bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence of Ipsilateral Femoral Neck and Shaft Fractures in Pediatric and Adolescent Patients
Authors: Borden Timothy C. , Haidar Layla A. , Vanodia Rohini M. , Vemu Sree M. , Dennis Garrett S. , Mundluru Surya N. , Crawford Lindsay M. , Traver Jessica L. , Younas Shiraz A. , Gary Joshua L. , Prasarn Mark L. , Achor Timothy S. , Munz John W. , Mansour Alfred A.
Published: July 2024

OBJECTIVES:

To identify the incidence, patient characteristics, and effectiveness of radiographic screening methods for detecting ipsilateral femoral neck and shaft fractures in pediatric and adolescent trauma patients.

METHODS:

Design:

Retrospective cohort study.

Setting:

This study was conducted at a tertiary pediatric trauma hospital.

Patient Selection Criteria:

Patients younger than 18 years treated for a femoral shaft fracture between 2004 and 2018 were reviewed. Pathologic (metabolic bone disease or bone lesion), periprosthetic, and penetrating traumatic femoral shaft fractures were excluded.

Outcome Measurements and Comparisons:

Patient demographics, mechanisms of injury, treatment methods, and associated injuries were analyzed. Pretreatment x-rays and computed tomography (CT) scans were reviewed for the identification of ipsilateral femoral neck and shaft fractures.

RESULTS:

Among the 840 pediatric patients included in this study, 4 patients (0.5%) sustained ipsilateral femoral neck and shaft fractures. All the femoral neck fractures were observed in adolescents (aged 13–17 years) and involved in high-energy traumas. In adolescents involved in high-energy trauma, the incidence increased to 1.7%. Pretreatment sensitivity of both x-rays and CT scans was only 50% for the detection of femoral neck fractures.

CONCLUSIONS:

This study reveals that ipsilateral femoral neck and shaft fractures in pediatric patients are rare, occurring in adolescents involved in high-energy trauma. The findings suggest the need for a selective, rather than routine, use of CT scans based on the patient's age and the mechanism of injury. The use of alternative imaging methods such as magnetic resonance imaging should be considered to balance diagnostic accuracy while minimizing radiation exposure.

LEVEL OF EVIDENCE:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Regulation of cervical cancer via G15-mediated inhibition of G protein-coupled estrogen receptor
Authors: Zhu Ziyan , Nie Xinyi , Deng Lexiu , Ding Jia , Chen Jiangping , Zhu Jingyi , Yin Xiaoxia , Guo Bowei , Zhang Fan
Published: July 2024

Cervical cancer is among the most common gynecological malignancies. G protein-coupled estrogen receptor (GPER) is involved in the development of various tumors; however, its role in cervical cancer remains unclear. We investigated whether G15, an inhibitor of GPER, can regulate its expression and affect cervical cancer progression. We examined the biological behaviors of G15-treated SiHa and HeLa cells using Cell Counting Kit-8, monoclonal proliferation, plate scratching, and Transwell invasion experiments. Western blotting was used to detect the expression of GPER, E-cadherin, N-cadherin, vimentin, Bcl-2, Bax, phosphatidylinositol-3-kinase (PI3K)/AKT, and programmed death ligand 1 (PD-L1). The expression of GPER, E-cadherin, vimentin, and PD-L1 in cervical cancer and adjacent tissues was detected using immunohistochemistry. The correlation between GPER expression and clinicopathological characteristics was analyzed. The expression of GPER in cervical cancer tissues was significantly higher than that in paracancerous tissues, and it was detected in the membrane and cytoplasm of SiHa and HeLa cells. The proliferation, migration, and invasion abilities of SiHa and HeLa cells were reduced after G15 treatment. The G15-treated groups exhibited higher expression of E-cadherin and Bax and lower expression of N-cadherin, vimentin, Bcl-2, GPER, p-PI3K, p-AKT, and PD-L1 than the control group. The expression of E-cadherin was lower and that of vimentin was higher in cancer tissues than in paracancerous tissues; PD-L1 was highly expressed in tumor and stromal cells in cancer tissues but not in paracancerous tissues. G15 functions by regulating the GPER/PI3K/AKT/PD-L1 signaling pathway and may serve as a new immunotherapy for treating patients with cervical cancer.
Deriving Automated Device Metadata From Intracranial Pressure Waveforms: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury ICU Physiology Cohort Analysis
Authors: Ack Sophie E. , Dolmans Rianne G.F. , Foreman Brandon , Manley Geoffrey T. , Rosenthal Eric S. , Zabihi Morteza
Published: July 2024

IMPORTANCE:

Treatment for intracranial pressure (ICP) has been increasingly informed by machine learning (ML)-derived ICP waveform characteristics. There are gaps, however, in understanding how ICP monitor type may bias waveform characteristics used for these predictive tools since differences between external ventricular drain (EVD) and intraparenchymal monitor (IPM)-derived waveforms have not been well accounted for.

OBJECTIVES:

We sought to develop a proof-of-concept ML model differentiating ICP waveforms originating from an EVD or IPM.

DESIGN, SETTING, AND PARTICIPANTS:

We examined raw ICP waveform data from the ICU physiology cohort within the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury multicenter study.

