bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicle fusion visualized by cryo-electron microscopy
Authors: Morandi Mattia I , Busko Petro , Ozer-Partuk Efrat , Khan Suman , Zarfati Giulia , Elbaz-Alon Yael , Abou Karam Paula , Napso Shogan Tina , Ginini Lana , Gil Ziv , Regev-Rudzki Neta , Avinoam Ori
Published: August 2022

Extracellular vesicles (EVs) transfer bioactive molecules between cells in a process reminiscent of enveloped viruses. EV cargo delivery is thought to occur by protein-mediated and pH-dependent membrane fusion of the EV and the cellular membrane. However, there is a lack of methods to identify the fusion proteins and resolve their mechanism. We developed and benchmarked an in vitro biophysical assay to investigate EV membrane fusion. The assay was standardized by directly comparing EV and viral fusion with liposomes. We show that EVs and retroviruses fuse with liposomes mimicking the membrane composition of the late endosome in a pH- and protein-dependent manner. Moreover, we directly visualize the stages of membrane fusion using cryo-electron tomography. We find that, unlike most retroviruses, EVs remain fusogenic after acidification and reneutralization. These results provide novel insights into the EV cargo delivery mechanism and an experimental approach to identify the EV fusion machinery.
Estimation of Discrete Games with Weak Assumptions on Information
Authors: Magnolfi Lorenzo , Roncoroni Camilla
Published: August 2022

We propose a method to estimate static discrete games with weak assumptions on the information available to players. We do not fully specify the information structure of the game but allow instead for all information structures consistent with players knowing their own payoffs. To make this approach tractable, we adopt as a solution concept Bayes correlated equilibrium (BCE). We characterize the sharp identified set under BCE and unrestricted equilibrium selection, and find that in simple games with limited variation in covariates identified sets are informative. In an application, we estimate a model of entry in the Italian supermarket industry and quantify the effect of large malls on local supermarkets. Estimates and predictions differ from those obtained under more restrictive assumptions.
Echo Chambers
Authors: Cookson J Anthony , Engelberg Joseph E , Mullins William
Published: August 2022

We find evidence of selective exposure to confirmatory information among 400,000 users on the investor social network StockTwits. Self-described bulls are five times more likely to follow a user with a bullish view of the same stock than are self-described bears. Consequently, bulls see 62 more bullish messages and 24 fewer bearish messages than bears do over the same 50-day period. These “echo chambers” exist even among professional investors and are strongest for investors who trade on their beliefs. Finally, beliefs formed in echo chambers are associated with lower ex post returns, more siloing of information, and more trading volume.
Navigating the Intersection of Scepticism, Gender Blindness, and Ethnocentricity in the Asylum Tribunal: the Urgent Case For Empathy Enhancement
Authors: O’Nions Helen
Published: August 2022

Adopting a critical legal studies position, informed by procedural justice theory, this article argues that the intersection of scepticism with ethnocentric and gender-blind expectations of behaviour from tribunal judges impacts the fairness of proceedings, to the particular detriment of women asylum-seekers in the UK. Procedural justice theorists argue that fair procedures help court users to accept adverse outcomes. Yet an attempt to apply these principles to the asylum tribunal where there is no common experience and where decision-making occurs within a culture of disbelief proves futile. This analysis is informed by the experiences of 14 women who appealed an adverse asylum decision before the tribunal. It is evident that whilst judicial discretion allows judges to make procedural enhancements, this leads to inconsistency (itself a marker of unfairness) and the opportunity for an appellant to rebut assumptions through meaningful participation is rarely available. It is argued that principles of procedural justice need to be tailored in the specific context of asylum. Empathy-informed reasoning is urgently required. This needs to be embedded, through training, guidelines, and greater accountability. Without such enhancement, the tribunal appears to lack impartiality and serves only to replicate the flaws of initial decision-making.
Fidelity to Best Practices in EPA Implementation: Outcomes Supporting Use of the Core Components Framework From the University of Virginia Entrustable Professional Activity Program
Authors: Keeley Meg G. , Bray Megan J. , Bradley Elizabeth B. , Peterson Christine M. , Waggoner-Fountain Linda A. , Gusic Maryellen E.
Published: August 2022

Problem

The rapid expansion of entrustable professional activity (EPA) assessment programs has led to calls to ensure fidelity in implementation and integrity in meeting the goals of competency-based medical education. Initiated in July 2017, in advance of the articulated core components of EPA implementation, this article describes the structure and outcomes of the University of Virginia (UVA) EPA Program and provides support for the identified essential components.

Approach

The UVA EPA Program includes workplace assessments by residents/fellows, attending faculty, and master assessors (MAs), experienced clinicians who assess students across disciplines and clinical settings. All assessors participate in formal professional development and provide verbal and written comments to support their supervision ratings. The Entrustment Committee, composed of 12 MAs, uses a shared mental model and aggregates all assessor data to make a high-stakes summative entrustment decision about students’ readiness to assume the role of an acting intern.

