bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced Infestation by Xylosandrus germanus (Coleoptera: Curculionidae: Scolytinae) in Apple Trees Treated with Host Plant Defense Compounds
Authors: Agnello Arthur M , Combs David B , Filgueiras Camila C , Willett Denis S , Mafra-Neto Agenor
Published: July 2021

The ambrosia beetle Xylosandrus germanus (Blandford) is an invasive pest that has caused tree decline and death in numerous NY dwarf apple orchards during the past ten years, despite efforts to control them using trunk sprays of chlorpyrifos or pyrethroids, either alone or combined with the repellent verbenone. From 2017 to 2019, we tested trunk applications of different repellents and plant defense compounds for protection against X. germanus in potted apple trees adjacent to infested orchards. Treatments included topical formulations of verbenone and methyl salicylate (MeSa), alone and in combination, at different rates and timings. Additional treatments evaluated included the systemic acquired resistance activators acibenzolar-S-methyl, Reynoutria sachalinensis extract, and salicylic acid. The combination verbenone+MeSa treatments had the lowest incidences of attack sites and galleries containing adults or brood, although results varied among years. In a separate trial, we found no significant difference in numbers of adults caught in ethanol-baited traps placed 5–20 m from an apple bolt treated with the verbenone+MeSa repellent, suggesting that the repellent’s effect did not extend to those distances from the treated target. Cross-sectional discs of trunk tissue sampled in August were analyzed for levels of phytohormones. Quantities of ergosterol, abscissic acid, salicylic acid, jasmonic acid, methyl salicylate, methyl jasmonate, trans-cinnamic acid, and indole-3-cinnamic acid did not significantly vary across treatments; however, trees with greater beetle damage contained higher levels of jasmonic and salicylic acid, which are key molecules in plant defense pathways.
Implementation of Direct Access Physical Therapy Within the Military Medical System
Authors: Szymanek Eliza , Jones Megan , Shutt-Hoblet Casey , Halle Robert
Published: July 2021

Introduction

Readiness is the Army’s number one priority. Physical therapists (PTs) are musculoskeletal (MSK) experts and have been serving as physician extenders in a direct access role in the military since Vietnam. Utilizing a PT in the direct access role has demonstrated a reduction in imaging, medication prescribed, number of physical therapy visits, and overall reduction in healthcare utilization.

Materials and Methods

The Joint Base Lewis-McChord physical therapy service line initiated a readiness-focused direct access initiative in May 2018. A simple algorithm was developed to help screen and identify appropriate service members for direct access physical therapy sick call. Physical therapy sick call hours were established at seven Joint Base Lewis-McChord Physical Therapy clinics.

Results

During the initial 18 months of this direct access PT initiative, a total of 3,653 initial physical therapy evaluations were completed. Injury location included 26% (953) knee, 26% (945) ankle, 16% (585) low back, 15% (551) shoulder, 9% (316) hip, and 8% (303) leg.

Conclusion

In the military, where readiness is the number one priority, it is essential that we optimize the medical resources available to our service members in order to minimize lost duty days and overall long-term disability. This project demonstrates a way to optimize the military healthcare system in order to reduce cost and healthcare utilization and minimize duty days lost to MSK injuries. Utilizing a conservative estimate, $3.6 million was potentially saved in military healthcare utilization costs. The subanalysis performed at one clinic comparing referral-based care with the direct access model demonstrated a reduction in imaging, days on profile, cost savings, reduction in referral to specialty care, and decreased long-term disability. In the military healthcare system, where our primary care team resources are limited, it is important to consider the PT as part of the acute MSK injury management team.
Increased Scholarly Activity: A Benefit of 4-Year Family Medicine Residencies
Authors: Sullivan John F , Keck James W , Stephens Mark B , O’Connell Tara A , Smith Dustin K , Sanchack Kristian E , Lennon Robert P
Published: July 2021

Introduction

The optimal length of Family Medicine Residency is unknown. As part of the American Board of Family Medicine 4-year Length of Training (LoT) pilot project, Naval Hospital Jacksonville (NHJ) maintained a dual-track 3- and 4-year Family Medicine Residency, graduating seven 4-year residents over consecutive 4 years of the LoT program. One measure of success regarding the impact of 4-year residents on program outcomes is scholarly output during residency.

Materials and Methods

Cumulative scholarly activity points are tracked for all NHJ residents. Cumulative scholarly activity points, points per year per, and raw percentile USMLE/COMLEX scores from academic years 2016–17 to 2019–20 were compared between PGY3 and PGY4 graduates using one-way ANOVA to 95% confidence with post hoc Tukey honestly significant difference pairwise comparison to evaluate pairwise significance between groups where multi-group differences were found.

