bluuebunny/crossref_metadata_2025 huggingface dataset:
Consensus statement and recommendations on the treatment of COVID-19: 2021 update
Authors: Ko Hsin-Kuo , Yu Wen-Kuang , Pan Sheng-Wei , Chen Wei-Chih , Yang Kuang-Yao , Lin Yi-Tsung , Wang Fu-Der , Yang Muh-Hwa , Chen Yuh-Min ,   on behalf of Research Center for Epidemic Prevention—National Yang Ming Chiao Tung University (RCEP-NYCU)
Published: September 2021

Many treatments including antiviral and non-antiviral drugs, and critical care are considered for the management of coronavirus disease 2019 (COVID-19). Practice recommendations need to be updated and graded according to the critical evaluation of rapidly emerging literature. In June 2020, Research Center for Epidemic Prevention—National Yang Ming Chiao Tung University formed a task group comprising infectious disease clinicians, pulmonologists, and intensivists with varied areas of expertise. The steering committee prioritized questions and outcomes. The keywords for the searches were COVID-19 and prone position, extracorporeal membrane oxygenation (ECMO), noninvasive positive pressure ventilation (NIPPV), remdesivir, lopinavir, hydroxychloroquine/chloroquine (HCQ/CQ), azithromycin, corticosteroid, tocilizumab, convalescent plasma therapy, and intravenous immunoglobin (IVIG). A systematic review of peer-reviewed literature was performed by the consensus panel. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used in assessing the certainty of evidence and making recommendations. The effects of COVID-19 treatments on mortality and clinical improvement were summarized in 11 tables, and GRADE was presented to define the strength and quality of evidence for recommendation. The consensus recommended that prone position implanted in COVID-19 patients with hypoxic respiratory failure (IIC), careful selection for the support of ECMO (IIB), NIPPV being feasible but a risk of staff contamination (IIC), remdesivir generally administered in mild-to-moderate COVID-19 patients (IA), the use of dexamethasone in critically ill COVID-19 patients (IA), and the use of tociliziumab in hospitalized severe/critical COVID-19 patient with elevated markers of systemic inflammation (IA). The consensus recommended against the use of lopinavir/ritonavir (IB), HCQ/CQ (IA), azithromycin (IA), convalescent plasma therapy (IA), and IVIG (IA). The inception of the consensus and task group has provided much-needed evidence of the efficacy and safety of various therapies for the management of COVID-19 patients, and make a description about the benefits and harms for most treatments.
Time in Therapeutic Range Significantly Impacts Survival and Adverse Events in Destination Therapy Patients
Authors: Macaluso Gregory P. , Pagani Francis D. , Slaughter Mark S. , Milano Carmelo A. , Feller Erika D. , Tatooles Antone J. , Rogers Joseph G. , Wieselthaler Georg M.
Published: September 2021

The study aim was to examine the impact time in therapeutic range (TTR, International Normalized Ratio [INR] 2.0–3.0) has on survival and adverse events in patients receiving the HeartWare HVAD System in the ENDURANCE and ENDURANCE Supplemental Trials. Evaluable subjects (n = 495) had >1 INR value recorded 1–24 months postimplant and were categorized as: low TTR (10–39%), moderate TTR (40–69%), and high TTR (≥70%). Baseline characteristics, adverse events, and survival were analyzed. Low TTR patients experienced higher rates of major bleeding (1.69 vs. 0.54 events per patient year [EPPY]; p < 0.001), GI bleeding (1.22 vs. 0.38 EPPY; p < 0.001), stroke (0.47 vs. 0.17 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.02), infection (1.44 vs. 0.69 EPPY; p < 0.001), and renal dysfunction (0.23 vs. 0.05 EPPY; p < 0.001) compared with high TTR. Moderate TTR had higher rates of major bleeding (0.75 vs. 0.54 EPPY; p < 0.001), thrombus requiring exchange (0.05 vs. 0.01 EPPY; p = 0.007), cardiac arrhythmia (0.32 vs. 0.24 EPPY; p = 0.04), and infection (0.90 vs. 0.69 EPPY; p = 0.001) compared with high TTR. Two year survival was greater among moderate and high versus low cohorts (Log-rank p = 0.001). The significant reduction in morbidity and mortality in destination therapy (DT) HVAD patients with well-controlled TTR (≥70%) emphasizes the importance of vigilant anticoagulation management.
Physician Prescribing and Referral Patterns in Children with Cerebral Visual Impairment
Authors: Rice Melissa L. , Sandoval Monica A. , Castleberry Katherine M. , Schwartz Terry L.
Published: September 2021

SIGNIFICANCE

Cerebral visual impairment (CVI) is the leading cause of visual impairment in the developed world. Providing children with CVI with the appropriate treatment ensures the best possible visual outcome and potentially improves quality of life.

PURPOSE

The purpose of this study was to determine physician prescribing and visual rehabilitation referral patterns in children with CVI.