MAIN OUTCOMES AND MEASURES:

Nested patient-wise five-fold cross-validation and group analysis with bagged decision trees (BDT) and linear discriminant analysis were used for feature selection and fair evaluation. Nine patients were kept as unseen hold-outs for further evaluation.

RESULTS:

ICP waveform data totaling 14,110 hours were included from 82 patients (EVD, 47; IPM, 26; both, 9). Mean age, Glasgow Coma Scale (GCS) total, and GCS motor score upon admission, as well as the presence and amount of midline shift, were similar between groups. The model mean area under the receiver operating characteristic curve (AU-ROC) exceeded 0.874 across all folds. In additional rigorous cluster-based subgroup analysis, targeted at testing the resilience of models to cross-validation with smaller subsets constructed to develop models in one confounder set and test them in another subset, AU-ROC exceeded 0.811. In a similar analysis using propensity score-based rather than cluster-based subgroup analysis, the mean AU-ROC exceeded 0.827. Of 842 extracted ICP features, 62 were invariant within every analysis, representing the most accurate and robust differences between ICP monitor types. For the nine patient hold-outs, an AU-ROC of 0.826 was obtained using BDT.

CONCLUSIONS AND RELEVANCE:

The developed proof-of-concept ML model identified differences in EVD- and IPM-derived ICP signals, which can provide missing contextual data for large-scale retrospective datasets, prevent bias in computational models that ingest ICP data indiscriminately, and control for confounding using our model’s output as a propensity score by to adjust for the monitoring method that was clinically indicated. Furthermore, the invariant features may be leveraged as ICP features for anomaly detection.
Opioid Administration Practice Patterns in Patients With Acute Respiratory Failure Who Undergo Invasive Mechanical Ventilation
Authors: Myers Laura C. , Bosch Nicholas A. , Soltesz Lauren , Daly Kathleen A. , Campbell Cynthia I. , Schwager Emma , Salvati Emmanuele , Stevens Jennifer P. , Wunsch Hannah , Rucci Justin M. , Jafarzadeh S. Reza , Liu Vincent X. , Walkey Allan J.
Published: July 2024

IMPORTANCE:

The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths.

OBJECTIVES:

To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation.

DESIGN:

Retrospective cohort study.

SETTING AND PARTICIPANTS:

Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute.

MAIN OUTCOMES AND MEASURES:

We assessed whether patients received opioid infusion and the dose of said opioid infusion.

RESULTS:

We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3–11%) and 39% (95% CI, 28–49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129–1341 µg) in the KPNC cohort and 200 µg (IQR, 0–1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1–7%) and 20% (95% CI, 15–26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively.

CONCLUSIONS AND RELEVANCE:

In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals’ analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.
Beyond the Pandemic
Authors: Moser Carolina Meira , Tietbohl-Santos Bárbara , Laskoski Pricilla Braga , Hauck Simone
Published: July 2024

Objectives

To assess occupational burnout (OB) changes among Brazilian healthcare workers (HCWs) from COVID-19 onset to 6 months later (T1) and identify risk and protective factors.

Methods

Using the Copenhagen Burnout Inventory and hierarchical multivariate linear regression in a two-stage online survey (initial n = 1054; T1 n = 316), this study examined the impact of various factors on OB.

Results

Significant increases in personal and work-related OB were observed by T1. Psychiatric diagnosis and workload emerged as risk factors (P < 0.01), while having a partner, good family relations, workplace well-being, and adequate sleep were protective (P < 0.001).

Conclusions

OB levels among Brazilian HCWs increased during the COVID-19 pandemic. Interventions should target personal and organizational wellness to alleviate burnout, emphasizing the importance of strong relationships, workplace health, and good sleep practices.
The DAISY Award
Authors: Swartwout Ellen
Published: July 2024

This review demonstrates the impact of The DAISY Award and how meaningful recognition (MR) through gratitude affects nurse engagement, healthy work environments (HWEs), and patient/families' (PFs) experiences. MR has mutual benefits for nurses and PFs, promoting therapeutic healing and resiliency. MR in HWEs can impact organizations' care quality, fiscal health and influence public perceptions. Nurse leaders should create an environment where MR is a core strategic imperative that impacts nurse, patient, and organizational outcomes.
Experimental Tests on External and Terminal Ballistics of Different Types of Projectiles Fired From .38 SPL Caliber Cartridges and Study of Permanent Cavitation in Anatomical Modeling With 10% Ballistic Gelatin
Authors: Pereira dos Santos Lucas Meciano , Mardegan Issa João Paulo
Published: July 2024

The present study investigated the main morphological differences between the permanent cavities formed by 4 different types of projectiles fired from .38 SPL caliber cartridges in blocks of 10% ballistic gelatin with standardized formulation (Federal Bureau of Investigation Protocol), all fired from the same distance and from the same firearm, associated with its performances in external and terminal ballistics. The velocity or the mass presented by a firearm projectile will not always be solely responsible for the final configuration of the permanent cavity, in which the projectile design, for example, is an equally important element. Each type of projectile tested in the present work generated a different kind of permanent cavity, but they also varied in velocity (m/s) and energy (J). The use of 10% ballistic gelatin in scientific research that seeks to investigate the external and terminal ballistics of projectiles can contribute to the practice of professionals working either in forensic pathology or applied ballistics scenarios, as they can experimentally simulate the events that can occur in the tissues of victims inflicted by gunshot wounds, which also allows important applications in the medical, commercial, civil, and military sectors that deal with products and technologies related to the human body.
Is That Innocent to Touch the Adipose Tissue?
Authors: Buğra Aytül , Daş Taner , Gün Eylül , Karayel Ferah
Published: July 2024