Outcomes

Since 2017, over 2,000 assessors have completed 56,969 EPA assessments for 1,479 students. Ninety-four percent of assessments have been done during the clerkship phase. Residents/fellows have completed a mean of 18 assessments, attending faculty a mean of 27, and MAs a mean of 882. Seventy-four percent of observed encounters involved patients with acute concerns with or without a co-morbid condition. Fifty percent of assessments occurred in inpatient and 32% in ambulatory settings. Eighty-seven percent of assessments contained narrative comments with more than 100 characters.

Next Steps

Planned next steps will include earlier identification of students who require individualized learning to promote the development of skills related to EPAs, expansion of the remediation program to enable more students to engage in a clinical performance mastery elective, and creation of targeted professional development for assessors to reinforce the tenets of the EPA program.
Differential Contributions of Parental Warmth and Mindfulness to Child Executive Function and Pediatric Type 1 Diabetes Management
Authors: Yeo Anna J. , Ledsham Victoria , Halpern Leslie F. , Lin Betty , Riddick Linda , Sima Daniela , Wohlfahrt Kristine M. , Jones Nancy
Published: August 2022

Objective:

Positive parenting (e.g., parental warmth, mindful parenting) has been posited to promote effective pediatric type 1 diabetes mellitus (T1DM) management. This promotive effect may partly be conferred by fostering child self-regulatory development, such as executive function (EF). However, no research has examined whether better child EF serves as a mechanism underlying associations between positive parenting and child blood glucose levels (HbA1c). Moreover, it is unclear whether mindful parenting offers a unique benefit beyond that of parental warmth—a key pillar of effective parental involvement in T1DM management.

Methods:

Primary caregivers of children with T1DM (N = 101; Mage = 12.02) reported on parenting behaviors and child EF. Children's medical information was obtained through chart review. Path analysis was used to examine direct and indirect relations in the cross-sectional data.

Results:

The path analysis indicated that only parental warmth, not mindful parenting, was significantly associated with lower HbA1c. Both parental warmth and mindful parenting were significantly related to better child EF, but child EF did not mediate the associations between parenting and HbA1c.

Conclusion:

Parental warmth may constitute a key parenting behavior promoting effective pediatric T1DM management. Enhancing parental warmth may be an important target of interventions aiming to improve HbA1c. Although child EF was unrelated to HbA1c in this sample, given positive associations between parental warmth and mindfulness and child EF, longitudinal research is warranted to examine whether these positive parenting behaviors may confer long-term benefits for T1DM self-management through improved EF.
Efficacy and Safety of Shortened Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Hui Jiaojiao , Bai Ting , Liang Le , He Qingqing , Tian Nani , Li Xiao , Yang Rui , Zhu Lin
Published: August 2022

To update the efficacy and safety of short-term (≤3 months) dual antiplatelet therapy (DAPT) and standard (6–12 months) DAPT in patients undergoing percutaneous coronary intervention. In addition, we also explored the duration of DAPT in patients at high bleeding risk (HBR). In PubMed, Embase, and Cochrane Library, we electronically searched among all the studies from the establishment of the database to December 8, 2021, for randomized controlled trials (RCTs). Nine randomized controlled trials (45,661 patients) ultimately met the inclusion criteria. The pooled analysis revealed that, compared with standard DAPT, ≤3-month DAPT significantly reduced major adverse cardiovascular event {hazard ratio (HR) = 0.89, 95% confidence interval (CI) [0.82–0.97]}, all-cause mortality [HR = 0.88, 95% CI (0.78–0.99)], cardiovascular mortality [HR = 0.79, 95% CI (0.65–0.97)], major bleeding [HR = 0.72, 95% CI (0.56–0.93)], and any bleeding [HR = 0.57, 95% CI (0.50–0.66)], while no significant differences in the risk of myocardial infarction, stent thrombosis, and stroke. In patients with HBR, the results showed that ≤3-month DAPT significantly reduced major bleeding [HR = 0.35, 95% CI (0.14–0.88)] and any bleeding [HR = 0.53, 95% CI (0.41–0.67)] compared with standard DAPT, while the risk of other outcomes was not statistically different. In conclusion, this study showed that ≤3-month DAPT may be a valid option for most patients after percutaneous coronary intervention. Because reductions in major adverse cardiovascular event, all-cause mortality, and cardiovascular mortality were not seen in patients with HBR, this also highlights the need for specific studies in these patients about optimal duration of antiplatelet therapy.
Dofetilide Dose Reductions and Discontinuation in Obese Compared with Nonobese Patients
Authors: Anderson Keith , Greenlee Katie , Matteo Maria , Wilkoff Bruce
Published: August 2022