METHODS

A retrospective chart review was completed on children with CVI examined at Cincinnati Children's Hospital Medical Center from January 1, 2008, to March 1, 2018. Significant refractive error warranting correction was determined using the American Academy of Ophthalmology Preferred Guidelines and the American Association for Pediatric Ophthalmology and Strabismus Vision Screening Committee Guidelines. The CVI Range was used as a surrogate to categorize CVI severity.

RESULTS

A total of 194 children were included. Sixty-eight (35%) had refractive error warranting correction and were prescribed glasses (group RC), 99 (51%) did not have refractive error warranting correction and were not prescribed glasses (group NRNC), 20 (10%) had refractive error warranting correction but were not prescribed glasses (group RNC), and 7 (4%) did not have refractive error warranting correction but were prescribed glasses (group NRC). There was greater than one-line Snellen equivalent difference between group RC (20/156) and group RNC (20/221). There was greater than six-line Snellen equivalent difference between group NRNC (20/149) and group NRC (20/35). Mean CVI Range score 2 values for each group were 5.9, 4.6, 4.8, and 7.1.

CONCLUSIONS

Children with less severe CVI were less likely to have significant refractive error but given glasses. Despite significant refractive error, children with more severe CVI were not prescribed glasses. Children with very low visual function were not prescribed glasses as frequently, possibly limiting their visual rehabilitation. Providers should ensure that all children with CVI are correctly prescribed glasses to provide the best possible visual outcome.
The Interplay Between Stress and Fullness in Patients With Functional Dyspepsia and Healthy Controls: An Exploratory Experience Sampling Method Study
Authors: Klaassen Tim , Vork Lisa , Smeets Fabiënne G.M. , Troost Freddy J. , Kruimel Joanna W. , Leue Carsten , Masclee Ad A.M. , Keszthelyi Daniel
Published: September 2021

Objective

Fullness is a cardinal symptom in functional dyspepsia (FD). The use of real-time symptom assessment might provide more insight into factors, such as daily stress, that can influence fullness. Therefore, this study aimed to use the experience sampling method (a real-time, repeated-measurement method making use of repeated questionnaires available at random moments for a limited amount of time) to assess the association between stress and fullness in patients with FD and healthy controls (HCs).

Methods

Thirty-five patients with FD (25 female, mean age = 44.7 years) and 34 HCs (24 female, mean age = 44.1 years) completed the experience sampling method (a maximum of 10 random moments per day) for 7 consecutive days. Stress and fullness were rated on an 11-point Numeric Rating Scale. Data between patients with FD and HCs were statistically compared using a Student samples t test and linear mixed-effects models with repeated measures (level 1) nested within participants (level 2).

Results

Average fullness scores were 2.23 (standard error = 0.37) points higher in patients with FD compared with HCs (p < .001). Average stress scores were 1.37 (standard error = 0.30) points higher in patients with FD compared with HCs (p = .002).

In FD, fullness scores increased with 0.14 for every 1-point increase in concurrent stress scores (p = .010). Fullness scores at t = 0 increased with 0.12 for every 1-point increase in stress scores at t = −1 (p = .019). T = 0 stress scores were not associated with change in t = −1 fullness scores. No associations between concurrent symptom scores were found for HCs.

Conclusions

Concurrent and preceding stress scores are positively associated with fullness scores in patients with FD, but not in HCs. These findings indicate that increased levels of stress may precede feelings of fullness in patients with FD.

Trial registration

ClinicalTrials.gov identifier NCT04204421.
Prediction Model for Tumor Volume Nadir in EGFR-mutant NSCLC Patients Treated With EGFR Tyrosine Kinase Inhibitors
Authors: Nishino Mizuki , Lu Junwei , Hino Takuya , Vokes Natalie I. , Jänne Pasi A. , Hatabu Hiroto , Johnson Bruce E.
Published: September 2021

Purpose:

In patients with advanced non–small cell lung cancer (NSCLC) and oncogenic driver mutations treated with effective targeted therapy, a characteristic pattern of tumor volume dynamics with an initial regression, nadir, and subsequent regrowth is observed on serial computed tomography (CT) scans. We developed and validated a linear model to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKI).

Materials and Methods:

Patients with EGFR-mutant advanced NSCLC treated with EGFR-TKI as their first EGFR-directed therapy were studied for CT tumor volume kinetics during therapy, using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir in a training cohort of 34 patients, and then was validated in an independent cohort of 84 patients.

Results:

The linear model for tumor nadir prediction was obtained in the training cohort of 34 patients, which utilizes the baseline tumor volume before initiating therapy (V0) to predict the volume decrease (mm3) when the nadir volume (Vp) was reached: V0−Vp=0.717×V0−1347 (P=2×10−16; R
2=0.916). The model was tested in the validation cohort, resulting in the R
2 value of 0.953, indicating that the prediction model generalizes well to another cohort of EGFR-mutant patients treated with EGFR-TKI. Clinical variables were not significant predictors of tumor volume nadir.