Results

During the 2016–17 through 2019–20 academic years, NHJ had 28 residents complete 3 years of training without interruption (3 Years), 11 residents complete 3 years of training interrupted by general medical officer tours (Resiterns), and 7 residents complete 4 years of training without interruption (4 Years). There were no significant differences in average raw USMLE and COMLEX scores between 3 Year (71%), Resitern (68%), and 4 Year (76%) residents (P = .335). 4-Year residents had significantly more cumulative scholarly points (103) than 3-Year residents (32.6, P < .001) and Resiterns (18.7, P < .001) and also had more cumulative scholarly points per year of residency (27.8) than 3-Year residents (9.8, P < .001) and Resiterns (7.0, P < .001).

Conclusions

An observed benefit of a 4-year Family Medicine Residency was a marked increase in scholarly output at this program.
Origin of metals in old Milky Way halo stars based on GALAH and Gaia
Authors: Ishigaki Miho N , Hartwig Tilman , Tarumi Yuta , Leung Shing-Chi , Tominaga Nozomu , Kobayashi Chiaki , Magg Mattis , Simionescu Aurora , Nomoto Ken’ichi
Published: July 2021

Stellar and supernova nucleosynthesis in the first few billion years of the cosmic history have set the scene for early structure formation in the Universe, while little is known about their nature. Making use of stellar physical parameters measured by GALAH Data Release 3 with accurate astrometry from the Gaia EDR3, we have selected ∼100 old main-sequence turn-off stars (ages ≳12 Gyr) with kinematics compatible with the Milky Way stellar halo population in the Solar neighbourhood. Detailed homogeneous elemental abundance estimates by GALAH DR3 are compared with supernova yield models of Pop III (zero-metal) core-collapse supernovae (CCSNe), normal (non-zero-metal) CCSNe, and Type Ia supernovae (SN Ia) to examine which of the individual yields or their combinations best reproduce the observed elemental abundance patterns for each of the old halo stars (‘OHS’). We find that the observed abundances in the OHS with [Fe/H] > −1.5 are best explained by contributions from both CCSNe and SN Ia, where the fraction of SN Ia among all the metal-enriching SNe is up to 10–20 per cent for stars with high [Mg/Fe] ratios and up to 20–27 per cent for stars with low [Mg/Fe] ratios, depending on the assumption about the relative fraction of near-Chandrasekhar-mass SNe Ia progenitors. The results suggest that, in the progenitor systems of the OHS with [Fe/H] > −1.5, ∼ 50–60 per cent of Fe mass originated from normal CCSNe at the earliest phases of the Milky Way formation. These results provide an insight into the birth environments of the oldest stars in the Galactic halo.
Molecular Evolutionary Dynamics of Energy Limited Microorganisms
Authors: Shoemaker William R , Polezhaeva Evgeniya , Givens Kenzie B , Lennon Jay T
Published: July 2021

Microorganisms have the unique ability to survive extended periods of time in environments with extremely low levels of exploitable energy. To determine the extent that energy limitation affects microbial evolution, we examined the molecular evolutionary dynamics of a phylogenetically diverse set of taxa over the course of 1,000 days. We found that periodic exposure to energy limitation affected the rate of molecular evolution, the accumulation of genetic diversity, and the rate of extinction. We then determined the degree that energy limitation affected the spectrum of mutations as well as the direction of evolution at the gene level. Our results suggest that the initial depletion of energy altered the direction and rate of molecular evolution within each taxon, though after the initial depletion the rate and direction did not substantially change. However, this consistent pattern became diminished when comparisons were performed across phylogenetically distant taxa, suggesting that although the dynamics of molecular evolution under energy limitation are highly generalizable across the microbial tree of life, the targets of adaptation are specific to a given taxon.
Undivided Forward-Looking Moral Responsibility
Authors: Pereboom Derk
Published: July 2021

This article sets out a forward-looking account of moral responsibility on which the ground-level practice is directly sensitive to aims such as moral formation and reconciliation, and is not subject to a barrier between tiers. On the contrasting two-tier accounts defended by Daniel Dennett and Manuel Vargas, the ground-level practice features backward-looking, desert-invoking justifications that are in turn justified by forward-looking considerations at the higher tier. The concern raised for the two-tier view is that the ground-level practice will be insufficiently responsive to the forward-looking aims that are held to justify it. On the single-tier alternative, forward-looking considerations can more readily motivate substantial revisions, which the practice, due to serious and pervasive deficiencies, requires.
Sex-Related Differences in Clinical Presentation and Risk Factors for Mortality in Patients Hospitalized With Coronavirus Disease 2019 in New York City
Authors: Mathad Jyoti S , Lee Myung Hee , Chalem Andrea , Frey Melissa K , Chapman-Davis Eloise , Kopparam Rohini V , Dayal Ashlesha K , Wald Gal , Pinheiro Laura C , Satlin Michael J , Goyal Parag , Safford Monika M , Salvatore Mirella , Holcomb Kevin
Published: July 2021

We evaluated sex-related differences in symptoms and risk factors for mortality in 4798 patients hospitalized with coronavirus disease 2019 in New York City. When adjusted for age and comorbidities, being male was an independent predictor of death with mortality significantly higher than females, even with low severe acute respiratory syndrome coronavirus 2 viral load at admission.
Cortical and Subcortical Anatomy of the Orbitofrontal Cortex: A White Matter Microfiberdissection Study and Case Series
Authors: Rauch Philip , Serra Carlo , Regli Luca , Gruber Andreas , Aichholzer Martin , Stefanits Harald , Kadri Paulo Abdo do Seixo , Tosic Lazar , Gmeiner Matthias , Türe Uğur , Krayenbühl Niklaus
Published: July 2021

BACKGROUND

The literature on white matter anatomy underlying the human orbitofrontal cortex (OFC) is scarce in spite of its relevance for glioma surgery.