Dofetilide is an antiarrhythmic agent and primarily eliminated renally. Initial dosing is determined by creatinine clearance, calculated by total body weight in the Cockcroft–Gault equation. To date, there is no evidence comparing the dosing of dofetilide in obese versus nonobese patients. We conducted a retrospective review of 217 adults admitted for dofetilide loading to evaluate the tolerability of dofetilide in obese versus nonobese patients. The rate of dose adjustments, including dose reductions and discontinuations, was compared between obese versus nonobese patients in unadjusted and adjusted analyses. Electrocardiograms were collected throughout the loading period, and calculation of QT intervals was performed. Obese patients did not have a significantly higher frequency of dose adjustments compared with nonobese patients (51.5% vs. 44.8%, P = 0.33). Using total body weight to determine starting doses was associated with great odds of dose adjustments compared with ideal body weight (OR 3.69, P = 0.002) and adjusted body weight (OR 4.46, P = 0.02). Men required significantly fewer dose adjustments compared with women on multivariate analysis (OR 0.53, P = 0.03). Obesity is not associated with an increase in the rate of dose adjustments. Total body weight should be used with caution to calculate initial doses of dofetilide in women because it may lead to a higher rate of dose adjustments compared with ideal body weight. Additional studies are needed to confirm the optimal method for selecting starting doses of dofetilide in women, particularly those with a body mass index of ≥30.
Comparison of Extrapyramidal Symptoms Among Outpatients With Schizophrenia on Long-Acting Injectable Antipsychotics
Authors: Zhand Naista , Labelle Alain , Ghanem Dana , Gujral Preet , Han Tommy , Huneault Gabrielle , Jain Gaurav Kumar , Robertson Carrie
Published: August 2022

Background

Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics.

Methods

Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances.

Results

Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone.

Conclusions

Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the “maximum dose” of paliperidone could be considered and higher doses used with the same cautions as low-average doses.
The Use of Brexpiprazole Combined With a Stimulant in Adults With Treatment-Resistant Attention-Deficit/Hyperactivity Disorder
Authors: Reimherr Frederick W. , Gift Thomas E. , Steans Tammy A. , Reimherr Matthew L. , Rosenberg Leon I. , Wilson Melissa , Marchant Barrie K.
Published: August 2022

Background

This is the first controlled pharmacologic study in either adults or children with uncomplicated, treatment-resistant attention-deficit/hyperactivity disorder (ADHD). This study augmented stimulant therapy with the atypical antipsychotic brexpiprazole. The Food and Drug Administration preapproved primary outcome measure (Conners' Adult ADHD Rating Scale [CAARS]) showed no drug-placebo differences. Often studies showing no efficacy on the prestudy, defined primary outcome variable go unpublished. While this is decried, publishing studies with equivocal results remains rare. This reanalysis highlights trends in secondary measures having implications for treatment and research regarding treatment resistant ADHD.

Methods

Initially, 559 stimulant-naive and 174 prior stimulant nonresponders received methylphenidate osmotic-release oral system, dexmethylphenidate hydrochloride, lisdexamfetamine, or mixed amphetamine salts. After 5 weeks, 168 stimulant-naive patients and 68 prior stimulant nonresponders who failed treatment were randomized to brexpiprazole or placebo in a 2:1 ratio while the remaining were on the stimulant. Outcome was measured with the CAARS, Montgomery-Asberg Depression Rating Scale, Beck Depression Inventory, Clinical Global Impression, and the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS). The WRAADDS contains 2 factors: attention and emotional dysregulation.

Results

Stimulant-naive patients showed no improvement with adjunctive brexpiprazole. Prior stimulant nonresponders displayed no brexpiprazole effect on the CAARS, Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory. In contrast, the WRAADDS detected a trend in treatment benefit, primarily through emotional dysregulation symptoms. Adverse effects on brexpiprazole and placebo were equivalent.

Conclusions

Brexpiprazole might be effective in ADHD adults who are nonresponders to 2 or more stimulants. Future trials in treatment-resistant ADHD should use a 1:1 randomization and use a measure of ADHD symptoms that includes emotional dysregulation.
Group Medical Visits Versus Usual Care for Illness Perception and Hypertension: A Randomized Pilot Study
Authors: Acehan Orhan , Bozdemir Nafiz , Özcan Sevgi , Duran Olgun , Kurdak Hatice
Published: August 2022

Despite separate evidence regarding illness perception (IP) and group medical visits (GMVs) for hypertension, research on both is limited. Here, we have assessed and compared the effectiveness of GMVs and usual care (UC) on IP and blood pressure (BP) in patients with hypertension. This was a two-group parallel randomized controlled study with 1:1 allocation. Patients with essential hypertension on antihypertensive medication and no cognitive impairments were screened for BP control status and eligibility. A web-based program randomly assigned them to the GMV and UC groups. Group medical visits were held once a month for 3 months. Primary and secondary outcome measures included improvements in IP and BP control. Among 152 participants, 40 and 43 were assigned to the GMV and UC groups, respectively. The control group had a 9.3% dropout rate. The chronic timeline and illness coherence improved significantly in the intervention group (p < .01). Systolic BP in the intervention group decreased significantly compared with that of the control group (Δ: −18.8 ± 18.4 mm Hg vs. Δ: −10.6 ± 12.5 mm Hg, p = .025). The participation in GMVs had a significant association with the odds of an increase in BP regulation (OR 3.8, 95% confidence interval 1.4–10.3, p = .007). Therefore, GMVs may be feasible for BP control in hypertensive patients with similar characteristics.
Healthcare delivery and recovery after critical illness
Authors: Hope Aluko A. , McPeake Joanne
Published: August 2022

Purpose of review

To summarize improvements and innovations in healthcare delivery which could be implemented to improve the recovery experience after critical illness for adult survivors and their families.

