bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses
Authors: McCoy Eric S. , Park Sang Kyoon , Patel Rahul P. , Ryan Dan F. , Mullen Zachary J. , Nesbitt Jacob J. , Lopez Josh E. , Taylor-Blake Bonnie , Vanden Kelly A. , Krantz James L. , Hu Wenxin , Garris Rosanna L. , Snyder Magdalyn G. , Lima Lucas V. , Sotocinal Susana G. , Austin Jean-Sebastien , Kashlan Adam D. , Shah Sanya , Trocinski Abigail K. , Pudipeddi Samhitha S. , Major Rami M. , Bazick Hannah O. , Klein Morgan R. , Mogil Jeffrey S. , Wu Guorong , Zylka Mark J. 
Published: February 2024

Abstract
Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace (http://painface.net) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale. Platform accuracy was validated in 2 different laboratories, with 3 conditions that evoke grimacing—laparotomy surgery, bilateral hindpaw injection of carrageenan, and intraplantar injection of formalin. PainFace can generate up to 1 grimace score per second from a standard 30 frames/s video, making it possible to quantify facial grimacing over time, and operates at a speed that scales with computing power. By analyzing the frequency distribution of grimace scores, we found that mice spent 7x more time in a “high grimace” state following laparotomy surgery relative to sham surgery controls. Our study shows that PainFace reproducibly quantifies facial grimaces indicative of nonevoked spontaneous pain and enables laboratories to standardize and scale-up facial grimace analyses.
From biodiversity to nature deficiency in human health and disease
Authors: Haahtela Tari , Bousquet Jean , Antó Josep M. 
Published: February 2024

Abstract
Nature (biodiversity) loss is the loss or decline of the state of nature taking place in the wider environment. We present a novel concept, nature deficiency, referring to nature loss in the human body influencing health. Humans are connected with the natural environment and its microbes and biogenic chemicals through eating (drinking), breathing, and touching. The mental and sociocultural links to the environment are also strong. With medical and ecological research and guidelines, the diagnosis, prevention, and treatment of nature deficiency may become part of the clinical practice. Nature prescription is likely to find plausible forms in patient care and inspire preventive actions at the society level. Health professionals are in a key position to integrate public health promotion and environmental care.
Blue Sky Thinking: Physician Assistant Accreditation and the Potential Impact on the Programs, Faculty, and the Profession
Authors: Snyder Jennifer , Honda Trenton , Lohenry Kevin , Asprey David 
Published: February 2024

AbstractBlue sky thinking references the opportunity to brainstorm about a topic without limits… to consider what things might be like if creative thoughts were unconstrained by current philosophies or other boundaries. This article is a call to our fellow educators to consider how blue sky thinking applied to physician assistant (PA) program accreditation might further advance programs, faculty, and the profession. To develop and maintain a PA program, institutions must voluntarily undergo evaluation by the Accreditation Review Commission on Education for the Physician Assistant. Compliance with accreditation encourages sound educational practices, promotes program self-study, stimulates innovation, maintains confidence with the public, and focuses on continuous quality improvement. In addition, accreditation “can hold institutions accountable for desired outcomes and professional standards.” Indeed, while the PA profession has promulgated across the globe, the 50+ years of graduating PAs educated with the highest quality education assures that the United States remains a gold standard. As the 5th edition of the standards are implemented and planning for the 6th edition is underway, in the spirit of continuous quality improvement, we encourage stakeholders of the PA profession to contemplate ways in which accreditation might continue to purposefully advance a desired future state for the profession. In this article, we draw on examples from other health professions which might inform a discussion around the future of PA accreditation. Specifically, the topics of a unified profession title and degree, a specific title and position for program leadership, a modification to how PA programs receive medical direction, and efforts to advance scholarship are addressed.
Negative Impact of Synkinetic Mentalis Muscle on Smile Quality: Pathomechanism and Treatment with Mentalis-Targeted Selective Neurectomies
Authors: Facchin Federico , Sanchez Cristina V. , Gault Natalie A. , Rail Benjamin , Rozen Shai M. 
Published: February 2024

Background:
The treatment of postparetic facial synkinesis is based on a combination of nonsurgical and surgical strategies. Improvements toward the restoration of a natural smile have been obtained with selective neurectomies and depressor anguli oris myectomy, but the lower lip frequently remains asymmetric and cranially displaced. The aim of this study was to evaluate the effect of the mentalis muscle on the position and symmetry of the lower lip in patients with synkinesis and to assess the added benefit of neurectomies of nerves innervating the mentalis muscle in improving the lower lip configuration and mandibular teeth show.

