bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in Outpatient Healthcare Utilization and Costs Following Mild Traumatic Brain Injury Among Service Members in the Military Health System by Preexisting Behavioral Health Condition Status
Authors: Hoover Peter , Adirim-Lanza Andrew , Adams Rachel Sayko , Dismuke-Greer Clara E. , French Louis M. , Caban Jesus
Published: February 2023

Objective:

To evaluate changes in healthcare utilization and cost following an index mild traumatic brain injury (mTBI) diagnosis among service members (SMs). We hypothesized that differences in utilization and cost will be observed by preexisting behavioral health (BH) diagnosis status.

Setting:

Direct care outpatient healthcare facilities within the Military Health System.

Participants:

A total of 21 984 active-duty SMs diagnosed with an index mTBI diagnosis between 2017 and 2018.

Design:

This retrospective study analyzed changes in healthcare utilization and cost in military treatment facilities among SMs with an index mTBI diagnosis. Encounter records 1 year before and after mTBI were assessed; preexisting BH conditions were identified in the year before mTBI.

Main Measures:

Ordinary least squares regressions evaluated difference in the average change of total outpatient encounters and costs among SMs with and with no preexisting BH conditions (eg, posttraumatic stress disorder, adjustment disorder). Additional regressions explored changes in utilization and cost within clinic types (eg, mental health, physical rehabilitation).

Results:

There was a 39.5% increase in overall healthcare utilization during the following year, representing a 34.8% increase in total expenditures. Those with preexisting BH conditions exhibited smaller changes in overall utilization (β, −4.9; [95% confidence interval (CI), −6.1 to −3.8]) and cost (β, $−1873; [95% CI, $−2722 to $−1024]), compared with those with no BH condition. The greatest differences were observed in primary care clinics, in which those with prior BH conditions exhibited an average decreased change of 3.2 encounters (95% CI, −3.5 to −3) and reduced cost of $544 (95% CI, $−599 to $−490) compared with those with no prior BH conditions.

Conclusion:

Despite being higher utilizers of healthcare services both pre- and post-mTBI diagnosis, those with preexisting BH conditions exhibited smaller changes in overall cost and utilization. This highlights the importance of considering prior utilization and cost when evaluating the impact of mTBI and other injury events on the Military Health System.
Comparing the Etiology of Viral Acute Respiratory Illnesses Between Children Who Do and Do Not Attend Childcare
Authors: DeJonge Peter M. , Monto Arnold S. , Malosh Ryan E. , Petrie Joshua G. , Callear Amy , Segaloff Hannah E. , Truscon Rachel , Johnson Emileigh , Cheng Bonnie , Cranis Mara , Tiseo Katie , Foote Sydney , Musci Adrienne , Martin Emily T.
Published: February 2023

Background and Objective:

Childcare attendance is a common risk factor for acute respiratory illness (ARI) in young children. Our goal was to better understand the specific respiratory viruses that predominate in childcare, which may support the development of tailored illness prevention and intervention strategies in childcare settings.

Methods:

Using data from a prospective household cohort of ARI surveillance, we assessed specimen from 1418 ARIs reported by 359 childcare-aged children over 6 study seasons (2012/2013 through 2017/2018). Respiratory swabs were tested by polymerase chain reaction for 9 respiratory viruses. A mixed-effect logistic regression model was used to compare odds of various viral detection outcomes. The Shannon’s Diversity index was used to compare the richness (ie, number of species) and diversity (ie, relative species abundance) associated with respiratory viruses detected in both groups.

Results:

At least 1 virus was detected in 75.5% of childcare-associated ARIs and in 80.1% of homecare ARIs. Compared with illnesses among homecare children, childcare illnesses were associated with significantly higher odds of detected adenovirus (odds ratio = 1.86, 95% confidence interval = 1.05–3.28) and human metapneumovirus (odds ratio = 1.76, 95% confidence interval = 1.03–3.0). The pool of viruses associated with childcare ARI was found to be significantly richer and more diverse than that of viruses associated with homecare ARI (P < 0.0001).

Conclusions:

Children attending childcare experience a higher risk of adenovirus and human metapneumovirus infection and are regularly exposed to a rich and diverse pool of respiratory viruses in childcare environments. Our results underscore the necessity of thorough and multifaceted viral prevention strategies in childcare settings.
Botfly Myiasis Masquerading as Dacryocystitis
Authors: Rozanski Collin A. , DeSimone Joseph D. , Milman Tatyana , Ramesh Sathyadeepak
Published: February 2023

Cutaneous myiasis is an infection most commonly caused globally by Dermatobia hominus, the human botfly, which is endemic to Central and South America. In North America, the most common cause of cutaneous myiasis is infestation with the larvae of Cuterebra, the North American botfly. The authors describe a 44-year-old man who presented with a 1-month history of intermittent, severe, boring pain along the side of his nose that progressed to swelling and redness along his right inferior orbital rim and lacrimal sac. CT imaging showed a rim-enhancing collection at the right medial canthus with surrounding phlegmonous changes communicating with the skin. Pathologic evaluation revealed curvilinear pigmented material associated with a granulomatous and eosinophil-rich inflammatory infiltrate, consistent with botfly myiasis. This case describes the pathogenesis of the botfly infestation in humans, as well as the clinical, radiographic, and histopathologic features of this rare orbital infection, with an emphasis on its treatment.
Validation of a web-based distance visual acuity test
Authors: Labiris Georgios , Panagiotopoulou Eirini-Kanella , Delibasis Konstantinos , Duzha Erald , Bakirtzis Minas , Panagis Christos , Boboridis Kostas , Mokka Agni , Balidis Miltiadis , Damtsi Charoula , Ntonti Panagiota
Published: February 2023

Purpose:

To validate the Democritus Digital Acuity and Reading Test (DDART) as a distance VA (dVA) test against a series of prevalent conventional distance vision charts.

