bluuebunny/crossref_metadata_2025 huggingface dataset:
Introducing Music Therapy to Hospitalized Adults in Medical Settings: A Thematic Analysis
Authors: Hunt Chantise J , Silverman Michael J
Published: July 2021

Music therapy can decrease illness- and treatment-related symptoms for adults in medical settings. In these environments, service users often decide to accept or decline music therapy after a brief introduction by the music therapist. As there is limited literature exploring the challenges related to these introductions, the purpose of this interpretivist study was to describe how music therapists introduce music therapy in the form of patient-preferred live music (MT-PPLM) in adult medical settings to augment the likelihood of patients accepting treatment. We conducted semi-structured interviews with nine participants who had experience providing MT-PPLM in adult medical settings. In this exploratory interpretivist study, we used an inductive approach to thematic analysis and incorporated member-checking to augment trustworthiness and credibility of the results. We identified three themes (supported by eight subthemes depicted in parentheses): (A) Offer patient a unique interaction through verbal and nonverbal techniques (Provide opportunities for patient control; Engage patient through nonmedical dialogue; and Use affect and body language to convey a different demeanor); (B) Clarify expectations related to patient and session (Avoid the word “therapy”; Use the music to explain the intervention; and Mention clinical benefits to describe what the patient can expect from the session); and (C) Respond to patient’s verbal and nonverbal communication (Assess patient and adapt introduction; and Validate patient’s response). The findings offer introductory techniques for music therapists that may increase the likelihood of adults in medical settings accepting MT-PPLM. Implications for clinical practice, ethical considerations, limitations, and suggestions for future research are provided.
Training of Physical Therapists to Deliver Individualized Biopsychosocial Interventions to Treat Musculoskeletal Pain Conditions: A Scoping Review
Authors: Simpson Phoebe , Holopainen Riikka , Schütze Robert , O’Sullivan Peter , Smith Anne , Linton Steven J , Nicholas Michael , Kent Peter
Published: July 2021

Objective

Current guidelines recommend management of musculoskeletal pain conditions from a biopsychosocial approach; however, biopsychosocial interventions delivered by physical therapists vary considerably in effectiveness. It is unknown whether the differences are explained by the intervention itself, the training and/or competency of physical therapists delivering the intervention, or fidelity of the intervention. The aim was to investigate and map the training, competency assessments, and fidelity checking of individualized biopsychosocial interventions delivered by physical therapists to treat musculoskeletal pain conditions.

Methods

A scoping review methodology was employed, using Arksey and O’Malley’s framework. Seven electronic databases were searched between January and March 2019, with a bridge search completed in January 2020. Full-text peer-reviewed articles, with an individualized biopsychosocial intervention were considered, and 35 studies were included.

Results

Reporting overall was sparse and highly variable. There was a broad spectrum of training. More sophisticated training involved workshops combining didactic and experiential learning over longer durations with supervision and feedback. Less sophisticated training was brief, involving lectures or seminars, with no supervision or feedback. Competency assessments and fidelity testing were underperformed.

Conclusions

Training in some interventions might not have facilitated the implementation of skills or techniques to enable the paradigm shift and behavior change required for physical therapists to effectively deliver a biopsychosocial intervention. Lack of competency assessments and fidelity checking could have impacted the methodological quality of biopsychosocial interventions.

Impact

This study highlighted problematic reporting, training, assessment of competency, and fidelity checking of physical therapist–delivered individualized biopsychosocial interventions. Findings here highlight why previous interventions could have shown small effect sizes and point to areas for improvement in future interventions. These findings can help inform future research and facilitate more widespread implementation of physical therapist–delivered biopsychosocial interventions for people with musculoskeletal pain and thereby improve their quality of life.
The Dutch foundation—statutory objectives and new disclosure requirements
Authors: Steensel Martijn van , Velden Rick van der
Published: July 2021

The governance and operations of a Dutch foundation are regularly affected by case law and legislative developments. In this contribution, we discuss recent case law illustrating the importance of clearly formulated objectives of a foundation. We also address the recently introduced Bill on Civil Society Organizations.
Private trusts in China and some lessons from Australia
Authors: Wang Mi
Published: July 2021

Due to the increasing requirements of wealth management and diversification, it has become necessary to develop private trusts in China. Private trusts are well developed in Australia, especially the private business trust, which plays a significant role in stimulating economic development in Australia. This article considers what might be learned from the Australian example. It considers that some of the obstacles to private trusts development in China could be the lack of tax incentives, the incomplete registration system for private trusts, and unascertainable trust legislation. The article posits that China could absorb useful ideas with regard to developing private trusts in the future. It concludes by making some proposals for Chinese private trusts development.
The Persistence of Unfree Labor in the American Southwest
Authors: Kiser William S
Published: July 2021

This article explores the continuities of forced labor in the Southwest, where peonage and the partido system lasted for more than a century after the Thirteenth Amendment outlawed slavery, and places it within the broader context of modern global slavery. Debt peonage and peasant sharecropping—known locally as the partido—are usually classified as two different forms of unfree labor, but in the nineteenth- and twentieth-century Southwest they had much in common and were oftentimes mutually reinforcing. Through the legal and cultural intricacies of the partido system, thousands of landless Hispanos in the northern half of New Mexico and southern reaches of Colorado worked full-time in exchange for a small share of the annual wool harvest. Many of those same men became debt-bound to the tiny percentage of wealthy families who owned the sheep herds and grazing ranges. Through these means, partidarios (sheep renters) lost much if not all of their autonomy and became, to varying degrees depending on the disposition of their creditor and benefactor, debt peons.
10Animal Studies
Authors: Giraud Eva Haifa
Published: July 2021