Methods:
A retrospective cohort study of all patients with postparetic synkinesis was performed at the authors’ institution. A nonmentalis neurectomy group including 12 patients treated with selective neurectomies without targeting the branches to mentalis muscle was compared with a mentalis neurectomy group including 16 patients who underwent additional specific mentalis branches neurectomies. All patients underwent depressor anguli oris myectomy. Analyses of standardized images were performed with ImageJ software.

Results:
Postoperative comparisons between the 2 groups showed superior and significant improvements in the mentalis neurectomy group across all measures, including lower and upper border deviation (P = 0.035 and P = 0.004, respectively), inclination of the lower lip (P = 0.019), and lower quadrant dental show (P = 0.004).

Conclusion:
The addition of targeted selective neurectomies to the branches innervating the mentalis muscle significantly improved dental show and caudal position and symmetry of the lower lip during open-mouth smile.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
Dyadic Investigation of Posttraumatic Stress Symptoms and Daily Sleep Health in Patients With Cancer and Their Caregivers
Authors: Tsai Thomas C. , Mitchell Hannah-Rose , Zeitzer Jamie , Ting Amanda , Laurenceau Jean-Philippe , Spiegel David , Kim Youngmee 
Published: February 2024

Objective
Cancer can be a traumatic experience affecting multidimensional aspects of sleep among patients and caregivers. This study examined the differential associations of cancer-related posttraumatic stress symptoms (PTSS) with various sleep markers in this population.

Methods
Patients newly diagnosed with colorectal cancer (n = 138, mean age = 56.93 years, 31.88% female, 60.14% Hispanic, 6.53 months after diagnosis) and their sleep-partner caregivers (n = 138, mean age = 55.32 years, 68.12% female, 57.97% Hispanic) completed questionnaires assessing the four PTSS clusters (intrusion, avoidance, alterations in arousal and reactivity, negative alterations in cognitions and mood). Participants also completed daily sleep diaries for 14 consecutive days, from which sleep onset latency (SOL), wake after sleep onset (WASO), and sleep duration were derived.

Results
Actor-partner interdependence model revealed that caregivers’ greater alterations in arousal and reactivity were associated with their own longer SOL (b = 15.59, p < .001) and their patients’ longer sleep duration (b = 0.61, p = .014), whereas patients’ arousal and reactivity were associated with their caregivers’ shorter SOL (b = −8.47, p = .050). Patients’ and caregivers’ greater negative alterations in cognitions and mood were associated with patients’ longer SOL (b = 9.15, p = .014) and shorter sleep duration (b = −0.41, p = .050), respectively. Caregivers’ greater intrusion was related to their own shorter SOL (b = −10.14, p = .004).

Conclusions
The four PTSS clusters, particularly arousal and reactivity and negative cognitions and mood, have distinct associations with sleep markers individually and dyadically in patients and caregivers affected by cancer. Investigations of psychosocial and biobehavioral pathways underlying these relations are warranted. Tailored trauma treatments and sleep interventions may improve the well-being of this population.
Associations Between Structural Stigma and Allostatic Load Among Sexual Minorities: Results From a Population-Based Study
Authors: Juster Robert-Paul , Rutherford Caroline , Keyes Katherine , Hatzenbuehler Mark L. 
Published: February 2024

ABSTRACT

Objective
Structural forms of stigma and discrimination are associated with adverse health outcomes across numerous stigmatized groups, including lesbian, gay, and bisexual (LGB) individuals. However, the biological consequences of structural stigma among LGB populations are understudied. To begin to address this gap, we assessed associations between indicators of structural stigma (i.e., state-level policies) targeting LGB individuals and allostatic load (AL) indices representing physiological dysregulations.

