bluuebunny/crossref_metadata_2025 huggingface dataset:
Single Ventricular Assist Device Care and Outcomes for Failed Stage I Palliation: A Single-Center Decade of Experience
Authors: Kulp Blaire E. , Khan Marium N. , Gazit Avihu Z. , Eghtesady Pirooz , Scheel Janet N. , Said Ahmed S. , Rabinowitz Edon J.
Published: February 2024

Single ventricular assist device (SVAD) use before and after stage I palliation (S1P) is increasing with limited data on outcomes. To address this knowledge gap, we conducted a single-center retrospective review to assess pre- and post-SVAD clinical status, complications, and outcomes. We leveraged a granular, longitudinal, local database that captures end-organ support, procedural interventions, hematologic events, laboratory data, and antithrombotic strategy. We identified 25 patients between 2013 and 2023 implanted at median age of 53 days (interquartile range [IQR] = 16–130); 80% had systemic right ventricles and underwent S1P. Median SVAD days were 54 (IQR = 29–86), and 40% were implanted directly from ECMO. Compared to preimplant, there was a significant reduction in inotrope use (p = 0.013) and improved weight gain (p = 0.008) post-SVAD. Complications were frequent including bleeding (80%), stroke (40%), acute kidney injury (AKI) (40%), infection (36%), and unanticipated catheterization (56%). Patients with in-hospital mortality had significantly more bleeding complications (p = 0.02) and were more likely to have had Blalock–Thomas–Taussig shunts pre-SVAD (p = 0.028). Survival to 1 year postexplant was 40% and included three recovered and explanted patients. At 1 year posttransplant, all survivors have technology dependence or neurologic injury. This study highlights the clinical outcomes and ongoing support required for successful SVAD use in failed single-ventricle physiology before or after S1P.
Adsorption Mass Transfer Zone of Vancomycin in Cartridges With Styrene-Divinylbenzene Sorbent
Authors: Reis Thiago , Ronco Claudio , Ramírez-Guerrero Gonzalo , Marcello Matteo , de Cal Massimo , Neves Francisco A. R. , Lorenzin Anna
Published: February 2024

Cartridges for hemoadsorption containing styrene-divinylbenzene sorbent are used for multiple conditions, such as intoxication. The mass transfer zone comprises the extension along the longitudinal span of the cartridge where adsorption occurs. The aim of this experiment is to evaluate the mass transfer zone for vancomycin in the HA380 cartridge. The experiment was carried out twice. A saline solution with vancomycin passed through a HA380-modified cartridge at 100 ml/min in a single-pass fashion. The cartridge had four openings along its longitudinal dimension, at 3, 6, 9, and 12 cm. In both experiments, the collection of aliquots occurred at minute 4, in the four openings and pre- and post-cartridge, and an additional sample from the effluent bag at the end of each experiment. In the second experiment, an additional sampling of the same six sites occurred at minute 14. The sigmoidal shape of the curve for the mass transfer zone of vancomycin was similar to the theoretical one. In experiment one, at minute 4, vancomycin clearance was 98.75 ml/min. In experiment two, vancomycin clearance at minutes 4 and 14 was 93.76 and 93.20 ml/min, respectively. This implies an adequate and optimal design of the HA380 cartridge.
An Evolutionary Concept Analysis of the “Fighter” in the Intensive Care Unit
Authors: Moreines Laura Tycon , Brody Abraham A. , Murali Komal Patel
Published: February 2024

The purpose of this article was to analyze the concept of “the fighter in the intensive care unit (ICU)” per the scientific literature and the impact this mentality has on care administered in the ICU. A literature review and a concept analysis based on Rodger's evolutionary method were performed to identify surrogate terms, antecedents, attributes, and consequences pertaining to the “fighter” in the ICU. Thirteen articles with a focus on “the fighter” were included in this analysis. There is a strong desire to remain optimistic and maintain high spirits as a coping mechanism in the face of extreme prognostic uncertainty. Themes that emerged from the literature were the need to find inner strength and persist in the face of adversity. The concept of “the fighter in the ICU” can serve as either adaptive or maladaptive coping, depending on the larger clinical picture. Patient experiences in the ICU are fraught with physical and psychological distress. How the patient and family unit cope during this anxiety-provoking time is based on the individual. Maintaining optimism and identifying as a fighter can be healthy ways to adapt to the circumstances. This concept analysis highlights the importance of holistic care and instilling hope particularly as patients may be nearing the end of life.
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