Setting:

Ophthalmology Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece; Ophthalmology Department, AHEPA University Hospital, Thessaloniki, Greece; and Ophthalmica Institute of Ophthalmology & Microsurgery, Thessaloniki, Greece.

Design:

Prospective multicenter validation study.

Methods:

The distance best spectacle-corrected visual acuity (dBSCVA) was compared in normal (NVG) and low (LVG) vision participants against 4 prevalent conventional distance vision charts (ETDRS, Snellen, Landolt C, and Tumbling E) by a predefined 2.5-symbol noninferiority margin and intraclass correlation coefficients (ICCs). DDART's test–retest (TRT) reliability was assessed with ICCs.

Results:

534 participants (471 and 63 with normal and low vision, respectively) were included in the study. The mean difference between dBSCVA measured with DDART and conventional charts ranged between −0.84 and +0.85 symbols, without exceeding the 2.5-symbol noninferiority margin. ICCs indicated an excellent level of agreement for all patient groups (from 0.848 to 0.985). TRT reliability indicated differences below 1 symbol both for the NVG and LVG, with ICCs ranging between 0.912 and 0.964 for the 4 DDARTs.

Conclusions:

DDART was a valid web-based dVA test that provided reliable measurements in clinical and telemedical settings, both for normal and low vision patients.
Fill levels, cost comparisons, and expulsion force requirements of commonly used topical ophthalmic nonsteroidal anti-inflammatory drugs
Authors: Heath Michael , McDonald Michael C. , Murphy David A. , Shah Simren V. , Shah Semony , Ding Kai , Riaz Kamran M.
Published: February 2023

Purpose:

To determine volume fill levels, estimated costs, and force expulsion requirements per bottle of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) commonly perioperatively in the United States.

Setting:

Tertiary care academic medical center.

Design:

Prospective laboratory investigation.

Methods:

8 commercially available NSAIDs (3 branded, 5 generic) were tested: branded bromfenac 0.07%, generic bromfenac 0.09%, diclofenac 0.1%, flurbiprofen 0.03%, generic ketorolac 0.5%, branded ketorolac 0.5%, ketorolac 0.47%, and branded nepafenac 0.3%. 10 bottles of each medication were tested, with an additional bottle tested for expulsion force requirements. A double-blinded method was used to measure the actual bottle fill volume and number of drops per bottle. The total cost per drop was calculated using published cash prices. Force requirements were measured using a customized force gauge apparatus. Formulations were compared using the Kruskal-Wallis test, followed by pairwise comparisons with the Dwass, Steel, Critchlow-Fligner Method.

Results:

2 branded NSAIDs (bromfenac and nepafenac) had slightly lower-than-sticker volumes while generics other than ketorolac had higher-than-sticker volumes. Diclofenac and branded bromfenac had the highest and lowest adjusted number of drops respectively. Generic bromfenac and generic ketorolac had the highest and lowest adjusted volume compared with sticker volume respectively. Branded bromfenac was the most expensive medication, while generic diclofenac was the least expensive. Force expulsion requirements varied significantly among generic and branded NSAIDs.

Conclusions:

Volume fill levels, patient-incurred costs, and expulsion force requirements per bottle of topical NSAID medications vary significantly. Surgeons may wish to consider these factors when deciding how best to use these medications perioperatively.
Erythrocyte pyruvate kinase activation in red cell disorders
Authors: Matte Alessandro , Federti Enrica , De Franceschi Lucia
Published: February 2023

Purpose of review

In red cells, pyruvate kinase is a key enzyme in the final step of glycolytic degradative process, which generates a constant energy supply via ATP production. This commentary discusses recent findings on pyruvate kinase activators as new therapeutic option in hereditary red cell disorders such as thalassemic syndromes or sickle cell disease (SCD).

Recent findings

Mitapivat and etavopivat are two oral pyruvate kinase activators. Studies in a mouse model for β thalassemia have shown beneficial effects of mitapivat on both red cell survival and ineffective erythropoiesis, with an amelioration of iron homeostasis. This was confirmed in a proof-of-concept study in patients with nontransfusion-dependent thalassemias. Both mitapivat and etavopivat have been evaluated in mouse models for SCD, showing an increased 2-3DPG/ATP ratio and a reduction in haemolysis as well as in sickling. These data were confirmed in proof-of-concept clinical studies with both molecules carried in patients with SCD.

