social media (depressive symptoms 1 time OR=1.22, 2 times OR=1.71; self-harm 1 time OR=1.17, 2 times OR=1.53), but not for social media to mental health. Changes in social media use and changes in mental health were not associated with each other. We found no evidence to suggest that either social media use or mental health interacted with pre-existing risk for mental ill health.

Conclusions

Findings highlight the possibility that observed longitudinal associations between social media use and mental health might reflect other risk processes or vulnerabilities and/or the precision of measures used. More detailed and frequently collected prospective data about online experiences, including those from social media platforms themselves will help to provide a clearer picture of the relationship between social media use and mental health.
Physical activity-correlated changes in plasma enzyme concentrations in fragile sarcolemmal muscular dystrophies
Authors: Blank Paul S. , Golding Adriana E. , Benavides Ivonne Morales , Waters Hang , Mekhedov Elena , Bezrukov Ludmila , Wachter Rebecca D. , Mikhailenko Irina , Brown Robert H. , Bönnemann Carsten G. , Demidowich Andrew P. , Jain Minal S. , Yanovski Jack A. , Zimmerberg Joshua
Published: April 2022

STRUCTURED ABSTRACT

Background and Objectives

Muscular dystrophies associated with decreased sarcolemma integrity lack validated clinical measures of sarcolemma fragility that can be used to assess disease progression and the effects of therapies designed to reduce sarcolemma fragility. We conducted a pilot study to test the hypothesis that physical activity leads to significant changes in muscle-derived plasma enzymes in participants with “fragile sarcolemmal muscular dystrophies” (FSMD).

Methods

We enrolled ambulatory individuals clinically affected with genetically confirmed FSMD neither taking anti-inflammatory medications nor having relevant co-morbidities for an inpatient study. Over five days, blood samples at 20 time points were obtained. Plasma enzymes alanine and aspartate aminotransferase (ALT, AST), creatine kinase (CK), and lactate dehydrogenase (LDH), all found in muscle, were measured before and after routine morning activities and motor function testing. Analysis of Z-transformed time series data led to feature and kinetic models that revealed activity-dependent feature and kinetic parameters.

Results

Among the 11 enrolled participants, (LGMD Type 2B/R2 Dysferlin-related (4F/1M), LGMD Type 2L/R12 Anoctamin-5-related (3F/2M), LGMD Type 2I/R9 FKRP-related (1M)), plasma enzymes increased with activity. The average % change +/- SEM with morning activity across all participants was ALT 12.8 ± 2.8%, AST 11.6 ± 2.9%, CK 12.9 ± 2.8%, and LDH 12.2 ± 3.9%, suggesting the increases originate from the same stimulated source, presumably skeletal muscle. For ALT, AST, CK, and LDH, characteristic kinetic features include (a) elevated enzyme activities on arrival that decreased overnight; (b) a longer decay trend observed over the week, and (c) for ALT, AST, and CK, a similar decay trend observed with post-morning activity blood draws.

Discussion

Controlled activity-dependent changes in plasma ALT, AST, and CK on time scales of days to weeks can serve as common outcome measures for sarcolemma integrity and may be efficient and effective tools for monitoring disease progression and treatment efficacy for both individuals and patient populations. In addition, this study provides data that may benefit patient management as it can inform guidance on duration and type of activity that minimizes muscle damage.
Summaries, Analysis and Simulations of Recent COVID-19 Epidemics in Mainland China
Authors: Min Lequan
Published: April 2022

Background

Globally COVID-19 epidemics have caused tremendous disasters. China prevented effectively the spread of COVID-19 epidemics before 2022. Recently Omicron and Delta variants cause a surge in reported COVID-19 infections.

Methods

Using differential equations and real word data, this study modelings and simulates COVID-19 epidemic in mainland China, estimates transmission rates, recovery rates, and blocking rates to symptomatic and asymptomatic infections. The transmission rates and recovery rates of the foreign input COVID-19 infected individuals in mainland China have also been studied.