Conclusion:

The linear model was built to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR-TKIs, which provide an important metrics in treatment monitoring and therapeutic decisions at nadir such as additional local abrasive therapy.
A flexible anatomical set of mechanical models for the organ of Corti
Authors: Berger Jorge , Rubinstein Jacob
Published: September 2021

We build a flexible platform to study the mechanical operation of the organ of Corti (OoC) in the transduction of basilar membrane (BM) vibrations to oscillations of an inner hair cell bundle (IHB). The anatomical components that we consider are the outer hair cells (OHCs), the outer hair cell bundles, Deiters cells, Hensen cells, the IHB and various sections of the reticular lamina. In each of the components we apply Newton’s equations of motion. The components are coupled to each other and are further coupled to the endolymph fluid motion in the subtectorial gap. This allows us to obtain the forces acting on the IHB, and thus study its motion as a function of the parameters of the different components. Some of the components include a nonlinear mechanical response. We find that slight bending of the apical ends of the OHCs can have a significant impact on the passage of motion from the BM to the IHB, including critical oscillator behaviour. In particular, our model implies that the components of the OoC could cooperate to enhance frequency selectivity, amplitude compression and signal to noise ratio in the passage from the BM to the IHB. Since the model is modular, it is easy to modify the assumptions and parameters for each component.
Antibacterial and osteogenic activities of clindamycin-releasing mesoporous silica/carboxymethyl chitosan composite hydrogels
Authors: Sungkhaphan Piyarat , Thavornyutikarn Boonlom , Kaewkong Pakkanun , Pongkittiphan Veerachai , Pornsuwan Soraya , Singhatanadgit Weerachai , Janvikul Wanida
Published: September 2021

Conventional treatment of jaw bone infection is often ineffective at controlling bacterial infection and enhancing bone regeneration. Biodegradable composite hydrogels comprised of carboxymethyl chitosan (CMCS) and clindamycin (CDM)-loaded mesoporous silica nanoparticles (MCM-41), possessing dual antibacterial activity and osteogenic potency, were developed in the present study. CDM was successfully loaded into both untreated and plasma-treated MCM-41 nanoparticles, denoted as (p)-MCM-41, followed by the incorporation of each of CDM-loaded (p)-MCM-41 into CMCS. The resulting CDM-loaded composite hydrogels, (p)-MCM-41-CDM-CMCS, demonstrated slow degradation rates (about 70% remaining weight after 14-day immersion), while the CDM-free composite hydrogel entirely disintegrated after 4-day immersion. The plasma treatment was found to improve drug loading capacity and slow down initial drug burst effect. The prolonged releases of CDM from both (p)-MCM-41-CDM-CMCS retained their antibacterial effect against
Streptococcus sanguinis
for at least 14 days
in vitro. In vitro
assessment of osteogenic activity showed that the CDM-incorporated composite hydrogel was cytocompatible to human mesenchymal stem cells (hMSCs) and induced hMSC mineralization via p38-dependent upregulated alkaline phosphatase activity. In conclusion, novel (p)-MCM-41-CDM-CMCS hydrogels with combined controlled release of CDM and osteogenic potency were successfully developed for the first time, suggesting their potential clinical benefit for treatment of intraoral bone infection.
Parameterized neural ordinary differential equations: applications to computational physics problems
Authors: Lee Kookjin , Parish Eric J.
Published: September 2021

This work proposes an extension of neural ordinary differential equations (NODEs) by introducing an additional set of ODE input parameters to NODEs. This extension allows NODEs to learn multiple dynamics specified by the input parameter instances. Our extension is inspired by the concept of parameterized ODEs, which are widely investigated in computational science and engineering contexts, where characteristics of the governing equations vary over the input parameters. We apply the proposed parameterized NODEs (PNODEs) for learning latent dynamics of complex dynamical processes that arise in computational physics, which is an essential component for enabling rapid numerical simulations for time-critical physics applications. For this, we propose an encoder–decoder-type framework, which models latent dynamics as PNODEs. We demonstrate the effectiveness of PNODEs on benchmark problems from computational physics.
Shapes of a filament on the surface of a bubble
Authors: Prasath S. Ganga , Marthelot Joel , Govindarajan Rama , Menon Narayanan
Published: September 2021

The shape assumed by a slender elastic structure is a function both of the geometry of the space in which it exists and the forces it experiences. We explore, by experiments and theoretical analysis, the morphological phase space of a filament confined to the surface of a spherical bubble. The morphology is controlled by varying bending stiffness and weight of the filament, and its length relative to the bubble radius. When the dominant considerations are the geometry of confinement and elastic energy, the filament lies along a geodesic and when gravitational energy becomes significant, a bifurcation occurs, with a part of the filament occupying a longitude and the rest along a curve approximated by a latitude. Far beyond the transition, when the filament is much longer than the diameter, it coils around the selected latitudinal region. A simple model with filament shape as a composite of two arcs captures the transition well. For better quantitative agreement with the subcritical nature of bifurcation, we study the morphology by numerical energy minimization. Our analysis of the filament’s morphological space spanned by one geometric parameter, and one parameter that compares elastic energy with body forces, may provide guidance for packing slender structures on complex surfaces.
The measure of spatial position within groups that best predicts predation risk depends on group movement
Authors: Lambert Poppy J. , Herbert-Read James E. , Ioannou Christos C.
Published: September 2021