Recent findings

For survivors of critical illness, the transitions in care during their recovery journey are points of heightened vulnerability associated with adverse events. Survivors of critical illness often have errors in the management of their medications during the recovery period. A multicomponent intervention delivered for 30 days that focused on four key principles of improved recovery care after sepsis care was associated with a durable effect on 12-month rehospitalization and mortality compared with usual care. A recent multicentre study which piloted integrating health and social care for critical care survivors demonstrated improvements in health-related quality of life and self-efficacy at 12 months. Multiple qualitative studies provide insights into how peer support programmes could potentially benefit survivors of critical illness by providing them mechanism to share their experiences, to give back to other patients, and to set more realistic expectations for recovery.

Future research could focus on exploring safety outcomes as primary endpoints and finding ways to develop and test implementation strategies to improve the recovery after critical illness.
Applying the RIME Framework to Level Nurse Practitioner Curriculum Competencies
Authors: Johnson Heather L. , Beatty Jonathan R. , Archer Holly R. , Best Natasha I. , Trautmann Jennifer L. , Williams Janice K. , Williamson John M. , Seibert Diane C. , Taylor Laura A.
Published: August 2022

Background:

Nurse practitioner (NP) faculty assess student acquisition of knowledge through examinations, simulation, and clinical performance.

Problem:

Developing appropriately leveled curriculum, assessments, and clinical expectations that accurately capture student maturation presents a challenge.

Approach:

The Reporter, Interpreter, Manager, Educator (RIME) provided the framework for doctor of nursing practice NP curriculum redesign to enhance student performance and content mastery. Faculty used a gap analysis approach, iteratively leveling specialty content, course competencies, examination questions, simulation cases, and clinical expectations using the building blocks of RIME.

Outcomes:

Objective scores on student evaluations for clinical courses exceeded the threshold established, including 83% of simulation encounters. Faculty implemented targeted methods to remediate areas of underperformance.

Conclusions:

Structuring the course competencies and preceptor feedback around RIME made it easier to pinpoint specific deficiencies and target remediation. It also helped guide discussions about the minimum acceptable standard for student performance.
Multiarterial Phase Acquisition in Gadoxetic Acid–Enhanced Liver MRI for the Detection of Hypervascular Hepatocellular Carcinoma in High-Risk Patients
Authors: Kim Jae Hyun , Yoon Jeong Hee , Bae Jae Seok , Park Sungeun , Han Seungchul , Lee Jeong Min
Published: August 2022

Objectives

The aim of this study was to compare compressed sensing (CS) and view sharing (VS) techniques for single breath-hold multiarterial phase imaging with respect to image quality and focal liver observation detectability during gadoxetic acid–enhanced magnetic resonance imaging in patients at high risk for hepatocellular carcinoma (HCC).

Materials and Methods

A total of 385 patients who underwent gadoxetic acid–enhanced magnetic resonance imaging, including triple arterial phases using either CS (n = 224) or VS (n = 161) techniques, were retrospectively included. Among them, 117 patients had 171 focal liver observations (median diameter, 1.3 cm), which were classified according to Liver Imaging Reporting and Data System version 2018. The acquisition rate of optimally timed late arterial phase (LAP) was assessed, and image quality, including respiratory motion artifact and observation conspicuity, was rated on a 4-point scale by 3 radiologists. The Mann-Whitney U test and nonparametric test for repeated measures data were used for image quality and observation conspicuity analysis. The jackknife alternative free-response receiver operating characteristics method was used to compare the observation detectability between the 2 techniques.

Results

The CS technique showed significantly higher acquisition rate of optimally timed LAP without transient severe motion (82.1% [184/224] vs 71.4% [115/161]; P = 0.013) than the VS technique. The CS technique also demonstrated significantly improved overall image quality (3.42 ± 0.70 vs 2.97 ± 0.61; P < 0.001) compared with the VS technique. Regarding the detection of hyperenhancing observations, there was no significant difference between the figure of merits of CS and VS techniques (0.660 vs 0.665; P = 0.890). However, the CS technique showed a higher detection rate in Liver Imaging Reporting and Data System M (LR-M, probably or definitely malignant but not HCC specific) observations than the VS technique (100.0% [9/9] vs 44.4% [8/18]; P = 0.009).

Conclusion

The CS technique tended to provide optimally timed LAP without transient severe motion and demonstrated greater detection rate of LR-M observations than the VS technique in patients at high risk of HCC.
Peripheral Nerve Involvement at First Diagnosis of Multiple Sclerosis
Authors: Foesleitner Olivia , Jäger Laura Bettina , Schwarz Daniel , Hayes Jennifer , Sam Georges , Wildemann Brigitte , Wick Wolfgang , Bendszus Martin , Heiland Sabine
Published: August 2022

Objectives

The aim of this study was to assess peripheral nerve involvement in patients with multiple sclerosis (MS) at first clinical presentation using quantitative magnetic resonance (MR) neurography in correlation with clinical, laboratory, electrophysiological, and central nervous MR imaging data.