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

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.
Meralgia Paresthetica as a Result of Surgery With an Emphasis on Harvesting Iliac Bone Grafts: A Review
Authors: Singh Sonia N. , Taylor Ruby R. , Oualid Chaimae , Habal Mutaz B. , Thaller Seth R.
Published: February 2024

Meralgia paresthetica is a neurological disorder characterized by a symptom complex of numbness, burning, tingling, aching, or stabbing in the anterolateral portion of the upper thigh. Typically, this disorder is seen in patients with diabetes mellitus, obesity, and pregnancy. Also, it may result from a wide array of surgical interventions involving the region of the anterior superior iliac spine. Underlying pathophysiology concentrates on entrapment neuropathy of the lateral femoral cutaneous nerve (LFCN). Due to its location and wide anatomic variation, the LFCN is susceptible to compression, scarring, and injury during surgery. It is important to understand the regional anatomy. In addition, the plastic surgeon must have a working knowledge of the most common variations that can precipitate entrapment and increase susceptibility to injury during surgery. Surgeons lacking a substantial background on the numerous risk factors, origins, and anatomic variations of the LFCN may place patients at an even higher risk of damage to the nerve. An extensive knowledge of the anatomy and careful technique may be utilized by surgeons to prevent iatrogenic neuropathy of the LFCN.
Efficacy and Safety of Oral Propranolol or Topical Timolol for the Treatment of Superficial Infantile Hemangiomas
Authors: Han Kun , Wei Jingjian , Zheng Hao , Li Xiaodong , Zhang Aixia , Ma Yanhong , Meng Jian , Hu Yuanyuan
Published: February 2024

Infantile hemangiomas (IHs) are the most common benign soft tissue tumors of infancy. Oral propranolol has become a first-line treatment option since the unexpected discovery of its surprising efficacy in the treatment of IHs in 2008. However, oral propranolol causes systemic complications, including hypotension, bradycardia, and hypoglycemia. To minimize systemic adverse effects of oral propranolol, timolol maleate, a nonselective β-blocker similar to propranolol, has been used as a topical agent to treat superficial IHs. The authors evaluated the efficacy and safety of oral propranolol or topical timolol in 60 patients with IHs. Of the 60 patients recruited, 30 patients were treated using orally administrated propranolol and an additional 30 patients received topical timolol. The efficacy rate of the oral propranolol and topical timolol was 96.7% and 93.3%, respectively. There were no significant differences between the two treatment patterns for the efficacy rate. The incidence of systemic adverse effects for patients treated with oral propranolol was significantly higher than that for cases received topically timolol treatment. Topical timolol maleate is effective and well-tolerated in the treatment of IHs. It could be considered as the first-line treatment choice, especially for superficial IHs.
Mechanical Ptosis by Medial Upper Eyelid Fat Prolapse
Authors: Park Tae Hwan
Published: February 2024

Common symptoms of medial fat pad prolapse may include a noticeable bulge in the inner corner of the upper eyelid, puffiness, and a tired or aged appearance. In some cases, this condition may contribute to mechanical ptosis. However, mechanical ptosis caused by medial upper eyelid fat prolapse has not been reported previously. The purpose of the current study is to report the author’s experience of successful treatment of ptosis caused by medial upper eyelid fat prolapse in a 67-year-old woman. The patient complained of slowly aggravating asymmetric upper eyelids starting from 5 years ago. At the time of her visit, she had to use her left forehead to open her eyes, making her left eyebrow upwardly positioned. This condition might be related to medial upper eyelid fat prolapse-related mechanical ptosis. The author explored her left upper eyelid with a 9 mm height incision. The author found a substantial amount of medial fat herniation and levator aponeurosis tear. After fat pad removal, the author fixed the levator aponeurosis tear with nylon 6-0, and transdermal sutures were done. The patient was happy with esthetically pleasing results 2 months after the initial surgery. The author successfully treated this rare condition with basic principles, such as fat removal, levator aponeurosis repair, and transdermal sutures.
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.

