bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships among feed efficiency traits across production segments and production cycles in cattle
Authors: Lancaster Phillip A , Davis Michael E , Rutledge Jack J , Cundiff Larry V
Published: June 2021

Understanding the relationships between feed efficiency traits measured in different stages of production is necessary to improve feed efficiency across the beef value chain. The objective of this study was to evaluate relationships among feed efficiency traits measured as growing heifers and breeding females and in their progeny in three full production cycles, and relationships of dam residual feed intake (RFI) with lifetime and lifecycle cow efficiency traits. Data were collected on 160 mixed-breed heifers from 240 d of age to weaning of their third progeny, and postweaning performance of progeny until harvest in experiments initiated in 1953, 1954, 1959, 1964, 1969, and 1974. Individual feed offered was recorded daily, and feed refusals measured every 28 d. Milk yield was measured at 14-d intervals throughout lactation by machine or hand milking. Females and progeny were weighed at 28-d intervals and progeny were harvested at a constant endpoint of live grade or age depending upon the experiment. Feed efficiency traits of RFI and residual BW gain (RG) were computed as the residual from linear regression for developing heifers, dams (RFI and residual energy-corrected milk [RECM]), and postweaning progeny. Feed:gain ratio (FCR) was computed for developing heifers and postweaning progeny, and feed:milk energy ratio (FME) was computed for dams. Various measures of cow efficiency were calculated on either a life cycle or lifetime basis using ratios of progeny and dam weight outputs to progeny and dam feed inputs. Pearson correlations were computed among traits adjusted for a random year-breed-diet group effect. Heifer RFI (0.74) and RG (−0.32) were correlated (P ≤ 0.05) with dam RFI in parity 1 only, but were not correlated (P > 0.05) with dam RECM in any parity. Heifer RFI was correlated (P ≤ 0.05) with progeny RFI (0.17) in parity 3 only. Heifer FCR was not correlated with dam FME or progeny FCR in any parity. Dam RFI was weakly correlated (r = 0.25 to 0.36; P ≤ 0.05) among parities, whereas dam FME and RECM were strongly correlated (r = 0.49 to 0.72; P ≤ 0.05) among parities. Dam RFI in parity 1 and 2 was weakly correlated (r = −0.20 to −0.33; P ≤ 0.05) with cow efficiency ratios that included dam weight as an output, whereas dam RFI in parity 3 was not correlated with any cow efficiency ratio. In conclusion, feed efficiency traits were poorly correlated across production segments, but moderately repeatable across production cycles.
Cost, reach, and representativeness of recruitment efforts for an online skin cancer risk reduction intervention trial for young adults
Authors: Heckman Carolyn J , Riley Mary , Khavjou Olga , Ohman-Strickland Pamela , Manne Sharon L , Yaroch Amy L , Bhurosy Trishnee , Coups Elliot J , Glanz Karen
Published: June 2021

Despite its increasing use, few studies have reported on demographic representativeness and costs of research recruitment via social media. It was hypothesized that cost, reach, enrollment, and demographic representativeness would differ by social media recruitment approach. Participants were 18–25 year-olds at moderate to high risk of skin cancer based on phenotypic and behavioral characteristics. Paid Instagram, Facebook, and Twitter ads, unpaid social media posts by study staff, and unpaid referrals were used to recruit participants. Demographic and other characteristics of the sample were compared with the 2015 National Health Interview Survey (NHIS) sample. Analyses demonstrated significant differences among recruitment approaches regarding cost efficiency, study participation, and representativeness. Costs were compared across 4,274 individuals who completed eligibility screeners over a 7-month period from: Instagram, 44.6% (of the sample) = 1,907, $9 (per individual screened); Facebook, 31.5% = 1,345, $8; Twitter, 1% = 42, $178; unpaid posts by study staff, 10.6% and referred, 6.5%, $1. The lowest rates of study enrollment among individuals screened was for Twitter. Most demographic and skin cancer risk factors of study participants differed from those of the 2015 NHIS sample and across social media recruitment approaches. Considering recruitment costs and number of participants enrolled, Facebook and Instagram appeared to be the most useful approaches for recruiting 18–25 year-olds. Findings suggest that project budget, target population and representativeness, and participation goals should inform selection and/or combination of existing and emerging online recruitment approaches.
Sex Differences in Pulmonary Eicosanoids and Specialized Pro-Resolving Mediators in Response to Ozone Exposure
Authors: Yaeger Michael J , Reece Sky W , Kilburg-Basnyat Brita , Hodge Miles X , Pal Anandita , Dunigan-Russell Katelyn , Luo Bin , You Dorothy J , Bonner James C , Spangenburg Espen E , Tokarz Debra , Hannan Johanna , Armstrong Michael , Manke Jonathan , Reisdorph Nichole , Tighe Robert M , Shaikh S Raza , Gowdy Kymberly M
Published: June 2021