Preclinical and clinical evidence indicate that pyruvate kinase activators represent new therapeutic option in hemoglobinopathies or SCD. Other red cell disorders such as hereditary spherocytosis or hereditary anaemias characterized by defective erythropoiesis might represent additional areas to investigate the therapeutic impact of pyruvate kinase activators.
Getting to Zero in Allegheny County: Implementation of a Collective Impact Model to Achieve Ending the HIV Epidemic Objectives
Authors: Whitfield Darren L. , Chung Ashley , Mangum Laurenia , Stoner Jerone T. , Seagle Emma E. , Och Julia , Steele Sue ,   for AIDS Free Pittsburgh
Published: February 2023

Background

Allegheny County Pennsylvania has the second highest HIV prevalence in the state. In the county, racial and ethnic minorities are disproportionately impacted by HIV.

Methods

In responses to HIV epidemic in the Allegheny County, AIDS Free Pittsburgh was created with the goals of reducing new HIV infections by 75% and declaring Allegheny County AIDS free (no new AIDS cases) by 2020. AIDS Free Pittsburgh uses a collective impact framework in which partners pledge to collect and share data uniformly across health systems, to co-organize events for provider and community education, and to enhance access to quality healthcare by developing resources and referral networks.

Results

Since its inception, there has been nearly a 43% decrease in new HIV cases, a 23% decrease in new AIDS cases, and other promising trends related to HIV testing, preexposure prophylaxis, linkage to care, and viral load suppression for people living with HIV in Allegheny County.

Conclusions

This article provides a detailed description of the community-level project, the activities conducted by collective group, a summary of project outcomes, and lessons learned for replicating this project in other midsized, mid-HIV incidence jurisdictions.
Excellence in Pediatric Physical Therapy Education: Recommendations and Action Items
Authors: Birkmeier Marisa , Lundeen Heather , Furze Jennifer , Moore James G. , Dannemiller Lisa , Anderson Deborah
Published: February 2023

Purpose:

This special communication identifies evidence-based recommendations and offers action items to facilitate the uptake of new knowledge from the National Study of Excellence in Pediatric Physical Therapy Education (NSE-Peds).

Summary of Key Points:

The NSE-Peds identified a conceptual framework consisting of 4 key dimensions and associated elements that dynamically interact to prepare future physical therapists to meet the needs of society. The conceptual framework serves as the Knowledge Creation component of the knowledge to action (KTA) framework, but translation into practice requires the Action Cycle, the second component of the KTA framework. Recommendations and action items provide tangible products derived from the NSE-Peds conceptual framework for application in the Action Cycle.

Conclusions:

Using the KTA framework, implementation of the recommendations at the level of the individual, program, and organization should enhance pediatric physical therapy education and ultimately physical therapy care provided to children and families.
Modified Ride-on Car Intervention for Children With Profound Intellectual and Multiple Disabilities: A Case Series
Authors: Sloane Bethany M. , Case Felicity , Quinn Emily , Sanford-Keller Hannah , Logan Samuel W.
Published: February 2023

Purpose:

To describe a pilot clinical case series of a modified ride-on car (MROC) intervention on mobility and alertness for young children with profound intellectual and multiple disabilities (PIMD).

Methods:

Four young children with PIMD participated in 4 baseline observations and 5 intervention sessions (A-B design). Data collection occurred via video. Assessment of mobility and alertness duration used structured visual analysis.

Results:

Three of the 4 children increased their independent mobility during the intervention sessions. One of the 4 children increased their active alertness during the intervention sessions.

Conclusions:

This pilot study demonstrates the initial feasibility of an MROC intervention in a clinical setting and outcome measures of mobility and alertness for children with PIMD. This provides support that this population should be considered for power mobility in early childhood. Further, this study used a novel, caregiver-implemented prompting protocol to teach children how to use the MROC.
Truth of Colorectal Enhanced Recovery Programs: Process Measure Compliance in 151 Hospitals
Authors: Shah Tejen A , Knapp Leandra , Cohen Mark E , Brethauer Stacy A , Wick Elizabeth C , Ko Clifford Y
Published: February 2023

BACKGROUND:

Commonly cited studies have reported substantial improvements (defined as >20%) in process measure compliance after implementation of colorectal enhanced recovery programs (ERPs). However, hospitals have anecdotally reported difficulties in achieving similar improvement gains. This study evaluates improvement uniformity among 151 hospitals exposed to an 18-month implementation protocol for 6 colorectal ERP process measures (oral antibiotics, mechanical bowel preparation, multimodal pain control, early mobilization, early liquid intake, and early solid intake).

STUDY DESIGN:

One hundred fifty-one hospitals implemented a colorectal ERP with pathway, educational and supporting materials, and data capture protocols; 906 opportunities existed for process compliance improvement across the cohort (151 hospitals × 6 process measures). However, 240 opportunities were excluded due to high starting compliance rates (ie compliance >80%) and 3 opportunities were excluded because compliance rates were recorded for fewer than 2 cases. Thus, 663 opportunities for improvement across 151 hospitals were studied.

RESULTS:

Of 663 opportunities, minimal improvement (0% to 20% increase in compliance) occurred in 52% of opportunities, substantial improvement (>20% increase in compliance) in 20%, and worsening compliance occurred in 28%. Of the 6 processes, multimodal pain control and use of oral antibiotics improved the most.