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

Infection 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.
The ideotype for drought tolerance in bioenergyPopulus nigra
Authors: Smith Hazel K , Puértolas Jaime , Douthe Cyril , Emiliani Giovanni , Giovannelli Alessio , Rowland Libby S , Allwright Mike , Bailey-Bale Jack H , Valdes-Fragoso Pili M , Larsen Elisabeth K , Alberti Giorgio , Zaldei Alessandro , Hirons Andrew D , Alasia Franco , Ribas-Carbo Miquel , Flexas Jaume , Dodd Ian C , Davies William J , Taylor Gail
Published: February 2024

Fast-growing perennial trees such as Populus nigra L. are important species for wood, plywood, pulp, and bioenergy feedstock production, yet tree vigor in a changing climate is poorly understood. This research aimed to identify breeding targets for yield in water-limited environments, alongside unraveling the relationship between drought, yield, and glucose release in P. nigra. A diversity panel of 20 P. nigra genotypes, selected from a wide natural association population, was grown at three divergent European sites. Through extensive phenotyping of physiological and morphological productivity and water-use traits, under irrigated conditions and when exposed to a progressive drought, we elucidated the adaptive and plastic drivers underlying tree productivity. We have identified the underpinning traits for drought tolerance, whereby high yields can be maintained under water deficit, in this key species. This highlighted the importance of examining the yield stress index (YSI) over the drought resistance index (DRI) to assess genotypes for performance under moderate drought. In this way, we found genotypes with high hydraulic capacity, and large leaves made up of many cells to be best suited to multiple European environments, with contrasting water availability. Moreover, we identified genotypes that combine yield and water use efficiency, with good glucose release potential, which will be important traits for the future of poplar as a bioenergy crop. Vigorous poplar genotypes, which are adapted to wet climates showed high environmental plasticity. However, in European drought scenarios, these trees outperform drought resistant genotypes, and some exhibit good glucose release. These trees are a valuable resource for the future.
Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock
Authors: Brenna Andrea , Borsa Micaela , Saro Gabriella , Ripperger Jürgen A. , Glauser Dominique A. , Yang Zhihong , Adamantidis Antoine , Albrecht Urs
Published: February 2024

The circadian clock enables organisms to synchronize biochemical and physiological processes over a 24-hour period. Natural changes in lighting conditions, as well as artificial disruptions like jet lag or shift work, can advance or delay the clock phase to align physiology with the environment. Within the suprachiasmatic nucleus (SCN) of the hypothalamus, circadian timekeeping and resetting rely on both membrane depolarization and intracellular second-messenger signaling. Voltage-gated calcium channels (VGCCs) facilitate calcium influx in both processes, activating intracellular signaling pathways that triggerPeriod(Per) gene expression. However, the precise mechanism by which these processes are concertedly gated remains unknown.

Our study demonstrates that cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and regulates phase shifts of the circadian clock. We observed that knocking down Cdk5 in the SCN of mice affects phase delays but not phase advances. This is linked to uncontrolled calcium influx into SCN neurons and an unregulated protein kinase A (PKA) – calcium/calmodulin-dependent kinase (CaMK) – cAMP response element-binding protein (CREB) signaling pathway. Consequently, genes such asPer1are not induced by light in the SCN of Cdk5 knock-down mice. Our experiments identified Cdk5 as a crucial light-modulated kinase that influences rapid clock phase adaptation. This finding elucidates how light responsiveness and clock phase coordination adapt activity onset to seasonal changes, jet lag, and shift work.
Biomechanical Implications of Spinopelvic Alignment on Femoral Head Cartilage and the Proximal Femoral Physis in Slipped Capital Femoral Epiphysis: A Theoretical Finite Element Analysis
Authors: Kumaran Yogesh , Mumtaz Muzammil , Quatman Carmen , Balch-Samora Julie , Soehnlen Sophia , Hoffman Brett , Tripathi Sudharshan , Nishida Norihiro , Goel Vijay K.
Published: February 2024

Background

Slipped capital femoral epiphysis (SCFE) is a prevalent pediatric hip disorder. Recent studies suggest the spine’s sagittal profile may influence the proximal femoral growth plate’s slippage, an aspect not extensively explored. This study utilizes finite element analysis to investigate how different spinopelvic alignments affect shear stress and potential slippage at the growth plate.

