bluuebunny/crossref_metadata_2025 huggingface dataset:
Survey of feedlot nutritionists gives insight on information-seeking behavior
Authors: Rients Emma , VanDerWal Allison , Loy Daniel , Reynolds Mary , Hansen Stephanie
Published: August 2022

Nutrition critically affects feedlot cattle health and growth, and ultimately cost of production. Feedlot producers rely on professionals such as nutritionists, extension educators, feed company representatives, and others to assist them in developing the best nutritional program for their operation. In turn, these professionals depend on feedlot nutrition research to drive decisions for their clients. A survey of feedlot professionals was conducted regarding how published resources are used. Surveys were included in the spring 2020 mailing to potential Plains Nutrition Council meeting attendees; 61 surveys were returned. The objective of this survey was to aid feedlot nutrition researchers to make more informed decisions when publishing new research to maximize impact on the feedlot industry. The survey asked 15 questions regarding the participant’s career, professional organization memberships, frequency and intentions of using research, and ranking the importance of resources, peer-reviewed journals, and learning platforms. Survey respondents primarily served the Midwest and Plains regions (83.1%) with employment by feed companies (34.4%), private consulting firms (21.3%), other aspects of feedlot production (26.2%), or were self-employed (18%). Survey participants found great importance in peer-reviewed journals, though the relevance of peer-reviewed journals sometimes differed due to the professional age of respondents. The main strategies for accessing journals were via society memberships and through open access; utilizing open access publishing may increase the number of industry professionals reached. Looking to the future, we may see a shift in resources used by industry professionals due to the differences seen in preferences of early and late career survey participants, specifically increases in the use of technology-based platforms. These data may inform feedlot researchers on the information-seeking behaviors of feedlot professionals, such as the importance of publishing data in open access formats, allowing for greater impact through increased utilization of newly published research.
Influence of high cyclic ambient temperature and water drinker design on growth performance and water disappearance of growing-finishing pigs
Authors: Vande Pol Katherine D , Grohmann Nicholas S , Weber Thomas E , Ritter Matthew J , Ellis Michael
Published: August 2022

The objective of this study was to determine effects of room temperature and drinker design on growth and water disappearance of growing-finishing pigs (26.9 ± 3.67 to 130.9 ± 5.10 kg live body weight). A split-plot design was used with a 2 × 2 factorial arrangement of treatments: Room Temperature (RT) [Thermoneutral (TN) vs. High (HI); main plot], Drinker Design (DD; Nipple vs. Cup; sub-plot). A total of 316 pigs were used, housed in 32 pens in 4 rooms (8 pens/room; 7 pens of 10 pigs and 1 pen of 9 pigs). Two rooms were on each RT treatment. Room temperature for the TN treatment was constant throughout each day but decreased from 24°C at the start to 20°C and 18°C on d 14 and 45 of the study period, respectively. For the HI treatment, a single, cyclic RT protocol was used throughout the study (30°C from 08:00 to 19:00 h and 20°C from 20:00 to 07:00 h, with 1-h transition periods). Pens had fully-slatted concrete floors and 1 feeder and drinker (either nipple or cup); floor space was 0.67 m2/pig. Pigs had ad libitum access to standard corn-soybean diets, formulated to meet or exceed NRC (2012) nutrient requirements. Water disappearance was measured using a meter fitted to the water line supplying each drinker. There were no interactions (P > 0.05) between RT and DD treatments. Drinker Design did not affect (P > 0.05) growth performance; water disappearance was 7.3% greater (P ≤ 0.05) for Nipple than Cup drinkers. Compared to the TN treatment, the HI treatment had no effect (P > 0.05) on gain:feed ratio, but resulted in lower (P ≤ 0.05) average daily gain (6.5%) and average daily feed intake (5.5%) and greater (P ≤ 0.05) average daily water disappearance (16.8%). These results suggest that both drinker design and RT can affect water disappearance, and that the high, cyclic RT regime used reduced growth performance of growing-finishing pigs. Further research is needed to determine the contribution of water intake and wastage to treatment differences in water disappearance.
Toxicity mechanism of patulin on 293 T cells and correlation analysis of Caspase family
Authors: Zhang Baigang , Xu Dongmei , Shao Lin , Liang Hairong , Li Jinliang , Huang Chenghui
Published: August 2022