CONCLUSIONS:

Contrary to published ERP literature, the majority of study hospitals had difficulty improving process compliance with 80% of the opportunities not achieving substantial improvement. This discordance between ERP implementation success rates reported in the literature and what is observed in a large sample could reflect differences in hospitals’ culture or characteristics, or a publication bias. Attention needs to be directed toward improving ERP adoption across the spectrum of hospital types.
Chimeric chikungunya virus-like particles with surface exposed SARS-CoV-2 RBD elicits potent immunogenic responses in mice
Authors: Singh Vedita Anand , Nehul Sanket , Kumar Chandra Shekhar , Banerjee Manidipa , Kumar Pravindra , Sharma Gaurav , Tomar Shailly
Published: February 2023

The SARS-CoV-2 pandemic has reinforced efforts for developing effective vaccination strategy for existing and emerging viruses. Currently there are various vaccine technology available for treating viral diseases, however it is imperative to develop and investigate second-generation vaccines such as chimeric virus-like particles (chi-VLPs) vaccine for increased immunogenicity, ease of production and scalability to supplement the worldwide vaccine supply. Intriguingly, chi-VLPs expresses more than one antigenic epitope on its surface, hence it is expected to be a more effective vaccine candidate. Hereby, this study reports, a novel bivalent vaccine design of chimeric alphavirus coronavirus virus-like particles (ChAC-VLPs), displaying fusion glycoproteins of CHIKV and receptor binding domain (RBD) of SARS-CoV-2 on its surface. Uniqueness and versatility of ChAC-VLPs has been demonstrated via a various techniques including Western blot, Immunofluorescence, cryoEM, and dynamic light scattering (DLS). The multimeric epitope display of immunogenic antigens, i.e CHIKV envelop glycoprotein and SARS-CoV-2 RBD was validated by cell-based assays. ChAC-VLP immunized mice has shown substantial neutralization titres for CHIKV (PRNT50 of 1:25) from the serum collected after 2ndbooster doses. Similarly, serum antibodies were detected for SARS-CoV2 RBD as observed by antigen specific ELISA and validated using surface plasmon resonance (SPR). SPR binding response was detected to be >200 RU for anti-RBD antibody in post-immunized mice sera. In conclusion, present study proposes ChAC-VLPs as a potential hybrid vaccine candidate for CHIKV and SARS-CoV-2 infection and contributes valuable insights in chi-VLPs domain.
The development and usability testing of two arts-based knowledge translation tools for pediatric anaphylaxis
Authors: Scott Shannon D. , Hartling Lisa
Published: February 2023

Anaphylaxis, or anaphylactic reactions, are a severe allergic reaction with a rapid onset and can be fatal. Children are disproportionately at risk for hospitalization and emergency department visits due to anaphylaxis. A previously conducted mixed studies systematic review and qualitative descriptive study found that parents lacked confidence in recognizing and treating an anaphylactic reaction in their child, and were unsure of when to bring their child to the emergency department. This demonstrates that more effective knowledge translation (KT) tools are needed to satisfy parent information needs.

The purpose of this research was to work with parents to develop and test the usability of an animated video and an interactive infographic about anaphylactic reactions in children. These tools merge the best available research evidence with narratives of parent experiences to respond to their information needs. Prototypes were evaluated by parents (video n=31; infographic n=30) through usability testing in an urban emergency department waiting room in Alberta. Parents viewed the tools on an iPad and answered questions via an electronic survey. The usability survey consisted of 9, 5-point Likert items, which assessed: 1) usefulness, 2) aesthetics, 3) length, 4) relevance, and 5) future use. Parents were also asked to provide their positive and negative opinions of the tool via two free text boxes. Overall, results were positive and the tools were highly rated across most usability items. Mean scores across usability items were 4.26 to 4.71 for the video and 3.83 to 4.43 for the infographic. The scores from the usability testing suggest arts-based digital tools are useful in sharing complex health information with parents about managing an anaphylactic reaction in their child and provide meaningful guidance on how to improve KT tools to better reflect the needs of parents.
A global test of hybrid ancestry from genome-scale data
Authors: Haque Md Rejuan , Kubatko Laura
Published: February 2023

Methods based on the multi-species coalescence have been widely used in phylogenetic tree estimation using genome-scale DNA sequence data to understand the underlying evolutionary relationship between the sampled species. Evolutionary processes such as hybridization, which creates new species through interbreeding between two different species, necessitate inferring a species network instead of a species tree. A species tree is strictly bifurcating and thus fails to incorporate hybridization events which require an internal node of degree three. Hence, it is crucial to decide whether a tree or network analysis should be performed given a DNA sequence data set, a decision that is based on the presence of hybrid species in the sampled species. Although many methods have been proposed for hybridization detection, it is rare to find a technique that does so globally while considering a data generation mechanism that allows both hybridization and incomplete lineage sorting. In this paper, we consider hybridization and coalescence in a unified framework and propose a new test that can detect whether there are any hybrid species in a given set of species. We propose that based on this global test of hybridization, one can decide whether a tree or network analysis is appropriate for a given data set.
Relying on the relationship with known disease-causing variants in homologous proteins to predict pathogenicity ofSORL1variants in Alzheimer’s disease
Authors: Andersen Olav M. , Monti Giulia , Jensen Anne Mette G. , de Waal Matthijs , Hulsman Marc , Olsen Johan G. , Holstege Henne
Published: February 2023

