bluuebunny/crossref_metadata_2025 huggingface dataset:
Phytotoxicity Trials on Bedding Plants, California, 1982
Authors: Parrella M. P. , Robb K. L.
Published: March 2022

Phytotoxicity tests were conducted on 13 species of plants with 3 rates of fenpropathrin 0.075, 0.10 and 0.40 lb ai/100 gal. The material was applied to runoff with a hand gun operating from a 2.5 gpm piston pump at 125 psi with a 5003 nozzle. Plants were sprayed outdoors in early morning (T = 23.9°C) at a cooperating nursery on Jun 29 and Jul 5. One flat consisting of 9 pony-paks with 6 plants/pony-pak were sprayed per dosage except for chrysanthemums with 94-in pots per flat. After spraying, plants were left at the nursery where they were under normal nursery maintenance. Phytotoxicity readings were made weekly for 4 wk after spraying and compared to a water check.
Phytotoxicity on Woody Ornamentsla, 1980
Authors: Swier Stanley R. , Spinney Tim
Published: March 2022

Four insecticides were evaluated for phytotoxicity on English Yew, Taxus baccata and Blue Spruce, Picea pungens at the University of New Hampshire Horticultural Farm in Durham, NH. Plants were sparyed on Sep 4 & 8 at rates of O.5, IX (recommended rates), 2X and 4X using a CO2 compression sprayer at 40 psi. Each experimental rate was applied to 4 single plant replicates, to the point of runoff. The ornamentals were examined 3, 4, 7, 14, 20, and 27 days after application.
Control of Winter Grain Mites in Rye Grass Turf, 1982
Authors: Kennedy M. Keith , Rodencal Jeff
Published: March 2022

The experimental site consisted of a stand of 100% improved rye grass surrounding a commercial office building in Whitehall, OH. Several locations on the property showed heavy mite damage on Apr 16 and active adults were easily visible in the thatch and on the foliage. Environmental conditions at the time of application were as follows: air temperature, 55 F; relative humidity, 90%; wind from the south at 5-10 mph; overcast skies; and moist soil conditions. Mowing height of the turf was 2.5-3 in. Six treatments replicated 4 times were applied to 5 ft × 10 ft (1.5m × 3m) experimental plots arranged in a RCB design. Applications were made Apr 17 using a CO2 pressurized sprayer with three 9520 nozzles mounted on a 5 ft aluminum bloom, operating at 25 psi with a 4 gal/1000 ft2 spray rate. None of the treatments was 2 irrigated following application. Rainfall 4 DAT was ca 0.09 in. Pretreatment counts showed.a range of 450 to 1660 mites/ft . The experimental plots were evaluated at 4 DAT by randomly taking 4 cup-cutter plugs (0.1 ft) from each plot and extracting the active WGM's/plug in a Berlese funnel for 24 hr (25 watt bulb).
Japanese Beetle Grub Control on Perennial Ryegrass at University Park, PA, 1982
Authors: Heller P. R. , Shetlar D. J. , Boggs J.
Published: March 2022

Three insecticides were applied Sep 14 to a Japanese beetle grub infested perennial ryegrass experimental area. Treatment plots were 10 × 10 ft, arranged in a randomized complete block design and replicated 3 times. Liquid formulations were applied in 3 gal of water with a hand-held sprinkling can. Granular formulations were applied with a hand-held shaker, followed by watering-in with 3 gal water. At treatment time, the following environmental conditions existed: air temperature, 75 F; soil temperature, 58 F; soil type, silt-clay-loam; soil pH, 6.4; percent organic matter, 2.6; soil condition, moist; amount of thatch, 0.125; and skies were heavily overcast. Post-treatment counts were made 42 days later (Oct 26). Four 1-ft2 sod-samples were randomly taken from each replicate, and the total number of surviving Japanese beetle grubs was recorded for each ft2 sample.
Spruce Budworm Control on Balsam Fir Christmas Trees, 1981
Authors: Swier Stanley R.
Published: March 2022

Nine insecticides were evaluated on balsam fir for the control of spruce budworm larvae at the Weir Christmas Tree Farm, Colebrook, N.H. The chemicals were applied on May 29. The treatments were rated 4 days after application. Treatments were applied with a 1-gal 8 & G sprayer at 30 psi. Treatments were replicated 4 times. Each replicate represented one, 6-ft balsam fir tree. When rating the replicates, 10 three-inch branch tips were evaluated for number of dead and alive budworm per tree.
Dry Season Control of Leafminer on Pole Beans, 1982
Authors: Nafus D. M. , Schreiner I. H. , Bjork C.
Published: March 2022

The test was located at the Agricultural Experiment Station in Inarajan, Guam. Seeds were planted Mar 12, at a density of 2 seeds per hill with 1 ft spacing between hills. Each plot consisted of 3 rows, 15 ft long and 4 ft apart. Treatment plots were replicated 4 times in a randomized block design. A barrier row of sweet corn was planted between rows to reduce drift. Sprays were applied with a Solo backpack sprayer 425. Triton B 1956 was used as a sticker at the rate of 1 tsp/3 gal. Once flowering began, all plots were treated with Dipel twice weekly to reduce pod borer numbers, otherwise the check would have produced no yield. Sulfur was applied as needed to control broad mites. The plots were treated both preplant and one month after planting with Terrachlor and Captan to control Rhizoctonia root rot, despite which some plants died from the fungus.
Wet Season Control of Leafminer on Pole Beans, 1981
Authors: Schreiner I. H. , Nafus D. M.
Published: March 2022