Patulin (PAT), a kind of mycotoxin, is a widely disseminated mycotoxin found in agricultural products. Although the existing research results show that PAT can cause nerve, immune, and skin toxicities, resulting in heart, liver, and kidney damages. However, evidence on the underlying mechanisms of PAT is still lacking. Present study aims to investigate the renal toxicity and related mechanisms of PAT on 293 T cells. Cell Counting Kit-8 method was used to reveal the dose-effect relationship and the time-effect relationship of PAT toxicity. Trypan blue staining and Hoechst 33342 staining were used to analyze PAT, which induced apoptosis on 293 T cells. Superoxide-dismutase (SOD), GSH, and malondialdehyde (MDA) were used to measure the changes of oxidative stress status of 293 T cells induced by PAT. The changes of reactive oxygen species (ROS) and ATP in mitochondria indicate the role of mitochondria when PAT induced cell damage and apoptosis. Through Cyt-C release assay analysis, caspase activity change, and correlation analysis, the potential mechanism of mitochondrial apoptosis pathway was proved. Results demonstrated that PAT significantly induced cell injury, and with the increase of time and concentration, the cell survival rate decreased significantly. Hoechst 33342 staining and Trypan blue staining showed that apoptosis rate was elevated by PAT. As PAT concentration increased, intracellular SOD, glutathion peroxidase activities were decreased and the MDA content was increased. The decrease of intracellular ATP level and accumulation of ROS content indicated an increased permeability of the mitochondrial membrane. Overexpression of Cyt-C activated the cascade reaction of caspase enzyme, leading to apoptosis. The results of enzyme activity assay and correlation analysis indicated that caspase 3 was the most critical caspase in the cascade system and that it was most correlated with caspase 8 and caspase 9.
Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
Authors: Boswell M T , Nazziwa J , Kuroki K , Palm A , Karlson S , Månsson F , Biague A , da Silva Z J , Onyango C O , de Silva T I , Jaye A , Norrgren H , Medstrand P , Jansson M , Maenaka K , Rowland-Jones S L , Esbjörnsson J
Published: August 2022

HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
Optimal depth of electromyographic endotracheal tube: A novel approach using video laryngoscopy
Authors: Lin Yu-Chun , Lin Ming-Chih , Lin Wen-Chun , Shen Ching-Hui
Published: August 2022

Background:

Electromyographic (EMG) endotracheal tubes with surface electrodes are used during neck surgery to prevent recurrent laryngeal nerve (RLN) injury. Proper positioning of the EMG tube is of paramount importance. In this study, we aimed to compare the use of video laryngoscopy with other methods for achieving the optimal depth of the EMG tube.

Methods:

We retrospectively enrolled 489 adult patients (with 675 nerves at risk(NAR)) undergoing surgery using the EMG endotracheal tube. Patients were categorized into three groups with: rigid laryngoscope (n = 140, NAR = 187), conventional laryngoscope (n = 262, NAR = 370), and video laryngoscope (n = 87, NAR = 118). A formula for predicting optimal depths of the EMG tube was obtained from data of the standard group with rigid laryngoscope. Depths of the EMG endotracheal tube were measured and postoperative RLN injuries were analyzed.

Results:

Based on linear regression, the formula was derived for predicting the optimal depth of EMG endotracheal tube (cm) = 11.028 + 0.635 * gender (female = 0; male = 1) + 0.069 * height (cm). Compared to conventional laryngoscope, intubation of EMG tube with video laryngoscope resulted in less discrepancy between its actual value and optimal value, and the tube depth was more correct (OR = 2.888, 95%CI = 1.753- 4.757, p < 0.001). All five postoperative permanent RLN injuries were found in the group with conventional laryngoscope.

Conclusion:

EMG endotracheal tube insertion with video laryngoscopy is superior to conventional laryngoscopy, as well as an alternative to rigid laryngoscopy. The video laryngoscopy is a novel approach to get optimal depth of EMG endotracheal tube during neck surgery.
Spontaneous Volumetric Tumor Regression During Wait-and-Scan Management of 952 Sporadic Vestibular Schwannomas
Authors: Marinelli John P. , Killeen Daniel E. , Schnurman Zane , Nassiri Ashley M. , Hunter Jacob B. , Lees Katherine A. , Lohse Christine M. , Roland Thomas J. , Golfinos John G. , Kondziolka Douglas , Link Michael J. , Carlson Matthew L.
Published: August 2022

Objective

Spontaneous tumor shrinkage during wait-and-scan management of sporadic vestibular schwannoma is generally considered an uncommon phenomenon. However, most data informing this understanding stem from single-slice linear tumor measurements taken in the axial imaging plane. The objective of the current work was to characterize the regression capacity of sporadic vestibular schwannomas using volumetric tumor measurements.

Study Design

Retrospective cohort study using slice-by-slice, three-dimensional volumetric tumor measurements.

Setting

Three tertiary referral centers.

Patients

Patients with sporadic vestibular schwannoma.

Interventions

Wait-and-scan.

Main Outcome Measures

Regression-free survival rates with regression defined as a decrease of at least 20% of the tumor volume.

Results

Among 952 patients undergoing a total of 3,505 magnetic resonance imaging studies during observation, 123 experienced volumetric tumor regression after diagnosis at a median of 1.2 years (interquartile range, 0.6–2.9 yr). Volumetric regression-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after diagnosis were 94% (92–95%; 662), 86% (83–89%; 275), and 78% (73–82%; 132), respectively. Among 405 patients who demonstrated an initial period of tumor growth but continued wait-and-scan management, 48 experienced volumetric regression at a median of 1.2 years (interquartile range, 0.8–2.6 yr) after initial growth. Volumetric regression-free survival rates at 1, 3, and 5 years after initial growth were 94% (92–97%; 260), 84% (79–89%; 99), and 75% (67–83%; 43), respectively. Ultimately, only 82 of the 952 patients studied showed exclusively volumetric tumor regression (i.e., without any periods of tumor growth) by the time of last follow-up.