Ozone (O3) is a criteria air pollutant known to increase the morbidity and mortality of cardiopulmonary diseases. This occurs through a pulmonary inflammatory response characterized by increased recruitment of immune cells into the airspace, pro-inflammatory cytokines, and pro-inflammatory lipid mediators. Recent evidence has demonstrated sex-dependent differences in the O3-induced pulmonary inflammatory response. However, it is unknown if this dimorphic response is evident in pulmonary lipid mediator metabolism. We hypothesized that there are sex-dependent differences in lipid mediator production following acute O3 exposure. Male and female C57BL/6J mice were exposed to 1 part per million O3 for 3 h and were necropsied at 6 or 24 h following exposure. Lung lavage was collected for cell differential and total protein analysis, and lung tissue was collected for mRNA analysis, metabololipidomics, and immunohistochemistry. Compared with males, O3-exposed female mice had increases in airspace neutrophilia, neutrophil chemokine mRNA, pro-inflammatory eicosanoids such as prostaglandin E2, and specialized pro-resolving mediators (SPMs), such as resolvin D5 in lung tissue. Likewise, precursor fatty acids (arachidonic and docosahexaenoic acid; DHA) were increased in female lung tissue following O3 exposure compared with males. Experiments with ovariectomized females revealed that loss of ovarian hormones exacerbates pulmonary inflammation and injury. However, eicosanoid and SPM production were not altered by ovariectomy despite depleted pulmonary DHA concentrations. Taken together, these data indicate that O3 drives an increased pulmonary inflammatory and bioactive lipid mediator response in females. Furthermore, ovariectomy increases susceptibility to O3-induced pulmonary inflammation and injury, as well as decreases pulmonary DHA concentrations.
La responsabilité civile du demandeur pour le préjudice causé par une mesure provisoire ordonnée par les arbitres
Authors: Dai Do Van
Published: June 2021

Au niveau international comme niveau national, les arbitres sont de plus en plus autorisés à ordonner les mesures provisoires. Il se peut cependant que ces mesures soient rétroactivement injustifiées et causent un préjudice à autrui. Lorsqu’une mesure provisoire arbitrale cause un préjudice, la personne lésée peut-elle en demander la réparation ? Qui en est responsable ? Comment la demande de la victime sera-t-elle traitée ? La loi type et certaines lois nationales en matière d’arbitrage reconnaissent la responsabilité du demandeur en réparation du préjudice causé par une mesure provisoire arbitrale mais laissent sans réponse plusieurs questions. Le problème de réparation du préjudice causé aux tiers demeure également incertain pour ces systèmes. Pour avoir une vue d’ensemble, la présente étude envisage alors la responsabilité du demandeur (admission, conditions et régime) à l’égard d’une partie aussi bien qu’à l’égard des tiers.
An unusual extranodal natural killer/T-cell lymphoma presenting as chronic laryngitis
Authors: Cruz Julio , Vargas Daniela , Goecke Annelisse , Molina Maria Luisa
Published: June 2021

Rationale:

Nasal-type, extranodal natural killer (NK)/T-cell lymphoma is a rare lymphoma. The tumor usually shows ulcerative and necrotic lesions in the nasal cavities and sinuses. Tissue involvement outside the nasal cavity is uncommon.

Patient concern:

We describe a 30-year-old man with a 2-month history of hoarseness, weight loss, and dyspnea.

Diagnosis:

Magnetic resonance image (MRI) showed edema of the larynx with obliteration of the airway. Laryngoscopic examination described necrotic tissue in the glottis and larynx. The biopsy showed chronic, necrotizing laryngitis, with no granulomas, vasculitis, or atypical cells. The immunologic and microbiologic study was negative. Later, after immunosuppressive therapy, the patient presented erythema and diffuse enlargement of the right arm. MRI showed myositis of the biceps and brachial muscles. Infection was rule out, and direct microscopy showed an extensive muscle infiltration by mononuclear cells and abundant mitosis. Immunohistochemistry was positive for CD3, CD8, Ki 67 (90%), and CD56 compatible with extranodal NK/T cell lymphoma.

Interventions:

The patient initially received immunosuppression treatments (corticoids, cyclofosfamide, and Rituximab) with relapsing episodes. When lymphoma was diagnosed, chemotherapy was started.

Outcomes:

The patient died during chemotherapy.

Lessons:

Nasal-type, extranodal NK/T-cell lymphoma should be suspected even when there are no classical findings of neoplasms on histology. Immunohistochemistry is mandatory to rule it out.
Group characterization of impact-induced,in vivohuman brain kinematics
Authors: Gomez Arnold D. , Bayly Philip V. , Butman John A. , Pham Dzung L. , Prince Jerry L. , Knutsen Andrew K.
Published: June 2021

Brain movement during an impact can elicit a traumatic brain injury, but tissue kinematics vary from person to person and knowledge regarding this variability is limited. This study examines spatio-temporal brain–skull displacement and brain tissue deformation across groups of subjects during a mild impactin vivo. The heads of two groups of participants were imaged while subjected to a mild (less than 350 rad s−2) impact during neck extension (NE,n= 10) and neck rotation (NR,n= 9). A kinematic atlas of displacement and strain fields averaged across all participants was constructed and compared against individual participant data. The atlas-derived mean displacement magnitude was 0.26 ± 0.13 mm for NE and 0.40 ± 0.26 mm for NR, which is comparable to the displacement magnitudes from individual participants. The strain tensor from the atlas displacement field exhibited maximum shear strain (MSS) of 0.011 ± 0.006 for NE and 0.017 ± 0.009 for NR and was lower than the individual MSS averaged across participants. The atlas illustrates common patterns, containing some blurring but visible relationships between anatomy and kinematics. Conversely, the direction of the impact, brain size, and fluid motion appear to underlie kinematic variability. These findings demonstrate the biomechanical roles of key anatomical features and illustrate common features of brain response for model evaluation.
Operads for complex system design specification, analysis and synthesis
Authors: Foley John D. , Breiner Spencer , Subrahmanian Eswaran , Dusel John M.
Published: June 2021