The test was located at the Agricultural Experiment Station in Inarajan, Guam. Seeds were planted on Aug 19 at a density of 2 seeds per hill with a 1 ft spacing between hills. Each plot consisted of 2 rows, 21 ft long and 3 ft apart. Treatment plots were replicated 4 times in a randomized block design. A barrier row of the same variety of beans was planted between rows to reduce drift. Sprays were applied with a Solo backpack sprayer 425. Once flowering began, all plots were treated with Dipel once a week to control pod borer. Sulfur was applied as needed to control broad mites. Leaves were examined for the presence of live miners. Rhizoctonia root rot caused considerable plant death so yields are not reported.
Evaluation of Dipel in Late Snap Beans, 1982
Authors: Klostermeyer L. E. , Mullins C. A.
Published: March 2022

Snap beans were planted at the Plateau Experiment Station, Crossville, TN on Jul 15. Plots were 3 rows × 20 ft with 1 untreated row between plots. Row spacing was 38 inches. Treatments were replicated 5 times in a randomized complete block design. Insecticides were applied on Aug 20 and Sep 10 with a 2-gal hand sprayer at 50 gal/acre. Sevin, Lannate, and Orthene were included as standards. One treated row/plot was sampled by taking 5 sweeps along the row (ca 15-row ft) with a 15-inch diameter insect net. A different row was sampled on each date to reduce plant damage. There were 0.2 lepidopterous caterpillars (mainly corn earworms and European corn borers), 1.8 Mexican bean beetle (MBB) adults and 0.45 MBB larvae per plot prior to the initial treatment. A 3-ft section from each middle row was hand harvested on Sep 14.
Seasonal thermal performance evaluation of the composite planted roof in subtropical area
Authors: Li Yi , Yang Wansheng , Ling Zipeng , Wang Jing
Published: March 2022

Planted roof works as a passive technology of saving building as well as reducing the building energy consumption. Actual projects show that the structure of the planted roof, for example, the soil, may decrease the heat dissipation capacity of the planted roof, resulting in the temperature rise, higher than the non-planted roof when it is at night, in the bottom of planted roof and, thus, the energy consumption of planted roof might be increased. In regard of this, four novel composite planted roofs that combined water storage and ventilation technology were proposed. Theoretically, the innovative roofs can enhance the dissipation capacity of planting layer and reduce the reverse heat transfer at night. Four types of composite planted roof models have been tested under the subtropical climate in Guangzhou. The results show that the heat insulation effect of the composite planted roof performs better than the ordinary in summer. The average total heat flow, when in summer, of modules A, B, C and D are 424.6, 333.9, 627.1 and 292.7 W/m2, respectively. In comparison with the bare roof, the intake heat of the control room was reduced by 50.1%, 60.7%, 26.2% and 65.6%, respectively. Also, the mechanical ventilation in soil layer can improve the insulation effect of the roof. However, the module with water storage and planting displayed the worst insulation performance. In addition, a mathematical model of the composite planted roof was established, and the average error between the calculated soil temperature value and the experimental data was less than 6%.
Multiplex LC-MS/MS Testing for Early Detection of Kidney Injury: A Next-Generation Alternative to Conventional Immunoassays?
Authors: van Duijl Tirsa T , Ruhaak L Renee , van Kooten Cees , de Fijter Johan W , Cobbaert Christa M
Published: March 2022

Background

LC-MS/MS has enabled the translation of many novel biomarkers to the clinical laboratory, but its potential for measurement of urinary proteins is still unexplored. In this study we examined the correlation and agreement between immunoassay and LC-MS/MS in the quantitation of kidney injury biomarkers and evaluated the application of technical LC-MS/MS meta-data assessment to ensure test result validity.

Methods

NGAL, IGFBP7, TIMP2, and KIM-1 were quantified in 345 urine samples with one multiplex lab-developed test that combines immunocapture with mass spectrometry read-out and 4 singleplex sandwich-type immunoassays. Assay performance and imprecision were monitored by 2 urine-based quality controls. Ion ratios, signal intensity, and retention time were monitored over all study samples.

Results

The LC-MS/MS retention time drift was ≤1.2%, ion ratios were within 20% of the target values at concentrations of >100 pmol/L, and peptides originating from the same protein were in agreement (slopes between 1.03 and 1.41). The interassay CV was between 9.3% and 19.1% for LC-MS/MS analysis and between 4.2% and 10.9% for immunoassay. Direct LC-MS/MS analysis was correlated with immunoassay in the quantitation of NGAL (r = 0.93; range: 0.01–37 nmol/L), IGFBP7 (r = 0.80; range: 0.01–2.6 nmol/L), TIMP2 (r = 0.85; range: 0.01–6.3 nmol/L), and KIM-1 (r = 0.70; range 0.01–0.4 nmol/L), but the analytical methodologies differed in measurands and calibration strategies.

Conclusions

LC-MS/MS is explored as a next-generation technology for multiplex urinary protein measurement. It has great potential to overcome nonselectivity and lack of standardization because of its capability of directly measuring well-defined molecular proteins.
Validation Study for PathogenDx EnviroX-F Assay for the Detection of Listeria, L. monocytogenes, and Salmonella in Environmental Surface Samples: AOAC Performance Tested MethodSM 092001
Authors: Katchman Benjamin A , Newland Cory S , Eggers Rick , Wen Fushi , O’Brien Kevin
Published: March 2022

Background

The PathogenDx EnviroX-F uses microarray technology to simultaneously detect Listeria species, Listeria monocytogenes, and Salmonella species from environmental samples without the need for enrichment.