Conclusion

Spontaneous volumetric tumor shrinkage during wait-and-scan management occurs more frequently than suggested by previous studies using linear tumor measurements and can even occur after previous episodes of documented tumor growth. These data further highlight the dynamic nature of vestibular schwannoma growth. To this end, the application of natural history data to patient management requires a nuanced approach that parallels the complex tumor behavior of vestibular schwannoma.
A diversified and segregated mRNA spliced-leader system in the parasitic Perkinsozoa
Authors: Alacid Elisabet , Irwin Nicholas A. T. , Smilansky Vanessa , Milner David S. , Kilias Estelle S. , Leonard Guy , Richards Thomas A.
Published: August 2022

Spliced-leader
trans
-splicing (SLTS) has been described in distantly related eukaryotes and acts to mark mRNAs with a short 5′ exon, giving different mRNAs identical 5′ sequence-signatures. The function of these systems is obscure. Perkinsozoa encompasses a diversity of parasitic protists that infect bivalves, toxic-tide dinoflagellates, fish and frog tadpoles. Here, we report considerable sequence variation in the SLTS-system across the Perkinsozoa and find that multiple variant SLTS-systems are encoded in parallel in the ecologically important Perkinsozoa parasite
Parvilucifera sinerae
. These results demonstrate that the transcriptome of
P. sinerae
is segregated based on the addition of different spliced-leader (SL) exons. This segregation marks different gene categories, suggesting that SL-segregation relates to functional differentiation of the transcriptome. By contrast, both sets of gene categories are present in the single SL-transcript type sampled from
Maranthos,
implying that the SL-segregation of the
Parvilucifera
transcriptome is a recent evolutionary innovation
.
Furthermore, we show that the SLTS-system marks a subsection of the transcriptome with increased mRNA abundance and includes genes that encode the spliceosome system necessary for SLTS-function. Collectively, these data provide a picture of how the SLTS-systems can vary within a major evolutionary group and identify how additional transcriptional-complexity can be achieved through SL-segregation.
Functional extinction of dugongs in China
Authors: Lin Mingli , Turvey Samuel T. , Han Chouting , Huang Xiaoyu , Mazaris Antonios D. , Liu Mingming , Ma Heidi , Yang Zixin , Tang Xiaoming , Li Songhai
Published: August 2022

Dugongs (
Dugong dugon
) experienced a serious population decline in China during the twentieth century, and their regional status is poorly understood. To determine their current distribution and status, we conducted a large-scale interview survey of marine resource users across four Chinese provinces and reviewed all available historical data covering the past distribution of dugongs in Chinese waters. Only 5% of 788 respondents reported past dugong sightings, with a mean last-sighting date of 23 years earlier, and only three respondents reported sightings from within the past 5 years. Historical records of dugongs peak around 1960 and then decrease rapidly from 1975 onwards; no records are documented after 2008, with no verified field observations after 2000. Based on these findings, we are forced to conclude that dugongs have experienced rapid population collapse during recent decades and are now functionally extinct in China. Our study provides evidence of a new regional loss of a charismatic marine megafaunal species, and the first reported functional extinction of a large vertebrate in Chinese marine waters. This rapid documented population collapse also serves as a sobering reminder that extinctions can occur before effective conservation actions are developed.
Biomechanical effects of the addition of a precision constraint on a collective load carriage task
Authors: Sghaier Nour , Fumery Guillaume , Fourcassié Vincent , Turpin Nicolas A. , Moretto Pierre
Published: August 2022

Team lifting is a complex and collective motor task comprising motor and cognitive components. The purpose of this research is to investigate how individual and collective performances are impacted during load transport combined with a cognitive task. Ten dyads performed a first condition in which they transported a load (CC), and a second one in which they transported the load while maintaining a ball on its top (PC). The recovery-rate, amplitude and period of the centre-of-mass (COM) trajectory were computed for the system (dyad + table = PACS). We analysed the forces and moments exerted at each joint of the upper limbs of the participants. We observed a decrease in the overall performance of the dyads during PC: (i) the velocity and amplitude of CoM
PACS
decreased by 1.7% and 5.8%, respectively, (ii) inter-participant variability of the Moment-Cost-Function and recovery rate decreased by 95%, and 19.2%, respectively during PC. Kinetic synergy analysis showed that the participants reorganized their coordination in the PC. We demonstrated that adding a precision task affects the economy of collective load carriage at the PACS level while the upper-limbs joint moments were better balanced across the paired participants for the PC.
Washing the air: enhanced condensation of water on aerosols to enable their removal
Authors: Clement C. F.
Published: August 2022