As the complexity and heterogeneity of a system grows, the challenge of specifying, documenting and synthesizing correct, machine-readable designs increases dramatically. Separation of the system into manageable parts is needed to support analysis at various levels of granularity so that the system is maintainable and adaptable over its life cycle. In this paper, we argue that operads provide an effective knowledge representation to address these challenges. Formal documentation of a syntactically correct design is built up during design synthesis, guided by semantic reasoning about design effectiveness. Throughout, the ability to decompose the system into parts and reconstitute the whole is maintained. We describe recent progress in effective modelling under this paradigm and directions for future work to systematically address scalability challenges for complex system design.
Buckling between soft walls: sequential stabilization through contact
Authors: Wang Zhenkui , van der Heijden Gert H. M.
Published: June 2021

Motivated by applications of soft-contact problems such as guidewires used in medical and engineering applications, we consider a compressed rod deforming between two parallel elastic walls. Free elastica buckling modes other than the first are known to be unstable. We find the soft constraining walls to have the effect of sequentially stabilizing higher modes in multiple contacts by a series of bifurcations, in each of which the degree of instability (the index) is decreased by one. Further symmetry-breaking bifurcations in the stabilization process generate solutions with different contact patterns that allow for a classification in terms of binary symbol sequences. In the hard-contact limit, all these bifurcations collapse into highly degenerate ‘contact bifurcations’. For any given wall separation at most a finite number of modes can be stabilized and eventually, under large enough compression, the rod jumps into the inverted straight state. We chart the sequence of events, under increasing compression, leading from the initial straight state in compression to the final straight state in tension, in effect the process of pushing a rod through a cavity. Our results also give new insight into universal features of symmetry-breaking in higher mode elastic deformations. We present this study also as a showcase for a practical approach to stability analysis based on numerical bifurcation theory and without the intimidating mathematical technicalities often accompanying stability analysis in the literature. The method delivers the stability index and can be straightforwardly applied to other elastic stability problems.
Cohnella terricola sp. nov., isolated from soil
Authors: Kim Jiyoun , Chhetri Geeta , Kim Inhyup , Kang Minchung , Seo Taegun
Published: June 2021

A Gram-positive, aerobic, flagellated, endospore-forming, rod-shaped strain, designated as G13T, was isolated from soil. The results of 16S rRNA gene sequence analysis led to the conclusion that strain G13T was phylogenetically related to

Cohnella boryungensis

BR29T (97.5 %) and

Cohnella phaseoli

CECT 7287T (96.9 %) with digital DNA–DNA hybridization values of 21.0 and 21.4 %, and distantly related to

Cohnella thermotolerans

CCUG 47242T (94.8 %), type species of the genus

Cohnella

, at 19.0 %. The genome size of strain G13T was 5 387 258 bp, with 51.3 mol% G+C content. The predominant fatty acids were summed feature 9 (iso-C17 : 1
 ω9c and/or C16 : 0 10-methyl), anteiso-C17 : 0, iso-C17 : 0 and iso-C15 : 0. The predominant quinone was menaquinone-7 and the major polar lipids were diphosphatidyglycerol, phosphatidylethanolamine, phosphatidylglycerol, lysylphosphatidylglycerol, three aminophospholipids, two phosphoglycolipids, three aminolipids and two unidentified lipids. Based on the data from phenotypic tests and the genotypic differences between strain G13T and its close phylogenetic relatives, strain G13T represents a new species belonging to the genus

Cohnella

, for which the name Cohnella terricola sp. nov. (=KACC 19905T=NBRC 113748T) is proposed.
Trueperella pecoris sp. nov. isolated from bovine and porcine specimens
Authors: Schönecker Lutz , Schnydrig Philipp , Brodard Isabelle , Thomann Andreas , Hemphill Andrew , Rodriguez-Campos Sabrina , Perreten Vincent , Jores Joerg , Kittl Sonja
Published: June 2021

A novel Gram-stain-positive bacterium was isolated from a purulent bovine milk sample, the bovine placenta from an abortion, the udder secretion of a heifer and the lung of a pig that had succumbed from suppurative bronchopneumonia in Switzerland from 2015 to 2019. The strains grew best under aerobic conditions with 5 % CO2 and colonies were non-haemolytic and greyish-white. They were non-motile and negative for catalase and oxidase. The genomes of the four strains 19M2397T, 15A0121, 15IMD0307 and 19OD0592 were obtained by sequencing. The results of phylogenetic analyses based on the 16S rRNA gene grouped them within the genus