Objective

The validation study included a matrix study of four matrices (stainless steel, plastic, rubber, and sealed concrete) comparing the PathogenDx EnviroX-F assay to the US Food and Drug Administration (FDA) Bacteriological Analytical Manual (BAM) Chapter 10, “Detection of L. monocytogenes in Foods and Environmental Samples, and Enumeration of L. monocytogenes in Foods” (revised March 2017), and FDA BAM Chapter 5,“Salmonella” (revised February 2020). Other required Performance Tested MethodSM parameters evaluated included: inclusivity and exclusivity, robustness, instrument variation, and product consistency and stability.

Methods

The PathogenDx EnviroX-F assay was evaluated with 30 unpaired replicate surface areas for each environmental surface. The candidate method was evaluated without an enrichment step.

Results

In the inclusivity and exclusivity study 50 out of 50 Listeria isolates were detected, 50 out of 50 L. monocytogenes strains were detected, 108 out of 108 Salmonella strains were detected, and 95 out of 95 exclusivity strains were correctly excluded. In the matrix study, the PathogenDx EnviroX-F assay showed no significant differences between confirmed results or between candidate and reference method results for 4” × 4” environmental surface areas for each matrix.

Conclusion

The PathogenDx EnviroX-F assay is an effective method for the qualitative detection of Listeria spp., L. monocytogenes, and Salmonella spp. from environmental surface swabs.

Highlights

The PathogenDx EnviroX-F assay will be the first PTM-approved multiplex assay for Listeria spp., L. monocytogenes, and Salmonella without the need for an environment step.
Association Between Baloxavir Marboxil Prescription for Children with Influenza B Infections and Short-Term Healthcare Consumption in Japan During the 2018–2019 Influenza Season
Authors: Shinno Kazuma , Takeuchi Masato , Kawakami Koji
Published: March 2022

Background

Baloxavir marboxil is an anti-influenza medication that was newly introduced into clinical practice in 2018. Baloxavir might be more beneficial than neuraminidase inhibitors (NAIs), as suggested by a subgroup analysis of a clinical trial. Although the association between baloxavir prescription and healthcare use pertains mainly to influenza A, few studies have investigated the association in influenza B.

Methods

We evaluated the healthcare utilization of children (0–15 years old) treated with either baloxavir or NAIs between December 2018 and May 2019 using claims records in Japan. The primary endpoint was the composite of medical resource utilization, including hospitalization, antibiotic use, laboratory tests, radiological images, and fluid replacement therapy, over 1–9 days after antiviral prescription. Secondary outcomes representing each single outcome in the composite were examined. Subgroup analyses comparing baloxavir with each NAI were also performed.

Results

Of 4490 patients with influenza B who received antiviral treatment, 51.6% were male, and the median age was 8 years old. Baloxavir was prescribed for 29.4% of the population, and NAIs were prescribed for 70.6%. In the total cohort, 49.3% of patients had any comorbidity related to complicated influenza infection. Concerning the composite endpoint, baloxavir prescription was not associated with a risk of subsequent medical resource use (adjusted odds ratio 1.11; 95% confidence interval 0.90–1.38; P = 0.34). Secondary outcomes and subgroup analyses showed similar results to the primary outcome.

Conclusions

In a single-year comparative study in Japan, baloxavir prescription for influenza B was not associated with less healthcare consumption than NAIs within 9 days of treatment.
Incidence rate and management of diaphragmatic injury during laparoscopic nephrectomies: single-center experience
Authors: Baio Raffaele , Molisso Giovanni , Caruana Christian , Intilla Oliviero , Di Mauro Umberto , Pane Umberto , Campitelli Antonio , Pentimalli Francesca , Sanseverino Roberto
Published: March 2022

Pneumothorax is a rare complication in laparoscopic renal surgery. However, due to the increasing renal pathologies managed by laparoscopic technique, this infrequent complication is a potential risk. We investigated the incidence rate of this complication in our experience of laparoscopic renal surgery, taking into account the laparoscopic approach, the type of intervention, the character of the pathology (neoplastic or other), the site of the intervention, as well as the localization of the lesion (in case of malignant pathology). About 384 laparoscopic nephrectomies were reviewed at our institution, with a total of four cases (1.04%) of diaphragmatic injury. Diaphragmatic repair was always carried out by intracorporeal suturing, with no complications. Repair of diaphragmatic injuries should always be attempted with intracorporeal suture since this is a safe and effective technique. Then, although in the retroperitoneal approach pneumothorax is more likely, our experience has shown that transperitoneal access is not free from this complication.
Geotrichum spp: An overlooked and fatal etiologic agent in immunocompromised patients. A case series from a referral center in Mexico
Authors: Rajme-López Sandra , González-Lara María F , Martínez-Gamboa R Areli , Rangel-Cordero Andrea , Ponce-de-León Alfredo
Published: March 2022

Geotrichum spp. is an emergent pathogen. We aimed to describe Geotrichum spp. invasive fungal infections (IFI) in patients from Mexico. We reviewed cases with Geotrichum spp. isolated in clinical samples, from 2001 to 2019. Descriptive analysis was used for clinical data. Twenty patients with proven/probable Geotrichum spp. IFI were analyzed. The median age was 43; 55% were males. Hematologic malignancy was found in 60% (12/20); 75% (15/20) received systemic immunosuppressors. The most common presentation was lower respiratory tract infection. In-hospital mortality was 45% (9/20). Geotrichum spp. should be acknowledged as a pathogen causing atypical pneumonia in immunocompromised Latin American patients.

