bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of Myopia Correction Pattern of Children and Parent's Attitudes in China
Authors: Yang Yongmei , Jiang Jun
Published: May 2023

SIGNIFICANCE

This survey provides information about Chinese children's myopia correction status and parents' attitudes toward myopia correction.

PURPOSE

Under the background of a guideline of appropriate techniques for the prevention and control of children's myopia, this study aimed to investigate the current myopia correction pattern of children and parents' attitudes.

METHODS

Two self-administered questionnaires were distributed to 684 children with myopia corrections and 450 parents (384 mothers and 66 fathers) to explore children's myopia correction patterns and parental attitudes. The questionnaire investigated the pattern of children's myopia correction, prescribing of children's myopia correction, the incidence of high myopia, parental attitudes toward various myopia corrections methods, and preferred initial age for contact lens usage.

RESULTS

Single-vision spectacles (n = 600; 88.2 ± 7.4%) are widely used in China because of their comfort and affordability. More than 80% of children use single-vision spectacles prescribed by ophthalmologists and opticians. Children who used single-vision spectacles at an earlier age had more incidence of high myopia (18.4 ± 4.2%) than those who used single-vision spectacles at a later age (0.7 ± 0.9%). Effective myopia control was the primary reason parents preferred to choose different optical corrections, followed by safety, convenience, clarity, affordability, comfort, and other reasons. The survey indicated that 52.4% of parents whose children used orthokeratology lenses would have preferred safe and convenient options if available. In addition, 50% of the parents preferred delaying their children's use of orthokeratology lenses and other contact lenses to an older age.

CONCLUSIONS

Single-vision spectacles are still a popular option to correct myopia in children. There was a demonstrated increase in myopia in children who used single spectacles at an earlier age. Parents' attitudes were important factors for selecting myopia corrections in children.
Regularly Playing First-Person Shooter Videogames Improves Dynamic Visual Acuity
Authors: Argilés Marc , Erickson Graham , Quevedo-Junyent Lluïsa
Published: May 2023

Significance

This study investigated the dynamic visual acuity (DVA) in young adults that play action video games regularly compared with non-action video games players and those without regular experience in videogame play. The results indicate better performance in some measurements of DVA in action video game players.

Purpose

This study aims to provide new insights about performance on DVA assessments in young adults who play action video games regularly.

Methods

A cross-sectional study was conducted between action video game and non-action video game players with 47 participants, range from 20 to 30 years old. DVA with 2 different angular velocities, 57 °/s and 28.5 °/s and three different contrast, 100%, 50% and 10% were evaluated. A second analysis with 33 participants compared DVA between action video game players and non-experience videogames or less than 1 hour/week in gaming.

Results

Dynamic visual acuity in the first analysis revealed a non-statistical significance between groups in all the experimental conditions with 57 °/s and 28.5 °/s in three different contrasts. The second analysis with 33 participants revealed a statistical significance in DVA at 57 °/s and 28.5 °/s with contrast 100 %, P = .003 and P < .001, respectively.

Conclusions

Dynamic visual acuity seems to have better performance in young adults spending more than 5 hours/week with action videogames, mostly first-person shooter games.
The Emerging Leaders in Public Health Initiative: Leadership Development to Advance Public Health Practice
Authors: Schenck Anna P. , Suttie Janet , Orton Stephen , Carter-Edwards Lori , Herrick Jeannine , Meadows Phyllis D. , Dinkin Donna R.
Published: May 2023

Context:

Effective leadership is essential for governmental public health agencies to promote and protect the health of their communities.

Objective:

The Emerging Leaders in Public Health Initiative, a program of The Kresge Foundation, was implemented to strengthen leadership in governmental public health. We seek to examine lessons from the initiative to contribute to the field a better understanding of leadership development practices.

Design:

An external evaluator conducted a retrospective analysis of participant responses postinitiative to assess the overall impact of the initiative and explore which components were most valuable.

Setting:

United States.

Participants:

Directors and other staff from governmental public health agencies were recruited in 2-person teams to participate in 3 successive cohorts.

Intervention:

Drawn from adaptive leadership principles, a framework was developed to guide the selection and implementation of educational and experiential activities. Participants were challenged to develop a new role for their public health agency, which provided a learning laboratory to practice individual and team leadership skills. The Kresge Foundation provided participants with a resource grant and a National Program Office offered convenings, webinars, coaching, and technical assistance over the 18 months of the developmental experience.

Main Outcome Measures:

Satisfaction, perceived value of components, and future intentions were assessed from participants in cohorts II and III (n = 70). The overall response rate was 93%.

Results:

One hundred four diverse leaders from 52 agencies, representing 30 states participated in the initiative. Participants were extremely satisfied with the program (94%) and indicated a strong likelihood of recommending it to a colleague (96%). Unrestricted grant funding, peer learning, and in-person learning sessions were the program components rated most highly valuable.