This overview of animal studies scholarship from 2020 covers a diverse range of sites – from escaped primates in IKEA carparks to boar hunting in colonial India – and disciplinary contexts, drawing together research from philosophy, literary theory, the environmental humanities, animal geographies, imperial history, and ecofeminism. What unites these texts is their engagement with one of the most significant themes in animal studies: the politics of anthropocentrism. The first sections of the essay engage with work that has sought to critique anthropocentric logics and practices. Through focusing on research related to the exotic pet trade, avian extinction, and colonial science, I illustrate how anthropocentric hierarchies are being enacted – but also complicated – but particular socio-economic relationships and knowledge-frameworks. In the second sections of the essay, I engage more explicitly with scholarship that has foregrounded the complex relationships between anthropocentrism, colonialism, gendered inequalities, and racialization. Although this research is wide-ranging, what it shares is an insistence on the need to better situate narratives about the intersection of human and animal oppression, in light of the way these relations are shaped by specific national and cultural contexts. The essay culminates by discussing contemporary critiques of animal studies due to the primacy it has given to anthropocentrism over other oppressive social relations, particularly race. At the same time as arguing that the field needs to meaningfully engage with these critiques moving forward, I conclude by suggesting that there is something important about anthropocentrism that means it retains value as a critical concept for animal studies.
Measuring Proximal Tibial Metaphyseal Width and Lateral Epiphyseal Height Improves Determination of Remaining Growth in Children
Authors: Kahan Joseph B. , Li Don T. , Schneble Christopher A. , Elabd Ahmed , Attia Elsayed , Esparza Rachel , Cui Jonathan J. , Li Eric , Moran Jay , Smith Brian G. , Cooperman Daniel R.
Published: July 2021

Background:

Accurate assessments of skeletal maturity is of critical importance to guide type and timing of orthopaedic surgical interventions. Several quantitative markers of the proximal tibia were recently developed using historical knee radiographs. The purpose of the present study was to determine which marker would be most effective in assessment of full-length radiographs in a modern pediatric patient population.

Methods:

All full-length radiographs at our institutions between 2013 and 2018 were reviewed. Inclusion criteria for our study required that the child reached final height as defined by 2 consecutive unchanged heights, at least 6 months apart, after age 16 for boys and 14 for girls. Patients with metabolic bone disease, prior surgery such as epiphysiodesis, or previous infections around the knee were excluded. Summary statistics for each of the 3 proximal tibial ratios were calculated and multiple linear regression was performed with percent of growth remaining as a dependent variable. A recommended regression model is presented and evaluated.

Results:

A total of 692 full-length radiographs met inclusion criteria. Proximal tibial ratios were calculated and averaged values for each percent of growth remaining was presented. Multiple linear regression demonstrated that using all 3 variables led to overfitting of the model so tibial metaphyseal width/lateral tibial epiphyseal height was selected as the optimal ratio for use by clinicians. The optimal model for determining growth was found to have R
2=0.723 in the developmental set and R
2=0.762 in an excluded validation set.

Conclusions:

This study demonstrates that the proximal tibial metaphyseal width/lateral tibial epiphyseal height is the ideal measurement for clinicians seeking to determine growth remaining in children. It presents average values between 0% and 25% of growth remaining. This study also develops and validates a multivariable regression model for determining percentage of growth remaining in children that will allow for quantitative determination of growth using full-length radiographs.

Level of Evidence:

Level III.
Ramifications of Postoperative Dysphagia on Health Care Resource Utilization Following Elective Anterior Cervical Discectomy and Interbody Fusion for Cervical Spondylotic Myelopathy
Authors: Elsamadicy Aladine A. , Koo Andrew B. , David Wyatt B. , Freedman Isaac G. , Reeves Benjamin C. , Ehresman Jeff , Pennington Zach , Sarkozy Margot , Laurans Maxwell , Kolb Luis , Shin John H. , Sciubba Daniel M.
Published: July 2021

Study Design:

This is a retrospective cohort study.

Objective:

The aim of this study was to investigate patient risk factors and health care resource utilization associated with postoperative dysphagia following elective anterior cervical discectomy and fusion (ACDF) for cervical spondylotic myelopathy.

Summary of Background Data:

There is a paucity of data on factors predisposing patients to dysphagia and the burden this complication has on health care resource utilization following ACDF.

Methods:

A retrospective cohort study was performed using the Nationwide Inpatient Sample (NIS) database from 2016 to 2017. All adult (above 18 y old) patients undergoing ACDF for cervical spondylotic myelopathy were identified using the ICD-10-CM diagnosis and procedural coding system. Patients were then categorized by whether they had a recorded postoperative dysphagia or no dysphagia. Weighted patient demographics, comorbidities, perioperative complications, length of hospital stay (LOS), discharge disposition, and total cost of admission were assessed. A multivariate stepwise logistic regression was used to determine both the odds ratio for risk-adjusted postoperative dysphagia as well as extended LOS.

