bluuebunny/crossref_metadata_2025 huggingface dataset:
Inotrope and vasopressor use in cardiogenic shock: what, when and why?
Authors: Hu Kira , Mathew Rebecca
Published: July 2022

Purpose of review

Despite increasing interest in the management of cardiogenic shock (CS), mortality rates remain unacceptably high. The mainstay of supportive treatment includes vasopressors and inotropes. These medications are recommended in international guidelines and are widely used despite limited evidence supporting safety and efficacy in CS.

Recent findings

The OptimaCC trial further supports that norepinephrine should continue to be the first-line vasopressor of choice in CS. The CAPITAL DOREMI trial found that milrinone is not superior to dobutamine in reducing morbidity and mortality in CS. Two studies currently underway will offer the first evidence of the necessity of inotrope therapy in placebo-controlled trials: CAPITAL DOREMI2 will randomize CS patients to inotrope or placebo in the initial resuscitation of shock to evaluate the efficacy of inotrope therapy and LevoHeartShock will examine the efficacy of levosimendan against placebo in early CS requiring vasopressor therapy.

Review of the current literature fails to show significant mortality benefit with any specific vasopressor or inotropic in CS patients. The upcoming DOREMI 2 and levosimendan versus placebo trials will further tackle the question of inotrope necessity in CS. At this time, inotrope selection should be guided by physician experience, availability, cost, and most importantly, individual patients’ response to therapy.
Caring for adolescents and young adults with attention-deficit/hyperactivity disorder in primary care: seizing opportunities to address youth mental health needs
Authors: Driscoll Hannah , Kimberg Amanda D. , Chung Richard J.
Published: July 2022

Purpose of review

To provide primary care providers (PCPs) with updated practical guidance around the assessment and management of attention-deficit/hyperactivity disorder (ADHD) in adolescents and young adults (AYA).

Recent findings

Of the three different presentations of ADHD delineated in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Predominantly Inattentive presentation is the most common among AYA. Multiple rating scales exist to assist clinicians in identifying ADHD symptoms and monitoring treatment effects. Importantly, ADHD frequently persists into adulthood with negative impacts in many life domains if left untreated. It is important for PCPs to provide support for AYA as they transition to adulthood, as treatment adherence often drops sharply at that time, and, once treatment is discontinued, it is rarely restarted. Further, clinicians should be aware of the negative psychological, behavioral, and social impacts that COVID-19 has had on AYA with ADHD.

AYA with ADHD often seek care first from PCPs. However, diagnosis and management of ADHD among AYA are challenging, and many clinicians feel ill-equipped, creating concern that many youth may go undiagnosed and untreated. Despite these long-standing challenges, recent advances have opened up critical opportunities for PCPs to proactively address ADHD in primary care settings and make a profound impact on youth as they seek to realize their full potential.
Comparing Eosinophilic Esophagitis in a Black and Non-Black Pediatric Cohort
Authors: Edwards-Salmon Sofia , Moraczewski Jason , Offerle Thomas , Sinclair Elizabeth M. , Xiang Yijin , Gillespie Scott , Kruszewski Patrice
Published: July 2022

Objectives:

To compare presenting symptoms, comorbidities, disease, and treatment characteristics of a black pediatric eosinophilic esophagitis (EoE) group to a non-black pediatric EoE group.

Methods:

A retrospective chart review consisting of pediatric patients diagnosed with EoE between the years of 2010 and 2018 at a single urban pediatric hospital system comprising 143 black pediatric patients compared with 142 non-black pediatric patients with similar distribution of age and sex.

Results:

Both groups were majority male, and the median age of diagnosis between the black and non-black group was 5.1 and 6.7 years old, respectively. Comorbidities more commonly seen in the black group included food allergies, atopic dermatitis, asthma, and allergic rhinitis. Black patients were more likely to present with failure to thrive (FTT)/poor growth, whereas non-black patients were more likely to present with abdominal pain. There was no statistically significant difference between the groups in achieving remission using current therapies. The black group had higher rates of nonadherence to medical therapies.

Conclusions:

This is the largest study to date comparing a black versus non-black pediatric EoE population. The black population had more atopic comorbidities and FTT at presentation and had significantly more issues with nonadherence. This new knowledge describing EoE in a minority population will hopefully improve awareness, diagnosis, and management of EoE in this population.
Blood Pressure Cuff Inflation Briefly Increases Female Adolescents’ Restlessness During Sleep on the First But Not Second Night of Ambulatory Blood Pressure Monitoring
Authors: Lehrer H. Matthew , Zhang Gehui , Matthews Karen A. , Krafty Robert T. , Evans Marissa A. , Taylor Briana J. , Hall Martica H.
Published: July 2022

Objective

Ambulatory blood pressure monitoring (ABPM) increases restlessness during adults’ sleep in laboratory settings, but there is little evidence of an association among adolescents or in naturalistic environments. This study examined activity levels before and after blood pressure cuff inflation during sleep to determine whether and for how long ABPM increased restlessness during sleep in healthy adolescents.