Conclusions:

This initiative offers insights into principles and processes to be considered for future public health leadership development.
Symptomatic neuroma development following en bloc resection of skeletal and soft tissue tumors: A retrospective analysis of 331 cases
Authors: Aslami Zohra V. , Leland Christopher R. , Strike Sophie A. , Forsberg Jonathan A. , Morris Carol D. , Levin Adam S. , Tuffaha Sami H.
Published: May 2023

Background:

While symptomatic neuroma formation has been described in other patient populations, these data have not been studied in patients undergoing resection of musculoskeletal tumors. This study aims to characterize the incidence and risk factors of symptomatic neuroma formation following en bloc resection in this population.

Methods:

We retrospectively reviewed adults undergoing en bloc resections for musculoskeletal tumors at a high-volume sarcoma center from 2014-2019. We included en bloc resections for an oncologic indication and excluded non-en bloc resections, primary amputations, and patients with insufficient follow-up. Data are provided as descriptive statistics and multivariable regression modeling was performed.

Results:

We included 231 patients undergoing 331 en bloc resections (46% female; mean age 52 years). Nerve transection was documented in 87 resections (26%). There were 81 symptomatic neuromas (25%) meeting criteria of Tinel sign or pain on exam and neuropathy in the distribution of suspected nerve injury. Factors associated with symptomatic neuroma formation included age 18-39 (aOR, 3.6; 95% CI, 1.5-8.4; p < 0.01) and 40-64 (aOR, 2.2; 95% CI, 1.1-4.6; p = 0.04), multiple resections (aOR, 3.2; 95% CI, 1.7-5.9; p < 0.001), preoperative neuromodulator requirement (aOR, 2.7; 95% CI 1.2-6.0; p = 0.01) and resection of fascia or muscle (aOR, 0.5; 95% CI, 0.3-1.0; p = 0.045).

Conclusion:

Our results highlight the importance of adequate preoperative optimization of pain control and intraoperative prophylaxis for neuroma prevention following en bloc resection of tumors, particularly for younger patients with a recurrent tumor burden.

Level of Evidence:

Level III, prognostic study.
Co-development and bidirectional associations between psychological stress and obesity in school-aged children: A longitudinal study in China
Authors: Tang Lei , Yin Ruoyun , Xi Xuan , Hu Qian , Zhang Fan , Liu Qin
Published: May 2023

Objective

Psychological stress (PS) has always been a hot topic for researchers to investigate the potential determinants of childhood overweight/obesity. Up to now, cohort studies investigating the relationship between PS and childhood obesity have used different ways to assess PS, different indicators to measure obesity, different analysis methods, and the results were also inconsistent.

Methods

Data were obtained from the second to eighth follow-up of an ongoing cohort of school-aged children in Chongqing, China (June 2015 - June 2018) with seven waves (W1-W7, NW1 = 1419). The latent growth curve model (LGCM) was used to estimate the co-developmental trends between PS and obesity (BMI, WHtR). Random intercept cross-lagged panel models (RI-CLPM) were constructed to examine their longitudinal bidirectional associations.

Results

The changes in PS and obesity (BMI, WHtR) were co-developing (rBMI
= -1.105, P = 0.003; rWHtR
= -0.991, P = 0.004). Longitudinal models showed significant negative correlations between PS and obesity at the between-person level (rBMI
= -4.993; rWHtR
= -1.591). BMI at W3 could negatively predict PS six months later (β = -1.508, P = 0.027), and WHtR at W1 could negatively predict PS at W3 (β = -2.809, P = 0.014). Different aspects of PS had different associations with obesity. Notably, there was a significant reciprocal relationship between peer interaction PS and obesity.

Conclusions

Different aspects of PS were differentially associated with obesity. Notably, there may be a clear reciprocal relationship between peer interaction PS and obesity. These findings provide new directions for protecting children's mental health to prevent or control childhood overweight/obesity.
Systematic review of alternative HIV pre-exposure prophylaxis (PrEP) care delivery models to improve PrEP services
Authors: Kamitani Emiko , Mizuno Yuko , DeLuca Julia B. , Collins Charles B.
Published: May 2023

Objectives:

To identify types, evidence, and study gaps of alternative HIV preexposure prophylaxis (PrEP) care delivery models in the published literature.

Design:

Systematic review and narrative synthesis

Methods:

We searched in the US Centers for Disease Control and Prevention (CDC) Prevention Research Synthesis (PRS) database through December 2022 (PROSPERO CRD42022311747). We included studies published in English that reported implementation of alternative PrEP care delivery models. Two reviewers independently reviewed the full text and extracted data by using standard forms. Risk of bias was assessed using the adapted Newcastle-Ottawa Quality Assessment Scale. Those that met our study criteria were evaluated for efficacy against CDC Evidence-Based Intervention (EBI) or Evidence-Informed Intervention (EI) criteria or Health Resources and Services Administration Emergency Strategy (ES) criteria, or for applicability by using an assessment based on the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework.

Results:

This review identified 16 studies published between 2018-2022 that implemented alternative prescriber (n = 8), alternative setting for care (n = 4), alternative setting for laboratory screening (n = 1), or a combination of the above (n = 3) . The majority of studies were US-based (n = 12) with low risk of bias (n = 11). None of the identified studies met EBI, EI, or ES criteria. Promising applicability was found for pharmacists prescribers, telePrEP , and mail-in testing.