Lay Summary

Geotrichum spp. causes invasive infection in immunocompromised hosts. We describe a case series of 20 patients from Mexico City. Hematologic malignancy was the most common comorbidity. Clinical presentation was mainly lower respiratory tract infection. Mortality was high despite antifungal therapy.
Discovery of quasi-periodic oscillations in the persistent X-ray emission of accreting binary X-ray pulsar LMC X-4
Authors: Rikame Ketan , Paul Biswajit , Pradhan Pragati , Paul K T
Published: March 2022

We report the discovery of quasi-periodic oscillations (QPOs) in the high-mass X-ray binary (HMXB) pulsar LMC X-4 in its non-flaring (persistent) state using observations with XMM–Newton. In addition to the 74 mHz coherent pulsations, the persistent emission light curve shows a QPO feature in the frequency range of 20–30 mHz. Quasi-periodic flares have been previously observed from LMC X-4 in observations made with Rossi X-ray Timing Explorer (RXTE). However, this is the first time QPOs have been observed in the persistent emission observations of LMC X-4. QPOs in X-ray binaries are generally thought to be related to the rotation of the inhomogeneous matter distribution in the inner accretion disc. In HMXBs such as LMC X-4 where the compact object is a neutron star with a high magnetic field, the radius of the inner accretion disc is determined by the mass accretion rate and the magnetic moment of the neutron star. In such systems, the QPO feature, along with the pulse period and X-ray luminosity measurement, helps us to constrain the magnetic field strength of the neutron star. We use considerations of magnetospheric accretion to have an approximate value of the magnetic field strength of the neutron star in LMC X-4.
A search for stellar structures around nine outer halo globular clusters in the Milky Way
Authors: Zhang Shumeng , Mackey Dougal , Da Costa Gary S
Published: March 2022

We use deep imaging from the Dark Energy Camera to explore the peripheral regions of nine globular clusters in the outer halo of the Milky Way. Apart from Whiting 1 and NGC 7492, which are projected against the Sagittarius stream, we see no evidence for adjacent stellar populations to indicate any of these clusters is associated with coherent tidal debris from a destroyed host dwarf. We also find no evidence for tidal tails around any of the clusters in our sample; however, both NGC 1904 and 6981 appear to possess outer envelopes. Motivated by a slew of recent Gaia-based discoveries, we compile a sample of clusters with robust detections of extra-tidal structure, and search for correlations with orbital properties. While we observe that clusters with tidal tails are typically on moderately or very eccentric orbits that are highly inclined to the Galactic plane and often retrograde, these are neither necessary nor sufficient conditions for the formation of extra-tidal structure. That many objects with tidal tails appear to be accreted leads us to speculate that this lack of consistency may stem from the inhomogeneous dynamical history of the Milky Way globular cluster system. Finally, we note that clusters with prominent stellar envelopes detected in ground-based imaging (such as NGC 1851 and 7089) are now all known from Gaia to possess long tidal tails – experimental confirmation that the presence of an extended envelope is indicative of tidal erosion.
Can radio emission escape from the magnetosphere of υ Andromedae b – a new method to constrain the minimum mass of Hot Jupiters
Authors: Erkaev N V , Weber C , Grießmeier J-M , Lammer H , Ivanov V A , Odert P
Published: March 2022

We investigate the atmospheric and magnetospheric conditions of the massive, close-in exoplanet υ Andromedae b (hereafter ups And b). In particular, we explore whether radio emission can be produced by the Cyclotron Maser Instability (CMI), and whether this emission can escape from its source region. For this, we compare the local cyclotron frequency to the local plasma frequency. The planetary mass has a decisive impact on both of these frequencies: the cyclotron frequency depends on the (mass-dependent) estimate of the planetary magnetic moment, and the plasma frequency is determined by the (gravity-dependent) atmospheric profile. For this reason, the planetary mass is one of the decisive parameters determining whether the CMI can operate efficiently. As the precise planetary mass is unknown in the case of ups And b, we compare the plasma conditions for a range of hypothetical masses of the planet in order to determine at which mass the atmosphere becomes ‘compact’, i.e. is not strongly extended, and thus provides favourable conditions for the CMI. In the case of detected planetary radio emission, this approach can provide a new way to constrain the mass of an exoplanet for which only a minimum mass is known.
State-to-state rate coefficients for HCS+ in rotationally inelastic collisions with H2 at low temperatures
Authors: Denis-Alpizar Otoniel , Quintas-Sánchez Ernesto , Dawes Richard
Published: March 2022

HCS+ ions have been detected in several regions of the interstellar medium (ISM), but an accurate determination of the chemical-physical conditions in the molecular clouds where this molecule is observed requires detailed knowledge of the collisional rate coefficients with the most common colliders in those environments. In this work, we study the dynamics of rotationally inelastic collisions of HCS+ + H2 at low temperature, and report, for the first time, a set of rate coefficients for this system. We used a recently developed potential energy surface for the HCS+–H2 van der Waals complex and computed state-to-state rotational rate coefficients for the lower rotational states of HCS+ in collision with both para- and ortho-H2, analysing the influence of the computed rate coefficients on the determination of critical densities. Additionally, the computed rate coefficients are compared with those obtained by scaling the ones from HCS+ in collision with He (an approximation that is sometimes used when data is lacking), and large differences are found. Furthermore, the approximation of using the rates for the HCO+ + H2 collision as a rough approximation for those of the HCS+ + H2 system is also evaluated. Finally, the complete set of de-excitation rate coefficients for the lowest 30 rotational states of HCS+ by collision with H2 is reported from 5 to 100 K.
Phylogenetic position of the deep-sea snail family Haloceratidae and new insights into caenogastropod relationships
Authors: Takano Tsuyoshi , Warén Anders , Kano Yasunori
Published: March 2022