Results:

A total of 17,385 patients were identified, of which 1400 (8.1%) experienced postoperative dysphagia. Compared with the No-Dysphagia cohort, the Dysphagia cohort had a greater proportion of patients experiencing a complication (P=0.004), including 1 complication (No-Dysphagia: 2.9% vs. Dysphagia: 6.8%), and >1 complication (No-Dysphagia: 0.3% vs. Dysphagia: 0.4%). The Dysphagia cohort experienced significantly longer hospital stays (No-Dysphagia: 1.9±2.1 d vs. Dysphagia: 4.2±4.3 d, P<0.001), higher total cost of admission (No-Dysphagia: $19,441±10,495 vs. Dysphagia: $25,529±18,641, P<0.001), and increased rates of nonroutine discharge (No-Dysphagia: 16.5% vs. Dysphagia: 34.3%, P<0.001). Postoperative dysphagia was found to be a significant independent risk factor for extended LOS on multivariate analysis, with an odds ratio of 5.37 (95% confidence interval: 4.09, 7.05, P<0.001).

Conclusion:

Patients experiencing postoperative dysphagia were found to have significantly longer hospital LOS, higher total cost of admission, and increased nonroutine discharge when compared with the patients who did not.

Level of Evidence:

Level III.
Age-dependency of the Propagation Rate of Coronavirus Disease 2019 Inside School Bubble Groups in Catalonia, Spain
Authors: Alonso Sergio , Alvarez-Lacalle Enric , Català Martí , López Daniel , Jordan Iolanda , García-García Juan José , Soriano-Arandes Antoni , Lazcano Uxue , Sallés Pilar , Masats Marta , Urrutia Julià , Gatell Anna , Capdevila Ramon , Soler-Palacin Pere , Bassat Quique , Prats Clara
Published: July 2021

Background:

We analyzed contagions of coronavirus disease 2019 inside school bubble groups in Catalonia, Spain, in the presence of strong nonpharmaceutical interventions from September to December 2020. More than 1 million students were organized in bubble groups and monitored and analyzed by the Health and the Educational departments.

Methods:

We had access to 2 data sources, and both were employed for the analysis, one is the Catalan school surveillance system and the other of the educational department. As soon as a positive index case is detected by the health system, isolation is required for all members of the bubble group, in addition to a mandatory proactive systematic screening of each individual. All infected cases are reported. It permits the calculation of the average reproductive number (R*), corresponding to the average number of infected individuals per index case.

Results:

We found that propagation inside of the bubble group was small. Among 75% index cases, there was no transmission to other members in the classroom, with an average R* across all ages inside the bubble of R* = 0.4. We found a significant age trend in the secondary attack rates, with the R* going from 0.2 in preschool to 0.6 in high school youth.

Conclusions:

The secondary attack rate depends on the school level and therefore on the age. Super-spreading events (outbreaks of 5 cases or more) in childhood were rare, only occurring in 2.5% of all infections triggered from a pediatric index case.
Effective and Safe Daclatasvir Drug Exposures Predicted in Children Using Adult Formulations
Authors: Cressey Tim R. , Abbassi Maggie , Lallemant Marc , Indolfi Giuseppe , Al-Nahari Mogeb , Farid Samar , Penazzato Martina , Easterbrook Philippa , El-Sayed Manal H.
Published: July 2021

Background:

Sofosbuvir (SOF)/daclatasvir (DCV) is the direct-acting antiviral regimen of choice in many low- and middle-income countries for curative treatment of chronic hepatitis C virus (HCV) infection in adults, but data on the use of DCV in children are lacking. We performed a population pharmacokinetic (PK) analysis to predict DCV exposure in children treated with available adult formulations.

Methods:

DCV concentration data from HCV-infected adolescents receiving SOF/DCV [400/60 mg, once daily (OD)] who participated in a PK study in Egypt were used for model development. PK parameters were estimated using a population approach. Monte Carlo simulations were run for virtual children weighing 10 to <35 kg receiving 60 or 30 mg OD, and DCV exposures were compared with adults ranges.

Results:

Seventeen HCV-infected adolescents (13 males) provided 151 DCV concentrations. Median (range) age was 14 (11–18) years and weight 50 (32–63) kg. In these adolescents receiving 60 mg DCV, median (interquartile range) DCV area under the concentration time curve 0 to 24 hours, maximum concentrations, and minimum concentrations were 11,130 (8140–14,690) ng·h/mL, 1030 (790–1220) ng/mL and 130 (110–220) ng/mL, respectively, compared with 10,343 (7661–14,095) ng·h/mL, 1132 (876–1518) ng/mL and 110 (55.7–192) ng/mL predicted in children 10 to <35 kg receiving 30 mg. The proportion of children with DCV exposures above the adult range rapidly increased for children <30 kg using 60 mg OD, similarly for children 10–14 kg using 30 mg.