OBJECTIVE

To describe the anatomy of the OFC and of the underlying white matter fiber anatomy, with a particular focus on the surgical structures relevant for a safe and efficient orbitofrontal glioma resection. Based on anatomical and radiological data, the secondary objective was to describe the growth pattern of OFC gliomas.

METHODS

The study was performed on 10 brain specimens prepared according to Klingler's protocol and dissected using the fiber microdissection technique modified according to U.T., under the microscope at high magnification.

RESULTS

A detailed stratigraphy of the OFC was performed, from the cortex up to the frontal horn of the lateral ventricle. The interposed neural structures are described together with relevant neighboring topographic areas and nuclei. Combining anatomical and radiological data, it appears that the anatomical boundaries delimiting and guiding the macroscopical growth of OFC gliomas are as follows: the corpus callosum superiorly, the external capsule laterally, the basal forebrain and lentiform nucleus posteriorly, and the gyrus rectus medially. Thus, OFC gliomas seem to grow ventriculopetally, avoiding the laterally located neocortex.

CONCLUSION

The findings in our study supplement available anatomical knowledge of the OFC, providing reliable landmarks for a precise topographical diagnosis of OFC lesions and for perioperative orientation. The relationships between deep anatomic structures and glioma formations described in this study are relevant for surgery in this highly interconnected area.
Residual and Recurrent Disease Following Endoscopic Endonasal Approach as a Reflection of Anatomic Limitation for the Resection of Midline Anterior Skull Base Meningiomas
Authors: Setty Pradeep , Fernandez-Miranda Juan C , Wang Eric W , Snyderman Carl H , Gardner Paul A
Published: July 2021

BACKGROUND

Endoscopic endonasal approaches (EEAs) to anterior skull base meningiomas have grown in popularity, though anatomic limitations remain unclear.

OBJECTIVE

To show the anatomic limits of EEA for meningiomas.

METHODS

Retrospective chart review for all patients that underwent EEA for anterior skull base meningiomas from 2005 to 2014.

RESULTS

A total of 100 patients averaged follow-up of 46.9 mo (24-100 mo). A total of 35 patients (35%) had olfactory groove, 33 planum sphenoidale (33%), and 32 tuberculum sella (32%) meningiomas. The average diameter was 2.9 cm (0.5-8.1 cm). Vascular encasement was seen in 11 patients (11%) and calcification in 20 (20%). Simpson Grade 1 (SG1) resection was achieved in 64 patients (64%). Only calcification impacted degree of resection (40% SG1, P = .012). The most common residual was on the anterior clinoid dura (11 patients [11%]). Six (6%) had residual superior/lateral to the optic nerve. Residual tumor was adherent to the optic apparatus or arteries in 5 patients (5%) each, and 3 patients (3%) had residual lateral to the mid-orbit. Rates of residual decreased over time. A total of 11 patients (11%) had tumor recurrence (mean of 40 mo): 4 (4%) on the anterior clinoid, 2 (2%) each on the lateral orbital roof, adherent to optic apparatus and superolateral to the optic nerve, and 1 (1%) was at the anterior falx.

CONCLUSION

Anterior skull base meningiomas can effectively be approached via EEA in most patients; tumors extending to the anterior clinoid, anterior falx, or superolateral to the optic nerve or orbital roof, especially if calcified, may be difficult to reach via EEA.
Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics
Authors: Liu Wenyi , Li Luoxi , Jiang Jianxin , Wu Min , Lin Ping
Published: July 2021

Clustered regularly interspaced short palindromic repeats (CRISPR)-associated systems (Cas) are efficient tools for targeting specific genes for laboratory research, agricultural engineering, biotechnology, and human disease treatment. Cas9, by far the most extensively used gene-editing nuclease, has shown great promise for the treatment of hereditary diseases, viral infection, cancers, and so on. Recent reports have revealed that some other types of CRISPR-Cas systems may also have surprising potential to join the fray as gene-editing tools for various applications. Despite the rapid progress in basic research and clinical tests, some underlying problems present continuous, significant challenges, such as editing efficiency, relative difficulty in delivery, off-target effects, immunogenicity, etc. This article summarizes the applications of CRISPR-Cas from bench to bedside and highlights the current obstacles that may limit the usage of CRISPR-Cas systems as gene-editing toolkits in precision medicine and offer some viewpoints that may help to tackle these challenges and facilitate technical development. CRISPR-Cas systems, as a powerful gene-editing approach, will offer great hopes in clinical treatments for many individuals with currently incurable diseases.
Small but Mighty: An Update on Small Molecule Plant Cellulose Biosynthesis Inhibitors
Authors: Larson Raegan T , McFarlane Heather E
Published: July 2021