Trueperella

in the family

Arcanobacteriaceae

. The genomes had DNA G+C contents of 61.2–62.2 mol% and showed digital DNA–DNA hybridization (dDDH) values of 21.4–22.8 % and average nucleotide identity (ANI) values of approximately 77 % to their closest relatives

Trueperella pyogenes

and

Trueperella bernardiae

. With respect to the presence in different livestock species we propose the name Trueperella pecoris sp. nov. The type strain is 19M2397T (=CCOS 1952T=DSM 111392T), isolated from the udder secretion of a heifer diagnosed with summer mastitis in 2019.
Emendation of Rules 5b, 8, 15 and 22 of the International Code of Nomenclature of Prokaryotes to include the rank of phylum
Authors: Oren Aharon , Arahal David R. , Rosselló-Móra Ramon , Sutcliffe Iain C. , Moore Edward R. B.
Published: June 2021

Following the International Committee on Systematics of Prokaryotes electronic discussion and vote on proposals to include the rank of phylum in the rules of the International Code of Nomenclature of Prokaryotes, we here announce the results of the ballot. We also present draft versions of the emended Rules 5b, 8, 15 and 22, based on the outcome of the ballot, to be included in the proposal for the preparation of a new revision of the International Code of Nomenclature of Prokaryotes.
Virus and helper component interactions favour the transmission of recombinant potato virus Y strains
Authors: Mondal Shaonpius , Wintermantel William M. , Gray Stewart M.
Published: June 2021

In recent years, several recombinant strains of potato virus Y, notably PVYNTN and PVYN:O have displaced the ordinary strain, PVYO, and emerged as the predominant strains affecting the USA potato crop. Previously we reported that recombinant strains were transmitted more efficiently than PVYO when they were acquired sequentially, regardless of acquisition order. In another recent study, we showed that PVYNTN binds preferentially to the aphid stylet over PVYO when aphids feed on a mixture of PVYO and PVYNTN. To understand the mechanism of this transmission bias as well as preferential virus binding, we separated virus and active helper component proteins (HC), mixed them in homologous and heterologous combinations, and then fed them to aphids using Parafilm sachets. Mixtures of PVYO HC with either PVYN:O or PVYNTN resulted in efficient transmission. PVYN:O HC also facilitated the transmission of PVYO and PVYNTN, albeit with reduced efficiency. PVYNTN HC failed to facilitate transmission of either PVYO or PVYN:O. When PVYO HC or PVYN:O HC was mixed with equal amounts of the two viruses, both viruses in all combinations were transmitted at high efficiencies. In contrast, no transmission occurred when combinations of viruses were mixed with PVYNTN HC. Further study evaluated transmission using serial dilutions of purified virus mixed with HCs. While PVYNTN HC only facilitated the transmission of the homologous virus, the HCs of PVYO and PVYN:O facilitated the transmission of all strains tested. This phenomenon has likely contributed to the increase in the recombinant strains affecting the USA potato crop.
Date of introduction and epidemiologic patterns of SARS-CoV-2 in Mogadishu, Somalia: estimates from transmission modelling of 2020 excess mortality data
Authors: Koltai Mihaly , Warsame Abdihamid , Bashiir Farah , Freemantle Terri , Williams Chris , Jit Mark , Flasche Stefan , Davies Nicholas G. ,   CMMID COVID-19 working group, Aweis Ahmed , Ahmed Mohamed , Dalmar Abdirisak , Checchi Francesco
Published: June 2021

Introduction

In countries with weak surveillance systems confirmed COVID-19 deaths are likely to underestimate the death toll of the pandemic. Many countries also have incomplete vital registration systems, hampering excess mortality estimation. Here, we fitted a dynamic transmission model to satellite imagery data on burial patterns in Mogadishu, Somalia during 2020 to estimate the date of introduction, transmissibility and other epidemiologic characteristics of SARS-CoV-2 in this low-income, crisis-affected setting.

Methods

We performed Markov chain Monte Carlo (MCMC) fitting with an age-structured compartmental COVID-19 model to provide median estimates and credible intervals for the date of introduction, the basic reproduction number (R0) and the effect of non-pharmaceutical interventions in Mogadishu up to September 2020.

Results

Under the assumption that excess deaths in Mogadishu February-September 2020 were directly attributable to SARS-CoV-2 infection we arrived at median estimates of October-November 2019 for the date of introduction and low R0 estimates (1.3-1.5) stemming from the early and slow rise of excess deaths. The effect of control measures on transmissibility appeared small.