Methods

Two hundred thirty-four healthy adolescents (mean age = 15.72 [1.30] years; 54% female; 57% Black) completed two consecutive nights of hourly ABPM and wrist-worn actigraphy. Activity counts during sleep, averaged across 5-minute bins, were compared in the 20 minutes before and after blood pressure cuff inflation using a four-level mixed model (bins within hours within nights within participants). Interactions of bin with night, sex, and race were examined. Covariates included age, sex, and race.

Results

Activity counts in the 5-minute bin immediately after cuff inflation were 10% to 14% higher than all other bins before (p < .001) and after (p < .001) cuff inflation. This effect differed by night and sex, as activity levels during 5-minute post–cuff inflation were elevated only on night 1 (p values < .001) and only in female participants (p values < .001). Effects did not differ by race.

Conclusions

Cuff inflation during ABPM briefly increased adolescent female participants’ restlessness during sleep. Habituation occurred after one night, so two nights of ABPM may minimize impact on sleep. If only one night of ABPM is feasible, excluding 5 minutes of actigraphy data after each cuff inflation may accommodate the impact of ABPM on restlessness during sleep.
Cognitive Function Is Associated With Multiple Indices of Adiposity in the Canadian Longitudinal Study on Aging: A Cross-Sectional Analysis
Authors: Sakib Mohammad Nazmus , Ramezan Reza , Thompson Mary E. , Best John R. , Hall Peter A.
Published: July 2022

Objective

Prior studies have suggested reciprocal relationships between cognitive function and adiposity, but this has not been investigated with population representative data sets. The purpose of this study was to examine the association between cognitive function and adiposity in a large population-based sample of middle-aged and older adults. It was hypothesized that better scores on tests of cognitive function would be associated with lower adiposity, and this association would be primarily mediated through life-style behavior and physical health status.

Methods

Using baseline data from the Canadian Longitudinal Study on Aging (N = 30,097), we tested our hypotheses using three indicators of cognitive function (animal fluency, Stroop interference, and reaction time) and four indicators of adiposity (body mass index, total fat mass, waist circumference, and waist-hip ratio). Hierarchical multivariable linear regression modeling was conducted followed by tests for moderation by socioeconomic status and mediation through diet, physical activity, hypertension, and diabetes status.

Results

All measures of cognitive indicators were significantly associated with adiposity after adjusting for confounders. In general, superior performance on animal fluency, Stroop, and reaction time tasks were associated with lower adiposity by most metrics. Stroop interference was associated with lower adiposity across all metrics, including body mass index (b = − 0.04, 95 % confidence interval [CI] = − 0.06  to − 0.01), total fat mass (b = 19.35, 95 % CI = 8.57  to 30.12), waist circumference (b = 33.83, 95 % CI = 10.08  to 57.58), and waist-hip ratio (b = 0.13, 95 % CI = 0.01  to 0.24). These associations were more substantial for moderate- and high-income subpopulations. Mediation analyses suggested that the aforementioned effects were mediated through life-style behavior (e.g., diet and physical activity) and physical health conditions (e.g., diabetes and hypertension).

Conclusions

Reliable associations exist between cognitive function and adiposity in middle-aged and older adults. The associations seem to be mediated through life-style behavior and physical health conditions.
Disparities in Adverse Event Reporting for Hospitalized Children
Authors: Halvorson Elizabeth Eby , Thurtle Danielle P. , Easter Ashley , Lovato James , Stockwell David
Published: July 2022

Objectives

Hospitals rely on voluntary event reporting (VER) for adverse event (AE) identification, although it captures fewer events than a trigger tool, such as Global Assessment of Pediatric Patient Safety (GAPPS). Medical providers exhibit bias based on patient weight status, race, and English proficiency. We compared the AE rate identified by VER with that identified using the GAPPS between hospitalized children by weight category, race, and English proficiency.

Methods

We identified a cohort of patients 2 years to younger than 18 years consecutively discharged from an academic children’s hospital between June and October 2018. We collected data on patient weight status from age, sex, height, and weight, race/ethnicity by self-report, and limited English proficiency by record of interpreter use. We reviewed each chart with the GAPPS to identify AEs and reviewed VER entries for each encounter. We calculated an AE rate per 1000 patient-days using each method and compared these using analysis of variance.

Results

We reviewed 834 encounters in 680 subjects; 262 (38.5%) had overweight or obesity, 144 (21.2%) identified as Black, and 112 (16.5%) identified as Hispanic; 82 (9.8%) of encounters involved an interpreter. We identified 288 total AEs, 270 (93.8%) by the GAPPS and 18 (6.3%) by VER. A disparity in AE reporting was found for children with limited English proficiency, with fewer AEs by VER (P = 0.03) compared with no difference in AEs by GAPPS. No disparities were found by weight category or race.