Although fat embolism in the pulmonary or systemic circulation is usually associated with long bone fractures, it can also occur less frequently during surgical operations, such as liposuction, fat grafting, and joint repair. This study aims to present cases of macro fat embolism resulting in sudden death during the perioperative period. Three cases with a history of sudden death during the perioperative period were included in this study. The surgical operation histories, autopsy findings, and histopathological findings of the cases were evaluated. Fat globules were detected in the medium-sized vessel lumens in the lungs of the cases who died suddenly during surgery. Grade 4 fat embolism was observed in the capillaries, which stained positively with Oil-Red-O in all three cases. Fat embolism syndrome is a rare but life-threatening condition that should be considered in patients with respiratory distress and impaired neurological status in the postoperative period.
How (Cautious) Social Media Use May Improve Education and Pipeline Efforts of a Growing Postpandemic Forensic Pathologist Workforce Shortage
Authors: Schukow Casey P. , Holmes Carley , Chambers Meagan , Rayes Omar , Jackson Nicole R. , Deeken Amy H. , Hlavaty Leigh A.
Published: July 2024

Many subspecialties of pathology have initiated novel methods and strategies to connect with medical students and residents, stimulate interest, and offer mentorship. Emerging concern about the future of forensic pathology has been highlighted in contemporary literature as recruitment of new fellows has stagnated and workforce shortage concerns have blossomed. Amidst these challenges, the potential role of social networking platforms like social media (SoMe) in enhancing autopsy pathology/forensics education has garnered attention, yet literature focusing specifically on its application in autopsy and forensic pathology remains limited. This review aims to provide a comprehensive narrative overview of the current literature on the established uses of SoMe in forensic pathology. It seeks to build upon existing recommendations, introducing a contemporary compilation of online resources designed to facilitate virtual engagement among pathologists, learners, patients, and families. The review supports the idea that strategic, ethical, and conscientious use of SoMe has a place in addressing the growing workforce shortages and closing educational gaps in forensic pathology by enhancing exposure to the field and dispelling antiquated stereotypes.
Tolerant or Intolerant? Learning From Studying Drug Concentrations in the Living and the Dead
Authors: Labay Laura M. , Kacinko Sherri L. , Casey Brittany K. , Brower Justin O.
Published: July 2024

Abstract

Tolerance is the diminished response to a drug that occurs when that drug is repeatedly used, and the body adapts to its continued presence. This means that greater blood concentrations are required to achieve desired effects, produce impairment, or cause death. Without case-specific information, the pharmacodynamic impacts of a drug on an individual are difficult to ascertain based on its concentration alone. One starting point, however, is to compare reported findings with reference ranges associated with therapeutic, toxic, and lethal outcomes. Toxicologists have observed concentrations dramatically increase over time in the living population for some drugs to concentrations that can easily be associated with impairment and lethal outcomes. It is, therefore, important to continually monitor and be familiar with drug concentrations found in the living to interpret postmortem concentrations. To emphasize this approach, we compared fentanyl concentrations from JAN 2010 to OCT 2023 in individuals investigated for driving under the influence of drugs to postmortem cases. This comparison highlights the changing nature of tolerance, stresses the importance of not relying solely on reference ranges for result interpretations, and discusses the importance of the autopsy in identifying or ruling out other potential causes of death.
Catastrophic CPR-Related Injuries in Vascular Ehlers-Danlos Syndrome
Authors: Fitzgerald Jesse L. , Vergonet Breanne N. , Warren Wendy S. , Rohrer Andrew J.
Published: July 2024

This article presents a case of severe CPR-related injuries leading to diagnosis of vascular Ehlers-Danlos syndrome. The subject is a 36-year-old female with a past medical history of a 10-mm aneurysm of the right internal carotid artery discovered on imaging 3 years prior to death. Major autopsy findings included subarachnoid hemorrhage in the base of the brain, bilateral hemothoraces, hemopericardium, laceration of the interatrial septum, laceration of the left pulmonary artery, and changes secondary to chronic alveolar hemorrhage in the lungs. The autopsy findings and subsequent unremarkable toxicology studies led to the suspicion of an underlying and clinically undiagnosed connective tissue disorder. Broad genetic exome testing revealed a mutation consistent with vascular Ehlers-Danlos syndrome. An overview of this disease, its diagnosis, and differential are further described herein, along with recommendations for forensic pathologists.
Comparison of the Cosmetic Efficacy of Extractum Cepae and Silicone-Based Gel in Upper Blepharoplasty
Authors: Güçlü Emin Serbülent , Özer Ömer , Çelik Seda , Eröz Pinar , Baysal Zeki
Published: July 2024

Background:

Upper eyelid blepharoplasty is one of the most common surgeries performed worldwide. However, an important problem after surgery is scar formation. The authors aimed to compare the efficacy of extractum cepae and silicone-based gels on postoperative scar appearance in patients undergoing upper eyelid blepharoplasty.