Cellulose is one of the most abundant biopolymers on Earth. It provides mechanical support to growing plant cells and important raw materials for paper, textiles and biofuel feedstocks. Cellulose biosynthesis inhibitors (CBIs) are invaluable tools for studying cellulose biosynthesis and can be important herbicides for controlling weed growth. Here, we review CBIs with particular focus on the most widely used CBIs and recently discovered CBIs. We discuss the effects of these CBIs on plant growth and development and plant cell biology and summarize what is known about the mode of action of these different CBIs.
A RADIOLUMINESCENCE STUDY OF DOSE CHARACTERISTICS OF LIF:MG,TI
Authors: Zhang Siyuan , Tang Kaiyong , Fan Haijun , Li Zhiyuan , Huang Guangwei , Wu Kun , Fu Li
Published: July 2021

A radioluminescence (RL) study of dose characteristics of tissue-equivalent LiF:Mg,Ti was carried out to determine the possible application as a real-time dosemeter. An RL measurements system based on LiF:Mg,Ti coupled with optical fiber was developed, and a blank fiber was set to remove the stem effect generated by the optical fiber due to direct radiation. A slight increase of RL sensitivity with accumulated dose and the afterglow effect due to shallow traps in LiF:Mg,Ti were observed, thus a set of algorithms was adopted to correct measured dose rate. A good linearity of dose-rate response using RL in LiF:Mg,Ti over more than four orders of magnitude (from 0.76 mGy/h to 8.02 Gy/h) was shown, and the deviation of calibrated dose rate is within 20%. Moreover, a satisfactory reproducibility (1.45%) of the measured dose rate after correction was represented. The results indicated that LiF:Mg,Ti might be promising for real-time dose monitoring.
Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder
Authors: Miglis Mitchell G , Zitser Jennifer , Schneider Logan , During Emmanuel , Jaradeh Safwan , Freeman Roy , Gibbons Christopher H
Published: July 2021

Study Objectives

To define the clinical implications of cutaneous phosphorylated α-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated rapid eye movement (REM) sleep behavior disorder (iRBD).

Methods

Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson’s disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients.

Results

P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use.

Conclusions

In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.
The Ideal Delegation: How Institutional Privilege Silences “Developing” Nations in the UN Climate Negotiations
Authors: Falzon Danielle
Published: July 2021

In the UN climate negotiations, national delegations cannot contribute equally. Scholars have shown that “developed” countries exert greater influence than “developing” nations. This study examines how these inequalities between delegations materialize under the United Nations Framework Convention on Climate Change (UNFCCC). Drawing on 30 interviews and over 200 hours of observation at five UNFCCC meetings, I ask (1) how are institutional structures in the UNFCCC aligned with normative ideals of national development; (2) how do these ideals impact the experiences of national delegations and their negotiators; and (3) what does this reveal about institutional inequality and privilege in this context? Building on institutional and organizational studies of work and literature on Developmental Ideals, I identify four characteristics of an ideal delegation to the UNFCCC that are based in norms of national development and privileged by the structures of the institution: they are large, English-speaking, equipped with Western scientific and legal expertise, and have the ability to send the same negotiators year after year. I demonstrate how non-normative countries that cannot send an ideal delegation find that the institutional structures prohibit them from engaging effectively. Ultimately, they must develop coping mechanisms to creatively compensate for their systemic disadvantages.
Seeking a pot of gold with integrated behavior therapy and research to improve health equity: insights from the RAINBOW trial for obesity and depression
Authors: Venditti Elizabeth M , Steinman Lesley E , Lewis Megan A , Weiner Bryan J , Ma Jun
Published: July 2021