Materials and Methods

In this prospective monocentric study, 30 patients first diagnosed with MS according to the McDonald criteria (19 women; mean age, 32.4 ± 8.8 years) and 30 age- and sex-matched healthy volunteers were examined with high-resolution 3 T MR neurography using a dual-echo T2-relaxometry sequence covering the tibial and peroneal nerves from proximal thigh to distal calf. Magnetic resonance biomarkers of T2 relaxation time (T2app), proton spin density (PSD), and nerve cross-sectional area (CSA) were correlated with clinical symptoms, intrathecal immunoglobulin (Ig) synthesis, nerve conduction study, and lesion load on brain and spine MR imaging. The diagnostic accuracy of MR biomarkers was assessed using receiver-operating characteristic curves.

Results

Diffuse nerve changes were detected along the tibial and peroneal nerves in MS patients, who showed decreased PSD (P < 0.001), increased T2app (P < 0.001), and smaller tibial nerve CSA (P < 0.001) compared with healthy subjects. Tibial PSD was identified as best parameter separating patients from controls (area under the curve = 0.876). Intrathecal IgG and IgM synthesis correlated with PSD values (r = −0.44, P = 0.016, and r = −0.42, P = 0.022). Contrast-enhancement of brain or spine lesions was related to larger tibial and peroneal CSA (P < 0.001, P = 0.033). Abnormal electrophysiology correlated with higher tibial and peroneal T2app (P < 0.001 and P = 0.033), lower tibial and peroneal PSD (P = 0.018 and P = 0.002), and smaller peroneal CSA (P < 0.001).

Conclusions

Quantitative MR neurography reveals peripheral nerve changes in patients with initial diagnosis of MS. Correlation of imaging findings with intrathecal immunoglobulin synthesis may indicate a primary coaffection of the peripheral nervous system in MS.
Alignment with neighbours enables escape from dead ends in flocking models
Authors: Joshi Varun , Popp Stefan , Werfel Justin , McCreery Helen F.
Published: August 2022

Coordinated movement in animal groups (flocks, schools, herds, etc.) is a classic and well-studied form of collective behaviour. Most theoretical studies consider agents in unobstructed spaces; however, many animals move in often complicated environments and must navigate around and through obstacles. Here we consider simulated agents behaving according to typical flocking rules, with the addition of repulsion from obstacles, and study their collective behaviour in environments with concave obstacles (dead ends). We find that groups of such agents heading for a goal can spontaneously escape dead ends without wall-following or other specialized behaviours, in what we term ‘flocking escapes’. The mechanism arises when agents align with one another while heading away from the goal, forming a self-stable cluster that persists long enough to exit the obstacle and avoids becoming trapped again when turning back towards the goal. Solitary agents under the same conditions are never observed to escape. We show that alignment with neighbours reduces the effective turning speed of the group while letting individuals maintain high manoeuvrability when needed. The relative robustness of flocking escapes in our studies suggests that this emergent behaviour may be relevant for a variety of animal species.
Optogenetic manipulation of cyclic guanosine monophosphate to probe phosphodiesterase activities in megakaryocytes
Authors: Zhang Yujing , Benz Pascal , Stehle Daniel , Yang Shang , Kurz Hendrikje , Feil Susanne , Nagel Georg , Feil Robert , Gao Shiqiang , Bender Markus
Published: August 2022

Cyclic guanosine monophosphate (cGMP) signalling plays a fundamental role in many cell types, including platelets. cGMP has been implicated in platelet formation, but mechanistic detail about its spatio-temporal regulation in megakaryocytes (MKs) is lacking. Optogenetics is a technique which allows spatio-temporal manipulation of molecular events in living cells or organisms. We took advantage of this method and expressed a photo-activated guanylyl cyclase,
Blastocladiella emersonii
Cyclase opsin (
Be
Cyclop), after viral-mediated gene transfer in bone marrow (BM)-derived MKs to precisely light-modulate cGMP levels.
Be
Cyclop-MKs showed a significantly increased cGMP concentration after illumination, which was strongly dependent on phosphodiesterase (PDE) 5 activity. This finding was corroborated by real-time imaging of cGMP signals which revealed that pharmacological PDE5 inhibition also potentiated nitric oxide-triggered cGMP generation in BM MKs. In summary, we established for the first-time optogenetics in primary MKs and show that PDE5 is the predominant PDE regulating cGMP levels in MKs. These findings also demonstrate that optogenetics allows for the precise manipulation of MK biology.
In the footsteps of sea stars: deciphering the catalogue of proteins involved in underwater temporary adhesion
Authors: Algrain Morgane , Hennebert Elise , Bertemes Philip , Wattiez Ruddy , Flammang Patrick , Lengerer Birgit
Published: August 2022