Previous theory (Clement 1985
Proc. R. Soc. A
398
, 307–339.) is applied to calculate water vapour condensation on aerosol in a chamber with a hot water base, a cooled roof and insulated walls. The fractional aerosol condensation of the water vapour is given by the surface condensation numbers,
Cn
, at the water surface and the roof. The magnitude of the aerosol condensation rate,
M
, per unit area of the base is then obtained from theory using heat transfer correlations. The central well-mixed turbulent region in the chamber is generally equilibrated, and maximum and minimum values of
M
are obtained from the limits of complete vapour condensation, and no condensation, in the boundary layers, respectively. Practically all their difference arises in the cold boundary layer where the supersaturation reaches up to 3 for no condensation. Results for
M
are obtained for water temperatures of 70 and 80°C and roof temperatures of 5–30°C, and range from 0.1 to 1.0 g m
−2
 s
−1
. Chamber properties are compared to those of the Pi chamber used to investigate cloud condensation. Estimations for aerosol growth in the chamber are made for varying chamber heights and aerosol number concentrations,
N
. Passage of air through such a chamber could effectively grow aerosols of even the highest
N
up to an easily removable size range in a matter of seconds, enabling the cleaning of polluted air, including that containing viruses.
Distinctive cross-ancestry genetic architecture for age-related macular degeneration
Authors: Gorman Bryan R. , Voloudakis Georgios , Igo Robert P. , Kinzy Tyler , Halladay Christopher W. , Bigdeli Tim B. , Zeng Biao , Venkatesh Sanan , Cooke Bailey Jessica N. , Crawford Dana C. , Markianos Kyriacos , Dong Frederick , Schreiner Patrick , Zhang Wen ,   VA Million Veteran Program,   International AMD Genomics Consortium (IAMDGC), Hadi Tamer , Anger Matthew D. , Stockwell Amy D. , Melles Ronald B. , Yin Jie , Choquet Hélène , Kaye Rebecca , Patasova Karina , Patel Praveen J. , Yaspan Brian L. , Jorgenson Eric , Hysi Pirro G. , Lotery Andrew J. , Gaziano J. Michael , Tsao Philip S. , Fliesler Steven J. , Sullivan Jack M. , Greenberg Paul B. , Wu Wen-Chih , Assimes Themistocles L. , Pyarajan Saiju , Roussos Panos , Peachey Neal S. , Iyengar Sudha K.
Published: August 2022

To effectively reduce vision loss due to age-related macular generation (AMD) on a global scale, knowledge of its genetic architecture in diverse populations is necessary. A critical element, AMD risk profiles in African and Hispanic/Latino ancestries, remains largely unknown due to lower lifetime prevalence. We combined genetic and clinical data in the Million Veteran Program with five other cohorts to conduct the first multi-ancestry genome-wide association study of AMD and discovered 63 loci (30 novel). We observe marked cross-ancestry heterogeneity at major risk loci, especially in African-ancestry populations which demonstrate a primary signal in a Major Histocompatibility Complex Class II haplotype and reduced risk at the established CFH and ARMS2/HTRA1 loci. Broadening efforts to include ancestrally-distinct populations helped uncover genes and pathways which boost risk in an ancestry-dependent manner, and are potential targets for corrective therapies.

One Sentence Summary

robing electronic health record data with genomics unearths novel paths to age-related macular degeneration.
Can a knee sleeve influence ground reaction forces and knee joint power during a step-down hop in participants following ACL reconstruction? An explanatory analysis
Authors: Sole Gisela , Pataky Todd , Hammer Niels , Lamb Peter
Published: August 2022

Purpose

Elastic knee sleeves are often worn following anterior cruciate ligament reconstruction but mechanisms underlying observed changes in movement patterns are still unclear. The aim of this study was to determine the immediate and 6-week effects of wearing a knee sleeve on ground reaction forces (GRF) and knee joint power during a step-down hop task.

Methods

Using a cross-over design, we estimated GRF and knee kinematics and kinetics during a step-down hop for 30 participants (age 26.1 [SD 6.7] years, 14 women) following ACL reconstruction (median 16 months post-surgery) with and without wearing a knee sleeve. In a subsequent randomised clinical trial, participants in the ‘Sleeve Group’ (n=9) then wore the sleeve for 6 weeks at least 1 hour daily, while a ‘Control Group’ (n=9) did not wear the sleeve. Statistical parametric mapping (SPM) was used to compare (1) GRF trajectories in the three planes as well as knee joint power between three conditions at baseline (uninjured side, unsleeved injured and sleeved injured side); (2) within-participant changes for GRF and knee joint power trajectories from baseline to follow-up between groups. We also compared discrete peak GRFs and power, rate of (vertical) force development, and mean knee joint power in the first 5% of stance phase.

Results

GRF did not differ for the (unsleeved) injured compared to the uninjured sides based on SPM analysis. Discrete variables showed lower peak anterior (propulsive) GRF for the injured side, and lower peak eccentric and concentric power, and mean power in the first 5% of stance. When wearing the sleeve on the injured side, mean power in the first 5% of stance increased significantly [mean difference (95% CIs) 1.3 (0.6, 2.0) N/BW*ht] from a concentric to an eccentric power when wearing the knee sleeve. After six weeks, the direction of change for vertical GRF differed between the groups: while the Control Group had slightly decreased forces, the Sleeve Group presented increased forces.