More than one third of adults in the United States (U.S.) live with multiple chronic conditions that affect their physical and mental health, functional outcomes, independence, and mortality. The COVID-19 pandemic has exposed not only an increased risk for infection, morbidity, and mortality among those with chronic conditions but long-standing health inequities by age, race, sex, and other social determinants. Obesity plus depression represent one such prevalent comorbidity for which few effective integrated interventions exist, prompting concern about the potential for secondary physical and mental health pandemics post COVID-19. Translational behavioral medicine research can play an important role in studying integrated collaborative healthcare approaches and advancing scientific understanding on how to engage and more effectively treat diverse populations with physical and mental health comorbidities. The RAINBOW (Research Aimed at Improving Both Mood and Weight) clinical trial experience offers a wealth of insights into the potential of collaborative care interventions to advance behavior therapy research and practice. Primary care patients with co-occurring obesity and depression were assigned to either Integrated Coaching for Mood and Weight (I-CARE), which blended Group Lifestyle Balance (GLB) for weight management and the Program to Encourage Active Rewarding Lives (PEARLS) for depression, or usual care, to examine clinical, cost-effectiveness, and implementation outcomes. This commentary highlights the empirical findings of eight RAINBOW research papers and discusses implications for future studies, including their relevance in the U.S. COVID-19 context. Organized by key principles of translational behavioral medicine research, the commentary aims to examine and embrace the heterogeneity of baseline and intervention response differences among those living with multiple chronic conditions. We conclude that to prevent health and healthcare disparities from widening further, tailored engagement, dissemination, and implementation strategies and flexible delivery formats are essential to improve treatment access and outcomes among underrepresented populations.
Comparing the Predictivity of Human Placental Gene, microRNA, and CpG Methylation Signatures in Relation to Perinatal Outcomes
Authors: Clark Jeliyah , Avula Vennela , Ring Caroline , Eaves Lauren A , Howard Thomas , Santos Hudson P , Smeester Lisa , Bangma Jacqueline T , O’Shea Thomas Michael , Fry Rebecca C , Rager Julia E
Published: July 2021

Molecular signatures are being increasingly integrated into predictive biology applications. However, there are limited studies comparing the overall predictivity of transcriptomic versus epigenomic signatures in relation to perinatal outcomes. This study set out to evaluate mRNA and microRNA (miRNA) expression and cytosine-guanine dinucleotide (CpG) methylation signatures in human placental tissues and relate these to perinatal outcomes known to influence maternal/fetal health; namely, birth weight, placenta weight, placental damage, and placental inflammation. The following hypotheses were tested: (1) different molecular signatures will demonstrate varying levels of predictivity towards perinatal outcomes, and (2) these signatures will show disruptions from an example exposure (ie, cadmium) known to elicit perinatal toxicity. Multi-omic placental profiles from 390 infants in the Extremely Low Gestational Age Newborns cohort were used to develop molecular signatures that predict each perinatal outcome. Epigenomic signatures (ie, miRNA and CpG methylation) consistently demonstrated the highest levels of predictivity, with model performance metrics including R2 (predicted vs observed) values of 0.36–0.57 for continuous outcomes and balanced accuracy values of 0.49–0.77 for categorical outcomes. Top-ranking predictors included miRNAs involved in injury and inflammation. To demonstrate the utility of these predictive signatures in screening of potentially harmful exogenous insults, top-ranking miRNA predictors were analyzed in a separate pregnancy cohort and related to cadmium. Key predictive miRNAs demonstrated altered expression in association with cadmium exposure, including miR-210, known to impact placental cell growth, blood vessel development, and fetal weight. These findings inform future predictive biology applications, where additional benefit will be gained by including epigenetic markers.
The explosive radiation, intense host-shifts and long-term failure to speciate in the evolutionary history of the feather mite genusAnalges(Acariformes: Analgidae) from European passerines
Authors: Dabert Jacek , Mironov Serge V , Dabert Miroslawa
Published: July 2021

Mites of the genus Analges (Acariformes: Analgidae) inhabit the down feathers of passeriform birds. The evolutionary history of Analges and the co-phylogentic relationships between these mites and their hosts are unknown. Our phylogenetic analysis supported the monophyly of the genus, but it did not support previous taxonomic hypotheses subdividing the genus into the subgenera Analges and Analgopsis or arranging some species into the A. chelopus and A. passerinus species groups. Molecular data reveal seven new species inhabiting Eurasian passerines and support the existence of several multi-host species. According to molecular dating, the origin of the Analges (c. 41 Mya) coincided with the Eocene diversification of Passerida into Sylvioidea and Muscicapoidea–Passeroidea. The initial diversification of Analges took place on the Muscicapoidea clade, while remaining passerine superfamilies appear to have been colonized because of host-switching. Co-speciation appears to be relatively common among Analges species and their hosts, but the most striking pattern in the co-phylogenetic scenario involves numerous complete host-switches, spreads and several failures to speciate. The mechanism of long-term gene-flow among different populations of multi-host Analges species is enigmatic and difficult to resolve. Probably, in some cases mites could be transferred between birds via feathers used as nest material.
Evaluation of Application Timing of Miravis Ace for Control of Fusarium Head Blight in Wheat
Authors: Singh Lovepreet , Schulden Taylor , Wight Jason P. , Crank Joseph , Thorne Louis , Erwin John E. , Dong Yanhong , Rawat Nidhi
Published: July 2021