SORL1encodes the retromer-associated receptor SORLA that functions in endosomal recycling. Rare variants inSORL1have been associated with Alzheimer’s disease (AD) and rare pathogenic variants are estimated to occur in up to 2.75% of early onset AD patients and in 1.5% of unrelated late onset AD patients. While truncation mutations are observed almost exclusively in AD patients, it is currently unknown which among the hundreds of rare missense variants identified inSORL1, are pathogenic. Here we address this question by relying on SORLA’s distinct molecular architecture. First, we completed a structure-guided sequence alignment for all the protein domains. Next, we identified proteins that contain domains homologous to those of SORLA, which include pathogenic variants for monogenic diseases. We identified the analogous domain positions of these variants in the SORLA protein sequence and showed that variants in these positions similarly impairSORL1, and lead to AD. Together, our findings represent a comprehensive compendium on SORLA protein variation and functional effects, which allowed us to prioritizeSORL1genetic variants into high or moderate priority mutations. We envision that this compendium will be used by clinical geneticists for assessing variants they identify in patients, allowing further development of diagnostic procedures and patient counseling strategies. Utimately, this compendium will inform investigations into the molecular mechanisms of endosomal recycling which will support the development of therapeutic treatment strategies forSORL1variant-carrying patients.
A generic binding pocket for small moleculeIKsactivators at the extracellular inter-subunit interface of KCNQ1 and KCNE1 channel complexes
Authors: Chan Magnus , Sahakyan Harutyun , Eldstrom Jodene , Sastre Daniel , Wang Yundi , Dou Ying , Pourrier Marc , Vardanyan Vitya , Fedida David
Published: February 2023

The cardiacIKsion channel comprises KCNQ1, calmodulin, and KCNE1 in a dodecameric complex which provides a repolarizing current reserve at higher heart rates and protects from arrhythmia syndromes that cause fainting and sudden death. Pharmacological activators ofIKsare therefore of interest both scientifically and therapeutically for treatment ofIKsloss-of-function disorders. One group of chemical activators are only active in the presence of the accessory KCNE1 subunit and here we investigate this phenomenon using molecular modeling techniques and mutagenesis scanning in mammalian cells. A generalized activator binding pocket is formed extracellularly by KCNE1, the domain-swapped S1 helices of one KCNQ1 subunit and the pore/turret region made up of two other KCNQ1 subunits. A few residues, including K41, A44 and Y46 in KCNE1, W323 in the KCNQ1 pore, and Y148 in the KCNQ1 S1 domain, appear critical for the binding of structurally diverse molecules, but in addition, molecular modeling studies suggest that induced fit by structurally different molecules underlies the generalized nature of the binding pocket. Activation ofIKsis enhanced by stabilization of the KCNQ1-S1/KCNE1/pore complex, which ultimately slows deactivation of the current, and promotes outward current summation at higher pulse rates. Our results provide a mechanistic explanation of enhancedIKscurrents by these activator compounds and provide a map for future design of more potent therapeutically useful molecules.
Jet injection potentiates naked mRNA SARS-CoV-2 vaccine in mice and non-human primates by adding physical stress to the skin
Authors: Abbasi Saed , Matsui-Masai Miki , Yasui Fumihiko , Hayashi Akimasa , Tockary Theofilus A. , Akinaga Shiro , Kohara Michinori , Kataoka Kazunori , Uchida Satoshi
Published: February 2023

Naked mRNA-based vaccines may reduce the reactogenicity associated with delivery carriers, but their effectiveness has been suboptimal against infectious diseases. Herein, we aimed to enhance their efficacy by using a pyro-drive liquid jet injector that precisely controls pressure to widely disperse mRNA solution in the skin. The jet injection boosted naked mRNA delivery efficiency in the mouse skin. Mechanistic analyses indicate that dendritic cells, upon uptake of antigen mRNA in the skin, migrate to the draining lymph nodes for antigen presentation. Additionally, the jet injector activated innate immune responses in the skin, presumably by inducing physical stress, thus serving as a physical adjuvant. From a safety perspective, our approach, utilizing naked mRNA, restricted mRNA distribution solely to the injection site, preventing systemic pro-inflammatory reactions following vaccination. Ultimately, the jet injection of naked mRNA encoding SARS-CoV-2 spike protein elicited robust humoral and cellular immunity, providing protection against SARS-CoV-2 infection in mice. Furthermore, our approach induced plasma activity of neutralizing SARS-CoV-2 in non-human primates, comparable to that observed in mice, with no detectable systemic reactogenicity.
Modelling Speed-Accuracy Tradeoffs in the Stopping Rule for Confidence Judgments
Authors: Herregods Stef , Denmat Pierre Le , Vermeylen Luc , Desender Kobe
Published: February 2023