Results

The simulation results were in good agreement with the real word data. The recovery rates of the foreign input symptomatic and asymptomatic infected individuals are much higher than those of the mainland COVID-19 infected individuals. The blocking rates to symptomatic and asymptomatic mainland infections are lower than those of the previous epidemics in mainland China. The blocking rate implemented between March 24-31, 2022 may not prevent the rapid spreads of COVID-19 epidemics in mainland China. For the foreign input COVID-19 epidemics, the numbers of the current symptomatic individuals and the asymptomatic individuals charged in medical observations have decreased significantly after March 17 2022.

Conclusions

Need to implement more strict prevention and control strategies to prevent the spread of the COVID-19 epidemics in mainland China. Keeping the present prevention and therapy measures to foreign input COVID-19 infections can rapidly reduce the number of foreign input infected individuals to a very low level.
Classifying REM Sleep Behavior Disorder through CNNs with Image-Based Representations of EEGs
Authors: Srivastava Saurish
Published: April 2022

Objective

Rapid Eye Movement Sleep Behavior Disorder (RBD) is a parasomnia with a high conversion rate to α–synucleinopathies such as Parkinson’s Disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). The objective of this paper is to classify RBD in patients through a convolutional neural network utilizing imagebased representations of electroencephalogram (EEG) channels.

Methods

Analysis was conducted on polysomnography data from 22 patients with RBD and 12 healthy controls acquired from the Cyclic Alternating Pattern (CAP) Sleep Database. EEG channels were split into four frequency bands (theta, alpha, beta, and gamma). Power spectrum density was calculated through a Fast Fourier Transformation (FFT) and converted into 2D images through bicubic interpolation. RBD classification was accomplished through a pre-trained VGG-16 CNN with layer weights being fine-tuned.

Results

The model was successful in classifying RBD patients over non-RBD patients and achieved 97.92% accuracy over 40 epochs. Accuracy increased dramatically with increased data generated from FFT and interpolation (62.63% to 97.92%).

Conclusions

This project proposes a novel approach toward an automatic classification of RBD and highlights the importance of deep learning models in the field. The proposed transfer learning model outperforms state-of-the-art models and preliminarily accounts for the lack of computational resources in clinical spaces, thereby increasing the accessibility of automatic classification.

Significance

By leveraging transfer learning and raw data, the results demonstrate that a similar model for the classification of RBD patients could easily be translated to the clinical atmosphere, drastically accelerating the classification pipeline. The proposed methods are also applicable to α–synucleinopathies, including PD, DLB, and MSA.
Evaluation of Eight Lateral Flow Tests for the detection of anti-SARS-CoV-2 antibodies in a vaccinated population
Authors: Greenland-Bews Caitlin , Byrne Rachel. L. , Owen Sophie. I. , Watkins Rachel. L. , Bengey Daisy , Buist Kate , Clerkin Karina , Escadafal Camille , Finch Lorna. S. , Gould Susan , Giorgi Emanuele , Hodgkinson Andy , Mashenko Larysa , Powell Darren , Savage Helen. R. , Thompson Caitlin. R. , Turtle Lance , Wardale Jahanara , Wooding Dominic , Edwards Thomas , Atienzar Ana Cubas , Adams Emily. R.
Published: April 2022

With the distribution of COVID-19 vaccinations across the globe and the limited access in many countries, quick determination of an individual’s antibody status could be beneficial in allocating limited vaccine doses in low- and middle-income countries (LMIC). Antibody lateral flow tests (LFTs) have potential to address this need as a quick, point of care test, they also have a use case for identifying sero-negative individuals for novel therapeutics, and for epidemiology. Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n=60), AZD1222 (AstraZeneca, n=31), mRNA-1273 (Moderna, n=2) and Undeclared Vaccine Brand (n=2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies. These tests are quick, low-cost point-of-care tools that can be used without prior training to establish antibody status and may prove valuable for allocating limited vaccine doses in LMICs to ensure those in at risk groups access the protection they need. Further investigation into their performance in vaccinated peoples is required before more widespread utilisation is considered.
EARLY OUTPATIENT TREATMENT OF COVID-19: A RETROSPECTIVE ANALYSIS OF 392 CASES IN ITALY
Authors: Cosentino Marco , Vernocchi Veronica , Martini Stefano , Marino Franca , Allasino Barbara , Balzola Maria , Burigana Fabio , Dallari Alberto , Pagano Carlo Servo Florio , Palma Antonio , Rango Mauro ,   the IppocrateOrg Association Working Group for the Early Outpatient Treatment of COVID-19
Published: April 2022