Conclusions:

Delivery of PrEP services outside of the traditional care system by expanding providers of PrEP care (e.g., pharmacist prescribers), as well as the settings of PrEP care (i.e., telePrEP) and laboratory screening (i.e., mail-in testing) may increase PrEP access and care delivery.
Dietary Iron Intake and HIV-Related Outcomes Among Adults Initiating Antiretroviral Therapy in Tanzania
Authors: Abioye Ajibola Ibraheem , Hughes Michael D. , Sudfeld Christopher R. , Noor Ramadhani Abdallah , Isanaka Sheila , Lukmanji Zohra , Mugusi Ferdinand , Fawzi Wafaie W.
Published: May 2023

Objective:

Anemia is highly prevalent among people living with HIV (PLWHIV) and is often due to iron deficiency. This study evaluated the relationship of dietary iron intake levels and sources with mortality and clinical outcomes among adults initiating HAART.

Design:

We conducted a secondary analysis of a multivitamin supplementation trial among 2293 PLWHIV initiating HAART in Dar es Salaam, Tanzania.

Methods:

Dietary iron intake was assessed with a food frequency questionnaire at HAART initiation, and participants followed until death or censoring. Total, animal-, and plant-sourced iron were categorized into quartiles. Intake of food groups was categorized into 0–1, 2–3, and ≥4 servings/wk. Cox proportional hazards models estimated hazard ratios for mortality and incident clinical outcomes.

Results:

There were 175 deaths (8%). Red meat intake was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.35 to 0.83), AIDS-related mortality (HR: 0.49; 95% CI: 0.28 to 0.85), and severe anemia (HR: 0.57; 95% CI: 0.35 to 0.91), when intake ≥4 servings/wk, compared with 0–1 servings/wk. Legume intake was a lower risk of associated with all-cause mortality (HR: 0.49; 95% CI: 0.31 to 0.77) and AIDS-related mortality (HR: 0.37; 95% CI: 0.23 to 0.61), when intake ≥4 servings/wk, compared with 0–1 servings/wk. Although total dietary iron and overall plant-sourced iron intake were not associated with the risk of mortality or HIV-related outcomes, the highest quartile of animal-sourced iron intake was associated with a lower risk of all-cause mortality (HR: 0.56; 95% CI: 0.35 to 0.90) and a lower risk of AIDS-related mortality (HR: 0.50; 95% CI: 0.30 to 0.90), compared with the lowest quartile.

Conclusion:

Intake of iron-rich food groups may be associated with a lower risk of mortality and critical HIV-related outcomes among adults initiating HAART.

Trial registration:

The parent trial was registered at Clinicaltrials.gov. Identifier: NCT00383669.
CIRC_0026466 KNOCKDOWN PROTECTS HUMAN BRONCHIAL EPITHELIAL CELLS FROM CIGARETTE SMOKE EXTRACT–INDUCED INJURY BY PROMOTING THE MIR-153-3P/TRAF6/NF-ΚB PATHWAY
Authors: Wang Cong , Tang Yanfen , Hou Haihui , Su Chengcheng , Gao Yemeng , Yang Xu
Published: May 2023

Background: Considerable data have shown that circular RNAs (circRNAs) mediate the pathogenesis of chronic obstructive pulmonary disease (COPD). The study aims to analyze the function and mechanism of circ_0026466 in COPD. Methods: Human bronchial epithelial cells (16HBE) were treated with cigarette smoke extract (CSE) to establish a COPD cell model. Quantitative real-time polymerase chain reaction and Western blot were used to detect the expression of circ_0026466, microRNA-153-3p (miR-153-3p), TNF receptor associated factor 6 (TRAF6), cell apoptosis-related proteins, and NF-κB pathway-related proteins. Cell viability, proliferation, apoptosis, and inflammation were investigated by cell counting kit-8, EdU assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Oxidative stress was evaluated by lipid peroxidation malondialdehyde assay kit and superoxide dismutase activity assay kit. The interaction between miR-153-3p and circ_0026466 or TRAF6 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results: Circ_0026466 and TRAF6 expression were significantly increased, but miR-153-3p was decreased in the blood samples of smokers with COPD and CSE-induced 16HBE cells when compared with controls. CSE treatment inhibited the viability and proliferation of 16HBE cells but induced cell apoptosis, inflammation, and oxidative stress, but these effects were attenuated after circ_0026466 knockdown. Circ_0026466 interacted with miR-153-3p and regulated CSE-caused 16HBE cell damage by targeting miR-153-3p. Additionally, TRAF6, a target gene of miR-153-3p, regulated CSE-induced 16HBE cell injury by combining with miR-153-3p. Importantly, circ_0026466 activated NF-κB pathway by targeting the miR-153-3p/TRAF6 axis. Conclusion: Circ_0026466 absence protected against CSE-triggered 16HBE cell injury by activating the miR-153-3p/TRAF6/NF-κB pathway, providing a potential therapeutic target for COPD.
RESPIRATORY VARIABILITY OF VALVULAR PEAK SYSTOLIC VELOCITY AS A NEW INDICATOR OF FLUID RESPONSIVENESS IN PATIENTS WITH SEPTIC SHOCK
Authors: Ma Qiang , Ding Caiyun , Jiang Feng , Hu Guobin , Wu Jingyi , Zhang Xia
Published: May 2023