Methods
Pooled data from the continuous 2001–2014 National Health and Nutritional Examination Survey were analyzed (LGB: n = 864; heterosexual: n = 20,310). Ten state-level LGB-related policies (e.g., employment nondiscrimination protections, same-sex marriage) were used to operationalize structural stigma. A sex-specific AL index representing 11 immune, metabolic, and cardiovascular biomarkers was estimated. Multilevel models were used to examine associations between structural stigma and AL, net of nine individual-level characteristics (e.g., education, race/ethnicity, age, and health behaviors).

Results
Sexual minority men living in states with low levels of structural stigma experienced significantly lower AL (β = −0.45, p = .02) compared with sexual minority men living in states with high structural stigma (i.e., fewer protective policies). There was no significant association between structural stigma and AL among sexual minority women.

Conclusions
By demonstrating direct associations between structural stigma and indices of physiological dysregulation, our findings provide a mechanistic understanding of how the social environment can “get under the skin and skull” for sexual minority men in the United States. Future research should explore whether these mechanisms generalize to other marginalized groups exposed to structural stigma.
Childhood Maltreatment and Leukocyte Telomere Length: Cardiac Vagal Activity Influences the Relation in Older Adults
Authors: Connor Alexandra , Deschamps Alain , Busque Lambert , Tardif Jean-Claude , Bourgoin Vincent , Dubé Marie-Pierre , Busseuil David , D’Antono Bianca 
Published: February 2024

ABSTRACT

Objective
Childhood maltreatment is associated with shorter leukocyte telomere length (LTL). However, the influence of cardiac vagal control on this relation is unknown. We examined whether cardiac vagal control at rest and in response to stress moderates or cross-sectionally mediates the relationship between childhood maltreatment and LTL.

Methods
Participants were 1179 men and women (aged 65 [7.2] years) suffering from coronary artery disease or non–cardiovascular chronic disease. They completed a childhood maltreatment questionnaire and underwent a stress protocol while electrocardiogram was monitored. High-frequency heart rate variability (HF-HRV) measures were obtained at rest, during stress, and after stress in absolute and normalized units (nu). LTL was measured using quantitative polymerase chain reaction. Mediation and moderation analyses were performed.

Result
HF-HRV and HF-HRV in normalized units (HFnu) measures did not mediate the childhood maltreatment–LTL relation. However, baseline HFnu (p = .027) and HFnu reactivity (p = .051) moderated the relation. Specifically, maltreatment was associated with significantly lower LTL among those with baseline HFnu at (b = −0.059, p = .003) or below the mean (b = −0.103, p < .001), but not among those with higher baseline HFnu. It was also associated with significantly lower LTL among participants who showed either blunted (b = −0.058, p = .004) or increased HFnu (b = −0.099, p = .001) responses to stress but not in those with large decreases in HFnu.

Conclusions
Childhood maltreatment was associated with lower LTL in those who showed a distinct cardiac vagal profile at baseline and in response to stress. The mechanisms and implications remain to be determined.
Identifying injuries suggestive of child physical abuse: An innovative application of the Trauma Quality Improvement Program
Authors: Reed Leighton , Odendal Lisa , Mercurio Danielle , Snyder Christopher W. 
Published: February 2024

BACKGROUND
Child physical abuse (CPA) carries high risk of morbidity and mortality. Screening for CPA may be limited by subjective risk criteria and racial and socioeconomic biases. This study derived, validated, and compared age-stratified International Classification of Diseases, 10th revision (ICD-10) diagnosis codes indicating high risk of CPA.

METHODS
Injured children younger than 6 years from the Trauma Quality Improvement Program (TQIP) database were included; years 2017 to 2018 were used for derivation and 2019 for validation. Confirmed CPA was defined as a report of abuse plus discharge with alternate caregiver. Patients were classified as high vs. low CPA risk by three methods: (1) abuse-specific ICD-10 codes, (2) previously validated high-risk ICD-9 codes crosswalked to equivalent ICD-10 codes, and (3) empirically-derived ICD-10 codes from TQIP. These methods were compared with respect to sensitivity, specificity, area under the receiver-operator curve (AUROC), and uniformity across race and insurance strata.