Conclusions

Increased knee power in the first 5% of landing when wearing the knee sleeve, combined with greater knee flexion, may indicate a protective response for ACL ruptures, most commonly occurring during that early phase of landing. The directional change of increased vertical GRF for the Sleeve group, combined with shorter stance duration at follow-up, may indicate enhanced performance when being prescribed such sleeve.
Clinical Validation of Segmentation-Based Detection of Glioma Progression
Authors: Damasceno Pablo F. , Gleason Tyler , Hawkins James , Luks Tracy , Majumdar Sharmila , Lupo Janine M. , Crane Jason C. , Villanueva-Meyer Javier E.
Published: August 2022

Purpose

To evaluate whether an AI-based method could be used routinely as part of patient care to assist in detecting non-enhancing glioma progression.

Materials and Methods

A 3D U-Net trained (n=481) and validated (n=121) to segment post-surgical lower grade gliomas was used to measure tumor volumes over time and assess progression in a clinical test set. Eight prospective and eight retrospective patients (total 72 exams) who were suspected of progression during their routine outpatient imaging were clinically assessed. Gold standards for progression were derived from clinical reports a posteriori using visual read, and radiologists were blinded to the AI decision at time of reporting.

Results

Progression assessments were presented to radiologists via an easy-to-use, interactive, and interpretable environment in under 10 minutes. Combining prospective and retrospective cases, a final sensitivity of 0.72 and specificity of 0.75 was achieved at progression detection.

Conclusions

Automated detection of glioma progression would provide valuable decision support for routine use.
Effectiveness of fourth dose COVID-19 vaccine against the Omicron variant compared to no vaccination
Authors: Zeng Jessie , Szanyi Joshua , Blakely Tony
Published: August 2022

In response to enhanced immune evasion properties of the Omicron SARS-CoV-2 variant and waning COVID-19 vaccine effectiveness (VE), several jurisdictions have rolled out fourth dose vaccination programs. Using a system of logistic regression equations and VE estimates for a fourth dose relative to a third dose reported in an Israeli study, we estimated absolute vaccine effectiveness for third and fourth doses of mRNA COVID-19 vaccine (c.f. no vaccination) against Omicron, by clinical outcome. We found that a fourth dose restores or even enhances protection conferred by a third dose at the same time since vaccination.
Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources
Authors: Sturkenboom Miriam , Messina Davide , Paoletti Olga , de Burgos-Gonzalez Airam , García-Poza Patricia , Huerta Consuelo , Llorente- García Ana , Martin-Perez Mar , Martinez Maria , Martin Ivonne , Overbeek Jetty , Padros-Goossens Marc , Souverein Patrick , Swart Karin , Klungel Olaf , Gini Rosa
Published: August 2022

Setting

Primary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, Spain

Participants

Individuals with complete data for the year preceding enrollment or those born at the start of observation time. The cohort comprised 25,720,158 subjects.

Interventions

First and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine.

Main outcome measures

29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells’ palsy, chilblain-like lesions death, erythema multiforme, Guillain Barré Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE)

Results

12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare <10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia.

Conclusion

We showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.
Impact of galvanic vestibular stimulation electrode current density on brain current flow patterns: Does electrode size matter?
Authors: Troung Dennis Q , Guillen Alexander , Nooristani Mujda , Maheu Maxime , Champoux Francois , Datta Abhishek
Published: August 2022

Background

Galvanic vestibular stimulation (GVS) uses at least one electrode placed on the mastoid process with one or multiple placed over other head areas to stimulate the vestibular system. The exact electrode size used is not given much importance in the literature and has not been reported in several studies. In a previous study, we compared the clinical effects of using different electrode sizes (3 cm2 and 35 cm2) with placebo but with the same injected current, on postural control. We observed significant improvement using the smaller size electrode but not with the bigger size electrode. The goal of this study was to simulate the current flow patterns with the intent to shed light and potentially explain the experimental outcome.

Methods

We used an ultra-high-resolution structural dataset and developed a model to simulate the application of different electrode sizes. We considered current flow in the brain and in the vestibular labyrinth.

Results

Our simulation results verified the focality increase using smaller electrodes that we postulated as the main reason for our clinical effect. The use of smaller size electrodes in combination with the montage employed also result in higher induced electric field (E-field) in the brain.