Sea stars adhere strongly but temporarily to underwater substrata via the secretion of a blend of proteins, forming an adhesive footprint that they leave on the surface after detachment. Their tube feet enclose a duo-gland adhesive system comprising two types of adhesive cells, contributing different layers of the footprint and de-adhesive cells. In this study, we characterized the catalogue of sea star footprint proteins (Sfps) in the species
Asterias rubens
to gain insights in their potential function. We identified 16 Sfps and mapped their expression to type 1 and/or type 2 adhesive cells or to de-adhesive cells by double fluorescent
in situ
hybridization. Based on their cellular expression pattern and their conserved functional domains, we propose that the identified Sfps serve different functions during attachment, with two Sfps coupling to the surface, six providing cohesive strength and the rest forming a binding matrix. Immunolabelling of footprints with antibodies directed against one protein of each category confirmed these roles. A de-adhesive gland cell-specific astacin-like proteinase presumably weakens the bond between the adhesive material and the tube foot surface during detachment. Overall, we provide a model for temporary adhesion in sea stars, including a comprehensive list of the proteins involved.
Loot box spending is associated with problem gambling but not mental wellbeing
Authors: Etchells Peter J. , Morgan Alexandra L. , Quintana Daniel S.
Published: August 2022

There are emerging concerns that loot boxes—digital video game items that can be purchased for a chance at randomized rewards—are associated with problematic gambling behaviours and, in turn, are potentially harmful. Current research suggests consistent correlations between loot box spending (LS) and problematic gambling symptomology; however, little research has looked at relationships with mental wellbeing. Here, we used a Bayesian hypothesis testing framework to assess the relative strength of evidence for relationships between LS, excessive gaming, problem gambling, mental wellbeing and psychological distress. Two thousand seven hundred twenty-eight participants who reported playing games containing loot box mechanics in the past month answered a survey assessing the above measures, as well as other forms of digital spending. The results showed extremely strong evidence for a positive correlation between LS and problem gambling; however, there was no evidence to suggest relationships between such spending and mental wellbeing or psychological distress. Exploratory results suggested that individuals who spend money on loot boxes also spend more across a range of digital purchases generally. The findings highlight an urgent need to understand what constitutes harm when considering LS effects and provide further context for discussions regarding how best to regulate such mechanisms.
No evidence of repeated song divergence across multiple urban and non-urban populations of dark-eyed juncos (
Junco hyemalis
) in Southern California
Authors: Wong Felisha , Diamant Eleanor S. , Walters Marlene , Yeh Pamela J.
Published: August 2022

Urbanization can affect species communication by introducing new selection pressures, such as noise pollution and different environmental transmission properties. These selection pressures can trigger divergence between urban and non-urban populations. Songbirds rely on vocalizations to defend territories and attract mates. Urban songbirds have been shown in some species and some populations to increase the frequencies, reduce the length and change other temporal features of their songs. This study compares songs from four urban and three non-urban populations of dark-eyed juncos (
Junco hyemalis
) throughout Southern California. We examined song length, trill rate, minimum frequency, maximum frequency, peak frequency and frequency bandwidth. We also compared songs recorded from one urban junco population in San Diego nearly two decades ago with recently collected data in 2018–2020. Over all comparisons, we only found significant differences between UCLA and the 2006/2007 UCSD field seasons in minimum and maximum frequencies. These findings partially support and are partially in contrast to previous urban song studies. As urban areas expand, more opportunities will arise to understand urban song divergence in greater detail.
Extreme natural size variation in both sexes of a sexually cannibalistic mantidfly
Authors: Lietzenmayer Laurel B. , Goldstein Lauren M. , Pasche Josephine M. , Taylor Lisa A.
Published: August 2022

In sexually cannibalistic animals, the relative sizes of potential mates often predict the outcome of aggressive encounters. Mantidflies are spider egg predators as larvae and generalist predators as adults. Unlike most cannibalistic species, there is considerable individual variation in body size in both sexes. Using preserved collections of
Dicromantispa sayi
, we focused on three body size metrics that we found to be positively correlated and accurately measured across researchers. We found extreme size variation in both sexes: the largest 10% of females were 1.72× larger than the smallest 10%, and the largest 10% of males were 1.65× larger than the smallest 10%. On average, females were 7.94% larger than males. In exploring possible causes of this variation, we uncovered differences among populations. To explore the effect of spider egg sac size on adult mantidfly size, we reared mantidfly larvae on egg sacs from two jumping spider species with small or large egg sacs. Mantidfly larvae reared on small egg sacs were smaller than those reared on large egg sacs. This study provides the groundwork to design ecologically relevant experiments exploring the causes and consequences of extreme size variation in an understudied system with intriguing natural history.
Physiological arousal explains infant gaze following in various social contexts
Authors: Ishikawa Mitsuhiko , Senju Atsushi , Kato Masaharu , Itakura Shoji
Published: August 2022