Fusarium head blight (FHB) is a serious disease of wheat and barley that not only lowers yield but also contaminates the grain with associated mycotoxins such as deoxynivalenol (DON). Chemical control options for FHB and DON include application of triazole fungicides at the anthesis or flowering stage. This presents practical challenges for growers in managing FHB, as the appropriate timing window typically lasts only 3 to 4 days. If this small window is missed, due to weather conditions or technical problems, fungicide application is less effective in controlling FHB and DON. The present work was conducted over 2 years (2019 and 2020) to test the efficacy of a new fungicide (pydiflumetofen + propiconazole) from Syngenta labeled as Miravis Ace in controlling FHB and DON content at 50% head emergence (Feekes 10.3), anthesis (Feekes 10.5.1), and end of flowering (Feekes 10.5.3) stages. Prosaro 421 SC, a standard FHB control triazole fungicide, was used at all three stages for comparison with the test fungicide. Miravis Ace application at 50% head emergence provided significant control over the nontreated check for FHB incidence (2020), FHB severity (2019), and DON content (2019) with control efficacies as high as 51, 69, and 52%, respectively. However, mean control percentages relative to the check were highest with Miravis Ace at anthesis in both 2019 and 2020 for all the FHB parameters. In conclusion, 50% head emergence provides statistically significant control on FHB and DON, but anthesis was the most effective application stage for Miravis Ace.
Proxalutamide (GT0918) Reduces the Rate of Hospitalization in mild-to-moderate COVID-19 Female Patients: A Randomized Double-Blinded Placebo-Controlled Two-Arm Parallel Trial
Authors: Cadegiani Flávio Adsuara , Zimerman Ricardo Ariel , do Nascimento Fonseca Daniel , do Nascimento Correia Michael , McCoy John , Wambier Carlos Gustavo , Goren Andy
Published: July 2021

Background

Antiandrogens were shown to be effective in mild-tomoderate COVID-19 male patients, supported by the SARS-CoV-2 dependency on transmembrane protease, serine 2 (TMPRSS2), which is solely modulated by androgens, for cell entry. While women with hyperandrogenism experiment more symptoms in COVID-19 compared to women without hyperandrogenism, and the chronic use of an antiandrogen seemed to mitigate these symptoms, whether the benefits would be observed in overall females is unknown. The objective of this study is to evaluate the efficacy of proxalutamide as a treatment for mild-to-moderate COVID-19 in females.

Methods

This was a randomized, double-blind, placebo-controlled, two-arm, parallel study on COVID-19 female outpatients, that compared the use of proxalutamide versus placebo. The primary outcome was hospitalization rates throughout 30 days after randomization. Patients with laboratory confirmed COVID-19 not hospitalized were recruited in two sites in Brasilia, Brazil, between January 4 and February 28, 2021, were randomized on a 2:3 ratio between proxalutamide and placebo, and were administered proxalutamide 200mg/day or placebo for seven days, in addition to usual care.

Results

A total of 177 women were randomized, including 75 in the proxalutamide arm and 102 patients in the placebo arm. None of the patients lost follow-up or discontinued treatment. The 30-day hospitalization rate was 2.7% in the proxalutamide arm and 18.6% in the placebo arm (p<0.001), with a hospitalization risk ratio (RR) of 0.14 [95% confidence interval (CI), 0.03-0.59].

Conclusions

These findings suggest that treatment of COVID-19 patients with proxalutamide in combination with standard of care was reduced hospitalization rate by 86% (p < 0.001), with no safety concerns. (Clinicaltrials.gov: NCT04853134)
Three-step rhythmic breathing exercise and COVID-19: A cross-sectional study
Authors: Pandya Apurvakumar , Mavalankar Dileep , Maithia Pravin
Published: July 2021

Introduction

The present study assessed the prevalence of COVID-19 among people practicing three-step rhythmic breathing (3SRB) exercise and those who were not practicing any breathing exercises, including 3SRB exercise.

Methods

A community-based cross-sectional observational study was conducted. Data was collected using a self-constructed online google survey tool from July 2020 to August 2020.

Results

Out of a total 1083 sample, a higher proportion of the participants (41.3%) belonged to the 34-49 years age group, followed by the age group of 50-65 (32.5%). The sample was almost equally distributed; about 51.9% of the population was male, and 48.4% were female. The COVID-19 positivity was recorded almost double (3.1%) in groups not practicing 3SRB exercises compared to a group (1.3%) practicing 3SRB exercises. Furthermore, the practice of 3SRB was significantly associated with a lower percentage of COVID-19 infection (p=0.046).