Conclusions

Voluntary event reporting may systematically underreport AEs in hospitalized children with limited English proficiency.
Social Distancing to Avoid SARS-CoV-2 Infection in Cancer and Noncancer Patients
Authors: Kloecker Goetz , Nolan Joseph , Korbee Leslie , Calhoun Royce , Logan Barbara , Flora Dan , Flora Douglas , Hartman Philip
Published: July 2022

Background

Social distancing has been recommended by the Centers for Disease Control and Prevention to avoid exposure to SARS-CoV-2 (Epidemiol Prev 2020;44:353–362).

Cancer patients on or after active therapy seem to be more prone to COVID being symptomatic and life-threatening. When evaluating cancer patients’ risk of acquiring COVID, it is essential to know the behavior of cancer patients that will affect their risk of exposure. However, it is not known to what degree social distancing is practiced by cancer patients compared with noncancer patients and what factors lead to the decision to distance oneself.

Method

After a pilot phase using patients’ MyChart messaging, links to the electronic questionnaires were texted to patients using Twillio. Responses were stored on REDCap (Vanderbilt University, Nashville, TN). Six questions about their social distancing behavior and mask wearing were posed and responses were compared between cancer and noncancer patients. Demographics, comorbidities, and a questionnaire about anxiety (Generalized Anxiety Disorder 7-item scale) were recorded. To assess differences between cancer and noncancer groups, Bonferroni-corrected χ2 tests and proportions confidence intervals were used.

Results

The pilot survey was sent in mid-2020 and the full survey followed in January 2021 during a high community COVID incidence. Three hundred eighty-seven cancer patients (32.4% responded) and 503 noncancer patients (22.9% responded) completed the survey. Questions about leaving their houses, driving, shopping, friends, and family indicated that patients with cancer are more cautious (P < 0.001). Cancer patients were up to 20% more likely to distance themselves. No difference was seen in wearing a mask—both groups wore approximately 90% of the time. Most respondents were female (63% versus 71%). Cancer patients were older (>60 y, 69% versus 45%) and less likely to work (52% versus 31%) or less likely to be White collar workers (21% versus 38%). In both groups, 54% marked “not at all anxious.”

Conclusions

Cancer patients’ responses revealed a distancing behavior that would likely lower the risk exposure to SARS-CoV-2. It is unclear which of the demographic differences would account for this behavior, although remarkably anxiety was not a clear motivating factor. The high acceptance of masks is encouraging. Early publications during the pandemic and patient education suggesting a higher COVID risk for cancer patients may have reduced risk prone behavior. Considering COVID’s impact on the vulnerable cancer population and uncertainty in immunosuppressed patients about clearing the virus or adequately responding to a vaccine, further studies about health behavior and health promotion during the pandemic are needed.
Accuracy of Spinal Anesthesia Drug Concentrations in Mixtures Prepared by Anesthetists
Authors: Heesen Michael , Steuer Christian , Wiedemeier Peter , Schwappach David
Published: July 2022

Objective

Medication errors include the indirect dosing of drugs. For spinal anesthesia mixtures of local anesthetics, opioids are drawn from ampoules and combined in a syringe, according to clinical practice. We set out to determine the accuracy of the drug mixtures.

Methods

Physicians of our department were invited to prepare the mixture used for spinal anesthesia for cesarean section, consisting of 10-mg hyperbaric bupivacaine (2-mL volume), 20-μg fentanyl (0.4-mL volume), and 100-μg morphine (0.1-mL volume). Concentrations of these drugs were determined by means of high performance liquid chromatography. Interindividual and intraindividual variations were assessed.

Results

We analyzed 96 samples from 31 physicians. Fifty-one percent of the measured bupivacaine concentrations were in ±10% deviation range of the intended concentration; 17% of the fentanyl and 24% of the morphine concentrations were in this range. A total of 2.1% of the samples had a bupivacaine concentration corresponding to a dose of 8 mg or less, and 11.5% of the samples had a morphine concentration corresponding to a dose of 150 μg or greater. Intraindividual variations were 10.9% for bupivacaine, 24.7% for fentanyl, and 38.9% for morphine.

Conclusions

Our results show a high deviation of the obtained from the intended concentrations. Two percent of the samples had bupivacaine concentrations that probably resulted into an insufficient analgesia, and 11% of the samples had morphine concentrations that, according to guidelines, would require a longer monitoring period than with the intended dose.
Brief Report: Financial Burden of Toxoplasmosis Encephalitis Treatment at a Safety Net Hospital
Authors: Bogard Sherri N. , Lee James T. , Patel Manish , Kempker Russell R.
Published: July 2022

Background:

Although the price increase of pyrimethamine in 2015 received heavy media coverage, there are little data regarding specific implications to hospitals and the total costs of treating inpatients with toxoplasmosis encephalitis (TE).

Methods:

Using average drug wholesale costs, we estimated the inpatient drug costs of TE drugs 3 years prepyrimethamine and postpyrimethamine price increase in August 2015. The drug regimens and total doses were determined through retrospective chart review of patients living with HIV who received treatment for TE while inpatient during this period.