Both empirical and theoretical studies show that an individual's spatial position within a group can impact the risk of being targeted by predators. Spatial positions can be quantified in numerous ways, but there are no direct comparisons of different spatial measures in predicting the risk of being targeted by real predators. Here, we assess these spatial measures in groups of stationary and moving virtual prey being attacked by three-spined sticklebacks (
Gasterosteus aculeatus
). In stationary groups, the limited domain of danger best predicted the likelihood of attack. In moving groups, the number of near neighbours was the best predictor but only over a limited range of distances within which other prey were counted. Otherwise, measures of proximity to the group's edge outperformed measures of local crowding in moving groups. There was no evidence that predators preferentially attacked the front or back of the moving groups. Domains of danger without any limit, as originally used in the selfish herd model, were also a poor predictor of risk. These findings reveal that the collective properties of prey can influence how spatial position affects predation risk, via effects on predators' targeting. Selection may therefore act differently on prey positioning behaviour depending on group movement.
Photorhabdus hindustanensis sp. nov., Photorhabdus akhurstii subsp. akhurstii subsp. nov., and Photorhabdus akhurstii subsp. bharatensis subsp. nov., isolated from Heterorhabditis entomopathogenic nematodes
Authors: Machado Ricardo A. R. , Somvanshi Vishal S. , Muller Arthur , Kushwah Jyoti , Bhat Chaitra G.
Published: September 2021

Two Gram-negative, rod-shaped bacteria, H1T and H3T, isolated from the digestive tract of Heterorhabditis entomopathogenic nematodes were biochemically and molecularly characterized to determine their taxonomic positions. The 16S rRNA gene sequences of these strains indicate that they belong to the Gammaproteobacteria, to the family

Morganellaceae

, and to the

Photorhabdus

genus. Deeper analyses using whole genome-based phylogenetic reconstructions show that strains H1T and H3T are closely related to

P. akhurstii

DSM 15138T, to

P. hainanensis

DSM 22397T, and to

P. namnaonensis

PB45.5T. In silico genomic comparisons confirm these observations and show that strain H1T shares 70.6, 66.8, and 63.5 % digital DNA–DNA hybridization (dDDH) with

P. akhurstii

DSM 15138T,

P. hainanensis

DSM 22397T, and

P. namnaonensis

PB45.5T, respectively, and that strain H3T shares 76.6, 69.4, and 59.2 % dDDH with

P. akhurstii

DSM 15138T,

P. hainanensis

DSM 22397T, and

P. namnaonensis

PB45.5T, respectively. Physiological and biochemical characterization reveals that these two strains differ from most of the validly described

Photorhabdus

species and from their more closely related taxa. Given the clear phylogenetic separations, that the threshold to discriminate species and subspecies is 70 and 79% dDDH, respectively, and that strains H1T and H3T differ physiologically and biochemically from their more closely related taxa, we propose to classify H1T and H3T into new taxa as follows: H3T as a new subspecies within the species

P. akhurstii

, and H1T as a new species within the

Photorhabdus

genus, in spite that H1T shares 70.6 % dDDH with

P. akhurstii

DSM 15138T, score that is slightly higher than the 70 % threshold that delimits species boundaries. The reason for this is that H1T and

P. akhurstii

DSM 15138T cluster apart in the phylogenetic trees and that dDDH scores between strain H1T and other

P. akhurstii

strains are lower than 70 %. Hence, the following names are proposed: Photorhabdus hindustanensis sp. nov. with the type strain H1T (=IARI-SGMG3T,=KCTC 82683T=CCM 9150T=CCOS 1975T) and

P. akhurstii

subsp. bharatensis subsp. nov. with the type strain H3T (=IARI-SGHR2T=KCTC 82684T=CCM 9149T=CCOS 1976T). These propositions automatically create

P. akhurstii

subsp. akhurstii subsp. nov. with DSM 15138T as the type strain (currently classified as

P. akhurstii

).
Novosphingobium decolorationis sp. nov., an aniline blue-decolourizing bacterium isolated from East Pacific sediment
Authors: Chen Xiunuan , Dong Bingxia , Chen Ting , Ren Na , Wang Jing , Xu Ying , Yang Jifang , Zhu Sidong , Chen Jigang
Published: September 2021

Aniline blue-decolourizing bacterial strain 502str22T, isolated from sediment collected in the East Pacific, was subjected to characterization by a polyphasic taxonomic approach. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain 502str22T belongs to the genus

Novosphingobium

, with closely related type strains ‘

Novosphingobium profundi

’ F72T (97.6%),

N. mathurense

SM117T (97.1%) and

N. arvoryzae

Jyi-02T (97.0%). Digital DNA–DNA hybridization and average nucleotide identity values between strain 502str22T and closely related type strains were 20.3–24.8% and 74.1–81.9%, respectively. The major cellular fatty acid (>10%) was C18:1
ω7c. The polar lipid profile consisted of a mixture of phosphatidylcholine, one sphingoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylmonomethylethanolamine. The DNA G+C content of strain 502str22T was 65.5 mol%. The polyphasic taxonomic results indicated that strain 502str22T represents a novel species of the genus