Conclusion

Subject to study assumptions, a very early SARS-CoV-2 introduction event may have occurred in Somalia. Estimated transmissibility in the first epidemic wave was lower than observed in European settings.
Prevalence and Incidence of Antibodies Against Sars-Cov-2 Among Primary Healthcare Providers in Belgium During One Year of the Covid-19 Epidemic: Prospective Cohort Study Protocol
Authors: Adriaenssens Niels , Scholtes Beatrice , Bruyndonckx Robin , Verbakel Jan Y , De Sutter An , Heytens Stefan , Van den Bruel Ann , Desombere Isabelle , Van Damme Pierre , Goossens Herman , Buret Laëtitia , Duysburgh Els , Coenen Samuel
Published: June 2021

Introduction

National severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence data provides essential information about population exposure to the virus and helps predict the future course of the epidemic. Early cohort studies have suggested declines in levels of antibodies in individuals, associated with, for example, illness severity, age and co-morbidities. This protocol focuses on the seroprevalence among primary health care providers (PHCPs) in Belgium. They manage the vast majority of COVID-19 patients in addition to other patients and therefore play an essential role in the efficient organisation of health care. Currently, evidence is lacking on 1. how many PHCPs get infected with SARS-CoV-2 in Belgium, 2. the rate at which this happens, 3. their clinical spectrum, 4. their risk factors, 5. the effectiveness of the measures to prevent infection and 6. the accuracy of the serology-based point-of-care test in a primary care setting.

Methods and analysis

This study will be set up as a prospective cohort study. General practitioners (GPs) and other PHCPs (working in a GP practice) will be recruited via professional networks and professional media outlets to register online to participate. Registered GPs and other PHCPs will be asked at each testing point (n=9) to perform a capillary blood sample antibody point-of-care test (OrientGene®) and complete an online questionnaire. The primary outcomes are the prevalence and incidence of antibodies against SARS-CoV-2 in PHCPs during a 12-month follow-up period. Secondary outcomes include the longevity of antibodies against SARS-CoV-2.

Ethics and dissemination

Ethical approval has been granted by the Ethics Committee of the University Hospital Antwerp/University of Antwerp (Belgian registration number: 3002020000237). Alongside journal publications, dissemination activities include the publication of monthly reports to be shared with the participants and the general population through the publicly available website of the Belgian health authorities (Sciensano).

Registration

Trial registration number:NCT04779424

Article summary

Strengths and limitations of this study

This large cohort study will provide regular, timely and precise data at national level on prevalence and incidence of antibodies against SARS-CoV-2 among primary health care providers (PHCPs) managing the vast majority of COVID-19 and other patients and therefore essential to organise health care efficiently.

This study will familiarise PHCPs with the use of serology-based point-of-care tests (POCTs) and validate the POCT in a primary care setting.

Missing data points and the use of a convenience sample could limit the validity of the study results.
AKI Risk Score (AKI-RiSc): Developing an Interpretable Clinical Score for Early Identification of Acute Kidney Injury for Patients Presenting to the Emergency Department
Authors: Ang Yukai , Hock Ong Marcus Eng , Xie Feng , Teo Su Hooi , Choong Lina , Koniman Riece , Chakraborty Bibhas , Wah Ho Andrew Fu , Liu Nan
Published: June 2021

Background

Acute kidney injury (AKI) in hospitalised patients is a common syndrome associated with poorer patient outcomes. Clinical risk scores can be used for the early identification of patients at risk of AKI.

Methods

We conducted a retrospective study using electronic health records of Singapore General Hospital emergency department patients who were admitted from 2008 to 2016. The primary outcome was inpatient AKI of any stage within 7 days of admission based on Kidney Disease Improving Global Outcome (KDIGO) 2012 guidelines. AutoScore, a machine learning based algorithm, was used to generate point based clinical scores from the study sample which was divided into training, validation and testing cohorts. Model performance was evaluated using area under the curve (AUC).

Results

Among the 119,468 admissions, 10,693 (9.0%) developed AKI. 8,491 were stage 1 (79.4%), 906 stage 2 (8.5%) and 1,296 stage 3 (12.1%). The AKI Risk Score (AKI-RiSc) was a summation of the integer scores of 6 variables: serum creatinine, serum bicarbonate, pulse, systolic blood pressure, and diastolic blood pressure. AUC of AKI-RiSc was 0.730 (95% CI: 0.713 – 0.747), outperforming an existing AKI Prediction Score model which achieved AUC of 0.665 (95% CI: 0.646 – 0.679) when evaluated on the same test cohort. At a cut-off of 4 points, AKI-RiSc had a sensitivity of 82.5% and specificity of 46.7%.

Conclusion

AKI-RiSc is a simple point based clinical score that can be easily implemented on the ground for early identification of AKI in high-risk patients and potentially be applied in healthcare settings internationally.
Small-molecule metabolome identifies potential therapeutic targets against COVID-19
Authors: Bennet Sean M. P. , Kaufmann Martin , Takami Kaede , Sjaarda Calvin , Douchant Katya , Moslinger Emily , Wong Henry , Reed David E. , Ellis Anne K. , Vanner Stephen , Colautti Robert I. , Sheth Prameet M.
Published: June 2021

Background

Respiratory viruses are transmitted and acquired via the nasal mucosa, and thereby may influence the nasal metabolome composed of biochemical products produced by both host cells and microbes. Studies of the nasal metabolome demonstrate virus-specific changes that sometimes correlate with viral load and disease severity. Here, we evaluate the nasopharyngeal metabolome of COVID-19 infected individuals and report several small molecules that may be used as potential therapeutic targets. Specimens were tested by qRT-PCR with target primers for three viruses: Influenza A (INFA), respiratory syncytial virus (RSV), and SARS-CoV-2, along with asymptomatic controls. The nasopharyngeal metabolome was characterized using an LC-MS/MS-based small-molecule screening kit capable of quantifying 141 analytes. A machine learning model identified 28 discriminating analytes and correctly categorized patients with a viral infection with an accuracy of 96% (R2=0.771, Q2=0.72). A second model identified 5 analytes to differentiate COVID19-infected patients from those with INFA or RSV with an accuracy of 85% (R2=0.442, Q2=0.301). Specifically, LysoPCaC18:2 concentration was significantly increased in COVID19 patients (P< 0.0001), whereas beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine concentrations were significantly decreased (P< 0.0001). This study demonstrates that COVID19 infection results in a unique NP metabolomic signature with carnosine and LysoPCaC18:2 as potential therapeutic targets.