Results:

The 3-year pre-increase TE drug costs for 66 admissions were estimated at $50,310 compared with a total drug cost of $1,026,006 for 61 admissions postincrease. Pyrimethamine made up 98% of the drug costs postincrease, compared with 57% pre-increase. Pyrimethamine-based regimens were the most frequently used throughout the study period.

Conclusions:

The price increase of pyrimethamine in 2015 led to a substantial and unnecessary financial burden to hospitals. This required health care systems to shift valuable resources to continue to provide medications to a vulnerable patient population. There has been more focus on providing high-value care in recent years. Our study highlights the need for further examination of pharmaceutical companies' arbitrary determination of medication costs and how they contribute to patient care.
Saving Money and Reducing Waste With a Tailored Hand Surgery Kit
Authors: Velicki Katherine , Schultz Michelle , Dy Christopher J.
Published: July 2022

Background and Objectives:

There is growing interest in containing cost and decreasing waste in the operating room. As part of a quality improvement initiative, we redesigned the supply kit used for 2 common surgical procedures (carpal tunnel release and trigger finger release) performed under local anesthesia.

Methods:

A hand surgeon, a medical student, and an operating room nurse examined each item that would be necessary for performing carpal tunnel release and trigger finger release. A new disposable supply kit was formulated on the basis of their recommendations and was implemented over a 7-month period. Cost savings and waste avoidance were calculated.

Results:

The streamlined kit ($43.40) produced a 53% cost savings relative to the standard hand pack ($92.83) per case. The local pack (2.896 kg) was 41% lighter than the standard pack (4.938 kg), translating to significant waste avoidance. The local hand pack was used for 46 cases from September 2020 to April 2021, saving a total of $2246.78 and avoiding 94 kg of waste. There have been no noted interruptions in delivery of surgical care.

Conclusion:

Our redesign of the local hand pack led to substantial cost savings and waste avoidance. We believe there are many opportunities for surgical teams to use similar strategies to decrease cost and environmental waste.
ISO 9001:2015 Internal Audits for Financial and Strategic Decisions in Reducing Blood Culture Contamination
Authors: Sharma Rohit , Szucs Theresa , Reinhartsen Teri Ann
Published: July 2022

Background and Objectives:

Blood cultures are vital diagnostic tests that detect harmful pathogens in a patient's bloodstream. In this study, we implemented a process-driven quality improvement program to reduce blood culture contamination rates.

Methods:

St Joseph Health (SJH) utilized the ISO 9001:2015 Internal Audit tool, failure mode effect analyses, and the Centers for Disease Control and Prevention's Hierarchy of Controls to identify opportunities for improvement and design effective corrective and preventive action plans. These actions included reeducation and ongoing coaching of staff on the blood culture collection process, reorganizing blood culture supplies on the nursing units, and adding multiple layers of supervision.

Results:

A statistically significant relationship was identified between 2 variables (“contamination rate” and “cumulative cost difference”). The 2 variables had a negative association, demonstrating that as the contamination rate decreased, the cumulative cost difference increased, indicating potential cost savings.

Conclusion:

The estimated value added to the institution through this initiative was approximately $215 743 to $228 543 in potential cost savings. SJH significantly reduced the number of blood culture contaminations in the critical care division, evidenced by a controlled 6-month mean below 1%. Review of the 6-month mean as a reference point demonstrated the sustainability of the implemented corrective and preventive measures.
Variability of Pediatric Cervical Spine Clearance Protocols
Authors: Letica-Kriegel Allison S. , Kaplan Amy , Orlas Claudia , Masiakos Peter T.
Published: July 2022

Objective:

The objective of this study was to better understand the variability that exists in the contemporary pediatric cervical spine (c-spine) clearance protocols and how this variability affects clinical practice and outcomes.

Background Data:

Pediatric c-spine injury is a rare but potentially devastating event. In the adult population, validated tools, such as the National Emergency X-Radiography Utilization Study (NEXUS) criteria and the Canadian C-spine Rule, are available to aid in safely clearing the c-spine clinically while reducing the utilization of radiography. In the pediatric population, no standardized, validated tool exists, leading to variability in protocols that are put to use.

Methods:

A systematic literature search was conducted in Cochrane, Embase, PubMed/MEDLINE, and Web of Science electronic databases from January 1, 2009 until April 30, 2021. Data were extracted from studies that met inclusion criteria. Quality of the included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria.

Results:

There were 19 studies included in this systematic review. From these 19 studies, there were 16 unique protocols, 12 of which (75%) utilized some or all NEXUS criteria. Of the protocols that provided a detailed imaging algorithm (N=14), 12 (85.7%) utilized x-rays as the initial imaging modality. Indications for computed tomography and magnetic resonance imaging varied widely across the protocols. The rate of x-rays, computed tomography, and magnetic resonance imaging utilization ranged from 16.7% to 97.8%, 5.4% to 100%, and 0% to 100%, respectively. Ten studies evaluated the efficacy of protocol implementation, with 9 (90%) of these studies showing an overall reduction of imaging rates in the postprotocol period. No clinically significant missed injuries were reported in the included studies.