Novosphingobium

, for which the name Novosphingobium decolorationis sp. nov is proposed. The type strain is 502str22T (=KCTC 82134T= MCCC 1K04799 T).
Antibody response to a fourth mRNA Covid-19 vaccine boost in weak responder kidney transplant recipients
Authors: Caillard Sophie , Thaunat Olivier , Benotmane Ilies , Masset Christophe , Blancho Gilles
Published: September 2021

The US FDA has recently authorized immunocompromised people to receive a third dose of mRNA Covid-19 vaccine following the two-doses regimen to further boost protection. Unfortunately, a non-negligible proportion of people treated with immunosuppressive drugs either do not respond or show only a weak response after a third boost and should, therefore, still be considered at risk of severe Covid-19. As of June 2021, we were granted the opportunity to offer a fourth vaccine dose to French solid organ transplant recipients who still showed a weak antibody response after the third dose. In this multicenter study, we demonstrate that that the protection conferred by a fourth dose is adequate for the majority of kidney transplant recipients.
Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications
Authors: Stone Mars , Grebe Eduard , Sulaeman Hasan , Di Germanio Clara , Dave Honey , Kelly Kathleen , Biggerstaff Brad , Crews Bridgit O. , Tran Nam , Jerome Keith R. , Denny Thomas N. , Hogema Boris , Destree Mark , Jones Jefferson M. , Thornburg Natalie , Simmons Graham , Krajden Mel , Kleinman Steve , Dumont Larry J. , Busch Michael P.
Published: September 2021

SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.
Microsaccades as a marker not a cause for attention-related modulation
Authors: Yu Gongchen , Herman James P. , Katz Leor N. , Krauzlis Richard J.
Published: September 2021

Recent evidence suggests that microsaccades are causally linked to the attention-related modulation of neurons – specifically, that microsaccades towards the attended location are required for the subsequent changes in firing rate. These findings have raised questions about whether attention-related modulation is due to different states of attention as traditionally assumed or might instead be a secondary effect of microsaccades. Here, in two rhesus macaques, we tested the relationship between microsaccades and attention-related modulation in the superior colliculus, a brain structure crucial for allocating attention. We found that attention-related modulation emerged even in the absence of microsaccades, was already present prior to microsaccades towards the cued stimulus, and persisted through the suppression of activity that accompanied all microsaccades. Nonetheless, consistent with previous findings, we also found significant attention-related modulation when microsaccades were directed towards, rather than away from, the cued location. Thus, in contrast to the prevailing hypothesis, microsaccades are not necessary for attention-related modulation, at least not in the superior colliculus. They do, however, provide an additional marker for the state of attention, especially at times when attention is shifting from one location to another.
Aggressive but not reproductive boldness in male green anole lizards correlates with baseline vasopressin activity
Authors: Kabelik David , Julien Allison R. , Waddell Brandon R. , Batschelett Mitchell A. , O’Connell Lauren A.
Published: September 2021

Across species, individuals within a population differ in their level of boldness in social encounters with conspecifics. This boldness phenotype is often stable across both time and social context (e.g., reproductive versus agonistic encounters). Various neural and hormonal mechanisms have been suggested as underlying these stable phenotypic differences, which are often also described as syndromes, personalities, and coping styles. Most studies examining the neuroendocrine mechanisms associated with boldness examine subjects after they have engaged in a social interaction, whereas baseline neural activity that may predispose behavioral variation is understudied. The present study tests the hypotheses that physical characteristics, steroid hormone levels, and baseline variation in Ile3-vasopressin (VP, a.k.a., Arg8-vasotocin) signaling predispose boldness during social encounters. Boldness in agonistic and reproductive contexts was extensively quantified in male green anole lizards (Anolis carolinensis), an established research organism for social behavior research that provides a crucial comparison group to investigations of birds and mammals. We found high stability of boldness across time, and between agonistic and reproductive contexts. Next, immunofluorescence was used to colocalize VP neurons with phosphorylated ribosomal protein S6 (pS6), a proxy marker of neural activity. Vasopressin-pS6 colocalization within the paraventricular and supraoptic nuclei of the hypothalamus was inversely correlated with boldness of aggressive behaviors, but not of reproductive behaviors. Our findings suggest that baseline vasopressin release, rather than solely context-dependent release, plays a role in predisposing individuals toward stable levels of displayed aggression toward conspecifics by inhibiting behavioral output in these contexts.
Stress-induced changes in inflammatory and atherosclerosis markers during official basketball games in professional coaches
Authors: Zerva Athina , Chronaki Marianna , Rojas Gil Andrea Paola , Paschalidis Nikolaos , Andriopoulos Panagiotis , Tsironi Maria
Published: September 2021

Objective

Top-level competitive sports coaches repeatedly cope with situations of acute stress in order to succeed and manage high team performance. Occupational stress-induced biochemical and immune system markers are not well studied for this specific group of people. The purpose of this study was to evaluate stress-induced alterations of inflammatory markers and atherosclerosis risk factors during an official basketball game in top-level professional basketball coaches (head and assistant).