Conclusions:

DCV 30 mg OD was predicted to achieve effective and safe exposures in children 14 to <35 kg, perhaps down to 10 kg. These results should be validated clinically. Low-cost available adult DCV formulations together with approved pediatric doses of SOF would expand global access to HCV treatment for children.
White matter changes in the trigeminal spinal tract in chronic migraineurs: an ex vivo study combining ultra–high-field diffusion tensor imaging and polarized light imaging microscopy
Authors: Henssen Dylan , Kluin Sanne J.P. , Kleerebezem Joost , Van Cappellen van Walsum Anne-Marie , Mulleners Wim M. , Vissers Kris
Published: July 2021

Chronic migraine (CM) is a disabling neurologic disorder that affects approximately 2% of the general population. Neuroimaging studies show functional involvement of trigeminal structures, such as the trigeminal spinal nucleus (Sp5) in migraine. However, structural changes in the Sp5 and the afferent trigeminal spinal tract (sp5) have never been found. The aim of this study was to test the hypothesis that white matter changes in the sp5 are a key feature of brain alterations in patients with CM. We used diffusion magnetic resonance imaging and polarized light imaging of postmortem brainstem specimens from healthy controls (n = 5) and patients with CM (n = 5) to study white matter alterations in the sp5. Within the sp5, diffusion magnetic resonance imaging metrics included fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity values. Polarized light imaging was used to assess myelin density by a measure of the retardance values in the sp5. This study provides histological evidence that structural alterations occur in the sp5 in patients with CM as compared with healthy controls. Myelin density, as assessed by retardance values, showed to be higher, and a corresponding increase in fractional anisotropy values was observed. In addition, accompanying decreases in mean diffusivity, axial diffusivity, and radial diffusivity values were observed. This study shows that the sp5 undergoes neuroplastic changes, a feature which substantiates evidence for the hyperactivity of the Sp5 in patients with migraine. More insights are needed to observe whether these changes only occur in patients with CM.
A Narrative Review of Nutrition Therapy in Patients Receiving Extracorporeal Membrane Oxygenation
Authors: Karpasiti Terpsi
Published: July 2021

The use of extracorporeal membrane oxygenation (ECMO) in patients with severe cardiorespiratory failure has seen significant growth in the last decade. Despite this, there is paucity of data surrounding the optimum nutritional management for ECMO patients. This review aimed to describe current nutrition practices in patients receiving ECMO, critically appraise available studies and identify areas for future research. A literature search was conducted in PubMed, MEDLINE, and CINAHL Plus to identify all randomized trials and observational studies published between July 2000 and July 2020 investigating nutrition practices in critically ill adults receiving ECMO. The primary outcomes were nutritional adequacy, gastrointestinal complications, and physical function. Secondary outcomes included mortality, length of stay, and duration on ECMO support. From a total of 31 studies identified, 12 met the inclusion criteria. Nine observational studies were reviewed following eligibility assessment. Early enteral nutrition was deemed safe and feasible for ECMO patients; however, meeting nutritional targets was challenging. Utilizing alternative nutrition routes is an option, although risks and benefits should be taken into consideration. Data on gastrointestinal complications and other clinical outcomes were inconsistent, and no data were identified investigating the effects of nutrition on the physical and functional recovery of ECMO patients. Nutrition therapy in ECMO patients should be provided in line with current guidelines for nutrition in critical illness until further data are available. Further prospective, randomized studies investigating optimum nutrition practices and effects on clinical and functional outcomes are urgently required.
Unexpected Poor Growth in Pediatric Patients on Food‐based Enteral Therapy
Authors: David Jennie , Huston Parker , Manville Kaylee , Burdo‐Hartman Wendelin , Kaiser Sarah , Arand Brian , Hockaday Maureen , Rosenston Lauren , Sejkora Ellen , Dempster Robert
Published: July 2021

Introduction:

Enteral feeding pumps at times may deliver different volumes than are prescribed, which can negatively impact growth, nutrition, and well‐being. This study sought to assess whether challenges with pump accuracy for patients on food‐based formulas contributed to challenges with weight gain.

Methods:

Chart review identified complex feeding patients receiving food‐based enteral nutrition via feeding pump with unexpected weight loss. Relevant data, such as enteral formula type, and anthropometric information were extracted.

Results:

Five complex pediatric feeding patients were identified and 2 of these cases were summarized as representative examples, showing weight loss in children following the introduction of enteral food‐based formulas because of feeding pump inaccuracy.

Conclusions:

Complex pediatric feeding patients may display unexpected and poor weight gain and growth while receiving food‐based enteral feeding interventions because of pump errors. It is vital for providers to be aware of these challenges for timely intervention.
Moderate‐to‐Vigorous Physical Activity Is Associated With Higher Bone Mineral Density in Children With Inflammatory Bowel Disease
Authors: Trivić Ivana , Sila Sara , Batoš Ana Tripalo , Mišak Zrinjka , Kolaček Sanja , Hojsak Iva
Published: July 2021

Objectives:

Decreased mineral bone density (BMD) and reduced lean body mass (LBM) are common amongst children with inflammatory bowel disease (IBD). The aim of our cross‐sectional, observational study was to evaluate the relationship between BMD, body composition and physical activity (PA) in children with IBD in remission.

Methods:

Total body less head (TLBH) dual energy X‐ray absorptiometry (DXA) was used to measure BMD, fat mass (FM) and lean body mass (LBM). Triaxial accelerometer for five consecutive days was used to objectivize PA.