Making a decision and reporting confidence in the accuracy of that decision are thought to be driven by the same mechanism: the accumulation of evidence. Previous research has shown that choices and reaction times are well accounted for by a computational model assuming noisy accumulation of evidence until crossing a decision boundary (e.g., the drift diffusion model). Decision confidence can be derived from the amount of evidence following post-decision evidence accumulation. Currently, the stopping rule for post-decision evidence accumulation is underspecified. In the current work, we quantitatively and qualitatively compare the ability of four prominent models of confidence couched within evidence accumulation to account for this stopping rule. In two experiments, participants were instructed to make fast or accurate decisions, and to give fast or carefully considered confidence judgments. We then compared the different models in their ability to capture the speed-accuracy effects on confidence. Both qualitatively and quantitatively, the data were best accounted for by our newly proposed Flexible Collapsing Boundaries model, in which post-decision accumulation terminates once it reaches one of two opposing slowly collapsing confidence boundaries. Inspection of the parameters of this model revealed that instructing participants to make fast versus accurate decisions influenced the height of the decision boundaries, while instructing participants to make fast versus careful confidence judgments influenced height of the confidence boundaries. Our data show that the stopping rule for confidence judgments can be well described as an accumulation-to-bound process, and that the height of these confidence boundaries are under strategic control.
Mitochondrial translocation of TFEB regulates complex I and inflammation
Authors: Calabrese Chiara , Nolte Hendrik , Pitman Melissa R , Ganesan Raja , Lampe Philipp , Laboy Raymond , Ripa Roberto , Fischer Julia , Chipurupalli Sandhya , Gutierrez Saray , Polara Ruhi , Thomas Daniel , Pitson Stuart M , Antebi Adam , Robinson Nirmal
Published: February 2023

TFEB is a master regulator of autophagy, lysosome biogenesis and mitochondrial metabolism that works, and immunity, primarily through transcription controlled by cytosol-to-nuclear translocation. Emerging data indicate additional regulatory interactions at the surface of organelles such as lysosomes. Here we show that TFEB has a non-transcriptional role in mitochondria, regulating the electron transport chain complex I to down-modulate inflammation. Proteomic analysis revealed extensive TFEB co-precipitation with several mitochondrial proteins, whose interactions are disrupted upon infection withS.Typhimurium. Localization of TFEB in the mitochondrial matrix was confirmed by high resolution confocal microscopy and biochemistry with translocation dependent on a conserved N-terminal TOMM20-binding motif enhanced by mTOR inhibition. Within the mitochondria, TFEB and protease LONP1 antagonistically co-regulate complex I, reactive oxygen species and the inflammatory response. Consequently, during infection, lack of TFEB specifically in the mitochondria exacerbates the expression of pro-inflammatory cytokines, contributing to innate immune pathogenesis.
Autophagy in maternal tissues contributes toArabidopsis thalianaseed development
Authors: Erlichman Ori , Weiss Shahar , Abu-Arkia Maria , Khaner Moria Ankary , Soroka Yoram , Jasinska Weronika , Rosental Leah , Brotman Yariv , Avin-Wittenberg Tamar
Published: February 2023

Seeds are an essential food source, providing nutrients for germination and early seedling growth. Degradation events in the seed and the mother plant accompany seed development. One degradation mechanism is autophagy, facilitating cellular component breakdown in the lytic organelle. Autophagy influences various aspects of plant physiology, specifically nutrient availability and remobilization, suggesting its involvement in source-sink interactions. During seed development, autophagy was shown to affect nutrient remobilization from mother plants and function in the embryo. Yet, these studies examined autophagy-knockout (atgmutant) plants, making it impossible to distinguish between the contribution of autophagy in the source (i.e., the mother plant) and the sink tissue (i.e., the embryo).

To address this, we employed a novel approach to differentiate between autophagy in source and sink tissues. We investigated how autophagy in the maternal tissue affects seed development by performing reciprocal crosses between WT andatgmutantArabidopsis thalianaplants. Although F1 seedlings possessed a functional autophagy mechanism, etiolated F1 plants from maternalatgmutants displayed reduced growth. This was attributed to altered protein but not lipid accumulation in the seeds, suggesting autophagy differentially regulates carbon and nitrogen remobilization. Surprisingly, F1 seeds of maternalatgmutants exhibited faster germination, resulting from different seed coat development.

Our study emphasizes the significance of examining autophagy in a tissue-specific manner, revealing valuable insights into the interplay between different tissues during seed development. It sheds light on the tissue-specific functions of autophagy, offering potential for new research into the underlying mechanisms governing seed development and crop yield.
Directing Protein Design Choices by Per-Residue Energy Breakdown Analysis with an Interactive Web Application
Authors: Engelberger Felipe , Zakary Jonathan D. , Künze Georg
Published: February 2023