Objective: The aim of this study was to evaluate the reliability and feasibility of pulse Doppler measurements of peak velocity respiratory variability of mitral and tricuspid valve rings during systole as new dynamic indicators of fluid responsiveness in patients with septic shock. Methods: Transthoracic echocardiography (TTE) was performed to measure the respiratory variability of aortic velocity-time integral (∆VTI), respiratory variability of tricuspid annulus systolic peak velocity (∆RVS), respiratory variability of mitral annulus systolic peak velocity (∆LVS), and other related indicators. Fluid responsiveness was defined as a 10% increase in cardiac output after fluid expansion, assessed by TTE. Results: A total of 33 patients with septic shock were enrolled in this study. First, there was no significant difference in the population characteristics between the fluid responsiveness positive group (n = 17) and the fluid responsiveness negative group (n = 16) (P > 0.05). Second, Pearson correlation test showed that ∆RVS, ∆LVS, and TAPSE with the relative increase in cardiac output after fluid expansion (R = 0.55, P = 0.001; R = 0.40, P = 0.02; R = 0.36, P = 0.041). Third, multiple logistic regression analysis demonstrated that ∆RVS, ∆LVS, and TAPSE were significantly correlated with fluid responsiveness in patients with septic shock. Fourth, receiver operating characteristic (ROC) curve analysis revealed that ∆VTI, ∆LVS, ∆RVS, and TAPSE had good predictive ability for fluid responsiveness in patients with septic shock. The area under the curve (AUC) of ∆VTI, ∆LVS, ∆RVS, and TAPSE for predicting fluid responsiveness was 0.952, 0.802, 0.822, and 0.713, respectively. The sensitivity (Se) values were 1.00, 0.73, 0.81, and 0.83, whereas the specificity (Sp) values were 0.84, 0.91, 0.76, and 0.67, respectively. The optimal thresholds were 0.128, 0.129, 0.130, and 13.9 mm, respectively. Conclusion: Tissue Doppler ultrasound evaluation of respiratory variability of mitral and tricuspid annular peak systolic velocity could be a feasible and reliable method for the simple assessment of fluid responsiveness in patients with septic shock.
Superiority of compensatory reserve measurement compared with the Shock index for early and accurate detection of reduced central blood volume status
Authors: Convertino Victor A. , Thompson Patrick , Koons Natalie J. , Le Tuan D. , Lanier J. Brian , Cardin Sylvain
Published: May 2023

BACKGROUND

Shock index (SI) equals the ratio of heart rate (HR) to systolic blood pressure (SBP) with clinical evidence that it is more sensitive for trauma patient status assessment and prediction of outcome compared with either HR or SBP alone. We used lower body negative pressure (LBNP) as a human model of central hypovolemia and compensatory reserve measurement (CRM) validated for accurate tracking of reduced central blood volume to test the hypotheses that SI: (1) presents a late signal of central blood volume status; (2) displays poor sensitivity and specificity for predicting the onset of hemodynamic decompensation; and (3) cannot identify individuals at greatest risk for the onset of circulatory shock.

METHODS

We measured HR, SBP, and CRM in 172 human subjects (19–55 years) during progressive LBNP designed to determine tolerance to central hypovolemia as a model of hemorrhage. Subjects were subsequently divided into those with high tolerance (HT) (n = 118) and low tolerance (LT) (n = 54) based on completion of 60 mm Hg LBNP. The time course relationship between SI and CRM was determined and receiver operating characteristic (ROC) area under the curve (AUC) was calculated for sensitivity and specificity of CRM and SI to predict hemodynamic decompensation using clinically defined thresholds of 40% for CRM and 0.9 for SI.

RESULTS

The time and level of LBNP required to reach a SI = 0.9 (~60 mm Hg LBNP) was significantly greater (p < 0.001) compared with CRM that reached 40% at ~40 mm Hg LBNP. Shock index did not differ between HT and LT subjects at 45 mm Hg LBNP levels. ROC AUC for CRM was 0.95 (95% CI = 0.94–0.97) compared with 0.91 (0.89–0.94) for SI (p = 0.0002).

CONCLUSION

Despite high sensitivity and specificity, SI delays time to detect reductions in central blood volume with failure to distinguish individuals with varying tolerances to central hypovolemia.