RESULTS
A total of 122,867 children were included (81,347 derivation cohort, 41,520 validation cohort). Age-stratified high-risk diagnoses derived from TQIP consisted of 40 unique codes for ages 0 year to 2 years, 30 codes for ages 3 years to 4 years, and 20 codes for ages 5 years to 6 years. In the validation cohort, 890 children (2.1%) had confirmed CPA. On comparison with abuse-specific and crosswalked ICD-9 codes, TQIP-derived codes had the highest sensitivity (70% vs. 19% vs. 54%) and the highest AUROC (0.74 vs. 0.59 vs. 0.68, p < 0.0001) for confirmed abuse across all age groups. Age-based risk stratification using TQIP-derived codes demonstrated low variability by race (25% White vs. 25% Hispanic vs. 28% Black patients considered high-risk) and insurance status (23% privately insured vs. 26% uninsured).

CONCLUSION
High-risk CPA injury codes empirically derived from TQIP produced the best diagnostic characteristics and minimized some disparities. This approach, while requiring further validation, has the potential to improve CPA injury surveillance and decrease bias in screening protocols.

LEVEL OF EVIDENCE
Diagnostic Test/Criteria; Level III.
Prevention of epileptogenesis – are we there yet?
Authors: Koepp Matthias , Trinka Eugen , Löscher Wolfgang , Klein Pavel 
Published: February 2024

Purpose of review
To review recent progress in preventing epileptogenesis in patients with epilepsy.

Recent findings
The recent success of epilepsy prevention and disease modification in tuberous sclerosis using simple EEG biomarkers to guide treatment initiation, and the identification of biomarkers to enrich the targeted patient population has made clinical trials of epilepsy prevention after acquired central nervous system (CNS) insults such as traumatic brain injury, stroke or infection both feasible and timely. Two such trials are currently on-going to prevent poststroke epilepsy.

Summary
No disease-modifying or preventive treatments exist for epilepsy, and their development remains a major unmet need.. We have entered though the era of change in the treatment of epilepsy from symptomatic only to disease prevention. In this review, we summarize developments and review opportunities, challenges, and potential solutions to develop preventive treatment for acquired epilepsies in humans. The ‘Holy Grail’ of epilepsy is within our reach.
Global geodiversity components are not equally represented in UNESCO Global Geoparks
Authors: Polman Emma M. N. , Seijmonsbergen Arie C. , Versteegh Hannes , Kissling W. Daniel 
Published: February 2024

The aim of UNESCO Global Geoparks (UGGs) is to protect globally significant geoheritage and geodiversity, but quantitative evidence on the global representativeness of geodiversity components (i.e. geology, soils, geomorphology and hydrology) in these geoparks is in short supply. Here, we provide a first assessment by deriving a global map of geodiversity to test whether the presence of geodiversity components in UGGs is representative for the global availability and distribution of geodiversity. Using openly accessible global datasets and a newly developed workflow, we have calculated metrics for each geodiversity component and a global geodiversity index; we then quantified whether UGGs represent global geodiversity and then compared their components to a randomized spatial distribution of geoparks. Our results show that lithological and topographical diversity are more represented in UGGs than outside these sites, while soil type and hydrological diversity are not significantly different. Furthermore, individual soil types and lithological classes are under-represented and unevenly distributed in Asian and European UGGs. This is probably caused by the concentration of geoparks in Asian and European mountains. To better conserve geodiversity, we suggest an initiative to consider the protection and representation of all geodiversity components in their global context.
This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
A framework for quantifying geodiversity at the local scale: a case study from the Rokua UNESCO Global Geopark
Authors: Tukiainen Helena , Maliniemi Tuija , Brilha José , Alahuhta Janne , Hjort Jan 
Published: February 2024