Methods:

After suture removal, patients were divided into 3 groups: group 1 [n=82, extractum cepae, sodium heparin, and allantoin mixture, Contractubex Gel (Merz Pharmaceuticals, Frankfurt, Germany)], group 2 [n=81, silicone-based gel (Dermatix Ultra Silicone Gel, Menarini, Singapore)], and group 3 (n=77, no additional treatment). Patients used the topical gels twice daily. All evaluations were performed on color photographs by 2 physicians during the postoperative first and third months.

Results:

The mean visual analog scale scores were significantly higher in all 3 groups in the postoperative first month (4.39±2.03, 4.41±2.57, and 4.33±2.46, respectively) compared with the postoperative third month (2.22±1.24, 2.15±1.38, and 2.29±1.47, respectively) (P=0.014, 0.037, and 0.026, respectively). The “Is the scar more stiff” score was higher in the postoperative first month compared with the third month.

Conclusions:

In conclusion, blepharoplasty scars improved up to the postoperative third month, but the topical gels used did not significantly improve the cosmetic appearance of blepharoplasty scars compared with the control group.
Near-Infrared Autofluorescence Signature: A New Parameter for Intraoperative Assessment of Parathyroid Glands in Primary Hyperparathyroidism
Authors: Akgun Ege , Ibrahimli Arturan , Berber Eren
Published: July 2024

BACKGROUND:

The success of parathyroidectomy in primary hyperparathyroidism depends on the intraoperative differentiation of diseased from normal glands. Deep learning can potentially be applied to digitalize this subjective interpretation process that relies heavily on surgeon expertise. In this study, we aimed to investigate whether diseased vs normal parathyroid glands have different near-infrared autofluorescence (NIRAF) signatures and whether related deep learning models can predict normal vs diseased parathyroid glands based on intraoperative in vivo images.

STUDY DESIGN:

This prospective study included patients who underwent parathyroidectomy for primary hyperparathyroidism or thyroidectomy using intraoperative NIRAF imaging at a single tertiary referral center from November 2019 to March 2024. Autofluorescence intensity and heterogeneity index of normal vs diseased parathyroid glands were compared, and a deep learning model was developed.

RESULTS:

NIRAF images of a total of 1,506 normal and 597 diseased parathyroid glands from 797 patients were analyzed. Normal vs diseased glands exhibited a higher median normalized NIRAF intensity (2.68 [2.19 to 3.23] vs 2.09 [1.68 to 2.56] pixels, p < 0.0001) and lower heterogeneity index (0.11 [0.08 to 0.15] vs 0.18 [0.13 to 0.23], p < 0.0001). On receiver operating characteristics analysis, optimal thresholds to predict a diseased gland were 2.22 in pixel intensity and 0.14 in heterogeneity index. On deep learning, precision and recall of the model were 83.3% each, and area under the precision-recall curve was 0.908.

CONCLUSIONS:

Normal and diseased parathyroid glands in primary hyperparathyroidism have different intraoperative NIRAF patterns that could be quantified with intensity and heterogeneity analyses. Visual deep learning models relying on these NIRAF signatures could be built to assist surgeons in differentiating normal from diseased parathyroid glands.
A review of the diverse applications of bond graphs in biology and physiology
Authors: Akbarpour Ghazani Mehran , Pan Michael , Tran Kenneth , Rampadarath Anand , Nickerson David P.
Published: July 2024

Computational biology and physiology is an interdisciplinary endeavour, requiring input from biologists, physiologists, mathematicians, chemists, engineers and clinicians. These systems are composed of complex phenomena across disparate temporal and spatial scales, and a holistic understanding of system behaviour typically requires the application of advanced multi-scale models. While many modelling techniques have been used, the bond graph (BG) is the only approach for modelling physical systems, where ‘causality’ is represented graphically. Additionally, the BG approach with its intrinsic properties allows the modular construction of models and verifying the conservation of mass and energy algorithmically. The BG approach has been widely used in engineering and, more recently, has been increasingly applied to biology and physiological systems. In this review, we briefly introduce the concepts and strengths of BG modelling. Following this, we review the history of BGs in modelling cellular mechanisms, biochemical reactions and musculoskeletal and cardiovascular systems. Then, current developments in BG software are reviewed, and opportunities and perspectives on the future application of BGs are discussed.
A novel closed-loop biotechnology for recovery of cobalt from a lithium-ion battery active cathode material
Authors: Pakostova Eva , Graves John , Latvyte Egle , Maddalena Giovanni , Horsfall Louise
Published: July 2024