The phylogenetic position of Haloceratidae, a little-known family of the subclass Caenogastropoda, is contested due to its extreme rarity in bathyal waters worldwide (c. 800–3,500 m deep). Haloceratids share several morphological and ecological traits with members of Vanikoroidea, Tonnoidea, Capuloidea and Velutinoidea, and were provisionally included in Vanikoroidea based on the absence of certain apomorphic features of the latter three taxa. Here, we first investigate the phylogenetic position of the family based on molecular data from both of the recognized genera, Haloceras and Zygoceras. Reconstruction based on three nuclear and three mitochondrial gene sequences suggests that the Haloceratidae constitute a sister clade to the Capulidae and that the two families collectively form the superfamily Capuloidea. This superfamily is united in a large, robust clade with Calyptraeoidea, Velutinoidea, Tonnoidea and Neogastropoda. The superfamily Cypraeoidea, as previously conceived, was found to be polyphyletic; we propose new concepts of Cypraeoidea (including Cypraeidae and Ovulidae) and Velutinoidea (including Velutinidae, Eratoidae and Triviidae). This topology also confirms the polyphyly of taxa with the ‘echinospira’ type of larvae (Echinospirida). The morphological resemblance of these polyphyletic taxa highlights parallel acquisition of traits in response to the same selective pressures.
Drug treatment algorithm and recommendations from the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis—secondary publication
Authors: Kawahito Yutaka , Morinobu Akio , Kaneko Yuko , Kohno Masataka , Hirata Shintaro , Kishimoto Mitsumasa , Seto Yohei , Sugihara Takahiko , Tanaka Eiichi , Ito Hiromu , Kojima Toshihisa , Matsushita Isao , Nishida Keiichiro , Mori Masaaki , Murashima Atsuko , Yamanaka Hisashi , Nakayama Takeo , Kojima Masayo , Harigai Masayoshi
Published: March 2022

Objective

The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPG) for the management of rheumatoid arthritis (RA; JCR CPG for RA) according to recent changes in the medical environment in Japan. This article is a digest version of the guidance.

Methods

We used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. A consensus was formed by CPG panel members.

Results

We identified 36 important clinical questions regarding drug treatment and developed corresponding recommendations for RA. The recommendations included the following RA medications: non-steroidal anti-inflammatory drugs, corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, biological disease-modifying antirheumatic drugs, anti-receptor activator for nuclear factor-κB ligand antibodies, and Janus kinase inhibitors, as well as the tapering and discontinuation of these medications. Recommendations regarding the efficacy and safety of treatments in the elderly and patients with comorbidities were also developed. Finally, we used these recommendations to create an original algorithm for drug treatment for RA based on the Treat-to-Target approach.

Conclusion

The 2020 JCR CPG for RA provides a useful tool for rheumatologists, health care professionals, and patients with RA, enabling shared decision-making in a variety of clinical situations.
Blood-Based Next-Generation Sequencing in Adrenocortical Carcinoma
Authors: Nazha Bassel , Zhuang Tony Z , Dada Hiba I , Drusbosky Leylah M , Brown Jacqueline T , Ravindranathan Deepak , Carthon Bradley C , Kucuk Omer , Goldman Jamie , Master Viraj A , Bilen Mehmet Asim
Published: March 2022

Background

Adrenocortical carcinoma (ACC) is a rare and heterogeneous malignancy with poor prognosis. We aimed to evaluate the feasibility of next-generation sequencing (NGS) testing of circulating cell-free tumor DNA (ctDNA) in patients with ACC, to characterize the genomic landscape of alterations, and to identify potential clinically actionable mutations.

Methods

Retrospective analysis of genomic data from 120 patients with ACC who had ctDNA testing between 12/2016 and 10/2021 using Guardant360 (Guardant Health, CA) was performed. ctDNA NGS analysis interrogated single nucleotide variants, fusions, indels, and copy number amplifications of up to 83 genes. The frequency of genomic alterations, landscape of co-occurring mutations, and pathogenic/likely pathogenic alterations with potential targeted therapies was identified. The prevalence of alterations identified in ctDNA was compared to those detected in tissue using a publicly available database (cBioPortal).

Results

The median age of this cohort was 53 years (range 21-81), and 56% of patients were female. Ninety-six patients (80%) had ≥1 somatic alteration detected. TP53 (52%), EGFR (23%), CTNNB1 (18%), MET (18%), and ATM (14%) were found to be the most frequently altered genes in ACC samples. Pathogenic and/or likely pathogenic mutations in therapeutically relevant genes were observed in 56 patients (47%) and included EGFR, BRAF, MET, CDKN2A, CDK4/6, and ATM. The most frequent co-occurring mutations were EGFR + MET (9%), MET + CDK4 (7%), EGFR + CDK4 (7%), and BRAF + MET (7%). The frequencies of mutations detected in ctDNA were similar to those detected in tissue.