Conclusions:

Details of c-spine clearance protocols differed significantly across the included studies, but many applied some or all NEXUS criteria. Overall, while variable, protocols served to safely treat pediatric patients without missing any clinically significant c-spine injuries, while reducing radiation exposure.
The Impact of Psychiatric Diagnoses on Patient-reported Satisfaction and Quality of Life in Postmastectomy Breast Reconstruction
Authors: Shamsunder Meghana G. , Chu Jacqueline J. , Polanco Thais O. , Yin Shen , Muniz Rosario C. , James Monique C. , Mehrara Babak J. , Pusic Andrea L. , Voineskos Sophocles , Nelson Jonas A.
Published: July 2022

Objective:

The purpose of this study was to determine the prevalence of psychiatric diagnoses among a sample of breast reconstruction patients and measure the association between these diagnoses and reconstruction-related, patient-reported outcomes.

Background:

The impact of psychiatric disorders in conjunction with breast cancer diagnosis, treatment, and reconstruction have the potential to cause significant patient distress but remains not well understood.

Methods:

A retrospective review of postmastectomy breast reconstruction patients from 2007 to 2018 at Memorial Sloan Kettering Cancer Center was conducted. Patient demographics, comorbidities, cancer characteristics, psychiatric diagnoses, and BREAST-Q Reconstruction Module scores (measuring satisfaction with breast, well-being of the chest, psychosocial, and sexual well-being) at postoperative years 1 to 3 were examined. Mixed-effects models and cross-sectional linear regressions were conducted to measure the effect of psychiatric diagnostic class type and number on scores.

Results:

Of 7414 total patients, 50.1% had at least 1 psychiatric diagnosis. Patients with any psychiatric diagnoses before reconstruction had significantly lower BREAST-Q scores for all domains at all time points. Anxiety (50%) and depression (27.6%) disorders were the most prevalent and had the greatest impact on BREAST-Q scores. Patients with a greater number of psychiatric diagnostic classes had significantly worse patient-reported outcomes compared with patients with no psychiatric diagnosis. Psychosocial (β: −7.29; 95% confidence interval: −8.67, −5.91), and sexual well-being (β: −7.99; 95% confidence interval: −9.57, −6.40) were most sensitive to the impact of psychiatric diagnoses.

Conclusions:

Mental health status is associated with psychosocial and sexual well-being after breast reconstruction surgery as measured with the BREAST-Q. Future research will need to determine what interventions (eg, screening, early referral) can help improve outcomes for breast cancer patients with psychiatric disorders undergoing breast reconstruction.
Apparent anomalous diffusion and non-Gaussian distributions in a simple mobile–immobile transport model with Poissonian switching
Authors: Doerries Timo J. , Chechkin Aleksei V. , Metzler Ralf
Published: July 2022

We analyse mobile–immobile transport of particles that switch between the mobile and immobile phases with finite rates. Despite this seemingly simple assumption of Poissonian switching, we unveil a rich transport dynamics including significant transient anomalous diffusion and non-Gaussian displacement distributions. Our discussion is based on experimental parameters for tau proteins in neuronal cells, but the results obtained here are expected to be of relevance for a broad class of processes in complex systems. Specifically, we obtain that, when the mean binding time is significantly longer than the mean mobile time, transient anomalous diffusion is observed at short and intermediate time scales, with a strong dependence on the fraction of initially mobile and immobile particles. We unveil a Laplace distribution of particle displacements at relevant intermediate time scales. For any initial fraction of mobile particles, the respective mean squared displacement (MSD) displays a plateau. Moreover, we demonstrate a short-time cubic time dependence of the MSD for immobile tracers when initially all particles are immobile.
Generation of ciliary beating by steady dynein activity: the effects of inter-filament coupling in multi-filament models
Authors: Woodhams Louis G. , Shen Yenan , Bayly Philip V.
Published: July 2022

The structure of the axoneme in motile cilia and flagella is emerging with increasing detail from high-resolution imaging, but the mechanism by which the axoneme creates oscillatory, propulsive motion remains mysterious. It has recently been proposed that this motion may be caused by a dynamic ‘flutter’ instability that can occur under steady dynein loading, and not by switching or modulation of dynein motor activity (as commonly assumed). In the current work, we have built an improved multi-filament mathematical model of the axoneme and implemented it as a system of discrete equations using the finite-element method. The eigenvalues and eigenvectors of this model predict the emergence of oscillatory, wave-like solutions in the absence of dynein regulation and specify the associated frequencies and waveforms of beating. Time-domain simulations with this model illustrate the behaviour predicted by the system's eigenvalues. This model and analysis allow us to efficiently explore the potential effects of difficult to measure biophysical parameters, such as elasticity of radial spokes and inter-doublet links, on the ciliary waveform. These results support the idea that dynamic instability without dynamic dynein regulation is a plausible and robust mechanism for generating ciliary beating.
Northward range expansion of rooting ungulates decreases detritivore and predatory mite abundances in boreal forests
Authors: Maaroufi Nadia I. , Taylor Astrid R. , Ehnes Roswitha B. , Andrén Henrik , Kjellander Petter , Björkman Christer , Kätterer Thomas , Klapwijk Maartje J.
Published: July 2022