In recent years, the demand for lithium-ion batteries (LIBs) has been increasing rapidly. Conventional recycling strategies (based on pyro- and hydrometallurgy) are damaging for the environment and more sustainable methods need to be developed. Bioleaching is a promising environmentally friendly approach that uses microorganisms to solubilize metals. However, a bioleaching-based technology has not yet been applied to recover valuable metals from waste LIBs on an industrial scale. A series of experiments was performed to improve metal recovery rates from an active cathode material (LiCoO2; LCO). (i) Direct bioleaching of ≤0.5 % LCO with two prokaryotic acidophilic consortia achieved >80 % Co and 90 % Li extraction. Significantly lower metal recovery rates were obtained at 30 °C than at 45 °C. (ii) In contrast, during direct bioleaching of 3 % LCO with consortia adapted to elevated LCO levels, the 30 °C consortium performed significantly better than the 45 °C consortium, solubilizing 73 and 93 % of the Co and Li, respectively, during one-step bioleaching, and 83 and 99 % of the Co and Li, respectively, during a two-step process. (iii) The adapted 30°C consortium was used for indirect leaching in a low-waste closed-loop system (with 10 % LCO). The process involved generation of sulfuric acid in an acid-generating bioreactor (AGB), 2–3 week leaching of LCO with the biogenic acid (pH 0.9), selective precipitation of Co as hydroxide, and recirculation of the metal-free liquor back into the AGB. In total, 58.2 % Co and 100 % Li were solubilized in seven phases, and >99.9 % of the dissolved Co was recovered after each phase as a high-purity Co hydroxide. Additionally, Co nanoparticles were generated from the obtained Co-rich leachates, using Desulfovibrio alaskensis, and Co electrowinning was optimized as an alternative recovery technique, yielding high recovery rates (91.1 and 73.6% on carbon felt and roughened steel, respectively) from bioleachates that contained significantly lower Co concentrations than industrial hydrometallurgical liquors. The closed-loop system was highly dominated by the mixotrophic archaeon Ferroplasma and sulfur-oxidizing bacteria Acidithiobacillus caldus and Acidithiobacillus thiooxidans. The developed system achieved high metal recovery rates and provided high-purity solid products suitable for a battery supply chain, while minimizing waste production and the inhibitory effects of elevated concentrations of dissolved metals on the leaching prokaryotes. The system is suitable for scale-up applications and has the potential to be adapted to different battery chemistries.
Adapting Lateral Stepping Control to Walk on Winding Paths
Authors: Render Anna C. , Cusumano Joseph P. , Dingwell Jonathan B.
Published: July 2024

Most often, gait biomechanics is studied during straight-ahead walking. However, real-life walking imposes various lateral maneuvers people must navigate. Such maneuvers challenge people’s lateral balance and can induce falls. Determining how people regulate their stepping movements during such complex walking tasks is therefore essential. Here, 24 adults (12F/12M; Age 25.8±3.5yrs) walked on wide or narrow virtual paths that were either straight, slowly-winding, or quickly-winding. From each trial, we computed time series of participants’ step widths and their lateral body positions relative to their path. We applied our Goal Equivalent Manifold framework – an analysis of how task-level redundancy impacts motor regulation – to quantify how participants adjusted their step width and lateral position from step to step as they walked on these paths. On the narrower paths, participants walked with narrower steps and less lateral position and step width variability. They did so by correcting step-to-step deviations in lateral position more, while correcting step-to-step deviations in step width less. On the winding paths, participants took both narrower and more variable steps. Interestingly, on slowly-winding paths, participants corrected step-to-step deviations in step width more by correcting step-to-step deviations in lateral position less: i.e., they prioritized maintaining step width over position. Conversely, on quickly-winding paths, participants strongly corrected step-to-step deviations in both step widthandlateral position: i.e., they prioritized maintaining both approximately equally, consistent with trying to maximize their maneuverability. These findings have important implications for persons with gait impairments who may have elevated fall risk.
ROLE OF FORELIMB MORPHOLOGY IN MUSCLE SENSORIMOTOR FUNCTIONS DURING LOCOMOTION IN THE CAT
Authors: Rahmati Seyed Mohammadali , Klishko Alexander N. , Martin Ramaldo S. , Bunderson Nate E. , Meslie Jeswin A. , Nichols T. Richard , Rybak Ilya A. , Frigon Alain , Burkholder Thomas J. , Prilutsky Boris I.
Published: July 2024

Previous studies established strong links between morphological characteristics of mammalian hindlimb muscles and their sensorimotor functions during locomotion. Less is known about the role of forelimb morphology in motor outputs and generation of sensory signals. Here, we measured morphological characteristics of 46 forelimb muscles from 6 cats. These characteristics included muscle attachments, physiological cross-sectional area (PCSA), fascicle length, etc. We also recorded full-body mechanics and EMG activity of forelimb muscles during level overground and treadmill locomotion in 7 and 16 adult cats of either sex, respectively. We computed forelimb muscle forces along with force- and length-dependent sensory signals mapped onto corresponding cervical spinal segments. We found that patterns of computed muscle forces and afferent activities were strongly affected by the muscle’s moment arm, PCSA, and fascicle length. Morphology of the shoulder muscles suggests distinct roles of the forelimbs in lateral force production and movements. Patterns of length-dependent sensory activity of muscles with long fibers (brachioradialis, extensor carpi radialis) closely matched patterns of overall forelimb length, whereas the activity pattern of biceps brachii matched forelimb orientation. We conclude that cat forelimb muscle morphology contributes substantially to locomotor function, particularly to control lateral stability and turning, rather than propulsion.
WITHDRAWN: The Neural efficiency score: Validation and application
Authors: Wenger Michael J. , Townsend James T. , Newbolds Sarah F.
Published: July 2024