Methods

Blood samples and vital signs were obtained from 27 healthy coaches (Greek A1 Men’s National Basketball League), 30 minutes before and 30 minutes after the games. We performed a full blood count and measured inflammatory cytokines, atherosclerosis markers and cortisol levels. Data were statistically analysed using two-tailed paired and independent samples t-tests and Pearson’s Correlations.

Results

Post-game neutrophils (NEU) and apolipoprotein B (ApoB) levels were significantly increased while lymphocytes (LYM) were significantly decreased in comparison to pre-game values. Blood pressure (systolic and diastolic) levels were considered as a pre-hypertension state at both measurements. We found significant alterations between head and assistant coaches in diastolic blood pressure and cortisol levels after the game. Cortisol was negatively correlated to inflammatory cytokine levels and positively correlated with ApoB levels.

Conclusions

Game-induced acute psychological stress initiates an aseptic inflammatory response in top-level professional coaches and can be related to the atherosclerosis pathways posing as an acute as well as chronic health threat for top-level coaches who have to deal with long periods of stressful working conditions.

SUMMARY BOX

What are the new findings?

Top-level basketball games induce an aseptic inflammatory response in professional basketball coaches mainly manifested by increased levels of peripheral blood neutrophils

The response to game conditions also included elevated levels of ApoB after the game that were positively correlated with cortisol levels

Stressful game conditions over a long season of games could pose as a serious health issue for professional coaches

Health monitoring for professional coaches in top-level competitive sports such as basketball should be implemented more often with particular focus on inflammatory and atherosclerosis markers
Predictors of real-world parents’ acceptance to vaccinate their children against the COVID-19
Authors: Galanis Petros , Vraka Irene , Siskou Olga , Konstantakopoulou Olympia , Katsiroumpa Aglaia , Moisoglou Ioannis , Kaitelidou Daphne
Published: September 2021

Background

As the COVID-19 pandemic continues to threaten public health, the vaccination of children against the disease appears to be a key factor to control the pandemic.

Objective

To investigate the prevalence of parents who have vaccinated their children against the COVID-19 and the factors influencing this decision.

Methods

We conducted a web-based cross-sectional study in Greece during the first week of September 2021. The study questionnaire was distributed through social media and a convenience sample was obtained. Only parents with children aged 12-17 years old could participate in the study. We collected socio-demographic data of parents and we measured their attitudes towards vaccination and COVID-19 pandemic.

Results

Study population included 656 parents. Mean age of parents was 45.5 years, while most of them were mothers with a high level of education. Regarding vaccination, 27.1% of parents had their children vaccinated against the COVID-19, while almost all children had a complete vaccination history (98.9%). The most important reasons for decline of COVID-19 vaccination were doubts about the safety and effectiveness of COVID-19 vaccines (45.3%) and fear of side effects (36.6%). Regarding the information about the COVID-19 vaccines, parents showed more trust in family doctors than in scientists and the government. Multivariate regression analysis identified that increased parents’ age, increased trust in COVID-19 vaccines, and positive attitude of parents towards vaccination had a positive effect on children’s vaccination.

Conclusions

Understanding the factors influencing parents’ decision to vaccinate their children against the COVID-19 is crucial to increase the COVID-19 vaccination coverage rate. Implementation of public health policies is necessary to spread knowledge about COVID-19 vaccines and to regain vaccine confidence.
Sex-dependent parameters of social behavior show marked variations between distinct laboratory mouse strains and their mixed offspring
Authors: Kopachev Natalia , Netser Shai , Wagner Shlomo
Published: September 2021

Background

The survival of individuals of gregarious species depends on their ability to properly form social interactions. In humans, atypical social behavior is a hallmark of several psychopathological conditions, such as depression and autism spectrum disorder, many of which have sex-specific manifestations. Various strains of laboratory mice are used to reveal the mechanisms mediating typical and atypical social behavior in mammals.

Methods

Here we used three social discrimination tests (social preference, social novelty preference, and sex preference) to characterize social behavior in males and females of three widely used laboratory mouse strains (C57BL/6J, BALB/c, and ICR).

Results

We found marked sex- and strain-specific differences in the preference exhibited by subjects in a test-dependent manner. Interestingly, we found some characteristics that were strain-dependent, while others were sex-dependent. Moreover, even in the social preference test, where both sexes of all strains prefer social over object stimuli, we revealed sex- and strain-specific differences in the behavioral dynamics. We then cross-bred C57BL/6J and BALB/c mice and demonstrated that the offspring of such cross-breeding exhibit a profile of social behavior which is different from both parental strains and depends on the specific combination of parental strains.