Conclusions

Utilizing blood-based NGS to characterize genomic alterations in advanced ACC is feasible in over 80% of patients. Almost half of the patients had actionable mutations with approved therapies in other cancers. This approach might inform the development of personalized treatment options or identify clinical trials available for this aggressive malignancy.
Contagious inequality: economic disparities and excess mortality during the COVID-19 pandemic
Authors: Zaki Bishoy Louis , Nicoli Francesco , Wayenberg Ellen , Verschuere Bram
Published: March 2022

The COVID-19 pandemic has emphasized the need to consider multiple and often novel perspectives on contemporary policymaking in the context of technically complex, ambiguous, and large-scale crises. In this article, we focus on exploring a territory that remains relatively unchartered on a large scale, namely the relationship between economic inequalities and excess mortality during the COVID-19 pandemic, using a dataset of 25 European countries spanning 300 regions. Our findings reveal two pathways by which economic asymmetries and inequalities can observably influence excess mortality: labor market structures (capturing concentrations of industrial jobs) and income inequalities (capturing concentrations and asymmetries in income distribution). We leverage our findings to offer recommendations for policymakers toward a more deliberate consideration of the multidimensionality of technically complex, large-scale crises with a high degree of societal embeddedness. These findings also urge future scholarship to utilize a range of parameters and indicators for better understanding the relationship between cues and outcomes in such complex settings.
A scenario for an evolutionary selection of ageing
Authors: Roget T. , MacMurray C. , Jolivet P. , Méléard S. , Rera M.
Published: March 2022

Signs of ageing become apparent only late in life, after organismal development is finalized. Ageing, most notably, decreases an individual’s fitness. As such, it is most commonly perceived as a non-adaptive force of evolution and considered a by-product of natural selection.

Building upon the evolutionarily conserved age-related Smurf phenotype, we propose a simple mathematical life-history trait model in which an organism is characterized by two core abilities: reproduction and homeostasis.

Through the simulation of this model, we observe 1) the convergence of fertility’s end with the onset of senescence, 2) the relative success of ageing populations, as compared to non-ageing populations, and 3) the enhanced evolvability (i.e. the generation of genetic variability) of ageing populations. In addition, we formally demonstrate the mathematical convergence observed in 1).

We thus theorize that mechanisms that link the timing of fertility and ageing have been selected and fixed over evolutionary history, which, in turn, explains why ageing populations are more evolvable and therefore more successful. Broadly speaking, our work suggests that ageing is an adaptive force of evolution.
Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability
Authors: Lü YiQing , Cho Tiffany , Mukherjee Saptaparna , Malik Ahmad , Gonzalez-Foutel Nicolas S. , Suarez Carmen Florencia , Dervovic Dzana , Oh Robin Hyunseo , Langille Ellen , Al-Zahrani Khalid N. , Lin Zhen Yuan , Tsai Ricky , Rotter Varda , Ashton-Prolla Patricia , Chemes Lucia B. , Moffat Jason , Gingras Anne-Claude , Oren Moshe , Durocher Daniel , Schramek Daniel
Published: March 2022

Tumour suppressor p53 (TP53) is the most frequently mutated gene in cancer. Several hotspot p53 mutants not only lose tumour suppressive capabilities, but also function in a dominant-negative manner, suppressing canonical wild-type p53 function. Furthermore, some hotspot p53 mutants promote oncogenesis by gain-of-function mechanisms. Levels of p53 are regulated predominantly through regulation of protein stability and while wild-type p53 is normally kept at very low levels at steady-state, p53 mutants are often stabilized in tumours, which may be vital for their oncogenic properties. Here, we systematically profiled the factors that regulate protein stability of wild-type and mutant p53 using marker-based genome-wide CRISPR screens. We found that most proteins that regulate wild-type p53 also regulate a subset of p53 mutants with the exception of p53 R337H regulators, which are largely private to this mutant. Mechanistically, we identified FBXO42 as a novel positive regulator of a subset of p53 mutants comprising R273H, R248Q and R248W. We show that FBXO42 acts together with CCDC6 to regulate USP28-mediated p53 stabilization. Our work also identifies C16orf72 as a negative regulator of the stability of wild-type p53 and of all p53 mutants tested. C16orf72 is amplified in breast cancer, and we show that C16orf72 regulates p53 levels in mammary epithelium of mice and its overexpression results in accelerated breast cancer with reduced p53 levels. Together, this work provides a network view of the processes that regulate p53 stability, which might provide clues for reinforcing wild-type p53 or targeting mutant p53 in cancer.
Two types of hand withdraw movement to place food in the mouth mediated by somatosensation in 22-species of strepsirrhines
Authors: Peckre Louise R , Fabre Anne-Claire , Wall Christine E , Pouydebat Emanuelle , Whishaw Ian Q
Published: March 2022