Withdrawal statement

The authors have withdrawn this manuscript because it has been substantially revised, expanded, and re-titled. The updated, revised, expanded and retitled version will be submitted as a new preprint. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Mandrel Diameter is a Dominating Parameter for Fiber Alignment Control in Rotating Mandrel Electrospinning Systems
Authors: Meinhold Katherine L. , Tankersley Tyler , Darlington Rylie , Robinson Jennifer L.
Published: July 2024

Aligned nano and micron-sized electrospun scaffolds are advantageous for 3Din vitromodels of fibrous, aligned tissue. A common approach to induce alignment is to collect on a rotating mandrel at high rotational speeds. Historically, rotating mandrel speed has been considered the major driver in tuning the degree of alignment even though mandrel diameter is known to modulate linear velocity and increase alignment. However, the comparative impact of mandrel diameter vs. rotating mandrel speed has not been systemically investigated. As such, this study aimed to investigate the role of mandrel diameter on fiber alignment, fiber fraction, and fiber diameter under controlled modulation of common processing parameters including applied voltage, distance to collector, and mandrel rotational speed. Analysis of all samples was performed using scanning electron microscopy (SEM) and image analysis by the DiameterJ and OrientationJ plugins in ImageJ. Using linear regression analysis in JMP software, mandrel diameter was shown to be the dominant factor influencing fiber diameter, fiber fraction, and fiber alignment of samples at all tested conditions including increased rotational speed. Overall, these findings suggest that rather than increasing rotational speed of the collector, fiber alignment can be more finely tuned by increasing mandrel diameter.

Graphical Abstract
Residual Microglia Following Short-term PLX5622 Treatment in 5xFAD Mice Exhibit Diminished NLRP3 Inflammasome and mTOR Signaling, and Enhanced Autophagy
Authors: Kodali Maheedhar , Madhu Leelavathi N. , Somayaji Yogish , Attaluri Sahithi , Huard Charles , Panda Prashanta Kumar , Shankar Goutham , Rao Shama , Shuai Bing , Gonzalez Jenny J. , Oake Chris , Hering Catherine , Babu Roshni Sara , Kotian Sanya , Shetty Ashok K.
Published: July 2024

Chronic neuroinflammation represents a prominent hallmark of Alzheimer’s disease (AD). While moderately activated microglia are pivotal in clearing amyloid beta (Aβ), hyperactivated microglia perpetuate neuroinflammation. Prior investigations have indicated that the elimination of ∼80% of microglia through a month-long inhibition of the colony-stimulating factor 1 receptor (CSF1R) during the advanced stage of neuroinflammation in 5xFamilial AD (5xFAD) mice mitigates synapse loss and neurodegeneration without impacting Aβ levels. Furthermore, prolonged CSF1R inhibition diminished the development of parenchymal plaques. Nonetheless, the immediate effects of short-term CSF1R inhibition during the early stages of neuroinflammation on residual microglial phenotype or metabolic fitness are unknown. Therefore, we investigated the effects of 10-day CSF1R inhibition in three-month-old female 5xFAD mice, a stage characterized by the onset of neuroinflammation and minimal Aβ plaques. We observed ∼65% microglia depletion in the hippocampus and cerebral cortex. The leftover microglia demonstrated a noninflammatory phenotype, with highly branched and ramified processes and reduced NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome complexes. Moreover, plaque-associated microglia were reduced in number with diminished Clec7a (dectin-1) expression. Additionally, both microglia and neurons displayed reduced mechanistic target of rapamycin (mTOR) signaling and autophagy. Biochemical assays validated the inhibition of NLRP3 inflammasome activation, decreased mTOR signaling, and enhanced autophagy. However, short-term CSF1R inhibition did not influence Aβ plaques, soluble Aβ-42 levels, or hippocampal neurogenesis. Thus, short-term CSF1R inhibition during the early stages of neuroinflammation in 5xFAD mice promotes the retention of homeostatic microglia with diminished inflammasome activation and mTOR signaling, alongside increased autophagy.
REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness
Authors: Mortazavi Nasrin , Talwar Puneet , Koshmanova Ekaterina , Sharifpour Roya , Beckers Elise , Berger Alexandre , Campbell Islay , Paparella Ilenia , Balda Fermin , Dardour Hamzaoui Ismael , Berthomier Christian , Bastin Christine , Phillips Christophe , Maquet Pierre , Collette Fabienne , Zubkov Mikhail , Lamalle Laurent , Vandewalle Gilles
Published: July 2024

Background

Animal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to sleep variability in humans is not yet established. Here, we investigated if thein vivoactivity of the LC is related to the variability in the quality of Rapid Eye Movement (REM) sleep.

Methods

We assessed the LC activity of 34 healthy younger (∼22y) and 18 older (∼61y) individuals engaged in bottom-up and top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). We further recorded their sleep electroencephalogram (EEG) to evaluate associations between LC fMRI measures and REM sleep EEG metrics.

Results

Theta oscillation energy during REM sleep was positively associated with LC response in the top-down task. In contrast, REM sleep theta energy was negatively associated with LC activity in older individuals during the bottom-up task. Importantly, sigma oscillations power immediately preceding a REM sleep episode was positively associated with LC activity in the top-down task.