Results:

Forty pediatric IBD patients in clinical remission (24 boys; age 15.3 ± 0.4 years; Crohn disease [CD], n = 20, ulcerative colitis [UC], n = 18, inflammatory bowel disease‐unclassified [IBD‐U], n = 2) were recruited. Mean BMD was 0.940 g/cm2 and mean BMD z score was −0.42 ± 0.14. Patients with CD had significantly lower BMD than UC counterparts (P < 0.001). Average time spent in PA was 247.24 ± 16.71 min/day with 45.73 ± 8.22 min/day spent in moderate‐to‐vigorous PA (MVPA). We observed a significant positive correlation between the time spent in MVPA and BMD z score (P = 0.003) and LBM z score (P = 0.026). Multivariate analysis confirmed that the positive correlation of MVPA and BMD z score. There was no significant correlation between daily protein intake and BMD. Cumulative glucocorticoid dose negatively correlated with LBM z score (P = 0.003), but not with BMD z score (P = 0.069).

Conclusions:

This study points to a strong positive relationship between MVPA, LBM and BMD. Longitudinal studies are required in order to elucidate the modifiable processes that determine body health and favorable body composition.
How Did the Lockdown Imposed Due to COVID-19 Affect Patients With Cerebral Palsy?
Authors: Dogruoz Karatekin Bilinc , İcagasioglu Afitap , Sahin Seyma Nur , Kacar Gülnihal , Bayram Fethullah
Published: July 2021

Background:

The novel coronavirus infection (SARS-CoV-2) caused disruption of the treatment and follow-up evaluations of children with cerebral palsy.

Aim:

The change in mobility, pain, functional status, and spasticity was investigated who were followed in a pediatric rehabilitation unit after the lockdown.

Methods:

One hundred ten children were evaluated. Pain, severity of spasticity, botulinum toxin administration dates, and continuity of home exercises were recorded. The functional status was evaluated with the Functional Independence Measure for Children (WeeFIM).

Results:

The WeeFIM self-care and mobility subscale scores and total scores were significantly worse. Only 5 of the participants had pain in the previous evaluations; in the last evaluation, 29 had pain complaints. The pain and spasticity severity of the participants whose botulinum toxin administration was delayed were significantly increased.

Conclusions:

The children with cerebral palsy should be followed with telemedicine at short intervals, and when necessary, in the hospital.
Maribrevibacterium harenarium gen. nov., sp. nov., represented by a marine strain of the family Oceanospirillaceae
Authors: Mo Kunlian , Wu Qingjuan , Hu Yonghua , Huang Huiqin
Published: July 2021

A Gram-stain-negative, non-motile, facultatively anaerobic, short rod-shaped bacterium, designated HB171799T, was isolated from seacoast sandy soil collected at Qishui Bay, Hainan, PR China. The chemotaxonomic analysis revealed that the respiratory quinones were Q-8 and Q-7, and the major cellular fatty acids were summed feature 8 (comprising C18 : 1
 ω7c and/or C18 : 1
 ω6c), C16 : 0 and C18 : 0. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid and an unidentified lipid. The size of the draft genome was 3.68 Mb with a DNA G+C content of 48.0 mol%. Results of phylogenetic analyses based on 16S rRNA gene and genome sequences showed that the novel isolate belonged to the family

Oceanospirillaceae

and formed a distinct subcluster at the base of the radiation of the genus

Marinomonas

. The highest sequence similarity (96.0 %) of the novel isolate was found to the type strains of

Marinomonas fungiae

JCM 18476T and

Marinomonas ostreistagni

DSM23425T. The whole genome-based phylogeny and differences in cellular fatty acids and polar lipids readily distinguished strain HB171799T from all the closely related validly published type strains. Strain HB171799T is therefore suggested to represent a novel species of a new genus in the family

Oceanospirillaceae

, for which the name Maribrevibacterium harenarium gen. nov., sp. nov. is proposed. The type strain is HB171799T (=CGMCC 1.16727T=JCM 33332T).
Reactive vaccination of workplaces and schools against COVID-19
Authors: Faucher Benjamin , Assab Rania , Roux Jonathan , Levy-Bruhl Daniel , Kiem Cécile Tran , Cauchemez Simon , Zanetti Laura , Colizza Vittoria , Boëlle Pierre-Yves , Poletto Chiara
Published: July 2021

Abstract

As vaccination against COVID-19 stalls in some countries, increased accessibility and more adaptive approaches may be useful to keep the epidemic under control. Here, we study the impact of reactive vaccination targeting schools and workplaces where cases are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, individuals’ demography and behaviour and social distancing. At an equal number of doses reactive vaccination produces a higher reduction in cases compared with non-reactive strategies, in the majority of scenarios. However, at high initial vaccination coverage or low incidence, few people are found to vaccinate around cases, thus the reactive strategy may be less effective than non-reactive strategies with moderate/high vaccination pace. In case of flare-ups, reactive vaccination could hinder spread if it is implemented quickly, is supported by enhanced test-trace-isolate and triggers an increased vaccine uptake. These results provide key information to plan an adaptive vaccination deployment.
Polygenic risk score and statin relative risk reduction for primary prevention in a real-world population
Authors: Oni-Orisan Akinyemi , Haldar Tanushree , Cayabyab Mari A. S. , Ranatunga Dilrini K. , Hoffmann Thomas J. , Iribarren Carlos , Krauss Ronald M. , Risch Neil
Published: July 2021

Abstracts

Background

Randomized-controlled trials demonstrate that high coronary heart disease (CHD) polygenic risk score modifies statin CHD relative risk reduction, but it is unknown if the association extends to statin users undergoing routine care.