LEVEL OF EVIDENCE

Diagnostic Test or Criteria; Level III.
A global survey of Salmonella plasmids and their associations with antimicrobial resistance
Authors: Robertson James , Schonfeld Justin , Bessonov Kyrylo , Bastedo Patrick , Nash John H. E.
Published: May 2023

Plasmids are the primary vector for horizontal transfer of antimicrobial resistance (AMR) within bacterial populations. We applied the MOB-suite, a toolset for reconstructing and typing plasmids, to 150 767 publicly available

Salmonella

whole-genome sequencing samples covering 1204 distinct serovars to produce a large-scale population survey of plasmids based on the MOB-suite plasmid nomenclature. Reconstruction yielded 183 017 plasmids representing 1044 primary MOB-clusters and 830 potentially novel MOB-clusters. Replicon and relaxase typing were able to type 83.4 and 58 % of plasmids, respectively, compared to 99.9 % for MOB-clusters. Within this work, we developed an approach to characterize the horizonal transfer of MOB-clusters and AMR genes across different serotypes, as well as the diversity of MOB-cluster associations with AMR genes. Aggregating conjugative mobility predictions provided by the MOB-suite and their corresponding serovar entropy demonstrated that non-mobilizable plasmids were associated with fewer serotypes compared to mobilizable or conjugative MOB-clusters. The host-range predictions for MOB-clusters also showed differences between the mobility classes, with mobilizable MOB-clusters accounting for 88.3 % of the multi-phyla (broad-host-range) predictions compared to 3 and 8.6 % for conjugative and non-mobilizable, respectively. A total of 296 (22 %) of identified MOB-clusters were associated with at least one resistance gene, indicating that the majority of

Salmonella

plasmids are not involved in AMR dissemination. Shannon entropy analysis of horizontal transfer of AMR genes across serovars and MOB-clusters demonstrated that horizonal transfer of genes is higher between serovars compared to transfer between different MOB-clusters. In addition to the population structure characterization based on primary MOB-clusters, we characterized a multi-plasmid outbreak responsible for the global dissemination of bla
CMY-2 across different serotypes using higher resolution MOB-suite secondary cluster codes. The plasmid characterization approach developed here can be applied to different organisms to identify plasmids and genes which pose high risks for horizontal transfer.
A Mixed-Methods Comparison of Gender Differences in Alcohol Consumption and Drinking Characteristics among Patients in Moshi, Tanzania
Authors: Pauley Alena , Buono Mia , West Kirstin , Metcalf Madeline , Rent Sharla , Kilasara Joseph , Sawe Yvonne , Mikindo Mariana , Mmbaga Blandina T. , Boshe Judith , Vissoci João Ricardo Nickenig , Staton Catherine A.
Published: May 2023

Background

Excessive alcohol use stands as a serious threat to individual and community well-being, having been linked to a wide array of physical, social, mental, and economic harms.

Alcohol consumption differs by gender, a trend seen both globally and in Moshi, Tanzania, a region with especially high rates of intake and few resources for alcohol-related care. To develop effective gender-appropriate treatment interventions, differences in drinking behaviors between men and women must be better understood. Our study aims to identify and explore gender-based discrepancies in alcohol consumption among Kilimanjaro Christian Medical Center (KCMC) patients.

Methods

A systematic random sampling of adult patients presenting to KCMC’s Emergency Department (ED) or Reproductive Health Center (RHC) was conducted from October 2020 until May 2021. Patients answered demographic and alcohol use-related questions and completed brief surveys including the Alcohol Use Disorder Identification Test (AUDIT). Through purposeful sampling, 19 subjects also participated in in-depth interviews (IDIs) focused on identifying gender differences in alcohol use.

Results

During the 8-month data collection timeline, 655 patients were enrolled. Men and women patients at KCMC’s ED and RHC were found to have significant differences in their alcohol use behaviors including lower rates of consumption among women, (average [SD] AUDIT scores were 6.76 [8.16] among ED men, 3.07 [4.76] among ED women, and 1.86 [3.46] among RHC women), greater social restrictions around women’s drinking, and more secretive alcohol use behaviors for where and when women would drink. For men, excess drinking was normalized within Moshi, tied to men’s social interactions with other men, and generally motivated by stress, social pressure, and despair over lack of opportunity.

Conclusion

Significant gender differences in drinking behaviors were found, primarily influenced by sociocultural norms. These dissimilarities in alcohol use suggest that future alcohol-related programs should incorporate gender in their conceptualization and implementation.
For Better or Worse? Subjective Expectations and Cost-Benefit Trade-Offs in Health Behavior
Authors: Conti Gabriella , Giustinelli Pamela
Published: May 2023

We provide a framework to disentangle the role of preferences and beliefs in health behavior, and we apply it to compliance behavior during the acute phase of the COVID-19 pandemic. Using rich data on subjective expectations collected during the spring 2020 lockdown in the UK, we estimate a simple model of compliance behavior with uncertain costs and benefits, which we employ to quantify the utility trade-offs underlying compliance, to decompose group differences in compliance plans, and to compute the monetary compensation required for people to comply. We find that, on average, individuals assign the largest disutility to passing away from COVID-19 and being caught transgressing, and the largest utility to preserving their mental health. But we also document substantial heterogeneity in preferences and/or expectations by vulnerability status, gender, and other individual characteristics. In our data, both preferences and expectations matter for explaining gender differences in compliance, whereas compliance differences by vulnerability status are mainly driven by heterogeneity in preferences. We also investigate the relationship between own and others’ compliance. When others fail to comply and trust breaks down, individuals respond heterogeneously depending on their own circumstances and characteristics. When others around them comply less, those with higher risk tolerance and those without prior COVID-19 experience plan to comply less themselves, while the vulnerables plan to comply more. When a high-level public figure breaches the rules, supporters of the opposing political party plan to comply less. These findings emphasize the need for public health policies to account for heterogenous beliefs, preferences, and responses to others in citizens’ health behaviors.