Conclusions

LC activity during wakefulness was related to REM sleep intensity and to a transient EEG change preceding REM sleep, a feature causally related to LC activity in animal studies. The associations depend on the cognitive task, suggesting that a balanced level of LC tonic activity during wakefulness is required for optimal expression of REM sleep. The findings may have implications for the high prevalence of sleep complaints reported in aging and for disorders such as insomnia, Alzheimer’s, and Parkinson’s disease, for which the LC may play pivotal roles through sleep.
ExPOSE: A comprehensive toolkit to perform expansion microscopy in plant protoplast systems
Authors: Cox Kevin L. , Pardi Sarah A. , O’Connor Lily , Klebanovych Anastasiya , Huss David , Nusinow Dmitri A. , Meyers Blake C. , Czymmek Kirk J.
Published: July 2024

Expansion microscopy (ExM) achieves nanoscale imaging by physical expansion of fixed biological tissues embedded in a swellable hydrogel, enhancing the resolution of any optical microscope several-fold. While ExM is commonly used in animal cells and tissues, there are few plant specific protocols. Protoplasts are a widely used cell system across plant species, especially in studying biomolecule localization. Here, we present an approach to achieve robust expansion of plant protoplasts, termedExpansion microscopy in plantPrOtoplastSystEms (ExPOSE). We demonstrate that coupling ExPOSE with other imaging techniques, immunofluorescence andin situhybridization chain reaction to visualize proteins and mRNAs, respectively, greatly enhances the spatial resolution of endogenous biomolecules. Additionally, in this study, we tested the effectiveness and versatility of this technique to observe biomolecular condensates inArabidopsisprotoplasts and transcription factors in maize protoplasts at increased resolution. ExPOSE can be relatively inexpensive, fast, and simple to implement.
CircCNNs, a convolutional neural network framework to better understand the biogenesis of exonic circRNAs
Authors: Wang Chao , Liang Chun
Published: July 2024

Circular RNAs (circRNAs) as biomarkers for cancer detection have been extensively explored, however, the biogenesis mechanism is still elusive. In contrast to linear splicing (LS) involved in linear transcript formation, the so-called back splicing (BS) process has been proposed to explain circRNA formation. To investigate the potential mechanism of BS via the machine learning approach, we curated a high-quality BS and LS exon pairs dataset with evidence-based stringent filtering. Two convolutional neural networks (CNN) base models with different structures for processing splicing junction sequences including motif extraction were created and compared after extensive hyperparameter tuning. In contrast to the previous study, we are able to identify motifs corresponding to well-established BS-associated genes such as MBNL1, QKI, and ESPR2. Importantly, despite prevalent high false positive rates in existing circRNA detection pipelines and databases, our base models demonstrated a notable high specificity (greater than 90%). To further improve the model performance, a novo fast numerical method was proposed and implemented to calculate the reverse complementary matches (RCMs) crossing two flanking regions and within each flanking region of exon pairs. Our CircCNNs framework that incorporated RCM information into the optimal base models further reduced the false positive rates leading to 88% prediction accuracy.
Cerebellar output shapes cortical preparatory activity during motor adaptation
Authors: Israely Sharon , Ninou Hugo , Rajchert Ori , Elmaleh Lee , Harel Ran , Mawase Firas , Kadmon Jonathan , Prut Yifat
Published: July 2024

The cerebellum plays a key role in motor adaptation by driving trial-to-trial recalibration of movements based on previous errors. In primates, this adaptive response is achieved by cerebellar modulation of motor cortical signals, but the nature and timing of this process are unknown. Specifically, cortical correlates of adaptation are encoded already in the pre-movement motor plan, but these early cortical signals could be driven by a cerebellar-to-cortical information flow or evolve independently through intracortical mechanisms. To address this question, we trained monkeys to reach against a viscous force field while blocking cerebellar outflow. During the force field trials, the cerebellar block led to impaired adaptation and a compensatory, re-aiming-like shift in motor cortical preparatory activity. In the null-field conditions, the cerebellar block altered neural preparatory activity by increasing task-representation dimensionality and impeding generalization. A computational model indicated that low-dimensional (cerebellar-like) feedback is sufficient to replicate these findings. We conclude that cerebellar signals carry task structure information that constrains the dimensionality of the cortical preparatory manifold and promotes generalization. In the absence of these signals, cortical mechanisms are harnessed to partially restore adaptation.
The efficacy of the Entomopathogenic Fungus,Beauveria bassiana, in Date Palm Protection against the Red Palm Weevil,Rhynchophorus Ferrugineus, Under Hot Dessert Climate
Authors: Aviv Omer Zer , Matveev Sabina , Ment Dana
Published: July 2024