Methods

A finite element model was developed from CT scans of a healthy adult male lumbar spine, pelvis, and femurs. The model was subjected to various sagittal alignments through rotational boundary conditions. Simulations of two-leg stance, one-leg stance, walking heel strike, ascending stairs heel strike, and descending stairs heel strike were conducted. Parameters measured included hip joint contact area, stress, and maximum Tresca (shear) stress on the growth plate.

Findings

Posterior pelvic tilt cases indicated larger shear stresses compared to the anterior pelvic tilt variants except in two leg stance. Two leg stance resulted in decreases in the posterior tilted pelvi variants compared to anterior tilted pelvi, however a combination of posterior pelvic tilt and high pelvic incidence indicated larger shear stresses on the growth plate. One leg stance and heal strike resulted in higher shear stress on the growth plate in posterior pelvic tilt variants compared to anterior pelvic tilt, with a combination of posterior pelvic tilt and high pelvic incidence resulting in the largest shear stress.

Interpretation

Our findings suggest that posterior pelvic tilt and high pelvic incidence can lead to increased shear stress at the growth plate. Activities performed in patients with these alignments may predispose to biomechanical loading that shears the growth plate, potentially causing slippage.
A live cell imaging-based assay for tracking particle uptake by clathrin-mediated endocytosis
Authors: Ashby Grant , Keng Kayla E. , Hayden Carl C. , Stachowiak Jeanne C.
Published: February 2024

A popular strategy for therapeutic delivery to cells and tissues is to encapsulate therapeutics inside particles that cells internalize via endocytosis. The efficacy of particle uptake by endocytosis is often studied in bulk using flow cytometry and Western blot analysis and confirmed using confocal microscopy. However, these techniques do not reveal the detailed dynamics of particle internalization and how the inherent heterogeneity of many types of particles may impact their endocytic uptake. Toward addressing these gaps, here we present a live-cell imaging-based method that utilizes total internal reflection fluorescence (TIRF) microscopy to track the uptake of a large ensemble of individual particles in parallel, as they interact with the cellular endocytic machinery. To analyze the resulting data, we employ an open-source tracking algorithm in combination with custom data filters. This analysis reveals the dynamic interactions between particles and endocytic structures, which determine the probability of particle uptake. In particular, our approach can be used to examine how variations in the physical properties of particles (size, targeting, rigidity), as well as heterogeneity within the particle population, impact endocytic uptake. These data impact the design of particles toward more selective and efficient delivery of therapeutics to cells.
Augmented-reality-based multi-person exercise has more beneficial effects on mood state and oxytocin secretion than standard solitary exercise
Authors: Shima Takeru , Iijima Junpei , Sutoh Hirotaka , Terashima Chiho , Matsuura Yuki
Published: February 2024

Exercise is known to have positive effects on psychological well-being, with team sports often associated with superior mental health compared to individual sports. Augmented reality (AR) technology has the potential to convert solitary exercise into multi-person exercise. Given the role of oxytocin in mediating the psychological benefits of exercise and sports, this study aimed to investigate the impact of AR-based multi-person exercise on mood and salivary oxytocin levels. Fourteen participants underwent three distinct regimens: non-exercise (Rest), standard solitary cycling exercise (Ex), and AR-based multi-person cycling exercise (Ex+AR). In both exercise conditions (Ex and Ex+AR), participants engaged in cycling at a self-regulated pace to maintain a Rating of Perceived Exertion of 10. In the Ex+AR condition, participants’ avatars were projected onto a tablet screen, allowing them to cycle alongside ten other virtual avatars in an AR environment. Mood states (assessed using POMS2) and saliva samples were collected before and immediately after each 10-minute regimen. Subsequently, the levels of salivary oxytocin were measured. Participants exhibited higher cycling speeds during Ex+AR compared to Ex, despite comparable levels of self-reported fatigue between the two groups. Notably, only the Ex+AR condition significantly improved mood states associated with depression-dejection and exhibited a trend toward suppressing anger-hostility in participants. Moreover, the Ex+AR condition led to a significant elevation in salivary oxytocin levels, while the Ex condition showed a trend toward an increase. However, changes in salivary oxytocin did not show a significant correlation with changes in mood states. These findings suggest that Ex+AR enhances mood states and promotes oxytocin release. AR-based multi-person exercise may offer greater psychological benefits compared to standard solitary exercise, although the relationship between oxytocin and mood changes remains inconclusive.