Geoconservation and related quantitative and qualitative geodiversity assessments are gaining increasing attention. However, methodologies for measuring geodiversity at local scale are currently rare. Here, we present a framework for assessing local-scale geodiversity of different landforms using field-based and digital elevation model (DEM-) derived data from the Rokua UNESCO Global Geopark in Finland. We observed the presence or absence of various geodiversity elements, such as geological or topographical elements in our study sites, and used these data to quantify alpha (α), gamma (γ) and beta (β) geodiversity of various landforms. In addition, we measured topographical heterogeneity in the field and from DEMs. The results showed distinct patterns in the geodiversity and topographical variation of the landforms. The differences between α, γ and β geodiversity of different landforms were particularly clear. According to the results, measures of topographical variability can be used to some extent as surrogates for geodiversity, but the choice of optimal variables is context and scale dependent. These results provide perspectives for further local-scale geodiversity assessments in different study areas and are applicable for a range of purposes, from scientific research to practical management and geoconservation.
This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
Towards a taxonomy of geodiversity
Authors: Hjort Jan , Seijmonsbergen Arie C. , Kemppinen Julia , Tukiainen Helena , Maliniemi Tuija , Gordon John E. , Alahuhta Janne , Gray Murray 
Published: February 2024

Geodiversity is a topical concept in earth and environmental sciences. Geodiversity information is needed to conserve nature, use ecosystem services and achieve sustainable development goals. Despite the increasing demand for geodiversity data, there exists no comprehensive system for categorizing geodiversity. Here, we present a hierarchically structured taxonomy that is potentially applicable in mapping and quantifying geodiversity across different regions, environments and scales. In this taxonomy, the main components of geodiversity are geology, geomorphology, hydrology and pedology. We propose a six-level hierarchical system where the components of geodiversity are classified at progressively lower taxonomic levels based on their genesis, physical–chemical properties and morphology. This comprehensive taxonomy can be used to compile geodiversity information for scientific research and various applications of value to society and nature conservation. Ultimately, this hierarchical system is the first step towards developing a global geodiversity taxonomy.This article is part of the Theo Murphy meeting issue ‘Geodiversity for science and society’.
A Single-shot ChAd3 Vaccine Provides Protection from Intramuscular and Aerosol Sudan Virus Exposure
Authors: Honko Anna N. , Hunegnaw Ruth , Moliva Juan I. , Ploquin Aurélie , Dulan Caitlyn N M , Murray Tamar , Carr Derick , Foulds Kathryn E. , Geisbert Joan B. , Geisbert Thomas W. , Johnson Joshua C. , Wollen-Roberts Suzanne E. , Trefry John C. , Stanley Daphne A. , Sullivan Nancy J. 
Published: February 2024

AbstractInfection with Sudan virus (SUDV) is characterized by an aggressive disease course with case fatality rates between 40-100% and no approved vaccines or therapeutics. SUDV causes sporadic outbreaks in sub-Saharan Africa, including a recent outbreak in Uganda which has resulted in over 100 confirmed cases in one month. Prior vaccine and therapeutic efforts have historically prioritized Ebola virus (EBOV), leading to a significant gap in available treatments. Two vaccines, Erbevo®and Zabdeno®/Mvabea®, are licensed for use against EBOV but are ineffective against SUDV. Recombinant adenovirus vector vaccines have been shown to be safe and effective against filoviruses, but efficacy depends on having low seroprevalence to the vector in the target human population. For this reason, and because of an excellent safety and immunogenicity profile, ChAd3 was selected as a superior vaccine vector. Here, a ChAd3 vaccine expressing the SUDV glycoprotein (GP) was evaluated for immunogenicity and efficacy in nonhuman primates. We demonstrate that a single dose of ChAd3-SUDV confers acute and durable protection against lethal SUDV challenge with a strong correlation between the SUDV GP-specific antibody titers and survival outcome. Additionally, we show that a bivalent ChAd3 vaccine encoding the GP from both EBOV and SUDV protects against both parenteral and aerosol lethal SUDV challenge. Our data indicate that the ChAd3-SUDV vaccine is a suitable candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks.One Sentence Summary:A single-dose of ChAd3 vaccine protected macaques from lethal challenge with Sudan virus (SUDV) by parenteral and aerosol routes of exposure.