Significance Statement

Efforts to elucidate how SARS-CoV-2 interacts with the host has become a global priority. To identify biomarkers for potential therapeutic interventions, we used a targeted metabolomics approach evaluating metabolite profiles in the nasal mucosa of COVID-19 patients and compared metabolite profiles to those of other respiratory viruses (influenza A, RSV). We identified a COVID-19-specific signature characterized by changes to LysoPCaC18:2, beta-hydroxybutyric acid, Met SO, succinic acid, and carnosine. Carnosine is a promising potential target against SARS-CoV-2 as it has been shown to interfere with binding of SARS-CoV-2 to the ACE2 receptor. This study provides compelling evidence for the use of metabolomics as an avenue for the identification of novel drug targets for viral respiratory infections in the nasopharynx.
EVALUATION OF HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH DIABETES IN DIFFERENT CARE SETTINGS A CROSS SECTIONAL STUDY IN ALAIN, UAE
Authors: Al kaabi Mariam Salem Khamis , Al Kaabi Bushra khamis Obaid , Al Marzooqi Fatima Mohammed Ahmed , Al Murri Shaima Ghazi , Baynouna AlKetbi Latifa Mohammad
Published: June 2021

Purpose

This study aims to assess health-related quality of life (HRQOL) in type 2 diabetic patients across four domains—physical, psychological, social, and environmental—and explore the possible determinants of these domains.

Methods

Using a cross-sectional study design, 397 type 2 diabetic patients in Alain city were interviewed using validated questionnaires in three different care settings: primary, secondary and private health care facilities. The WHO Quality of Life instrument, generalized anxiety disorder score, and Patient Health Questionnaire (PHQ9) were employed.

Results

The participants comprised 270 females (68%) and 127 males (32%), with 68.9% in the 41–65 years age group; 49.6% were married. The most common comorbidities were dyslipidemia (69.3%), hypertension (61%), and osteoarthritis (24.7%). On a scale of 0 to 100, the highest QOL mean score was reported in the social relationship domain (78.3), followed by the environmental (77.7), psychological health (74.2), and physical health (70.7) domains.

The risk of depression was a strong determinant of poor physical health. Social factors have great impact on a patient’s health and well-being. We noticed no difference in HRQOL outcome between primary, secondary, and private health care facilities.

Conclusion

The social and mental health domains were the most influential in HRQOL among the participants. This finding supports targeting QOL assessments of patients with type 2 diabetes at the regular chronic diseases clinics and in the planning of population health management programs to ensure the best outcomes.

Plain English Summary

Diabetes mellitus is considered a major cause of morbidity and mortality worldwide. In our study we are aiming to explore difference in quality of life and quality of care in patients who access different health care facilities, primary health care clinics versus patients following in secondary care center and private center in Alain. By doing so, we will expand the knowledge regarding health related quality of life of people with diabetes in the UAE and opens the door for future international collaborative research in Diabetes.
EEG-Based Focus Estimation Using Neurable’s Enten Headphones and Analytics Platform
Authors: Alcaide Ramses , Agarwal Nishit , Candassamy Jegan , Cavanagh Sarah , Lim Michelle , Meschede-Krasa Benyamin , McIntyre James , Ruiz-Blondet Maria V. , Siebert Brandon , Stanley David , Valeriani Davide , Yousefi Ali
Published: June 2021

We introduce Neurable’s research on focus using our recently developed Enten EEG headphones. First we quantify Enten’s performance on standard EEG protocols, including eyes-closed alpha rhythms, auditory evoked response and the P300 event-related potential paradigm. We show that Enten’s performance is on-par with established industry-standard hardware. We then introduce a series of experimental tasks designed to mimic how focus might be maintained or disrupted in a real-world office setting. We show that (A) these tasks induce behavioral changes that reflect underlying changes in focus levels and (B) our proprietary algorithm detects these changes across a large number of sessions without needing to adjust the model per participant or recording session. Through manipulation of our experimental protocol, we show that our algorithm is not dependent on gross EMG artifacts and it is driven by changes in EEG. Finally, we evaluated the model’s performance on the same subject across several days, and show that performance remained consistent over time. Our model correctly captured 80% ± 4.1% of distractions present in our experiments with statistical significance. This indicates that our model generalizes across subjects, time points, and conditions. Our findings are based on EEG data collected from 132 participants across 337 sessions and 45 different experiments.
Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins
Authors: Emmenegger Marc , Saseendran Kumar Sreedhar , Emmenegger Vishalini , Malinauskas Tomas , Büttner Thomas , Rose Laura , Schierack Peter , Sprinzl Martin F. , Sommer Clemens J. , Lackner Karl J. , Aguzzi Adriano , Roggenbuck Dirk , Frauenknecht Katrin B. M.
Published: June 2021