Conclusions

Electrode size and related current density is a critical parameter to characterize any GVS administration as the choice impacts the induced E-field. It is evident that the higher induced E-field likely contributed to the clinical outcome reported in our prior study.
Allosteric Inhibition of the T Cell Receptor by a Designed Membrane Ligand
Authors: Ye Yujie , Morita Shumpei , Wilhelm Kiera B. , Groves Jay T. , Barrera Francisco N.
Published: August 2022

The T cell receptor (TCR) is a complex molecular machine that directs the activation of T cells, allowing the immune system to fight pathogens and cancer cells. Despite decades of investigation, the molecular mechanism of TCR activation is still controversial. One of the leading activation hypotheses is the allosteric model. This model posits that binding of pMHC at the extracellular domain triggers a dynamic change in the transmembrane (TM) domain of the TCR subunits, which leads to signaling at the cytoplasmic side. We sought to test this hypothesis by creating a TM ligand for TCR. Previously we described a method to create a soluble peptide capable of inserting into membranes and bind to the TM domain of the receptor tyrosine kinase EphA2 (Alves et al., eLife 2018). Here we show that the approach is generalizable to complex membrane receptors, by designing a membrane ligand for TCR. We observed that the designed peptide caused a reduction of Lck phosphorylation of TCR at the CD3ζ subunit. As a result, in the presence of this Peptide Inhibitor of TCR (PITCR), the proximal signaling cascade downstream of TCR activation was significantly dampened in T cells. Co-localization and co-immunoprecipitation results in DIBMA native nanodiscs confirmed that PITCR was able to bind to the TCR. We propose that PITCR binds into a crevice present between the TM helices of the CD3ζ and CD3ε(δ) subunits. Our results additionally indicate that PITCR disrupts the allosteric changes in the compactness of the TM bundle that occur upon TCR activation, lending support to the allosteric TCR activation model. The TCR inhibition achieved by PITCR might be useful to treat inflammatory and autoimmune diseases and to prevent organ transplant rejection, as in these conditions aberrant activation of TCR contributes to disease.
Effects of HSP70 chaperones Ssa1 and Ssa2 on Ste5 scaffold and the mating mitogen-activated protein kinase (MAPK) Pathway in Saccharomyces cerevisiae
Authors: Farley Francis W. , McCully Ryan R. , Maslo Paul B. , Yu Lu , Sheff Mark A. , Sadeghi Homayoun , Elion Elaine A.
Published: August 2022

Ste5 is a prototype of scaffold proteins that regulate activation of mitogen-activated protein kinase (MAPK) cascades in all eukaryotes. Ste5 associates with many proteins including Gβγ (Ste4), Ste11 MAPKKK, Ste7 MAPKK, Fus3 and Kss1 MAPKs, Bem1, Cdc24. Here we show that Ste5 also associates with heat shock protein 70 chaperone (Hsp70) Ssa1 and that Ssa1 and its ortholog Ssa2 are together important for Ste5 function and efficient mating responses. The majority of purified overexpressed Ste5 associates with Ssa1. Loss of Ssa1 and Ssa2 has deleterious effects on Ste5 abundance, integrity, and localization particularly when Ste5 is expressed at native levels. The status of Ssa1 and Ssa2 influences Ste5 electrophoresis mobility and formation of high molecular weight species thought to be phosphorylated, ubiquitinylated and aggregated and lower molecular weight fragments. A Ste5 VWA domain mutant with greater propensity to form punctate foci has reduced predicted propensity to bind Ssa1 near the mutation sites and forms more punctate foci when Ssa1 Is overexpressed, supporting a dynamic protein quality control relationship between Ste5 and Ssa1. Loss of Ssa1 and Ssa2 reduces activation of Fus3 and Kss1 MAPKs and FUS1 gene expression and impairs mating shmoo morphogenesis. Surprisingly, ssa1, ssa2, ssa3 and ssa4 single, double and triple mutants can still mate, suggesting compensatory mechanisms exist for folding. Additional analysis suggests Ssa1 is the major Hsp70 chaperone for the mating and invasive growth pathways and reveals several chaperone-network proteins required for mating morphogenesis.
A shift in the pathotype diversity and complexity of Phytophthora sojae, causal agent of root and stem rot of soybean, in Brazil
Authors: Batista I.C.A. , Silva M.P.C. , Silva Junior A. L. , Gonzalez M.P. , Camargo M. P. , Figueiredo A. , Hora Junior B.T. , Mizubuti E.S.G.
Published: August 2022

Soybean root rot disease caused by the oomycete Phytophthora sojae is particularly destructive, once it is a host-specific pathogen that can infect and kill soybean plants at any stage of growth. The use of resistant cultivars is the most effective method of controlling the disease. Therefore, monitoring changes in the adaptability of P. sojae population to resistance genes (Rps) is extremely important not only from an epidemiological point of view but mainly for the management of the disease and durability of the Rps genes. We investigated the pathotypes of 40 isolates of P. sojae, sampled from the region with a higher incidence of soybean root rot in Brazil, using a set of 14 soybean differentials. The first study investigating pathotype diversity in Brazil was published in 2013. A decade later, we are reporting a major shift in pathotype diversity and complexity. This information can be useful for breeding programs aiming at developing soybean cultivars with resistance to root and stem rot and optimize the usage of genes and germplasm.
Redefining the structure of tip-links in hair-cells
Authors: Kaur Veerpal , Ghosh Sanat K. , Bhatia Tripta , Rakshit Sabyasachi
Published: August 2022