Conclusions

We conclude that social behavior of laboratory mice is highly sex- and strain-specific and strongly depends on genetic factors.
Myelin imaging of the basal forebrain in first-episode psychosis
Authors: Park Min Tae M. , Jeon Peter , French Leon , Dempster Kara , Chakravarty M. Mallar , MacKinley Michael , Richard Julie , Khan Ali R. , Théberge Jean , Palaniyappan Lena
Published: September 2021

Cholinergic dysfunction has been implicated in the pathophysiology of psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (∼ 31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used Magnetic Resonance Spectroscopy (1H-MRS) and transcriptomic data to support our findings. We used a cytoarchitectonic atlas of the BF to map the nuclei and obtained measures of myelin (quantitative T1, or qT1 as myelin surrogate) and microstructure (axial diffusion; AxD). In a clinical sample (n=85; 29 healthy controls, 56 first-episode psychosis), we found significant correlations between qT1 and 1H-MRS-based dorsal anterior cingulate choline in healthy controls, while this relationship was disrupted in FEP. Case-control differences in qT1 and AxD were observed in the Ch1-3, with increased qT1 (reflecting reduced myelin content) and AxD (reflecting reduced axonal integrity). We found clinical correlates between left NBM qT1 with manic symptom severity, and AxD with negative symptom burden in FEP. Intracortical and subcortical myelin maps were derived and correlated with BF myelin. BF-cortical and BF-subcortical myelin correlations demonstrate known projection patterns from the BF. Using data from the Allen Human Brain Atlas, cholinergic nuclei showed significant enrichment for schizophrenia and depression-related genes. Cell-type specific enrichment indicated enrichment for cholinergic neuron markers as expected. Further relating the neuroimaging correlations to transcriptomics demonstrated links with cholinergic receptor genes and cell type markers of oligodendrocytes and cholinergic neurons, providing biological validity to the measures. These results provide genetic, neuroimaging, and clinical evidence for cholinergic dysfunction in schizophrenia and other psychiatric disorders such as depression.
AtRBOHC/RHD2 vesicular delivery to the apical plasma membrane domain during root hair development
Authors: Kuběnová Lenka , Tichá Michaela , Šamaj Jozef , Ovečka Miroslav
Published: September 2021

Arabidopsis root hairs develop as long tubular extensions from the rootward pole of trichoblasts and exert polarized tip growth. The establishment and maintenance of root hair polarity is a complex process involving the local apical production of reactive oxygen species (ROS) generated by NADPH oxidase RESPIRATORY BURST OXIDASE HOMOLOG PROTEIN C/ROOT HAIR DEFECTIVE 2 (AtRBOHC/RHD2). It has been shown that loss-of-function rhd2 mutants have short root hairs that are unable to elongate by tip growth, and this phenotype was fully complemented by GFP-RHD2 expressed under the RHD2 promoter. However, the spatiotemporal mechanism of AtRBOHC/RHD2 subcellular redistribution and delivery to the plasma membrane (PM) during root hair initiation and tip growth are still unclear. Here, we used advanced microscopy for detailed qualitative and quantitative analysis of vesicular compartments containing GFP-RHD2 and characterization of their movements in developing bulges and growing root hairs. These compartments, identified by an independent marker such as the trans-Golgi network (TGN), deliver GFP-RHD2 to the apical PM domain, the extent of which correlates with the stage of root hair formation. Movements of TGN/early endosomes, but not late endosomes, were affected in the bulging domains of the rhd2-1 mutant. Finally, we reveal that accumulation in the growing tip, docking, and incorporation of TGN compartments containing GFP-RHD2 to the apical PM of root hairs requires structural sterols. These results help clarify the mechanism of polarized AtRBOHC/RHD2 targeting, maintenance, and recycling at the apical PM domain, coordinated with different developmental stages of root hair initiation and growth.

One-sentence summary

Advanced microscopy and quantitative analysis of vesicular TGN compartments revealed that delivering GFP-RHD2 to the apical plasma membrane domains of developing bulges and growing root hairs requires structural sterols.
Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro
Authors: Zhang Bingjie , Srivastava Avi , Mimitou Eleni , Stuart Tim , Raimondi Ivan , Hao Yuhan , Smibert Peter , Satija Rahul
Published: September 2021

New technologies that profile chromatin modifications at single-cell resolution offer enormous promise for functional genomic characterization. However, the sparsity of these measurements and the challenge of integrating multiple binding maps represent significant challenges. Here we introduce scCUT&Tag-pro, a multimodal assay for profiling protein-DNA interactions coupled with the abundance of surface proteins in single cells. In addition, we introduce scChromHMM, which integrates data from multiple experiments to infer and annotate chromatin states based on combinatorial histone modification patterns. We apply these tools to perform an integrated analysis across nine different molecular modalities in circulating human immune cells. We demonstrate how these two approaches can characterize dynamic changes in the function of individual genomic elements across both discrete cell states and continuous developmental trajectories, nominate associated motifs and regulators that establish chromatin states, and identify extensive and cell type-specific regulatory priming. Finally, we demonstrate how our integrated reference can serve as a scaffold to map and improve the interpretation of additional scCUT&Tag datasets.
Spatial and temporal diversity of astrocyte phenotypes in Spinocerebellar ataxia type 1 mice
Authors: Rosa Juao-Guilherme , Hamel Katherine , Sheeler Carrie , Borgenheimer Ella , Gilliat Stephen , Soles Alyssa , Ghannoum Fares , Sbrocco Kaelin , Handler Hillary P. , Rainwater Orion , Kang Ryan , Cvetanovic Marija
Published: September 2021