JEL Codes: C25, C83, D84, I12, I18.
Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification
Authors: Peretz Cheryl A. C. , Kennedy Vanessa E. , Walia Anushka , Delley Cyrille L. , Koh Andrew , Tran Elaine , Clark Iain C. , Hayford Corey E. , D’Amato Chris , Xue Yi , Fontanez Kristina M. , Roy Ritu , Logan Aaron C. , Perl Alexander E. , Abate Adam , Olshen Adam , Smith Catherine C.
Published: May 2023

Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.
Comparing mental imagery experiences across visual, auditory, and other sensory modalities
Authors: Sulfaro Alexander A , Robinson Amanda K , Carlson Thomas A
Published: May 2023

Although mental imagery is often studied as a visual phenomenon, it can occur in any sensory modality. Given that mental images may recruit similar modality-specific neural systems to those which support veridical perception, the properties of mental images may be constrained by the modality in which they are experienced. Yet, little is known about how mental images are experienced at all, let alone how such experiences may vary depending on the modality in which they occur. Here we explored how mental images are experienced in different modalities using an extensive questionnaire. Mainly focusing on visual and auditory mental imagery, we surveyed participants on if and how they experienced their thought content in a sensory way when thinking about the appearance or sound of the letter “O”. Specifically, we investigated temporal properties of imagined content (e.g. onset latency, duration), as well as spatial properties (e.g. apparent location), effort (e.g. ease, spontaneity, control), dependence on body movements (e.g. eye movements), interactions between real and imagined content (e.g. inner speech during reading), the perceived normality of imagery experiences, and how participants labeled their own experiences. Participants also ranked their mental imagery experiences in the five traditional sensory modalities and reported on the involvement of each modality during their thoughts, imagination, and dreams. Confidence ratings were taken for every answer recorded. Overall, visual and auditory experiences tended to dominate mental events relative to other sensory modalities. However, most people reported that auditory mental imagery was superior to visual mental imagery on almost every metric tested, except with respect to spatial properties. Our findings suggest that mental images are restrained in a similar matter to other modality-specific sensory processes in the brain. Broadly, our work also provides a wealth of insights and observations into how mental images are experienced by individuals, acting as a useful resource for future investigations.
Evidence that ultrafast non-quantal transmission underlies short-latency vestibular evoked potentials
Authors: Pastras Christopher J. , Curthoys Ian S. , Asadnia Mohsen , McAlpine David , Rabbitt Richard D. , Brown Daniel J.
Published: May 2023

Amniotes evolved a unique calyceal postsynaptic terminal in the vestibular organs of the inner ear that underpins quantal and non-quantal transmission at the synapse of sensory hair cells and vestibular afferent neurons. The non-quantal component is of particular interest as it includes an ultrafast synaptic current thought to underlie the exquisite synchronization of action potentials in vestibular afferent fibres to dynamic stimuli such as sound and vibration. Here we demonstrate evidence that non-quantal transmission is responsible for short latency vestibular evoked potentials (vCAPs) in the guinea pig utricle. We first show that, unlike auditory nerve responses which are completely abolished, vCAPs are insensitive to local administration of the AMPA receptor agonist CNQX. Moreover, latency comparisons between presynaptic hair cell and postsynaptic neural responses reveal that the vCAP occurs without measurable synaptic delay. Finally, using a paired-pulse stimulus designed to deplete the readily releasable pool of synaptic vesicles in hair cells, we reveal that forward masking is lacking in vestibular responses, compared to the equivalent cochlear responses. Our data support the hypothesis that the fast component of non-quantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimulation.

Significance

The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more pre-synaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of data in the guinea pig that reveal the pre-synaptic transmission of the most sensitive vestibular afferents are faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.
Enteric pharmacokinetics of monomeric and multimeric camelid nanobody single-domain antibodies
Authors: Debatis Michelle , Danz Hillary , Tremblay Jacqueline M. , Gaspie Kimberly , Kudej Raymond K. , Vigdorovich Vladimir , Sather Noah , Jaskiewicz Justyna J. , Tzipori Saul , Shoemaker Charles B.
Published: May 2023