Recent developments in machine learning have greatly facilitated the design of proteins with improved properties. However, accurately assessing the contributions of an individual or multiple amino acid mutations to overall protein stability to select the most promising mutants remains a challenge. Knowing the specific types of amino acid interactions that improve energetic stability is crucial for finding favorable combinations of mutations and deciding which mutants to test experimentally. In this work, we present an interactive workflow for assessing the energetic contributions of single and multi-mutant designs of proteins. Theenergy breakdown guided protein design (ENDURE) workflow includes several key algorithms, including per-residue energy analysis and the sum of interaction energies calculations, which are performed using the Rosetta energy function, as well as a residue depth analysis, which enables tracking the energetic contributions of mutations occurring in different spatial layers of the protein structure. ENDURE is available as a web application that integrates easy-to-read summary reports and interactive visualizations of the automated energy calculations and helps users selecting protein mutants for further experimental characterization. We demonstrate the effectiveness of the tool in identifying the mutations in a designed polyethylene terephthalate (PET)-degrading enzyme that add up to an improved thermodynamic stability. We expect that ENDURE can be a valuable resource for researchers and practitioners working in the field of protein design and optimization. ENDURE is freely available for academic use at:http://endure.kuenzelab.org.
Controlled protein activities with viral proteases, antiviral peptides, and antiviral drugs
Authors: Tague Elliot P. , McMahan Jeffrey B. , Tague Nathan , Dunlop Mary J. , Ngo John T.
Published: February 2023

Chemical control of protein activity is a powerful tool for scientific study, synthetic biology, and cell therapy; however, for broad use, effective chemical inducer systems must minimally crosstalk with endogenous processes and exhibit desirable drug delivery properties. Accordingly, the drug-controllable proteolytic activity of hepatitis Ccis-protease NS3 and its associated antiviral drugs have been used to regulate protein activity and gene modulation. These tools advantageously exploit non-eukaryotic/prokaryotic proteins and clinically approved inhibitors. Here we expand the toolkit by utilizing catalytically inactive NS3 protease as a high affinity binder to genetically encoded, antiviral peptides. Through our approach, we create NS3-peptide complexes that can be displaced by FDA-approved drugs to modulate transcription, cell signaling, split-protein complementation. With our developed system, we discover a new mechanism to allosterically regulate Cre recombinase. Allosteric Cre regulation with NS3 ligands enables orthogonal recombination tools in eukaryotic cells and functions in divergent organisms to control prokaryotic recombinase activity.
FREEDA: an automated computational pipeline guides experimental testing of protein innovation by detecting positive selection
Authors: Dudka Damian , Akins R. Brian , Lampson Michael A.
Published: February 2023

Cell biologists typically focus on conserved regions of a protein, overlooking innovations that can shape its function over evolutionary time. Computational analyses can reveal potential innovations by detecting statistical signatures of positive selection that leads to rapid accumulation of beneficial mutations. However, these approaches are not easily accessible to non-specialists, limiting their use in cell biology. Here, we present an automated computational pipeline FREEDA (Finder of Rapidly Evolving Exons in De novo Assemblies) that provides a simple graphical user interface requiring only a gene name, integrates widely used molecular evolution tools to detect positive selection, and maps results onto protein structures predicted by AlphaFold. Applying FREEDA to >100 mouse centromere proteins, we find evidence of positive selection in intrinsically disordered regions of ancient domains, suggesting innovation of essential functions. As a proof-of-principle experiment, we show innovation in centromere binding of CENP-O. Overall, we provide an accessible computational tool to guide cell biology research and apply it to experimentally demonstrate functional innovation.
Neutralizing antibody levels and epidemiological information of patients with breakthrough COVID-19 infection in Toyama, Japan
Authors: Tani Hideki , Inasaki Noriko , Shimada Takahisa , Saga Yumiko , Kaya Hiroyasu , Maruyama Yumiko , Matano Sadaya , Itoh Hiroyuki , Kashii Tatsuhiko , Yamazaki Emiko , Yazawa Shunsuke , Itamochi Masae , Oishi Kazunori
Published: February 2023

Breakthrough infection (BI) after coronavirus disease 2019 (COVID-19) vaccination has exploded owing to the emergence of various SARS-CoV-2 variants and has become a major problem at present. In this study, we analyzed the epidemiological information and possession status of neutralizing antibodies in patients with BI using SARS-CoV-2 pseudotyped viruses (SARS-CoV-2pv). Analysis of 44 specimens diagnosed with COVID-19 after two or more vaccinations showed high inhibition of infection by 90% or more against the Wuhan strain and the Alpha and Delta variants of pseudotyped viruses in 40 specimens. In contrast, almost no neutralizing activity was observed against the Omicron BA.1 variant. Many cases without neutralizing activity or BI were immunosuppressed individuals. The results of this study show that BI occurs even when there are sufficient neutralizing antibodies in the blood due to exposure to close contacts at the time of infection. Thus, even after vaccination, sufficient precautions must be taken to prevent infection.
A socio-technical system perspective to exploring the negative effects of social media on work performance
Authors: Cao Xiongfei , Xu Caixiang , Ali Ahsan
Published: February 2023

Purpose

This research aims to explore the potential negative effects of social media on employees' work performance in a stressful working environment.

Design/methodology/approach

This study model was tested using a sample of 398 social media users from China.

Findings

Structural equation modeling analysis provide support for most of the hypothesized relationships as results reveal that social stressors and technical stressors are related to exhaustion and anxiety of employees using social media. Furthermore, results reveal that exhaustion and anxiety exhibit a negative influence on employees' work performance.