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity and detect phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by – among other factors – viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL to prothrombin (PT) with the strength of the antibody response against SARS-CoV-2 and that it is further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity and aPL against PT in patients with SARS-CoV-2.
A UDP-GlcNAc : βGal β1-6 GlcNAc transferase involved in bloodstream formN-glycan and procyclic form GPI anchor elaboration inTrypanosoma brucei
Authors: Duncan Samuel M. , Nagar Rupa , Damerow Manuela , Yashunsky Dmitry V. , Buzzi Benedetta , Nikolaev Andrei V. , Ferguson Michael A.J.
Published: June 2021

Trypanosoma bruceihas large carbohydrate extensions on itsN-linked glycans and glycosylphosphatidylinositol (GPI) anchors in its bloodstream form (BSF) and procyclic form (PCF), respectively. The parasite’s glycoconjugate repertoire suggests at least 38 glycosyltransferase (GT) activities, 16 of which are unknown. Here, we probe the function(s) of a putative β3GT gene,TbGT10. The BSF null mutant is viablein vitroandin vivoand can differentiate into PCF, demonstrating non-essentiality. However, the absence of TbGT10 led to impaired elaboration ofN-glycans and GPI anchor sidechains in BSF and PCF parasites, respectively. Glycosylation defects include reduced BSF glycoprotein binding to ricin and to monoclonal antibodies mAb139 and mAbCB1. The latter bind a carbohydrate epitope of lysosomal glycoprotein p67 that we show here, using synthetic glycans, consists of (−6Galβ1-4GlcNAcβ1-)≥ 4poly-N-acetyllactosamine repeats. Methylation linkage analysis of Pronase glycopeptides isolated from BSF wild-type and TbGT10 null parasites show a reduction in 6-O-substituted- and 3,6-di-O-substituted-Gal residues. Together, these data suggest thatTbGT10encodes a UDP-GlcNAc : βGal β1-6 GlcNAc-transferase active in both BSF and PCF life-cycle stages elaborating complexN-glycans and GPI sidechains, respectively. The β1-6 specificity of this β3GT gene product and its dual roles inN-glycan and GPI glycan elaboration are notable.
Connectome-based model predicts individual psychopathic traits in college students
Authors: Ye Shuer , Zhu Bing , Zhao Lei , Tian Xuehong , Yang Qun , Krueger Frank
Published: June 2021

Background

Psychopathic traits have been suggested to increase the risk of violations of socio-moral norms. Previous studies revealed that abnormal neural signatures are associated with elevated psychopathic traits; however, whether the intrinsic network architecture can predict psychopathic traits at the individual level remains unclear.

Methods

The present study utilized connectome-based predictive modeling (CPM) to investigate whether whole-brain resting-state functional connectivity (RSFC) can predict psychopathic traits in the general population. RS functional magnetic resonance imaging data were collected from 84 college students with varying psychopathic traits measured by the Levenson Self-Report Psychopathy Scale (LSRP).

Results

We found that RSFC of the negative networks predicted individual differences in total LSRP and secondary psychopathy scores but not primary psychopathy score. Particularly, nodes with the most connections in the predictive connectome anchored in the prefrontal cortex (e.g., anterior prefrontal cortex and orbitofrontal cortex) and limbic system (e.g., anterior cingulate cortex and insula). In addition, the connections between the occipital network (OCCN) and cingulo-opercular network (CON) served as a significant predictive connectome for total LSRP and secondary psychopathy score.

Conclusion

CPM constituted by whole-brain RSFC significantly predicted psychopathic traits individually in the general population. The prefrontal cortex and limbic system at the anatomic level and the CON and OCCN at the functional network level plays a special role in the predictive model—reflecting atypical executive control and affective processing for individuals with elevated psychopathic traits. These findings may provide some implications for early detection and potential intervention of psychopathic tendency.
PARP7 mono-ADP-ribosylates the Agonist Conformation of the Androgen Receptor in the Nucleus
Authors: Kamata Teddy , Yang Chun-Song , Paschal Bryce M.
Published: June 2021

We recently described a signal transduction pathway that contributes to AR regulation based on sitespecific ADP-ribosylation by PARP7, a mono-ADP-ribosyltransferase implicated in several human cancers. ADP-ribosylated AR is specifically recognized by PARP9/DTX3L, a heterodimeric complex that contains an ADP-ribose reader (PARP9) and a ubiquitin E3 ligase (DTX3L). Here, we have characterized the cellular and biochemical requirements for AR ADP-ribosylation by PARP7. We found that the reaction requires nuclear localization of PARP7 and an agonist-induced conformation of AR. PARP7 contains a Cys3His1-type zinc finger (ZF), which we found is critical for AR ADP-ribosylation. The Parp7 ZF is required for efficient nuclear localization by the nuclear localization signal (NLS) encoded in PARP7, but rescue experiments indicate the ZF makes a contribution to AR ADP-ribosylation that is transport-independent. ZF structure appears to be dispensable for PARP7 catalytic activity and for PARP7 binding to AR. Androgen induction of theMYBPC1gene is regulated by AR and PARP7, and we determined that the ZF is required for the PARP7 transcriptional effect onMYBPC1.Our data indicate the PARP7 ZF plays an important role in modulating the subcellular localization of PARP7 and its capacity to ADP-ribosylate and promote AR-dependent transcription.
Did you see it? A Python tool for psychophysical assessment of the human blind spot
Authors: Ling Xiao , Silson Edward H. , McIntosh Robert D.
Published: June 2021