Abstract

Single-domain antibodies (sdAbs) derived fromCamelidaeheavy-chain-only antibodies (also called nanobodies or VHHs) have advantages over conventional antibodies in terms of their small size and stability to pH and temperature extremes, their ability to express well in microbial hosts, and to be functionally multimerized for enhanced properties. For these reasons, VHHs are showing promise as enteric disease therapeutics, yet little is known as to their pharmacokinetics (PK) within the digestive tract. To improve understanding of enteric VHH PK, we investigated the functional and structural stability of monomeric and multimeric camelid VHH-agents followingin vitroincubation with intestinal extracts (chyme) from rabbits and pigs or fecal extracts from human sources, andin vivoin rabbits. The results showed that unstructured domains such as epitopic tags and flexible spacers composed of different amino acid sequences were rapidly degraded by enteric proteases while the functional core VHHs were much more stable to these treatments. Individual VHHs were widely variable in their functional stability to GI tract proteases. Some VHH-based agents which neutralize enteric Shiga toxin Stx2 displayed a functional stability to chyme incubations comparable to that of Stx2-neutralizing IgG and IgA mAbs, thus indicating that selected nanobodies can approach the functional stability of conventional immunoglobulins. Enteric PK data obtained fromin vitroincubation studies were consistent with similar incubations performedin vivoin rabbit surgical gut loops. These findings have broad implications for enteric use of VHH-based agents, particularly VHH fusion proteins.
Characterisation of an Omnitrap-Orbitrap platform equipped with IRMPD, UVPD and ExD for the analysis of peptides and proteins
Authors: Smyrnakis Athanasios , Levin Nikita , Kosmopoulou Mariangela , Jha Ajay , Fort Kyle , Makarov Alexander , Papanastasiou Dimitris , Mohammed Shabaz
Published: May 2023

We describe an instrument configuration based on the Orbitrap Exploris 480 mass spectrometer that has been coupled to an Omnitrap platform. The Omnitrap possesses three distinct ion-activation regions, that can be used to perform resonant based collision induced dissociation, several forms of electron associated fragmentation, and ultraviolet photodissociation. Each section can also be combined with infrared multiphoton dissociation. In this work, we demonstrate all these modes of operation on a range of peptides and proteins. The results show that this instrument configuration produces similar data to previous implementations of each activation technique and at similar efficiency levels. We demonstrate that this unique instrument configuration is extremely versatile for the interrogation of polypeptides.
Memory at your fingertips: how viscoelasticity affects tactile neuron signaling
Authors: Saal Hannes P. , Birznieks Ingvars , Johansson Roland S.
Published: May 2023

Human skin and its underlying tissues constitute a viscoelastic medium, implying that any deformation depends not only on the currently applied force, but also the recent loading history. The extent to which this physical memory influences the signaling of first-order tactile neurons during natural hand use is not well understood. Here, we examined the effect of past loading on the responses of fast-adapting (FA-1) and slowly-adapting (SA-1 and SA-2) first-order tactile neurons innervating the human fingertip to loadings applied in different directions representative of object manipulation tasks. We found that variation in the preceding loading affected neurons’ overall signaling of force direction. Some neurons kept signaling the current direction, while others signaled both the current and preceding direction, or even primarily the preceding direction. In addition, ongoing impulse activity in SA-2 neurons between loadings signaled information related to the fingertip’s viscoelastic deformation state. We conclude that tactile neurons at the population level signal continuous information about the fingertip’s viscoelastic deformation state, which is shaped by both its recent history and current loading. Such information might be sufficient for the brain to correctly interpret current force loading and help in computing accurate motor commands for interactions with objects in manipulation and haptic tasks.
Divergent host innate immune response to the smooth-to-roughM. abscessusadaptation to chronic infection
Authors: Wheeler Emily A , Lenhart-Pendergrass Patricia M. , Rysavy Noel M. , Poch Katie , Caceres Silvia , Calhoun Kara M. , Serban Karina , Nick Jerry A. , Malcolm Kenneth C.
Published: May 2023

Mycobacterium abscessusis a nontuberculous mycobacterium emerging as a significant pathogen for individuals with chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. New strategies of bacterial control based on host defenses are appealing, but anti-mycobacterial immune mechanisms are poorly understood and are complicated by the appearance of smooth and rough morphotypes with distinct host responses. We explored the role of the complement system in the clearance ofM. abscessusmorphotypes by neutrophils, an abundant cell in these infections.M. abscessusopsonized with plasma from healthy individuals promoted greater killing by neutrophils compared to opsonization in heat-inactivated plasma. Rough clinical isolates were more resistant to complement but were still efficiently killed. Complement C3 associated strongly with the smooth morphotype while mannose-binding lectin 2 was associated with the rough morphotype. M. abscessus killing was dependent on C3, but not on C1q or Factor B; furthermore, competition of mannose-binding lectin 2 binding with mannan or N-acetyl-glucosamine during opsonization did not inhibit killing. These data suggest thatM. abscessusdoes not canonically activate complement through the classical, alternative, or lectin pathways. Complement-mediated killing was dependent on IgG and IgM for smooth and on IgG for roughM. abscessus. Both morphotypes were recognized by Complement Receptor 3 (CD11b), but not CR1 (CD35), and in a carbohydrate- and calcium-dependent manner. These data suggest the smooth-to-rough adaptation changes complement recognition ofM. abscessusand that complement is an important factor forM. abscessusinfection.
Optimization of 3-Cyano-7-cyclopropylamino-pyrazolo[1,5-a]pyrimidines Toward the Development of an In Vivo Chemical Probe for CSNK2A
Authors: Yang Xuan , Ong Han Wee , Dickmander Rebekah J. , Smith Jeffery L. , Brown Jason W. , Tao William , Chang Edcon , Moorman Nathaniel J. , Axtman Alison D. , Willson Timothy M.
Published: May 2023