Tip-link, the gating-spring in hearing, modulates the mechanoelectrotransduction process and protects the hearing sensory machineries from overexcited auditory inputs. Tip-links are formed by two exceptionally long cadherins, cadherin-23 and protocadherin-15. It is proposed that both the cadherins first independently form cis-dimers through lateral interactions and finally, engage in trans-interactions to form the heterotetrameric assembly in tip-links. In fact, the molecular details of the protocadherin cis-dimers are well-understood. However, little structural and molecular details are known for independent cis-dimer of cadherin-23. Using photo-induced cross-linking of unmodified proteins in solution and on lipid-membranes, we observed no trace of cadherin-23 cis-dimers, rather we captured trans-homodimers of cadherin-23. We thus, redefine the tip-link structure where protocadherin-15 remains as cis-dimers, however, two individual cadherin-23 binds to protocadherin-15 cis-dimer for tip linking.
Emerging fish pathogens Lactococcus petauri and L. garvieae in Nile tilapia (Oreochromis niloticus) farmed in Brazil
Authors: Egger Renata Catão , Rosa Júlio César Câmara , de Pádua Santiago Benites , de Oliveira Barbosa Fernanda , Zerbini Mariana Taíse , Tavares Guilherme Campos , Figueiredo Henrique César Pereira
Published: August 2022

Lactococcosis in fish has been associated with Lactococcus garvieae and the recently described L. petauri. However, the relevance of these emerging fish pathogens to Nile tilapia still requires thorough understanding. This study investigated lactococcosis outbreaks in Nile tilapia on Brazilian farms and characterized the isolates through molecular identification of the bacterial species, multilocus sequence typing (MLST) analysis, virulence to Nile tilapia, and antimicrobial susceptibility. Lactococcosis outbreaks were monitored from 2019 to 2022 throughout Brazil. The outbreaks occurred mainly during warmer months, and co-infections were observed in four farms, whereas concurrent bacterial infections were identified in all farms. Since the sequence of the 16S rRNA was not capable of differentiating between L. petauri and L. garvieae, Lactococcus spp. isolates were identified at the species level using the gyrB gene sequence. In total, 30 isolates were classified as L. petauri and two as L. garvieae. All L. petauri isolates were grouped in ST24, except for one isolate which belonged to the newly described ST47. A new ST was also described for the L. garvieae isolates identified, ST46. Furthermore, L. petauri ST24 and ST47 were characterized as singletons, whereas L. garvieae ST46 was grouped with ST16 and ST17 and formed CC17. For the challenge trial, an L. petauri ST24 isolate was chosen considering that this MLST lineage was the most frequently observed. L. petauri was reisolated from challenged Nile tilapia, confirming the pathogenicity of this bacterium to Nile tilapia. The infection in the fish progressed very rapidly, and within 48 h post-challenge clinical signs and the first mortalities were observed. The estimated LD50 was 5.74 × 103 CFU 15 days post-challenge. Provisional epidemiological cutoff values were determined for L. petauri for six antimicrobial agents from different drug classes. All isolates were characterized as wild type (WT) for neomycin and oxytetracycline, whereas 96.67 % of the isolates were characterized as WT for amoxicillin, erythromycin, and florfenicol, and 83.33 % were WT for norfloxacin. Of the 14 outbreaks analyzed, 12 were caused by L. petauri and two by L. garvieae. The gyrB gene sequence was used to differentiate L. petauri from L. garvieae and allowed for the correct identification of these pathogens. Two MSLT lineages of L. petauri were identified and ST24 was observed in different regions of the country, illustrating a rapid expansion of this bacterial lineage.

Highlights of the manuscript

Lactococcus petauri is pathogenic to Nile tilapia.

The MLST lineage most observed was L. petauri ST24, indicating its adaption to infect Nile tilapia.

The analysis of the gyrB gene sequence allowed for the correct identification of L. petauri and L. garvieae.
The Nematode Oscheius tipulae as A Genetic Model for Programmed DNA Elimination
Authors: Dockendorff Thomas C. , Estrem Brandon , Reed Jordan , Simmons James R. , Zadegan Sobhan Bahrami , Zagoskin Maxim V. , Terta Vincent , Seaberry Erin , Wang Jianbin
Published: August 2022

Programmed DNA elimination (PDE) is a notable exception to the paradigm of genome integrity. In metazoa, PDE often occurs during early embryogenesis, coincident with germline to somatic cell differentiation. During PDE, portions of genomic DNA are lost, resulting in reduced somatic genomes. Recent studies have described the sequences lost and chromosome behavior in metazoa. However, a system for studying the mechanisms and consequences of PDE in metazoa is lacking. Here, we established a functional and genetic model for PDE in the free-living nematode Oscheius tipulae, a member of the Rhabditidae family, which includes Caenorhabditis elegans. O. tipulae was recently suggested to eliminate DNA. Using staged embryos, we show that O. tipulae PDE occurs during embryogenesis at the 2-16 cell stages, similar to the human/pig parasitic nematode Ascaris. We identified a conserved motif, named Sequence For Elimination (SFE), for all 12 break sites on the six chromosomes at the junction of retained and eliminated DNA. SFE mutants exhibit a “fail-to-eliminate” phenotype only at the modified sites. END-seq revealed that breaks can occur at multiple positions within the SFE, with extensive end resection followed by telomere addition to both retained and eliminated ends. We identified through END-seq in the wild-type embryos, genome sequencing of SFE mutants, and comparative genomics of 23 wild isolates a large number of functional SFEs at the chromosome ends. We suggest these alternative SFEs provide flexibility in the sequences eliminated and a fail-safe mechanism for PDE. These studies establish O. tipulae as a new, attractive model to study the mechanisms and consequences of PDE in a metazoan.
Leveraging microfluidic dielectrophoresis to distinguish compositional variations of lipopolysaccharide inE. coli
Authors: Wang Qianru , Kim Hyungseok , Halvorsen Tiffany M. , Chen Sijie , Hayes Christopher S. , Buie Cullen R.
Published: August 2022