The blind spot is a region in the temporal monocular visual field in humans, which corresponds to a physiological scotoma within the nasal hemi-retina. This region has no photoreceptors, so is insensitive to visual stimulation. There is no corresponding perceptual scotoma because the visual stimulation is “filled-in” by the visual system. Investigations of visual perception in and around the blind spot allow us to investigate this filling-in process. However, because the location and size of the blind spot are individually variable, experimenters must first map the blind spot in every observer. We present an open-source tool, which runs in Psychopy software, to estimate the location and size of the blind spot psychophysically. The tool will ideally be used with an Eyelink eye-tracker (SR Research), but it can also run in standalone mode. Here, we explain the rationale for the tool and demonstrate its validity in normally-sighted observers. We develop a detailed map of the blind spot in one observer. Then, in a group of 12 observers, we propose a more efficient, pragmatic method to define a “safe zone” within the blind spot, for which the experimenter can be fully confident that visual stimuli will not be seen. Links are provided to this open-source tool and a manual.
Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation
Authors: Chen Hsu-Yu , Huang Chun , Tian Lu , Huang Xiaoli , Zhang Chennan , Llewellyn George N. , Rogers Geoffrey L. , Andresen Kevin , O’Gorman Maurice R.G. , Chen Ya-Wen , Cannon Paula M.
Published: June 2021

The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the protein’s function. Here, we optimized concentration methods for SARS-CoV-2 Spike pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers, but had no impact on sensitivity to convalescent serum inhibition. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but that this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions.

IMPORTANCE

Pseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we therefore recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration, if higher titer vectors are required.
Evidence for a bacterial Lands cycle phospholipase A: Structural and mechanistic insights into membrane phospholipid remodeling
Authors: Bleffert Florian , Granzin Joachim , Caliskan Muttalip , Schott-Verdugo Stephan N. , Siebers Meike , Thiele Björn , Rahme Laurence , Felgner Sebastian , Dörmann Peter , Gohlke Holger , Batra-Safferling Renu , Jaeger Karl-Erich , Kovačić Filip
Published: June 2021

Cells steadily adapt their membrane glycerophospholipid (GPL) composition to changing environmental and developmental conditions. While the regulation of membrane homeostasis via GPL synthesis in bacteria has been studied in detail, the mechanisms underlying the controlled degradation of endogenous GPLs remain unknown. Thus far, the function of intracellular phospholipases A (PLAs) in GPL remodeling (Lands cycle) in bacteria is not clearly established. Here, we identified the first cytoplasmic membrane-bound phospholipase A1 (PlaF) from Pseudomonas aeruginosa involved in the Lands cycle. PlaF is an important virulence factor, as the P. aeruginosa ΔplaF mutant showed strongly attenuated virulence in Galleria mellonella and macrophages. We present a 2.0-Å-resolution crystal structure of PlaF, the first structure that reveals homodimerization of a single-pass transmembrane (TM) full-length protein. PlaF dimerization, mediated solely through the intermolecular interactions of TM and juxtamembrane regions, inhibits its activity. A dimerization site and the catalytic sites are linked by an intricate ligand-mediated interaction network which likely explains the product (fatty acid) feedback inhibition observed with the purified PlaF protein. We used molecular dynamics simulations and configurational free energy computations to suggest a model of PlaF activation through a coupled monomerization and tilting of the monomer in the membrane, which constrains the active site cavity into contact with the GPL substrates. Thus, these data show the importance of the GPL remodeling pathway for virulence and pave the way for the development of a novel therapeutic class of antibiotics targeting PlaF-mediated membrane GPL remodeling.

Synopsis

Membrane homeostasis can be regulated by phospholipase-controlled deacylation of endogenous glycerophospholipids (GPLs) followed by reacylation of products, known as the Lands cycle in eukaryotes. Here we show that the human pathogen Pseudomonas aeruginosa uses intracellular phospholipase A1 (PlaF) to modulate membrane GPL composition, which is the first example in bacteria. This newly identified PLA1 indirectly regulates the bacterial virulence properties by hydrolyzing a specific set of membrane GPLs. The crystal structure of full-length PlaF dimers bound to natural ligands, MD simulations, and biochemical approaches provide insights into the molecular mechanism of dimerization-mediated inactivation of this single-pass transmembrane PLA1. Our findings shed light on a mechanism by which bacterial intracellular PLAs might regulate membrane homeostasis what showcases these enzymes as a promising target for a new class of antibiotics.