Gaze following (GF) is fundamental to central aspects of human sociocognitive development, such as acquiring language and cultural learning. Studies have shown that infant GF is not a simple reflexive orientation to an adult's eye movement. By contrast, infants adaptively modulate GF behaviour depending on the social context. However, arguably, the neurophysiological mechanisms underlying contextual modulation of GF remain somewhat unexplored. In this study, we tested the proposition about whether the contextual modulation of infant GF is mediated by the infant's heart rate (HR), which indicates the infant's physiological arousal. Forty-one 6- to 9-month-old infants participated in this study, and infants observed either a reliable face, which looked towards the location of an object, or an unreliable face, which looked away from the location of an object. Thereafter, the infants watched a video of the same model making eye contact or not making any ostensive signals, before shifting their gaze towards one of the two objects. We revealed that reliability and eye contact acted independently to increase HR, which then fully mediates the effects of these social cues on the frequency of GF. Results suggest that each social cue independently enhances physiological arousal, which then accumulatively predicts the likelihood of infant GF behaviour.
Size-selective harvesting affects the immunocompetence of guppies exposed to the parasite
Gyrodactylus
Authors: Bartuseviciute Vitalija , Diaz Pauli Beatriz , Salvanes Anne Gro Vea , Heino Mikko
Published: August 2022

Harvesting is typically size-selective, targeting large individuals. This is expected to lead to reduced average body size and earlier maturation (i.e. faster life histories). Such changes can also affect traits seemingly unrelated to harvesting, including immunocompetence. Here we test four hypotheses on how harvesting affects immunocompetence based on the pace-of-life syndrome, habitat area limitation and energy allocation and acquisition, respectively. We empirically evaluate these hypotheses using an experimental system consisting of the ectoparasite
Gyrodactylus turnbulli
and lines of guppies
Poecilia reticulata
that had been subjected to either small, random or large size-selective harvest for over 12 years. We followed the infection progression of individually infected fish for 15 days. We found significant differences between the harvested lines: fish from the small-harvested lines had the highest parasite loads. During the early phase of the infection, parasite loads were the lowest in the large-harvested lines, whereas the terminal loads were the lowest for the random-harvested lines. These results agree with the predictions from the energetic trade-off and surface area hypotheses. To our knowledge, this is the first demonstration of the consequences of size-selective harvesting on immunocompetence.
Anatomy and dietary specialization influence sensory behaviour among sympatric primates
Authors: Melin Amanda D. , Veilleux Carrie C. , Janiak Mareike C. , Hiramatsu Chihiro , Sánchez-Solano Karem G. , Lundeen Ingrid K. , Webb Shasta E. , Williamson Rachel E. , Mah Megan A. , Murillo-Chacon Evin , Schaffner Colleen M. , Hernández-Salazar Laura , Aureli Filippo , Kawamura Shoji
Published: August 2022

Senses form the interface between animals and environments, and provide a window into the ecology of past and present species. However, research on sensory behaviours by wild frugivores is sparse. Here, we examine fruit assessment by three sympatric primates (
Alouatta palliata
,
Ateles geoffroyi
and
Cebus imitator
) to test the hypothesis that dietary and sensory specialization shape foraging behaviours.
Ateles
and
Cebus
groups are comprised of dichromats and trichromats, while all
Alouatta
are trichomats. We use anatomical proxies to examine smell, taste and manual touch, and opsin genotyping to assess colour vision. We find that the frugivorous spider monkeys (
Ateles geoffroyi
) sniff fruits most often, omnivorous capuchins (
Cebus imitator
), the species with the highest manual dexterity, use manual touch most often, and that main olfactory bulb volume is a better predictor of sniffing behaviour than nasal turbinate surface area. We also identify an interaction between colour vision phenotype and use of other senses. Controlling for species, dichromats sniff and bite fruits more often than trichromats, and trichromats use manual touch to evaluate cryptic fruits more often than dichromats. Our findings reveal new relationships among dietary specialization, anatomical variation and foraging behaviour, and promote understanding of sensory system evolution.
Blue whales increase feeding rates at fine-scale ocean features
Authors: Fahlbusch James A. , Czapanskiy Max F. , Calambokidis John , Cade David E. , Abrahms Briana , Hazen Elliott L. , Goldbogen Jeremy A.
Published: August 2022

Marine predators face the challenge of reliably finding prey that is patchily distributed in space and time. Predators make movement decisions at multiple spatial and temporal scales, yet we have a limited understanding of how habitat selection at multiple scales translates into foraging performance. In the ocean, there is mounting evidence that submesoscale (i.e. less than 100 km) processes drive the formation of dense prey patches that should hypothetically provide feeding hot spots and increase predator foraging success. Here, we integrated environmental remote-sensing with high-resolution animal-borne biologging data to evaluate submesoscale surface current features in relation to the habitat selection and foraging performance of blue whales in the California Current System. Our study revealed a consistent functional relationship in which blue whales disproportionately foraged within dynamic aggregative submesoscale features at both the regional and feeding site scales across seasons, regions and years. Moreover, we found that blue whale feeding rates increased in areas with stronger aggregative features, suggesting that these features indicate areas of higher prey density. The use of fine-scale, dynamic features by foraging blue whales underscores the need to take these features into account when designating critical habitat and may help inform strategies to mitigate the impacts of human activities for the species.
Impact of COVID-19 pandemic on the socioeconomic inequality of health behavior among Japanese adolescents: a two-year-repeated cross-sectional survey
Authors: Kyan Akira , Takakura Minoru
Published: August 2022

Background

Although disparities in socioeconomic status in health behaviors have been highlighted globally, they are not well understood in Japanese adolescents. The purpose of this study was to clarify the changes in socioeconomic disparities in adolescents’ fundamental health behaviors, such as physical activity, screen time (ST), sleep, breakfast intake, and bowel movement before and during COVID-19.