Objectives

The primary objective was to determine how statin effectiveness is modified by CHD polygenic risk score in a real-world cohort of primary prevention participants.

Methods

We determined polygenic risk scores in participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Cox regression models were used to compare the risk of the cardiovascular outcomes between statin users and matched nonusers.

Results

The hazard ratio (HR) for statin effectiveness on incident myocardial infarction was similar within 10-year atherosclerotic cardiovascular disease (ASCVD) risk score groups at 0.65 (95% confidence interval [CI] 0.39-1.08; P=0.10), 0.65 (95% CI 0.56-0.77; P=2.1E-7), and 0.67 (95% CI 0.57-0.80; P=4.3E-6) for borderline, intermediate, and high ASCVD groups, respectively. In contrast, statin effectiveness by polygenic risk was largest in the high polygenic risk score group (HR 0.62, 95% CI 0.50-0.77; P=1.4E-5), intermediate in the intermediate polygenic risk score group (HR 0.70, 95% CI 0.61-0.80; P=5.7E-7), and smallest in the low polygenic risk score group (HR 0.86, 95% CI 0.65-1.16; P=0.33). ASCVD risk and statin LDL-C lowering did not differ across polygenic risk score groups.

Conclusions

In primary prevention patients undergoing routine care, CHD polygenic risk modified statin relative risk reduction of incident myocardial infarction independent of statin LDL-C lowering. Our findings extend prior work by identifying a subset of patients with attenuated clinical benefit from statins.
Emotional context sculpts action goal representations in the lateral frontal pole
Authors: Lapate RC , Ballard IC , Heckner MK , D’Esposito M
Published: July 2021

Emotional states provide an ever-present source of contextual information that should inform behavioral goals. Despite the ubiquity of emotional signals in our environment, the neural mechanisms underlying their influence on goal-directed action remains unclear. Prior work suggests that the lateral frontal pole (FPl) is uniquely positioned to integrate affective information into cognitive control representations. We used pattern similarity analysis to examine the content of representations in FPl and interconnected mid-lateral prefrontal and amygdala circuitry. Healthy participants (n=37; n=21 females) were scanned while undergoing an event-related Affective Go/No-Go task, which requires goal-oriented action selection during emotional processing. We found that FPl contained conjunctive emotion-action goal representations that were related to successful cognitive control during emotional processing. These representations differed from conjunctive emotion-action goal representations found in the basolateral amygdala. While robust action goal representations were present in mid-lateral prefrontal cortex, they were not modulated by emotional valence. Finally, converging results from functional connectivity and multivoxel pattern analyses indicated that FPl’s emotional valence signals likely originated from interconnected subgenual ACC (BA25), which was in turn functionally coupled with the amygdala. Thus, our results identify a key pathway by which internal emotional states influence goal-directed behavior.

Significance statement

Optimal functioning in everyday life requires behavioral regulation that flexibly adapts to dynamically changing emotional states. However, precisely how emotional states influence goal-directed action remains unclear. Unveiling the neural architecture that supports emotion-goal integration is critical for our understanding of disorders such as psychopathy, which is characterized by deficits in incorporating emotional cues into goals, as well as mood and anxiety disorders, which are characterized by impaired goal-based emotion regulation. Our study identifies a key circuit through which emotional states influence goal-directed behavior. This circuitry comprised the lateral frontal pole (FPl), which represented integrated emotion-goal information, as well as interconnected amygdala and subgenual ACC, which conveyed emotional signals to FPl.
Automated Reconstruction of Whole-Embryo Cell Lineages by Learning from Sparse Annotations
Authors: Malin-Mayor Caroline , Hirsch Peter , Guignard Leo , McDole Katie , Wan Yinan , Lemon William C. , Keller Philipp J. , Preibisch Stephan , Funke Jan
Published: July 2021

We present a method for automated nucleus identification and tracking in time-lapse microscopy recordings of entire developing embryos. Our method combines deep learning and global optimization to enable complete lineage reconstruction from sparse point annotations, and uses parallelization to process multi-terabyte light-sheet recordings, which we demonstrate on three common model organisms: mouse, zebrafish,Drosophila. On the most difficult dataset (mouse), our method correctly reconstructs 75.8% of cell lineages spanning 1 hour, compared to 31.8% for the previous state of the art, thus enabling biologists to determine where and when cell fate decisions are made in developing embryos, tissues, and organs.
Molecular surveillance of zoonotic bacterial pathogens in farm dwelling peridomestic rodents across the upper Midwest, USA
Authors: Jahan Nusrat A. , Lindsey Laramie L. , Kipp Evan J. , Heins Bradley J. , Runck Amy M. , Larsen Peter A.
Published: July 2021