Highlights

Exercise, especially team sports, has positive effects on mood state, and oxytocin partially supports these effects.

Augmented reality (AR) technology can potentially convert standard solitary exercise into multi-person exercise.

AR-based multi-person exercise (Ex+AR) significantly ameliorated depression-dejection and increased salivary oxytocin levels, but standard solitary exercise did not.

Ex+AR may provide more significant psychological benefits than standard solitary exercise.
The RNA demethylases ALKBH5 and FTO regulate translation of the ATF4 mRNA in sorafenib-treated hepatocarcinoma cells
Authors: Adjibade Pauline , Mazroui Rachid
Published: February 2024

Translation is one of the main gene expression steps targeted by cellular stress, commonly refereed as translational stress, which includes treatment with anticancer drugs. While translational stress blocks translation initiation of bulk mRNAs, it allows translation of a specific set of mRNAs known as short upstream open reading frames (uORFs)-mRNAs. Among these, ATF4 mRNA encodes a transcription factor that reprograms gene expression during various cellular stress towards functions required for cell response to stress. Stress-induced ATF4 mRNA translation occurs via a specialised mode that relies on the presence of uORFs upstream to the main ATF4 ORF. However, mechanisms regulating ATF4 mRNA translation, particularly towards chemoresistance, remained limited. Here, we report a role of both ALKBH5 and FTO, the two RNA demethylating enzymes in promoting translation of ATF4 mRNA in liver cancer Hep3B cells treated with sorafenib, a stress inducer used in chemotherapy. Depletion experiments confirmed that both enzymes are required for inducing ATF4 mRNA translation, while polyribosome assays coupled to RT-qPCR indicated that this induction of ATF4 mRNA translation occurs at its initiation step. Usingin vitromethylation assays, we found that ALKBH5 is required for the inhibition of the methylation of a reporter ATF4 mRNA at a conserved adenosine (A235) site located at its uORF2, suggesting that ALKBH5-mediated translation of ATF4 mRNA involves demethylation of its A235. Preventing methylation of A235 by introducing an A/G mutation into the ATF4 mRNA reporter renders that reporter insensitive to ALKBH5 depletion, supporting the role of ALKBH5 demethylation activity in translation. Finally, targeting either ALKBH5 or FTO sensitizes Hep3B to sorafenib-induced cell death, contributing to their resistance. We concluded that ALKBH5 and FTO are novel factors that promote resistance to sorafenib treatment, in part by mediating translation of ATF4 mRNA.
navigate: an open-source platform for smart light-sheet microscopy
Authors: Marin Zach , Wang Xiaoding , Collison Dax W. , McFadden Conor , Lin Jinlong , Borges Hazel , Chen Bingying , Mehra Dushyant , Shen Qionghua , Galecki Seweryn , Daetwyler Stephan , Fiolka Reto , Dean Kevin M.
Published: February 2024

navigateis a turnkey, open-source software solution designed to enhance light-sheet fluorescence microscopy (LSFM) by integrating smart microscopy techniques into a user-friendly framework. It enables automated, intelligent imaging with a Python-based control system that supports GUI-reconfigurable acquisition routines and the integration of diverse hardware sets. As a comprehensive package, navigate democratizes access to advanced LSFM capabilities, facilitating the development and implementation of smart microscopy workflows without requiring deep programming knowledge or specialized expertise in light-sheet microscopy.
Accurate Assembly of Circular RNAs with TERRACE
Authors: Zahin Tasfia , Shi Qian , Zang Xiaofei Carl , Shao Mingfu
Published: February 2024