Lipopolysaccharide (LPS) is the unique feature that composes the outer leaflet of the Gram-negative bacterial cell envelope. Variations in LPS structures affect a number of physiological processes, including outer membrane permeability, antimicrobial resistance, recognition by the host immune system, biofilm formation, and interbacterial competition. Rapid characterization of LPS properties is crucial for studying the relationship between these LPS structural changes and bacterial physiology. However, current assessments of LPS structures require LPS extraction and purification followed by cumbersome proteomic analysis. This paper demonstrates one of the first high-throughput and noninvasive strategies to directly distinguishEscherichia coliwith different LPS structures. Using a combination of three-dimensional insulator-based dielectrophoresis (3DiDEP) and cell tracking in a linear electrokinetics assay, we elucidate the effect of structural changes inE. coliLPS oligosaccharides on electrokinetic mobility and polarizability. We show that our platform is sufficiently sensitive to detect LPS structural variations at the molecular level. To correlate electrokinetic properties of LPS with the outer membrane permeability, we further examined effects of LPS structural variations on bacterial susceptibility to colistin, an antibiotic known to disrupt the outer membrane by targeting LPS. Our results suggest that microfluidic electrokinetic platforms employing 3DiDEP can be a useful tool for isolating and selecting bacteria based on their LPS glycoforms. Future iterations of these platforms could be leveraged for rapid profiling of pathogens based on their surface LPS structural identity.
H3K36M provokes cellular plasticity to drive aberrant glandular formation and squamous carcinogenesis
Authors: Ko Eun Kyung , Anderson Amy , Zou Jonathan , Huang Sijia , Cho Sohyun , Alawi Faizan , Prouty Stephen , Lee Vivian , Ge Kai , Seykora John T. , Capell Brian C.
Published: August 2022

Epigenetic dysregulation is pervasive in cancer, frequently impairing normal tissue development and differentiation1. Beyond alterations in histone modifying enzymes, “oncohistone” mutations have been described across a variety of cancers2-4, although the in vivo effects and underlying mechanisms behind these observations have not been well- studied and remain unclear. Here, by inducing the in vivo expression of histone H3.3 carrying a lysine to methionine (K to M) mutation at position 36 (H3K36M) in self- renewing stratifying epithelial tissues, we show that the H3K36M oncohistone dramatically disrupts normal epithelial differentiation, leading to extensive tissue dysplasia characterized by a significant increase in mitotic, proliferative basal stem cells. Furthermore, this differentiation blockade promotes increased cellular plasticity and enrichment of alternate cell fates, and in particular the aberrant generation of excessive glandular tissue including both hypertrophic salivary, sebaceous, and meibomian glands. Upon carcinogen stress, H3K36M mice display markedly enhanced squamous tumorigenesis. These aberrant phenotypic and gene expression manifestations are associated with global loss of H3K36me2 and concomitant gain of H3K27me3. Collectively, these results have revealed a previously unknown critical role for H3K36 methylation in both the in vivo maintenance of proper epithelial cell fate decisions and the prevention of squamous carcinogenesis. Additionally, they suggest that H3K36 methylation modulation may offer new avenues for the regulation of numerous common disorders driven by over- or under-active glandular function.
IL-2 secreting T helper cells promote EF B cell maturation via intrinsic regulation of B cell mTOR/AKT/Blimp-1 axis
Authors: Faliti Caterina E. , Mesina Maria , Choi Jinyong , Bélanger Simon , Schief William R. , Crotty Shane
Published: August 2022

B cells are fundamental players in the secretion of antibodies and the establishment of long-term memory-based immunity. Integration of signals from TLRs, BCR stimulation, and T helper cell-derived cytokines can all dictate B cell differentiation and their metabolic state. However, while important components of this interaction have been described, the precise signaling networks and mechanisms regulating B cell fate are not fully understood. Here, we elucidated the role of interleukin-2 (IL-2) in determining early B cell fate decisions and inducing plasma cell reprogramming. Using both in vitro culture systems and in vivo models of immunization, alongside CRISPR-based genome editing of antigen-specific T and B cells, we identify a role for T helper-secreted IL-2 in inducing high expression of Irf4 and Blimp-1 in activated cognate B cells, enhancing plasma cell differentiation. Induction of this cascade promotes their differentiation and drives metabolic reprogramming through the regulation of mTOR/AKT/Blimp-1 axis.