The effective control of rodent populations on farms is a critical component of food- safety, as rodents are reservoirs and vectors for many foodborne pathogens in addition to several zoonotic pathogens. The functional role of rodents in the amplification and transmission of pathogens is likely underappreciated. Clear links have been identified between rodents and outbreaks of pathogens throughout Europe and Asia, however, comparatively little research has been devoted to studying this rodent-agricultural interface in the USA, particularly across the Midwest. Here, we address this existing knowledge gap by characterizing the metagenomic communities of rodent pests collected from Minnesota and Wisconsin food animal farms. We leveraged the Oxford Nanopore MinION sequencer to provide a rapid real-time survey of the putative zoonotic food- borne and other human pathogens. Rodents (mice and rats) were live trapped from three dairy and mixed animal farms. Tissues and fecal samples were collected from all rodents. DNA extraction was performed on 90 rodent colons along with 2 shrew colons included as outgroups in the study. Full-length 16S amplicon sequencing was performed with the MinION. Our data suggests the presence of putative foodborne pathogens including Salmonella spp., Campylobacter spp., Staphylococcus aureus, and Clostridium spp., along with many important mastitis pathogens. A critically important observation is that we discovered these pathogens within all five species of rodents (Microtus pennsylvanicus, Mus musculus, Peromyscus leucopus, Peromyscus maniculatus, and Rattus norvegicus) and shrew (Blarina brevicauda) in varying abundances. Interestingly, we observed a higher abundance of enteric pathogens (e.g. Salmonella) in shrew feces compared to the rodents analyzed in our study, however more data is required to establish that connection. Knowledge gained from our research efforts will directly inform and improve upon farm-level biosecurity efforts and public health interventions to reduce future outbreaks of foodborne and zoonotic disease.
Development of lipidoid nanoparticles for siRNA delivery to neural cells
Authors: Khare Purva , Dave Kandarp M. , Kamte Yashika S. , Manoharan Muthiah A. , O’Donnell Lauren A. , Manickam Devika S
Published: July 2021

Lipidoid nanoparticles (LNPs) are the delivery platform in Onpattro, the first FDA-approved siRNA drug. LNPs are also the carriers in the Pfizer-BioNTech and Moderna COVID-19 mRNA vaccines. While these applications have demonstrated that LNPs effectively deliver nucleic acids to hepatic and muscle cells, it is unclear if LNPs could be used for delivery of siRNA to neural cells, which are notoriously challenging delivery targets. Therefore, the purpose of this study was to determine if LNPs could efficiently deliver siRNA to neurons. Because of their potential utility in either applications in the central nervous system and the peripheral nervous system, we used both cortical neurons and sensory neurons. We prepared siRNA-LNPs using C12-200, a benchmark ionizable cationic lipidoid along with helper lipids. We demonstrated using dynamic light scattering that the inclusion of both siRNA and PEG-lipid provided a stabilizing effect to the LNP particle diameters and polydispersity indices by minimizing aggregation. We found that siRNA-LNPs were safely tolerated by primary dorsal root ganglion neurons. Flow cytometry analysis revealed that Cy5 siRNA delivered via LNPs into rat primary cortical neurons showed uptake levels similar to Lipofectamine RNAiMAX—the gold standard commercial transfection agent. However, LNPs demonstrated a superior safety profile whereas the Lipofectamine-mediated uptake was concomitant with significant toxicity. Fluorescence microscopy demonstrated a time-dependent increase in the uptake of LNP-delivered Cy5 siRNA in a human cortical neuron cell line. Overall, our results suggest that LNPs are a viable platform that can be optimized for delivery of therapeutic siRNAs to neural cells.

Graphical Abstract
On the calculation of the electrostatic potential, electric field and electric field gradient from the aspherical pseudoatom model. II. Evaluation of the properties in an infinite crystal
Authors: Weatherly Jessie , Macchi Piero , Volkov Anatoliy
Published: July 2021

The previously reported exact potential and multipole moment (EP/MM) method for fast and precise evaluation of the intermolecular electrostatic interaction energies in molecular crystals using the pseudoatom representation of the electron density [Nguyen, Macchi & Volkov (2020),Acta Cryst.A76, 630–651] has been extended to the calculation of the electrostatic potential (ESP), electric field (EF) and electric field gradient (EFG) in an infinite crystal. The presented approach combines an efficient Ewald-type summation (ES) of atomic multipoles up to the hexadecapolar level in direct and reciprocal spaces with corrections for (i) the net polarization of the sample (the `surface term') due to a net dipole moment of the crystallographic unit cell (if present) and (ii) the short-range electron-density penetration effects. The rederived and reported closed-form expressions for all terms in the ES algorithm have been augmented by the expressions for the surface term available in the literature [Stenhammar, Trulsson & Linse (2011),J. Chem. Phys.134, 224104] and the exact potential expressions reported in a previous study [Volkov, King, Coppens & Farrugia (2006),Acta Cryst.A62, 400–408]. The resulting algorithm, coded using Fortran in theXDPROPmodule of the software packageXD, was tested on several small molecular crystal systems (formamide, benzene, L-dopa, paracetamol, amino acidsetc.) and compared with a series of EP/MM-based direct-space summations (DS) performed within a certain number of unit cells generated along both the positive and negative crystallographic directions. The EP/MM-based ES technique allows for a noticeably more precise determination of the EF and EFG and significantly better precision of the evaluated ESP when compared with the DS calculations, even when the latter include contributions from an array of symmetry-equivalent atoms generated within four additional unit cells along each crystallographic direction. In terms of computational performance, the ES/EP/MM method is significantly faster than the DS calculations performed within the extended unit-cell limits but trails the DS calculations within the reduced summation ranges. Nonetheless, the described EP/MM-based ES algorithm is superior to the direct-space summations as it does not require the user to monitor continuously the convergence of the evaluated properties as a function of the summation limits and offers a better precision–performance balance.
Exploring ligand dynamics in protein crystal structures with ensemble refinement
Authors: Caldararu Octav , Ekberg Vilhelm , Logan Derek T. , Oksanen Esko , Ryde Ulf
Published: July 2021