The evolution of visual control of the hand to assist feeding by primates is uncertain but in anthropoid primates vision contributes not only to reaching for food and grasping it but also to the withdraw movement that brings food to the mouth. The strepsirrhines are a relatively large monophyletic group of Euarchontoglires near the base of the primate cladogram that are described as using vision to reach for food, but it is not known whether they use vision to assist the withdraw movement. The present study answere this question in 22 species of captive strepsirrhines from 6 of the seven strepsirrhine families, Daubentoniidae, Cheirogaleidae, Indriidae, Lemuridae, Lorisidae and Galagidae. Animals were videorecorded as they ate their normal food provisions. Dependent measures for analyses were ground withdraw movements, bringing grasped food to the mouth, and inhand withdraw movements, brining food held in the hand to the mouth, as well as the posture and head movements associated with each type of withdraw. Frame-by-frame scores from the video record showed that there were large differences between and within strepsirrhine families in these movements. Nevertheless, for all species, the withdraw movement was mediated by somatosensation, with mouth reaching and perioral contact with food determining how food was eventually eaten. Nonvisual behavior also contributed to food grasping as many species sniffed food before or during grasping. Even amongst species that made most use of the hand for their withdraws, the insectivoresLoris lydekkerianusandGalago senegalensis, and herbivores,Hapalemur simusandEulemur flavifrons, perioral contact was used to orient food for biting. The use of somatosensation and the absence of vision in mediating getting food in strepsirrhines suggests that visual mediation of the withdraw is an anthropoid innovation.
New β-propellers are continuously amplified from single blades in all major lineages of the β-propeller superfamily
Authors: Pereira Joana , Lupas Andrei N.
Published: March 2022

β-Propellers are toroidal folds, in which consecutive supersecondary structure units of four anti-parallel β-strands – called blades – are arranged radially around a central axis. Uniquely among toroidal folds, blades span the full range of sequence symmetry, from near identity to complete divergence, indicating an ongoing process of amplification and differentiation. We have proposed that the major lineages of β-propellers arose through this mechanism and that therefore their last common ancestor was a single blade, not a fully formed β-propeller. Here we show that this process of amplification and differentiation is also widespread within individual lineages, yielding β-propellers with blades of more than 60% median pairwise sequence identity in most major β-propeller families. In some cases, the blades are nearly identical, indicating a very recent amplification event, but even in cases where such recently amplified β-propellers have more than 80% overall sequence identity to each other, comparison of their DNA sequence shows that the amplification occurred independently.
iSparse kmeans: a two-step clustering approach for big dynamic functional network connectivity data
Authors: Sendi Mohammad S. E. , Salat David H , Miller Robyn L , Calhoun Vince D
Published: March 2022

Background

Dynamic functional network connectivity (dFNC) estimated from resting-state functional magnetic imaging (rs-fMRI) studies the temporally varying of functional integration between brain networks. In a typical dFNC pipeline, a clustering stage to summarize the connectivity patterns that are transiently but reliably realized over the course of a scanning session. However, identifying the right number of clusters through a conventional clustering criterion computed by running the algorithm repeatedly, over a large range of cluster numbers is time-consuming and requires substantial computational power even for typical dFNC datasets, and the computational demands become prohibitive as datasets become larger and scans longer. Here we developed a new dFNC pipeline, called iterative sparse kmeans or iSparse kmeans, to analyze large dFNC data without having access to huge computational power.

Method

In iSparse kmeans, we implement two-step clustering. In the first step, we randomly use a sub-sample dFNC data and identify several sets of states at different model orders. In the second step, we aggregate all dFNC states estimated from all iterations in the first step and use this to identify the optimum number of clusters using the elbow criteria. Additionally, we use this new reduced dataset and estimate a final set of states by performing a second kmeans clustering on the aggregated dFNC states from the first k-means clustering. To validate the reproducibility of iSparse kmeans, we analyzed four dFNC datasets from the human connectome project (HCP).

Results

We found that both conventional kmeans and iSparse kmeans generate similar brain dFNC states while iSparse kmeans is 27 times faster than the traditional method in finding the optimum number of clusters. We show that the results are replicated across four different datasets from HCP.

Conclusion

We developed a new analytic pipeline which facilitates analysis of large dFNC datasets without having access to a huge computational power source. We validated the reproducibility of the result across multiple datasets.
Lipid-correlated alterations in the transcriptome are enriched in several specific pathways in the postmortem prefrontal cortex of Japanese patients with schizophrenia
Authors: Arihisa Wataru , Kondo Takeshi , Yamaguchi Katsushi , Matsumoto Junya , Nakanishi Hiroki , Kunii Yasuto , Akatsu Hiroyasu , Hino Mizuki , Hashizume Yoshio , Sato Shumpei , Sato Shinji , Niwa Shin-Ichi , Yabe Hirooki , Sasaki Takehiko , Shigenobu Shuji , Setou Mitsutoshi
Published: March 2022

Background

Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. A previous study showed that specific lipid molecules belong to phosphatidylinositol (PI) and phosphatidylserine (PS) was reduced in the postmortem prefrontal cortex of patients with schizophrenia1. However, signaling pathways contributing to the lipid changes remain unknown. Here we performed two types of transcriptome analyses in patients with schizophrenia: an un-biased transcriptome analysis solely based on RNA-seq data and a correlation analysis between levels of gene expression and lipids.

Methodology/Principal Findings

RNA-Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects which are the same samples in the previous lipidomics study1 (Table 1). Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes of gene expression levels in phosphoinositide 3-kinase (PI3K)-Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in several signaling/metabolic pathways including lipid-correlated genes, most of which are not found as DEGs in transcriptome analysis alone.

Table 1.

Characteristics of patients from whom postmortem brain samples were obtained.

Abbreviations: PMI, postmortem interval, the time that has elapsed since a person has died; DOI, duration of illness, The samples used in correlation analysis are shown by black circles.