In the last few decades wild boar populations have expanded northwards, colonizing boreal forests. The soil disturbances caused by wild boar rooting may have an impact on soil organisms that play a key role in organic matter turnover. However, the impact of wild boar colonization on boreal forest ecosystems and soil organisms remains largely unknown. We investigated the effect of natural and simulated rooting on decomposer and predatory soil mites (total, adult and juvenile abundances; and adult–juvenile proportion). Our simulated rooting experiment aimed to disentangle the effects of (i) bioturbation due to soil mixing and (ii) removing organic material (wild boar food resources) on soil mites. Our results showed a decline in the abundance of adult soil mites in response to both natural and artificial rooting, while juvenile abundance and the relative proportion of adults and juveniles were not affected. The expansion of wild boar northwards and into new habitats has negative effects on soil decomposer abundances in boreal forests which may cascade through the soil food web ultimately affecting ecosystem processes. Our study also suggests that a combined use of natural and controlled experimental approaches is the way forward to reveal any subtle interaction between aboveground and belowground organisms and the ecosystem functions they drive.
A survey on how preregistration affects the research workflow: better science but more work
Authors: Sarafoglou Alexandra , Kovacs Marton , Bakos Bence , Wagenmakers Eric-Jan , Aczel Balazs
Published: July 2022

The preregistration of research protocols and analysis plans is a main reform innovation to counteract confirmation bias in the social and behavioural sciences. While theoretical reasons to preregister are frequently discussed in the literature, the individually experienced advantages and disadvantages of this method remain largely unexplored. The goal of this exploratory study was to identify the perceived benefits and challenges of preregistration from the researcher’s perspective. To this end, we surveyed 355 researchers, 299 of whom had used preregistration in their own work. The researchers indicated the experienced or expected effects of preregistration on their workflow. The results show that experiences and expectations are mostly positive. Researchers in our sample believe that implementing preregistration improves or is likely to improve the quality of their projects. Criticism of preregistration is primarily related to the increase in work-related stress and the overall duration of the project. While the benefits outweighed the challenges for the majority of researchers with preregistration experience, this was not the case for the majority of researchers without preregistration experience. The experienced advantages and disadvantages identified in our survey could inform future efforts to improve preregistration and thus help the methodology gain greater acceptance in the scientific community.
Computation of Burgers vectors from elastic strain and lattice rotation data
Authors: Cloete J. , Tarleton E. , Hofmann F.
Published: July 2022

A theoretical framework for computation of Burgers vectors from strain and lattice rotation data in materials with low dislocation density is presented, as well as implementation into a computer program to automate the process. The efficacy of the method is verified using simulated data of dislocations with known results. A three-dimensional dataset retrieved from Bragg coherent diffraction imaging (BCDI) and a two-dimensional dataset from high-resolution transmission Kikuchi diffraction (HR-TKD) are used as inputs to demonstrate the reliable identification of dislocation positions and accurate determination of Burgers vectors from experimental data. For BCDI data, the results found using our approach show very close agreement to those expected from empirical methods. For the HR-TKD data, the predicted dislocation position and the computed Burgers vector showed fair agreement with the expected result, which is promising considering the substantial experimental uncertainties in this dataset. The method reported in this paper provides a general and robust framework for determining dislocation position and associated Burgers vector, and can be readily applied to data from different experimental techniques.
Mechanics of tension-induced film wrinkling and restabilization: a review
Authors: Wang Ting , Yang Yifan , Xu Fan
Published: July 2022

Wrinkling of thin films under tension is omnipresent in nature and modern industry, a phenomenon which has aroused considerable attention during the past two decades because of its intricate nonlinear behaviours and intriguing morphology changes. Here, we review recent advancements in the mechanics of tension-induced film wrinkling and restabilization, by identifying three major stages of its progress: small-strain (less than

5
%

) wrinkling of stiff sheets, finite-strain (up to

30
%

) wrinkling and restabilization (isola-centre bifurcation) of soft films, and the effects of curved configurations and material properties on pattern formation. Growing demand for fundamental understanding, quantitative prediction and precise tracking of secondary bifurcation transitions in morphological evolution of thin films helps to advance finite-strain plate/shell theories and sophisticated modelling methods. This progress not only promotes our insightful understanding of complex instability behaviour but also reveals novel phenomena and sheds light on developing wrinkle-tunable membrane structures and functional surfaces.
Descending control of nociception in insects?
Authors: Gibbons Matilda , Sarlak Sajedeh , Chittka Lars
Published: July 2022