Conclusions

Practice of 3SRB is significantly associated with a lower percentage of COVID-19 infection. A future study with a robust methodology is warranted to validate the findings of this study and determine the effects of 3SRB on physiological and biological markers.
Decoding Clinical Biomarker Space of COVID-19: Exploring Matrix Factorization-based Feature Selection Methods
Authors: Saberi-Movahed Farshad , Mohammadifard Mahyar , Mehrpooya Adel , Rezaei-Ravari Mohammad , Berahmand Kamal , Rostami Mehrdad , Karami Saeed , Najafzadeh Mohammad , Hajinezhad Davood , Jamshidi Mina , Abedi Farshid , Mohammadifard Mahtab , Farbod Elnaz , Safavi Farinaz , Dorvash Mohammadreza , Vahedi Shahrzad , Eftekhari Mahdi , Saberi-Movahed Farid , Tavassoly Iman
Published: July 2021

One of the most critical challenges in managing complex diseases like COVID-19 is to establish an intelligent triage system that can optimize the clinical decision-making at the time of a global pandemic. The clinical presentation and patients’ characteristics are usually utilized to identify those patients who need more critical care. However, the clinical evidence shows an unmet need to determine more accurate and optimal clinical biomarkers to triage patients under a condition like the COVID-19 crisis. Here we have presented a machine learning approach to find a group of clinical indicators from the blood tests of a set of COVID-19 patients that are predictive of poor prognosis and morbidity. Our approach consists of two interconnected schemes: Feature Selection and Prognosis Classification. The former is based on different Matrix Factorization (MF)-based methods, and the latter is performed using Random Forest algorithm. Our model reveals that Arterial Blood Gas (ABG) O2Saturation and C-Reactive Protein (CRP) are the most important clinical biomarkers determining the poor prognosis in these patients. Our approach paves the path of building quantitative and optimized clinical management systems for COVID-19 and similar diseases.
Ethnicity, migration, and weight misperception: a Born in Bradford study
Authors: Yang Tiffany C , Truesdale Kimberly P , Kelly Brian , Rasgado Marena Ceballos , Bryant Maria J
Published: July 2021

Background

Weight perception may differ by ethnicity but is not well-understood, particularly among migrants to the United Kingdom (UK). It is also unknown whether a figure rating scale (FRS) or perceived weight question (PWQ) is more accurate for assessing body weight perception.

Methods

At 24-months postpartum, women in the Born in Bradford cohort (Bradford, UK) completed the 9-item Stunkard FRS and a 7-category PWQ. Both scales were condensed to weight categories representing the World Health Organisation cut-offs. Weighted kappa statistics assessed agreement between measured and perceived weight categories. χ2 and Fisher’s exact tests assessed categories of misperception by ethnicity and migration and logistic regression was used to examine odds of underestimation.

Results

Thirty percent of white British and 23% of Pakistani-origin women had obesity. Agreement between measured and perceived weight categories were similar for white British women using either a visual scale or weight question (FRS: κ [95%CI]: 0.61 [0.56, 0.65]; PWQ: 0.61 [0.55, 0.68)]. Overall agreement was lower for Pakistani-origin women with the visual scale performing better (FRS (0.58 [0.52, 0.63]) vs PWQ (0.47 [0.40, 0.54]). Pakistani-origin women, particularly those born outside the UK, were more likely to underestimate their body weight compared to white British women; this was greater with the PWQ (18% vs 10%; p<0.001) than FRS (14% vs 6%; p<0.001). Pakistani-origin women were 154% more likely to underestimate their body weight compared to white British women with the FRS and 111% more likely to underestimate when using the PWQ.

Conclusion

We observed ethnic differences in weight misperception with Pakistani-origin women more likely to underestimate their weight compared to white British women. Our findings suggest visual scales, rather than perceived weight questions, are more appropriate for the self-assessment of body weight.
The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics
Authors: Austin-Zimmerman Isabelle , Wronska Marta , Wang Baihan , Irizar Haritz , Thygesen Johan Hilge , Bhat Anjali , Denaxas Spiros , Fatemifar Ghazaleh , Finan Chris , Harju-Seppänen Jasmine , Giannakopoulou Olga , Kuchenbaecker Karoline , Zartaloudi Eirini , McQuillin Andrew , Bramon Elvira
Published: July 2021

Background

CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these effects.

Methods

We identified 31,579 individuals taking antidepressants and 2,699 taking antipsychotics within UK Biobank. Participants were classified as poor, intermediate or normal metabolisers of CYP2D6, and as poor, intermediate, normal, rapid and ultra-rapid metabolisers of CYP2C19. Risk of diabetes mellitus represented by HbA1c level was examined in relation to the metabolic phenotypes. We analysed drugs either individually (where sample size permitted) or grouped by class.

Results

CYP2D6 poor metabolisers taking paroxetine had higher Hb1Ac than normal metabolisers (mean difference: 2.29mmol/mol; p < 0.001). Among participants with diabetes who were taking venlafaxine, CYP2D6 poor metabolisers had higher HbA1c levels compared to normal metabolisers (mean differences: 10.15 mmol/mol; p < 0.001. Among participants with diabetes who were taking fluoxetine, we observe that CYP2D6 intermediate metabolisers and decreased HbA1c, compared to normal metabolisers (mean difference - 7.74mmol/mol; p=0.017). We did not observe any relationship between CYP2D6 or CYP2C19 metabolic status and HbA1c levels in participants taking antipsychotic medication.