While astrocyte heterogeneity is an important feature of the healthy brain, less is understood about spatiotemporal heterogeneity of astrocytes in brain disease. Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a CAG repeat expansion mutation in the gene Ataxin1 (ATXN1). We characterized astrocytes across disease progression in the four clinically relevant brain regions, cerebellum, brainstem, hippocampus, and motor cortex of Atxn1154Q/2Q mice, a knock-in mouse model of SCA1. We found brain region specific changes in astrocyte density, GFAP expression and area, early in disease and prior to neuronal loss. Expression of astrocytic core homeostatic genes was also altered in a brain-region specific manner and correlated with neuronal activity indicating that astrocytes may compensate or exacerbate neuronal dysfunction in a brain region specific manner. Late in disease, expression of astrocytic homeostatic genes was reduced in all four brain regions indicating loss of astrocyte functions. We observed spatiotemporal changes in microglia with no obvious correlation with spatiotemporal astrocyte alterations indicating a complex orchestration of glial phenotypes in disease. These results support spatiotemporal diversity of glial phenotypes as an important feature of the brain disease that may contribute to SCA1 pathogenesis in a brain-region and disease stage-specific manner.
Random Forest Factorization Reveals Latent Structure in Single Cell RNA Sequencing Data
Authors: Brenerman Boris M. , Shapiro Benjamin D. , Schatz Michael C. , Battle Alexis
Published: September 2021

Single-cell RNA sequencing data contain patterns of correlation that are poorly captured by techniques that rely on linear estimation or assumptions of Gaussian behavior. We apply random forest regression to scRNAseq data from mouse brains, which identifies the co-regulation of genes within specific cellular contexts. By analyzing the estimators of the random forest, we identify several novel candidate gene regulatory networks and compare these networks in aged and young mice. We demonstrate that cell populations have cell-type specific phenotypes of aging that are not detected by other methods, including the collapse of differentiating oligodendrocytes but not precursors or mature oligodendrocytes.
Core genes can have higher recombination rates than accessory genes within global microbial populations
Authors: Steinberg Asher Preska , Lin Mingzhi , Kussell Edo
Published: September 2021

Recombination is essential to microbial evolution1–4, and is involved in the spread of antibiotic resistance, antigenic variation, and adaptation to the host niche5–8. Yet quantifying the impact of homologous recombination on different gene classes, which is critical to understanding how selection acts on variation to shape species diversity and genome structure, remains challenging. This is largely due to the dynamic nature of bacterial genomes, whose high intraspecies genome content diversity9 and complex phylogenetic relationships10–12 present difficulties for inferring rates of recombination, particularly for rare genes. In this work, we apply a computationally efficient, non-phylogenetic approach13,14 to measure homologous recombination rates in the core and accessory genome (genes present in all strains and only a subset of strains, respectively) using >100,000 whole genome sequences from 12 microbial species. Our analysis suggests that even well-resolved sequence clusters sampled from global populations interact with overlapping gene pools, which has implications for the role of population structure in genome evolution. We show that in a majority of species, core genes have shorter coalescence times and higher recombination rates than accessory genes, and that gene frequency is often positively correlated with increased recombination. Our results provide a new line of population genomic evidence supporting the hypothesis that core genes are under strong, purifying selection15–17, and indicate that homologous recombination may play a key role in increasing the efficiency of selection in those parts of the genome most conserved within each species.
Molecular and cellular adaptations in hippocampal parvalbumin neurons mediate behavioral responses to chronic social stress
Authors: Bhatti Dionnet L. , Medrihan Lucian , Chen Michelle X. , Jin Junghee , McCabe Kathryn , Wang Wei , Azevedo Estefania P. , Ledo Jose H. , Kim Yong
Published: September 2021

Parvalbumin-expressing interneurons (PV neurons) maintain inhibitory control of local circuits implicated in behavioral responses to environmental stressors. However, the roles of molecular and cellular adaptations in PV neurons in stress susceptibility or resilience have not been clearly established. Here, we show behavioral outcomes of chronic social defeat stress (CSDS) are mediated by differential neuronal activity and gene expression in hippocampal PV neurons in mice. Using in vivo electrophysiology and chemogenetics, we find increased PV neuronal activity in the ventral dentate gyrus is required and sufficient for behavioral susceptibility to CSDS. PV neuron-selective translational profiling indicates mitochondrial oxidative phosphorylation is the most significantly altered pathway in stress-susceptible versus resilient mice. Among differentially expressed genes associated with stress-susceptibility and resilience, we find Ahnak, an endogenous regulator of L-type calcium channels which are implicated in the regulation of mitochondrial function and gene expression. Notably, Ahnak deletion in PV neurons impedes behavioral susceptibility to CSDS. Altogether, these findings indicate behavioral effects of chronic stress can be controlled by selective modulation of PV neuronal activity or a regulator of L-type calcium signaling in PV neurons.