Introduction

The pandemic of severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) disease 2019 (COVID-19) was declared in march 2020. Knowledge of COVID-19 pathophysiology soon provided a strong rationale for the early use of anti-inflammatory, antiplatelet and anticoagulant drugs, however the evidence was only slowly and partially incorporated into institutional guidelines. Unmet needs of COVID-19 outpatients were soon taken care of by networks of physicians and researchers, using pharmacotherapeutic approaches based on the best available experiences.

Methods

Observational retrospective study investigating characteristics, management and outcomes in COVID-19 patients taken care of in Italy by physicians volunteering within the IppocrateOrg Association, one of the main international assistance networks, between 1st november 2020 and 31st march 2021.

Results

Ten doctors took part in the study and provided data about 392 consecutive COVID-19 patients. Patients’ mean age was 48,5 years (range: 0,5-97). They were 51,3% females and were taken care of when in COVID-19 stage 0 (15,6%), 1 (50,0%), 2a (28,8%), 2b (5,6%). Many patients were overweight (26%) or obese (11,5%), with chronic comorbidities (34,9%), mainly cardiovascular (23%) and metabolic (13,3%). Drugs most frequently prescribed included: vitamins and supplements (98,7%), aspirin (66,1%), antibiotics (62%), glucocorticoids (41,8%), hydroxychloroquine (29,6%), enoxaparin (28,6%), colchicine (8,9%), oxygen therapy (6,9%), ivermectin (2,8%). Hospitalization occurred in 5,8% of total cases, mainly in patients taken care of when in stage 2b (27,3%). Altogether, 390 patients (99,6%) recovered, one patient (0,2%) was lost at follow up, and one patient (0,2%) died after hospitalization. One doctor reported one grade 1 adverse drug reaction (ADR) (transient or mild discomfort), and 3 doctors reported in total 8 grade 2 ADR (mild to moderate limitation in activity).

Conclusions

This is the first study describing attitudes and behaviors of physicians caring for COVID-19 outpatients, and the effectiveness and safety of COVID-19 early treatment in the real world. COVID-19 lethality in our cohort was 0,2%, while the overall COVID-19 lethality in Italy in the same period was between 3% and 3,8%. The use of individual drugs and drug combinations described in this study appears therefore effective and safe, as indicated by the few and mild ADR reported. Present evidence should be carefully considered by physicians caring for COVID-19 patients as well as by political decision makers managing the current global crisis.
Long- and short-term effects of cross-immunity in epidemic dynamics
Authors: Atienza-Diez Iker , Seoane Luís F
Published: April 2022

The vertebrate immune system is capable of strong, focused adaptive responses that depend on T-cell specificity in recognizing antigenic sequences of a pathogen. Recognition tolerance and antigenic convergence cause cross-immune reactions that extend prompt, specific responses to rather similar pathogens. This suggests that reaching herd-immunity might be facilitated during successive epidemic outbreaks (e.g., SARS-CoV-2 waves with different variants). Qualitative studies play down this possibility because cross-immune protection is seldom sterilizing. We use minimal quantitative models to study how cross-immunity affects epidemic dynamics over short and long timescales. In the short scale, we investigate models of sterilizing and attenuating immunity, finding equivalences between both mechanisms—thus suggesting a key role of attenuating protection in achieving herd immunity. Our models render maps in epidemic-parameter space that discern threatening variants depending on acquired cross-immunity levels. We illustrate this application with SARS-CoV-2 data, including protection due to vaccination rates across countries. In the long-time scale, we model sterilizing cross-immunity between rolling pathogens to characterize statistical properties of successful strains. We find that sustained cross-immune protection alters the regions of epidemic-parameter space where large outbreaks happen. Our results suggest an optimistic revision concerning prospects for herd protection based on cross-immunity, including for the SARS-CoV-2 pandemics.