The Red Palm Weevil (RPW) is a devastating pest to palm trees. Commonly used insecticides for its control, can be harmful to the environment and humans. Moreover, some populations of the Red Palm Weevil have developed resistance to these compounds. Lab and semi-field data showed that Entomopathogenic fungi (EPF) can be a non-toxic and effective solution to reducing these pest infestations. However, the efficacy of EPF against the RPW has not been demonstrated in date palms on field trials with their variables. This study aims to examine the impact of various climate conditions the survival and efficacy of EPFBeauveria bassiana(B. bassiana) in prophylactic applications against the RPW in males and females Date palm groves cultivated using different agricultural practices. Healthy Date palms from the “Arava” region in Israel were selected and equipped with “IoTree” sensors to monitor RPW infestation. At the beginning of each season, the experimental group palms were treated withB. bassianaemulsions, while the control group was left untreated. Soil samples were gathered at the beginning and end of each season in both groves to quantify EPF survival rates and test their regression with EPF prophylactic treatments efficacy. Results showed significant effect for the season, on EPF treatments prophylactic efficacy, in the male and female groves. Generally, EPF treatments applied in the autumn season showed significant higher efficacy, while in the summer, the opposite results observed. Analysis of the results for males and females groves separately, displayed superiority for the spring season treatments on the males grove, and higher efficacy for autumn treatments on the females grove. Climate index significantly affects EPF treatment effectiveness. Analysis of soil tests at the end of each season revealed positive association between the number ofB. bassianafungus Colony-Forming units (CFUs) detected in the soil and the number of healthy palms within each group. Further research is needed to investigate the survival of EPF in various timeframes and explore diverse application schedules using larger palm samples to evaluate EPF efficacy against the RPW.
Marker Data Enhancement For Markerless Motion Capture
Authors: Falisse Antoine , Uhlrich Scott D. , Chaudhari Akshay S. , Hicks Jennifer L. , Delp Scott L.
Published: July 2024

Objective

Human pose estimation models can measure movement from videos at a large scale and low cost; however, open-source pose estimation models typically detect only sparse keypoints, which leads to inaccurate joint kinematics. OpenCap, a freely available service for researchers to measure movement from videos, addresses this issue using a deep learning model— the marker enhancer—that transforms sparse keypoints into dense anatomical markers. However, OpenCap performs poorly on movements not included in the training data. Here, we create a much larger and more diverse training dataset and develop a more accurate and generalizable marker enhancer.

Methods

We compiled marker-based motion capture data from 1176 subjects and synthesized 1433 hours of keypoints and anatomical markers to train the marker enhancer. We evaluated its accuracy in computing kinematics using both benchmark movement videos and synthetic data representing unseen, diverse movements.

Results

The marker enhancer improved kinematic accuracy on benchmark movements (mean error: 4.1°, max: 8.7°) compared to using video keypoints (mean: 9.6°, max: 43.1°) and OpenCap’s original enhancer (mean: 5.3°, max: 11.5°). It also better generalized to unseen, diverse movements (mean: 4.1°, max: 6.7°) than OpenCap’s original enhancer (mean: 40.4°, max: 252.0°).

Conclusion

Our marker enhancer demonstrates both accuracy and generalizability across diverse movements.

Significance

We integrated the marker enhancer into OpenCap, thereby offering its thousands of users more accurate measurements across a broader range of movements.
Chromosome-level genome assembly and annotation ofCorallium rubrum: a Mediterranean coral threatened by overharvesting and climate change
Authors: Ledoux Jean-Baptiste , Gomez-Garrido Jessica , Cruz Fernando , Camara Ferreira Francisco , Matos Ana , Sarropoulou Xenia , Ramirez-Calero Sandra , Aurelle Didier , Lopez-Sendino Paula , Grayson Natalie , Moore Bradley , Antunes Agostinho , Aguilera Laura , Gut Marta , Salces-Ortiz Judit , Fernández Rosa , Linares Cristina , Garrabou Joaquim , Alioto Tyler
Published: July 2024

Reference genomes are key resources in biodiversity conservation. Yet, sequencing efforts are not evenly distributed in the tree of life questioning our true ability to enlighten conservation with genomic data. Good quality reference genomes remain scarce in octocorals while these species are highly relevant target for conservation. Here, we present the first annotated reference genome in the red coral,Corallium rubrum(Linnaeus, 1758), a habitat-forming octocoral from the Mediterranean and neighboring Atlantic, impacted by overharvesting and anthropogenic warming-induced mass mortality events. Combining long reads from Oxford Nanopore Technologies (ONT), Illumina paired-end reads for improving the base accuracy of the ONT-based genome assembly and Arima Hi-C contact data to place the sequences into chromosomes, we assembled a genome of 475 Mb (21 chromosomes, 326 scaffolds) with contig and scaffold N50 of 1.6 Mb and 16.2 Mb, respectively. Fifty percent of the sequence (L50) was contained in eight superscaffolds. The consensus quality (QV) of the final assembly was 42 and the gene completeness reported by BUSCO was 74% (metazoa_odb10 database). We annotated 39,114 protein-coding genes and 32,678 non-coding transcripts. This annotated chromosome-level genome assembly, one of the first in octocorals, is currently used in a project based on whole genome re-sequencing dedicated to the conservation and management ofC. rubrum.

Significance Statement

The Mediterranean red coral,Corallium rubrum, is critically impacted by overharvesting and by mass mortality events linked to marine heat waves. Accordingly,C. rubrumis increasingly receiving conservation efforts. Previous population genetics studies based on microsatellites contributed to improving our knowledge of the species ecology. Yet, crucial questions regarding, admixture among lineages, demographic history, effective population sizes and local adaptation, are still open owing to a lack of genomic resources. Here, we present the first chromosome-level genome assembly for the species with high contiguity, good completeness and protein-coding genes and repeat sequence annotations. This genome, one of the first in octocorals, will pave the way for the integration of population genomics data into ongoing interdisciplinary conservation efforts dedicated toC. rubrum.