Modulation of nociception allows animals to optimize chances of survival by adapting their behaviour in different contexts. In mammals, this is executed by neurons from the brain and is referred to as the descending control of nociception. Whether insects have such control, or the neural circuits allowing it, has rarely been explored. Based on behavioural, neuroscientific and molecular evidence, we argue that insects probably have descending controls for nociception. Behavioural work shows that insects can modulate nocifensive behaviour. Such modulation is at least in part controlled by the central nervous system since the information mediating such prioritization is processed by the brain. Central nervous system control of nociception is further supported by neuroanatomical and neurobiological evidence showing that the insect brain can facilitate or suppress nocifensive behaviour, and by molecular studies revealing pathways involved in the inhibition of nocifensive behaviour both peripherally and centrally. Insects lack the endogenous opioid peptides and their receptors that contribute to mammalian descending nociception controls, so we discuss likely alternative molecular mechanisms for the insect descending nociception controls. We discuss what the existence of descending control of nociception in insects may reveal about pain perception in insects and finally consider the ethical implications of these novel findings.
Separating the effects of early and later life adiposity on colorectal cancer risk: a Mendelian randomization study
Authors: Papadimitriou Nikos , Bull Caroline J , Jenab Mazda , Hughes David J. , Bell Joshua A , Sanderson Eleanor , Timpson Nicholas J , Smith George Davey , Albanes Demetrius , Campbell Peter T , Küry Sébastien , Marchand Loic Le , Ulrich Cornelia M , Visvanathan Kala , Figueiredo Jane C , Newcomb Polly A , Pai Rish K , Peters Ulrike , Tsilidis Kostas K , Boer Jolanda M.A. , Vincent Emma E , Mariosa Daniela , Gunter Marc J , Richardson Tom G , Murphy Neil
Published: July 2022

Background

Observational studies have linked childhood obesity with elevated risk of colorectal cancer, however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.

Methods

We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.

Results

Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77).

Conclusions

Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
A personalized antibody score for predicting individual COVID-19 vaccine-elicited antibody levels from basic demographic and health information
Authors: Nakamura Naotoshi , Park Hyeongki , Kim Kwang Su , Sato Yoshitaka , Jeong Yong Dam , Iwanami Shoya , Fujita Yasuhisa , Zhao Tianchen , Tani Yuta , Nishikawa Yoshitaka , Yamamoto Chika , Kobashi Yurie , Kawamura Takeshi , Sugiyama Akira , Nakayama Aya , Kaneko Yudai , Aihara Kazuyuki , Iwami Shingo , Tsubokura Masaharu
Published: July 2022

Antibody titers wane after two-dose COVID-19 vaccinations, but individual variation in vaccine-elicited antibody dynamics remains to be explored. Here, we created a personalized antibody score that enables individuals to infer their antibody status by use of a simple calculation. We recently developed a mathematical model of B cell differentiation to accurately interpolate the longitudinal data from a community-based cohort in Fukushima, Japan, which consists of 2,159 individuals who underwent serum sampling two or three times after a two-dose vaccination with either BNT162b2 or mRNA-1273. Using the individually reconstructed time course of the vaccine-elicited antibody response, we first elucidated individual background factors that contributed to the main features of antibody dynamics, i.e., the peak, the duration, and the area under the curve. We found that increasing age was a negative factor and a longer interval between the two doses was a positive factor for individual antibody level. We also found that the presence of underlying disease and the use of medication affected antibody levels negatively, whereas the presence of adverse reactions upon vaccination affected antibody levels positively. We then applied to these factors a recently proposed computational method to optimally fit clinical scores, which resulted in an integer-based score that can be used to evaluate the antibody status of individuals from their basic demographic and health information. This score can be easily calculated by individuals themselves or by medical practitioners. There is a potential usefulness of this score for identifying vulnerable populations and encouraging them to get booster vaccinations.

Significance statement

Different individuals show different antibody titers even after the same COVID-19 vaccinations, making some individuals more prone to breakthrough infections than others. Such variability remains to be clarified. Here we used mathematical modeling to reconstruct individual post-vaccination antibody dynamics from a cohort of 2,159 individuals in Fukushima, Japan. Machine learning identified several positive and negative factors affecting individual antibody titers. Positive factors included adverse reactions after vaccinations and a longer interval between two vaccinations. Negative factors included age, underlying medical conditions, and medications. We combined these factors and developed an “antibody score” to estimate individual antibody dynamics from basic demographic and health information. This score can help to guide individual decision-making about taking further precautions against COVID-19.
First-in-patient dose prediction for adeno-associated virus-mediated hemophilia gene therapy using allometric scaling
Authors: Zou Peng
Published: July 2022