Circular RNA (circRNA) is a class of RNA molecules that forms a closed loop with its 5’ and 3’ ends covalently bonded. Due to this specific structure circRNAs are more stable than linear RNAs, admit distinct biological properties and functions, and have been proven to be promising biomarkers. Circular RNAs were severely overlooked previously owing to the biases in the RNA-seq protocols and in the detection algorithms, but recently gained tremendous attentions in both aspects. However, most existing methods for assembling circRNAs heavily rely on the annotated transcriptomes, and hence exhibit unsatisfactory accuracy when a high-quality transcriptome is unavailable. Here we present TERRACE, a new algorithm for full-length assembly of circRNAs from paired-end total RNA-seq data. TERRACE uses the splice graph as the underlying data structure to organize the splicing and coverage information. We transform the problem of assembling circRNAs into finding two paths that “bridge” the three fragments in the splice graph induced by back-spliced reads. To solve this formulation, we adopted a definition for optimal bridging paths and a dynamic programming algorithm to calculate such paths, an approach that was proven useful for assembling linear RNAs. TERRACE features an efficient algorithm to detect back-spliced reads that are missed by RNA-seq aligners, contributing to its much improved sensitivity. It also incorporates a new machine-learning approach that is trained to assign a confidence score to each assembled circRNA, which is shown superior to using abundance for scoring. TERRACE is compared with leading circRNA detection methods on both simulations and biological datasets. Our method consistently outperforms by a large margin in sensitivity while maintaining better or comparable precision. In particular, when the annotations are not provided, TERRACE can assemble 123%-412% more correct circRNAs than state-of-the-art methods on human tissues. TERRACE presents a major leap on assembling full-length circRNAs from RNA-seq data, and we expect it to be widely used in the downstream research on circRNAs.
Expression of Most Retrotransposons in Human Blood Correlates with Biological Aging
Authors: Tsai Yi-Ting , Seymen Nogayhan , Thompson I. Richard , Zou Xinchen , Mumtaz Warisha , Gerlevik Sila , Mufti Ghulam J. , Karimi Mohammad M.
Published: February 2024

Retrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we analyzed the relationship between RTE expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTE activity and chronological age, the expression of most RTE classes and families except short interspersed nuclear elements (SINEs) correlated with biological age-associated gene signature scores. Strikingly, we found that the expression of SINEs was linked to upregulated DNA repair pathways in multiple cohorts. We also observed DNA hypomethylation with aging and significant increase in RTE expression level in hypomethylated RTEs except for SINEs. Additionally, our single-cell transcriptomic analysis suggested a role for plasma cells in aging mediated by RTEs. Altogether, our multi-omics analysis of large human cohorts highlights the role of RTEs in biological aging and suggests possible mechanisms and cell populations for future investigations.
PuMA: PubMed Gene-Celltype-Relation Atlas
Authors: Bickmann Lucas , Sandmann Sarah , Walter Carolin , Varghese Julian
Published: February 2024

Rapid extraction and visualization of cell-specific gene expression is important for automatic celltype annotation, e.g. in single cell analysis. There is an emerging field in which tools such as curated databases or Machine Learning methods are used to support celltype annotation. However, complementing approaches to efficiently incorporate latest knowledge of free-text articles from literature databases, such as PubMed are understudied. This work introduces the PubMed Gene/Celltype-Relation Atlas (PuMA) which provides a local, easy-to-use web-interface to facilitate automatic celltype annotation. It utilizes pretrained large language models in order to extract gene and celltype concepts from Pub-Med and links biomedical ontologies to suggest gene to celltype relations. It includes a search tool for genes and cells, additionally providing an interactive graph visualization for exploring cross-relations. Each result is fully traceable by linking the relevant PubMed articles. The software framework is freely available and enables regular article imports for incremental knowledge updates. GitLab:imigitlab.uni-muenster.de/published/PuMA