Methods

This was a repeated cross-sectional study which used data from the 2019 and 2021 National Sports-Life Survey of Children and Young in Japan. Data of 766 and 725 participants in 2019 and 2021, respectively, were analyzed. Favorable health behaviors were defined as daily moderate-to-vigorous physical activity (MVPA) of at least 60 minutes, ST of less than 2 hours, sleep of 8 to 10 hours, daily breakfast intake, and bowel movement frequency of at least once in every 3 days. We calculated the slope index of inequality (SII) and relative index of inequality (RII) in each health behavior for equivalent household income levels for assessing absolute and relative economic inequalities.

Results

Compliance with MVPA and ST recommendation significantly declined from 20.1% and 23.0% in 2019 to 11.7% and 14.9% in 2021, respectively. The SII and RII increased in MVPA for income levels, but decreased in daily breakfast in 2019 to 2021. Although the widening and narrowing of the disparity was inconclusive for ST, it exacerbated for the higher income groups.

Conclusions

Our study revealed widening of economic disparities in the achievement of recommended MVPA and narrowing of it in breakfast intake among adolescents before and during COVID-19.
Modeling and Simulation of Neocortical Micro- and Mesocircuitry. Part I: Anatomy
Authors: Reimann Michael W. , Bolaños-Puchet Sirio , Courcol Jean-Denis , Egas Santander Daniela , Arnaudon Alexis , Coste Benoît , Delalondre Fabien , Delemontex Thomas , Devresse Adrien , Dictus Hugo , Dietz Alexander , Ecker András , Favreau Cyrille , Ficarelli Gianluca , Gevaert Mike , Herttuainen Joni , Isbister James B. , Kanari Lida , Keller Daniel , King James , Kumbhar Pramod , Lapere Samuel , Lazovskis Jᾱnis , Lu Huanxiang , Ninin Nicolas , Pereira Fernando , Planas Judit , Pokorny Christoph , Riquelme Juan Luis , Romani Armando , Shi Ying , Smith Jason P. , Sood Vishal , Srivastava Mohit , Van Geit Werner , Vanherpe Liesbeth , Wolf Matthias , Levi Ran , Hess Kathryn , Schürmann Felix , Muller Eilif B. , Markram Henry , Ramaswamy Srikanth
Published: August 2022

The function of the neocortex is fundamentally determined by its repeating microcircuit motif, but also by its rich, interregional connectivity. We present a data-driven computational model of the anatomy of non-barrel primary somatosensory cortex of juvenile rat, integrating whole-brain scale data while providing cellular and subcellular specificity. The model consists of 4.2 million morphologically detailed neurons, placed in a digital brain atlas. They are connected by 14.2 billion synapses, comprising local, mid-range and extrinsic connectivity. We delineated the limits of determining connectivity from neuron morphology and placement, finding that it reproduces targeting by Sst+ neurons, but requires additional specificity to reproduce targeting by PV+ and VIP+ interneurons. Globally, connectivity was characterized by local clusters tied together through hub neurons in layer 5, demonstrating how local and interegional connectivity are complicit, inseparable networks. The model is suitable for simulation-based studies, and a 211,712 neuron subvolume is made openly available to the community.
Comparative analysis of drug-salt-polymer interactions by experiment and molecular simulation improves biopharmaceutical performance
Authors: Mukesh Sumit , Mukherjee Goutam , Singh Ridhima , Steenbuck Nathan , Demidova Carolina , Joshi Prachi , Sangamwar Abhay T. , Wade Rebecca C.
Published: August 2022

The propensity of poorly water-soluble drugs to aggregate at supersaturation impedes their bioavailability. The emergence of supersaturated amorphous drug-salt-polymer systems provides a new approach to this problem. However, the effects of polymers on drug-drug interactions in aqueous phase are largely unexplored and it is unclear how to choose an optimal salt-polymer combination for a particular drug. We describe a comparative experimental and computational characterization of amorphous solid dispersions containing the drug celecoxib, and PVP-VA or HPMCAS polymers with or without Na+/K+salts. Classical models for drug-polymer interactions fail to identify the best drug-salt-polymer combination. In contrast, more stable drug-polymer interaction energies computed from molecular dynamics simulations correlate with prolonged stability of supersaturated amorphous drug-salt-polymer systems, along with better dissolution and pharmacokinetic profiles. The celecoxib-salt-PVP-VA formulations exhibit excellent biopharmaceutical performance, offering the prospect of less frequent administration and lower doses of this widely used anti-inflammatory, thereby increasing cost-effectiveness, and reducing side-effects.