Rational first-in-patient (FIP) dose selection is critical for successful clinical development of gene therapy. In this study, the author compared the performance of two allometric scaling approaches and body weight-based dose conversion approach for FIP dose prediction for adeno-associated virus (AAV)-mediated hemophilia gene therapy. The performance of the three approaches was examined using preclinical and clinical efficacy data of nine AAV vectors. In general, body weight-based direct conversion of effective doses in monkeys or dogs was more likely to underestimate FIP dose but worked better for one bioengineered vector with a high transduction efficiency specifically in humans. In contrast, allometric scaling between gene efficiency factor (logGEF) and body weight (logW) was likely to overestimate FIP dose but worked better than the other two approaches when vector capsid-specific T-cell responses were detected in patients. The third approach, allometric scaling between logGEF and W-0.25 was appropriate for FIP dose prediction in the absence of T-cell responses to AAV vectors or a dramatic difference in vector transduction efficiency between animals and humans. A decision tree was tentatively proposed to facilitate approach selection for FIP dose prediction in AAV-mediated hemophilia gene therapy.
Peri-saccadic orientation identification performance and visual neural sensitivity are higher in the upper visual field
Authors: Fracasso Alessio , Buonocore Antimo , Hafed Ziad M.
Published: July 2022

Visual neural processing is distributed among a multitude of sensory and sensory-motor brain areas exhibiting varying degrees of functional specializations and spatial representational anisotropies. Such diversity raises the question of how perceptual performance is determined, at any one moment in time, during natural active visual behavior. Here, exploiting a known dichotomy between the primary visual cortex and superior colliculus in representing either the upper or lower visual fields, we asked whether peri-saccadic orientation identification performance is dominated by one or the other spatial anisotropy. Humans (48 participants, 29 females) reported the orientation of peri-saccadic upper visual field stimuli significantly better than lower visual field stimuli, unlike their performance during steady-state gaze fixation, and contrary to expected perceptual superiority in the lower visual field in the absence of saccades. Consistent with this, peri-saccadic superior colliculus visual neural responses in two male rhesus macaque monkeys were also significantly stronger in the upper visual field than in the lower visual field. Thus, peri-saccadic orientation identification performance is more in line with oculomotor, rather than visual, map spatial anisotropies.

Significance statement

Different brain areas respond to visual stimulation, but they differ in the degrees of functional specializations and spatial anisotropies that they exhibit. For example, the superior colliculus both responds to visual stimulation, like the primary visual cortex, and controls oculomotor behavior. Compared to the primary visual cortex, the superior colliculus exhibits an opposite pattern of upper/lower visual field anisotropy, being more sensitive to the upper visual field. Here, we show that human peri-saccadic orientation identification performance is better in the upper compared to the lower visual field. Consistent with this, monkey superior colliculus visual neural responses to peri-saccadic stimuli follow a similar pattern. Our results indicate that peri-saccadic perceptual performance reflects oculomotor, rather than visual, map spatial anisotropies.
Single Cell RNA-Sequence Analyses Reveal Uniquely Expressed Genes and Heterogeneous Immune Cell Involvement in the Rat Model of Intervertebral Disc Degeneration
Authors: Rohanifar Milad , Clayton Sade W. , Easson Garrett , Patil Deepanjali S. , Lee Frank , Jing Liufang , Barcellona Marcos N. , Speer Julie E. , Stivers Jordan J. , Tang Simon Y. , Setton Lori A.
Published: July 2022

Intervertebral disc (IVD) degeneration is characterized by a loss of cellularity, and changes in cell-mediated activity that drives anatomic changes to IVD structure. In this study, we use single cell RNA-sequencing analysis of cells extracted from the degenerating tissues of the rat IVD following lumbar disc puncture. Two control, uninjured IVDs (L2-3, L3-4) and two degenerated, injured IVDs (L4-5, L5-6) from each animal were examined either at two- and eight-week post-operative time points. The cells from these IVDs were extracted and transcriptionally profiled at a single-cell resolution. Unsupervised cluster analysis revealed the presence of 4 known cell types in both non-degenerative and degenerated IVDs based on previously established gene markers: IVD cells, endothelial cells, myeloid cells, and lymphoid cells. As a majority of cells were associated with the IVD cell cluster, sub-clustering was used to further identify the cell populations of the nucleus pulposus, inner and outer annulus fibrosus. The most notable difference between control and degenerated IVDs was the increase of myeloid and lymphoid cells in degenerated samples at 2- and 8- weeks post-surgery. Differential gene expression analysis revealed multiple distinct cell types from the myeloid and lymphoid lineages, most notably macrophages and B lymphocytes and demonstrated a high degree of immune specificity during degeneration. In addition to the heterogenous infiltrating immune cell populations in the degenerating IVD, the increased number of cells in the AF sub-cluster expressingNgfandNgfr, encoding for p75NTR, suggest that NGF signaling may be one of the key mediators of the IVD crosstalk between immune and neuronal cell populations. These findings provide the basis for future work to understand the involvement of select subsets of non-resident cells in IVD degeneration.