Conclusion

Our results indicate that the impact of genetic variation in CYP2D6 differs depending on diabetes status. Although our findings support existing clinical guidelines, further research is essential to inform pharmacogenetic testing for people taking antidepressants and antipsychotics.
COVID-19 Serology Control Panel Using the Dried Tube Specimen Method
Authors: Windsor William J. , Knight Vijaya , Merkel Patricia A. , Lamb Molly M. , Santiago Mario L. , McCarthy Mary K. , Morrison Thomas E. , Kedl Ross M. , Frazer-Abel Ashley , Guo Kejun , Andersen Gillian , Huey Leah , Barrett Bradley S. , Colón-Franco Jessica M. , Chu May C.
Published: July 2021

We used the dried tube specimen (DTS) procedure to develop the COVID-19 Serology Control Panel (CSCP). The CSCP contains five well-characterized SARS-CoV-2 pooled plasma samples made available for labs around the world to compare test kits, use for external quality assurance, harmonize laboratory testing, and train laboratory workers.

Article Summary Line

The dried tube specimen system is a highly effective and resilient way to provide laboratories with well-characterized serology materials. The CSCP can help clinical laboratories inform their choice of diagnostic test to supplement clinical diagnoses of SARS-CoV-2 infection.
Myeloid-derived suppressor cells in the blood of Iranian COVID-19 patients
Authors: Mortaz Esmaeil , Movasaghi Mehrnaz , Basiri Ali , Dezfuli Neda K. , Roofchayee Neda Dalil , Jamaati Hamidreza , Garssen Johan , Adcock Ian M.
Published: July 2021

Background

A cytokine storm and lymphopenia are reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associated with coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs) that both suppress T-cell function. Serum IL-6 and IL-8 levels seem to correlate with the number of blood MDSCs.

Objective

To determine the frequency of MDSCs in severe COVID-19 patients from Iran and their correlations with serum IL-8 levels.

Methods

37 severe (8 on ventilation, 29 without ventilation) and 13 moderate COVID-19 patients together with 8 healthy subjects were enrolled at the Masih Daneshvari Hospital, Tehran-Iran between 10th April 2020-9th March 2021. Clinical and biochemical features, serum and whole blood were obtained. CD14, CD15, CD11b and HLA-DR expression on MDSCs was measured by flow cytometry.

Results

M-MDSCs (P≤0.0001) and G-MDSCs (P≤0.0001) frequency were higher in Iranian COVID-19 patients compared to healthy subjects. M-MDSC frequency was higher in non-ventilated compared to moderate COVID-19 subjects (P=0.004). Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (P=0.03). IL8 level was significant difference in ventilated, non-ventilated and moderate patients (P=0.005). The frequency of G-MDSCs correlated negatively with INR (r=-0.39, P=0.02).

Conclusion

Serum IL-8 levels did not correlate with the number of systemic MDSCs in COVID-19 patients. The highest levels of M-MDSCs were seen in the blood of severe non-ventilated patients. MDSC frequency in blood in the current study did not predict the survival and severity of COVID-19 patients.
Modulating amygdala activation to traumatic memories with a single ketamine infusion
Authors: Duek Or , Li Yutong , Kelmendi Ben , Amen Shelley , Gordon Charles , Milne Madison , Krystal John H. , Levy Ifat , Harpaz-Rotem Ilan
Published: July 2021

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be stored in an altered form. This concept might have significant clinical implications in treating PTSD. Using amygdala activity as a major biomarker of fear response, we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) to enhance post-retrieval extinction of PTSD trauma memories. Post-extinction, ketamine recipients (vs midazolam) showed a lower amygdala and hippocampus reactivation to trauma memories. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus, with no change in amygdala-vmPFC connectivity, which suggests that ketamine may enhance post-retrieval extinction of PTSD trauma memory in humans. These findings demonstrate the capacity to rewrite human traumatic memories and to modulate the fear response for at least 30 days post-extinction.
Lung function from school age to adulthood in primary ciliary dyskinesia
Authors: Halbeisen Florian S , Goutaki Myrofora , Pedersen Eva S L , Spycher Ben D , Amirav Israel , Boon Mieke , Malena Cohen-Cymberknoh , Crowley Suzanne , Emiralioglu Nagehan , Haarman Eric G , Karadag Bulent , Koerner-Rettberg Cordula , Latzin Philipp , Loebinger Michael R. , Lucas Jane S , Mazurek Henryk , Morgan Lucy , Marthin June , Pohunek Petr , Santamaria Francesca , Schwerk Nicolaus , Thouvenin Guillaume , Yiallouros Panayiotis , Nielsen Kim G , Kuehni Claudia E
Published: July 2021

Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents, and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the international PCD Cohort (iPCD) and calculated z-scores for forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1 and FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores) but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low BMI was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty, or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialized centres. It is essential to develop strategies to reverse this tendency and improve prognosis.

Take home message

Lung function in children with PCD is reduced by age 6 years and further declines during the growth period. It is essential to develop strategies to improve prognosis.