3-cyano-7-cyclopropylamino-pyrazolo[1,5-a]pyrimidines, including the chemical probe SGC-CK2-1, are potent and selective inhibitors of CSNK2A in cells but have limited utility in animal models due to their poor pharmacokinetic properties. While developing analogs with reduced intrinsic clearance and the potential for sustained exposure in mice, we discovered that Phase II conjugation by GST enzymes was a major metabolic transformation in hepatocytes. A protocol for co-dosing with ethacrynic acid, a covalent reversible GST inhibitor, was developed to improve the exposure of analog2hin mice. A double co-dosing protocol, using a combination of ethacrynic acid and irreversible P450 inhibitor 1-aminobenzotriazole increased the blood level of2hby 40-fold at a 5 h time point.

Graphical Abstract
Multivalent coiled-coil interactions enable full-scale centrosome assembly and strength
Authors: Rios Manolo U. , Bagnucka Małgorzata A. , Ryder Bryan D. , Gomes Beatriz Ferreira , Familiari Nicole , Yaguchi Kan , Amato Matthew , Joachimiak Łukasz A. , Woodruff Jeffrey B.
Published: May 2023

During mitotic spindle assembly, microtubules generate tensile stresses on pericentriolar material (PCM), the outermost layer of centrosomes. The molecular interactions that enable PCM to assemble rapidly and resist external forces are unknown. Here we use cross-linking mass spectrometry to identify interactions underlying supramolecular assembly of SPD-5, the main PCM scaffold protein inC. elegans. Crosslinks map primarily to alpha helices within the phospho-regulated region (PReM), a long C-terminal coiled-coil, and a series of four N-terminal coiled-coils. PLK-1 phosphorylation of SPD-5 creates new homotypic contacts, including two between PReM and the CM2-like domain, and eliminates numerous contacts in disordered linker regions, thus favoring coiled-coil-specific interactions. Mutations within these interacting regions cause PCM assembly defects that are partly rescued by eliminating microtubule-mediated forces. Thus, PCM assembly and strength are interdependent.In vitro, self-assembly of SPD-5 scales with coiled-coil content, although there is a defined hierarchy of association. We propose that multivalent interactions among coiled-coil regions of SPD-5 build the PCM scaffold and contribute sufficient strength to resist microtubule-mediated forces.
FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe
Authors: Jennings Lucy , Walters Heather Andrews , Mason Jennifer M.
Published: May 2023

WEE1 kinase phosphorylates CDK1 and CDK2 to regulate origin firing and mitotic entry. Inhibition of WEE1 has become an attractive target for cancer therapy due to the simultaneous induction of replication stress and inhibition of the G2/M checkpoint. WEE1 inhibition in cancer cells with high levels of replication stress results in induction of replication catastrophe and mitotic catastrophe. To increase potential as a single agent chemotherapeutic, a better understanding of genetic alterations that impact cellular responses to WEE1 inhibition is warranted. Here, we investigate the impact of loss of the helicase, FBH1, on the cellular response to WEE1 inhibition. FBH1-deficient cells have a reduction in ssDNA and double strand break signaling indicating FBH1 is required for induction of replication stress response in cells treated with WEE1 inhibitors. Despite the defect in the replication stress response, FBH1-deficiency sensitizes cells to WEE1 inhibition by increasing mitotic catastrophe. We propose loss of FBH1 is resulting in replication-associated damage that requires the WEE1-dependent G2 checkpoint for repair.
Lethal thermal limits in embryos of two intertidally brooding nassariid species, and evolution of a protective developmental mechanism conditioned by maternal experience
Authors: Goulding Morgan Q
Published: May 2023

Tritia obsoletaandPhrontis vibexare distant relatives in the neogastropod clade Nassariidae (1). Both species are common along coastline from Maine to the Caribbean; females deposit clutches of zygotes in capsules cemented to solid surfaces in intertidal flats (2), with swimming veliger larvae emerging after about a week of development. In this study, embryos ofT. obsoleta(from Massachusetts and Florida) andP. vibex(from Florida) were exposed to temperatures ranging from 33° to 37°C. In both species, very young embryos are especially sensitive to thermal stress. Brief early heat shock did not disturb spiral cleavage geometry but led to variable, typically severe defects in larval morphogenesis and tissue differentiation. InT. obsoletabut notP. vibex, early heat shock resulted in immediate slowing or arrest of interphase progression. This reversible arrest is correlated with improved prognosis for larval development, and (in Massachusetts snails) depends on parental exposure to warm temperature. Embryos from Massachusetts snails housed at lower temperature exhibited cytokinesis defects in response to even mild warming. Thus, parents informed by experience may or may not endow their young with a developmental braking mechanism that lets them withstand occasional perilous conditions during the most vulnerable stage of life.