Understanding the dynamics of ligands bound to proteins is an important task in medicinal chemistry and drug design. However, the dominant technique for determining protein–ligand structures, X-ray crystallography, does not fully account for dynamics and cannot accurately describe the movements of ligands in protein binding sites. In this article, an alternative method, ensemble refinement, is used on six protein–ligand complexes with the aim of understanding the conformational diversity of ligands in protein crystal structures. The results show that ensemble refinement sometimes indicates that the flexibility of parts of the ligand and some protein side chains is larger than that which can be described by a single conformation and atomic displacement parameters. However, since the electron-density maps are comparable and R
free values are slightly increased, the original crystal structure is still a better model from a statistical point of view. On the other hand, it is shown that molecular-dynamics simulations and automatic generation of alternative conformations in crystallographic refinement confirm that the flexibility of these groups is larger than is observed in standard refinement. Moreover, the flexible groups in ensemble refinement coincide with groups that give high atomic displacement parameters or non-unity occupancy if optimized in standard refinement. Therefore, the conformational diversity indicated by ensemble refinement seems to be qualitatively correct, indicating that ensemble refinement can be an important complement to standard crystallographic refinement as a tool to discover which parts of crystal structures may show extensive flexibility and therefore are poorly described by a single conformation. However, the diversity of the ensembles is often exaggerated (probably partly owing to the rather poor force field employed) and the ensembles should not be trusted in detail.
Structural and spectrophotometric investigation of two unnatural amino-acid altered chromophores in the superfolder green fluorescent protein
Authors: Olenginski Gregory M. , Piacentini Juliana , Harris Darcy R. , Runko Nicolette A. , Papoutsis Brianna M. , Alter Jordan R. , Hess Kenneth R. , Brewer Scott H. , Phillips-Piro Christine M.
Published: July 2021

The spectrophotometric properties of the green fluorescent protein (GFP) result from the post-translationally cyclized chromophore composed of three amino acids including a tyrosine at the center of the β-barrel protein. Altering the amino acids in the chromophore or the nearby region has resulted in numerous GFP variants with differing photophysical properties. To further examine the effect of small atomic changes in the chromophore on the structure and photophysical properties of GFP, the hydroxyl group of the chromophore tyrosine was replaced with a nitro or a cyano group. The structures and spectrophotometric properties of these superfolder GFP (sfGFP) variants with the unnatural amino acids (UAAs) 4-nitro-L-phenylalanine or 4-cyano-L-phenylalanine were explored. Notably, the characteristic 487 nm absorbance band of wild-type (wt) sfGFP is absent in both unnatural amino-acid-containing protein constructs (Tyr66pNO2Phe-sfGFP and Tyr66pCNPhe-sfGFP). Consequently, neither Tyr66pNO2Phe-sfGFP nor Tyr66pCNPhe-sfGFP exhibited the characteristic emission of wt sfGFP centered at 511 nm when excited at 487 nm. Tyr66pNO2Phe-sfGFP appeared orange due to an absorbance band centered at 406 nm that was not present in wt sfGFP, while Tyr66pCNPhe-sfGFP appeared colorless with an absorbance band centered at 365 nm. Mass spectrometry and X-ray crystallography confirmed the presence of a fully formed chromophore and no significant structural changes in either of these UAA-containing protein constructs, signaling that the change in the observed photophysical properties of the proteins is the result of the presence of the UAA in the chromophore.
Communicating customer value proposition in the French pharmaceutical industry. The case of OTC drugs
Authors: Castellano Sylvaine , Khelladi Insaf , Aouina Mejri Chiraz
Published: July 2021

Purpose

This paper aims to investigate how pharmacies communicate their customer value proposition (CVP) in a complex and multiple-stakeholder setting. More specifically, from the pharmacists’ perspective, the study analyzes how CVP is articulated in complex settings/offerings and among multiple stakeholders; and elucidates the communication gap among stakeholders of the CVP.

Design/methodology/approach

Two studies were conducted to examine how offerings are communicated throughout the value chain. Through six in-depth interviews, Study 1 aimed to analyze how pharmacies articulate CVP for over-the-counter (OTC) drugs in a complex business-to-business-to-consumer setting. For Study 2, the data were collected from 113 French pharmacists to investigate the communication issues and to unveil the tools used to promote OTC drugs among the different stakeholders.

Findings

From the pharmacists’ perspective, the longer the chain, the more complex the efficiency of the CVP. This study conceives a new and adapted CVP as iterative and cumulative. This paper also highlights how value is distributed across the customer relationship in a complex and regulated industry. The findings feature a reciprocal perspective of CVP between the pharmaceutical labs and their direct/indirect customers. Final customers aim at creating a reciprocal approach with the different stakeholders. Pharmacists use a unidirectional perspective of CVP with their direct customers (patients/final customers).

Originality/value

The study contributes to a better understanding of the CVP in complex industries characterized by a chain of value distributed among multiple stakeholders (i.e. business-to-consumer and business-to-business). The article also enriches past research that analyzed the way firms communicate their offerings from a CVP perspective.