Conclusions

This study provided results of the first integrated analysis of the schizophrenia-associated transcriptome and lipidome within the PFC and revealed that lipid-correlated alterations in the transcriptome are enriched in specific pathways including PI3K-Akt signaling.
Aberrant DNA methylation distorts developmental trajectories in atypical teratoid/rhabdoid tumors
Authors: Pekkarinen Meeri , Nordfors Kristiina , Uusi-Mäkelä Joonas , Kytölä Ville , Rauhala Minna , Urhonen Henna , Huhtala Laura , Häyrynen Sergei , Afyounian Ebrahim , Yli-Harja Olli , Zhang Wei , Helen Pauli , Lohi Olli , Haapasalo Hannu , Haapasalo Joonas , Nykter Matti , Kesseli Juha , Rautajoki Kirsi J.
Published: March 2022

Atypical teratoid/rhabdoid tumors (AT/RTs) are pediatric brain tumors known for their aggressiveness, exceptionally low mutation rate, and aberrant but still unresolved epigenetic regulation. To evaluate methylation associated regulation in AT/RTs, we compared them to medulloblastomas and choroid plexus tumors by integrating DNA methylation (507 samples), gene expression (120 samples), and public transcription factor (TF) binding data. We showed that elevated DNA methylation masks the binding sites of TFs driving neural development and is associated with reduced transcription for specific neural regulators in AT/RTs. Part of the hypermethylated sites behaved similarly in AT/RTs and pluripotent stem cells, revealing DNA methylation -driven halted cell differentiation. AT/RT-unique DNA hypermethylation was associated with polycomb repressive complex 2 members, like EZH2, and linked to suppressed genes with a role in neural development and tumorigenesis. The obtained results highlight and characterize these DNA methylation programs as drivers of AT/RT malignancy.
The physical properties of the stick insect pad secretion are independent of body size
Authors: Kaimaki Domna-Maria , Andrew Charlotte N. S. , Attipoe Andrea E. L. , Labonte David
Published: March 2022

Many insects use adhesive organs to climb. The ability to cling to surfaces is advantageous but is increasingly challenged as animals grow, due to the associated reduction in surface-to-volume ratio. Previous work has demonstrated that some climbing animals overcome this scaling problem by systematically altering the maximum force per area their adhesive pads can sustain; their adhesive organs become more efficient as they grow, an observation which is also of substantial relevance for the design of bio-inspired adhesives. What is the origin of this change in efficiency? In insects, adhesive contact is mediated by a thin film of a liquid, thought to increase adhesive performance via capillary and viscous forces. Here, we use interference reflection microscopy and dewetting experiments to measure the contact angle and dewetting speed of the secretion of pre-tarsal adhesive pads of Indian stick insects, varying in mass by over two orders of magnitude. Neither contact angle nor dewetting speed change significantly with body mass, suggesting that the key physical properties of the pad secretion – its surface tension and viscosity – are size-invariant. Thus, the observed change in pad efficiency is unlikely to arise from systematic changes of the physical properties of the pad secretion; the functional role of the secretion remains unclear.
Concurrent separation of phase-locked and non-phase-locked activity
Authors: Singhal Shubham , Ghosh Priyanka , Kumar Neeraj , Banerjee Arpan
Published: March 2022

Brain dynamics recorded via electroencephalography (EEG) is conceptualized as a sum of two components, “phase-locked” and “non-phase-locked” to the stimulus. Both activities are understood to be stemming from different neuronal mechanisms and hence accurately characterizing them is of immense importance in neuroscientific studies. Here, we discuss the drawbacks of currently used methods to separate the phase-locked and non-phase-locked activity and propose a new method that decomposes the two components simultaneously. First, we demonstrate that single-trial separation of phase-locked and non-phase-locked power is an ill-posed problem. Second, using simulations where ground truth validation is possible, we elucidate the drawbacks of the widely used averaging method and efficacy of the proposed concurrent phaser method (CPM). Using two experimental datasets, audio oddball EEG data and auditory steady-state responses (ASSR) we show how the empirical signal-to-noise estimates warrant the usage of CPM to separate phase-locked and non-phase-locked activity.
Attentional effects on local V1 microcircuits explain selective V1-V4 communication
Authors: Katsanevaki Christini , Bastos André M. , Cagnan Hayriye , Bosman Conrado A. , Friston Karl J. , Fries Pascal
Published: March 2022

Selective attention implements preferential routing of attended stimuli, likely through increasing the influence of the respective synaptic inputs on higher-area neurons. As the inputs of competing stimuli converge onto postsynaptic neurons, presynaptic circuits might offer the best target for attentional top-down influences. If those influences enabled presynaptic circuits to selectively entrain postsynaptic neurons, this might explain selective routing. Indeed, when two visual stimuli induce two gamma rhythms in V1, only the gamma induced by the attended stimulus entrains gamma in V4. Here, we modeled induced responses with a Dynamic Causal Model for Cross-Spectral Densities and found that selective entrainment can be explained by attentional modulation of intrinsic V1 connections. Specifically, local inhibition was decreased in the granular input layer and increased in the supragranular output layer of the V1 circuit that processed the attended stimulus. Thus, presynaptic attentional influences and ensuing entrainment were sufficient to mediate selective routing.

HIGHLIGHTS

We model selective visual attention in macaques using Dynamic Causal Modeling.

Intrinsic V1 modulation can explain attention effects in V1-V4 communication.

Modulation of superficial and granular inhibition is key to induce the effects.

Those modulations increase V1-V4 communication in a feedforward manner.

GRAPHICAL ABSTRACT