Originality/value

This study extends the authors’ understanding of how social stressors and technical stressors are related to work performance. The integration of the transactional theory of stress and coping with socio-technical systems offers a holistic view to explain the phenomenon of stress in the social media context.
Virtual grocery shopping intention: an application of the model of goal-directed behaviour
Authors: Thomas-Francois Kimberly , Jo WooMi , Somogyi Simon , Li Qianya , Nixon Andrew
Published: February 2023

Purpose

Virtual grocery shopping (VGS), or online grocery shopping, traditionally has seen slow adoption in Canada; however, the COVID-19 pandemic has forced consumers to seek safer ways to shop. Retailers have invested in building new infrastructure to meet the current consumer demands for VGS. However, the main driver for VGS behaviour has not been yet clearly identified. Additionally, it is also not unknown whether the shopping modalities will continue VGS after the pandemic. This study provides insights into consumer intentions to use VGS by extending the model of goal-directed behaviour (MGB) to incorporate consumer technological readiness.

Design/methodology/approach

The study collected 935 valid survey responses from an online survey panel of Canadian consumers. A two-step approach was applied to analyse the data, comprising confirmatory factor analysis (CFA) and structural equation modelling (SEM). The data quality and model fit were tested before testing the proposed relationships among the constructs: attitude, subjective norm, perceived behavioural control, positive and negative anticipated emotions, as well as technological readiness, desire and behaviour intentions. The mediation role of desire between frequency of past online grocery shopping behaviours and the future behavioural intention was also tested using SPSS PROCESS.

Findings

The study results showed that attitudes, subjective norms, perceived behavioural control, positive and negative emotions, technological readiness and frequency of past VGS have a major impact on consumers' desire to embrace VGS in the future. Consumer desire also played a significant mediating role between frequency of past VGS behaviours and future shopping intention online. In addition, the frequency of past VGS showed an even stronger impact on behavioural intention among female consumers than among male consumers.

Originality/value

The findings of this study provide an original insight into the social, cultural and psychological factors that impact consumers' use of VGS, particularly the impacts of gender.
Forecasting demand in the residential construction industry using machine learning algorithms in Jordan
Authors: Sammour Farouq , Alkailani Heba , Sweis Ghaleb J. , Sweis Rateb J. , Maaitah Wasan , Alashkar Abdulla
Published: February 2023

Purpose

Demand forecasts are a key component of planning efforts and are crucial for managing core operations. This study aims to evaluate the use of several machine learning (ML) algorithms to forecast demand for residential construction in Jordan.

Design/methodology/approach

The identification and selection of variables and ML algorithms that are related to the demand for residential construction are indicated using a literature review. Feature selection was done by using a stepwise backward elimination. The developed algorithm’s accuracy has been demonstrated by comparing the ML predictions with real residual values and compared based on the coefficient of determination.

Findings

Nine economic indicators were selected to develop the demand models. Elastic-Net showed the highest accuracy of (0.838) versus artificial neural networkwith an accuracy of (0.727), followed by Eureqa with an accuracy of (0.715) and the Extra Trees with an accuracy of (0.703). According to the results of the best-performing model forecast, Jordan’s 2023 first-quarter demand for residential construction is anticipated to rise by 11.5% from the same quarter of the year 2022.

Originality/value

The results of this study extend to the existing body of knowledge through the identification of the most influential variables in the Jordanian residential construction industry. In addition, the models developed will enable users in the fields of construction engineering to make reliable demand forecasts while also assisting in effective financial decision-making.
Power density improvement of axial flux permanent magnet synchronous motor by using different magnetic materials
Authors: Hebri Mohamed Amine , Rebhaoui Abderrahmane , Bauw Gregory , Lecointe Jean-Philippe , Duchesne Stéphane , Zito Gianluca , Abdenour Abdelli , Mediavilla Santos Victor , Mallard Vincent , Maier Adrien
Published: February 2023

Purpose

The purpose of this paper is to exploit the optimal performances of each magnetic material in terms of low iron losses and high saturation flux density to improve the efficiency and the power density of the selected motor.

Design/methodology/approach

This paper presents a study to improve the power density and efficiency of e-motors for electric traction applications with high operating speed. The studied machine is a yokeless-stator axial flux permanent magnet synchronous motor with a dual rotor. The methodology consists in using different magnetic materials for an optimal design of the stator and rotor magnetic circuits to improve the motor performance. The candidate magnetic materials, adapted to the constraints of e-mobility, are made of thin laminations of Si-Fe nonoriented grain electrical steel, Si-Fe grain-oriented electrical steel (GOES) and iron-cobalt Permendur electrical steel (Co-Fe).

Findings

The mixed GOES-Co-Fe structure allows to reach 10 kW/kg in rated power density and a high efficiency in city driving conditions. This structure allows to make the powertrain less energy consuming in the battery electric vehicles and to reduce CO2 emissions in hybrid electric vehicles.

Originality/value

The originality of this study lies in the improvement of both power density and efficiency of the electric motor in automotive application by using different magnetic materials through a multiobjective optimization.