bluuebunny/crossref_metadata_2025 huggingface dataset:
Hotline to Helpline: Reducing On-call Demands
Authors: Harbour Skylar , Mukherjee Hrijeeta , Davison Steven P. , DiLeonardo Michael
Published: October 2023

Background:

There is a growing societal trend in plastic surgery patients of viewing their medical care as a commodity product rather than as a healthcare service. Our four-provider private plastic surgery practice noticed this phenomenon through our patients’ trend of overusing the emergency after-hours service call line. To affect this behavior, we designed a study educating patients on the emergency service call line’s purpose and how to handle nonurgent issues independently.

Methods:

After a 6-month preintervention phase to categorize after-hours emergency calls, We improved preoperative patient education and implemented in-office protocols for quicker provider responses. Postintervention data were collected for another 6 months and compared statistically with the preintervention data.

Results:

In the preinterventional period, we saw a total of 236 after-hours phone calls. The intervention led to a 22% significant reduction in total calls (P = 0.007). Calls were categorized as nonurgent, urgent, and emergent. While emergent calls remained unchanged (P = 0.56), nonurgent calls significantly decreased (P = 0.005). The most common nonurgent calls were regarding pain, routine postoperative concerns, and drain care, with the intervention resulting in a significant reduction of routine postoperative swelling/bruising/discomfort calls (P = 0.04) but not changing pain (P = 0.23) or drain-related calls (P = 0.78).

Conclusions:

We found that targeted preoperative patient education coupled with a real-time action board in the office, to ensure timely response to patient questions during office hours, can positively impact after-hours call use, and improve overall patient outcomes by catching urgent issues earlier.
Defining Predictors of Future Academic Productivity in Plastic Surgery Residency
Authors: Wickenheisser Victoria A. , Biswas Sonali , Marks Caitlin , Geng Yisong , Phillips Brett T.
Published: October 2023

Background:

Research is a valued component of applications to plastic surgery residency. No prior studies have explored factors associated with increased resident research productivity. This study aims to compare the academic productivity levels of plastic surgery residency graduates based on their pre- and postresidency experiences.

Methods:

Residents graduating in 2019 and 2020 were identified from integrated programs. Metrics collected included the number of publications in medical school and residency. Descriptive statistics were completed along with linear regressions to evaluate the impact of these on academic productivity.

Results:

A total of 221 residents from the classes of 2019 and 2020 were included. Most residents completed fellowship (75.9%) although less than half went on to academic practice (42.3%). Approximately one in five residents obtained secondary degrees (17.4%). Subjects averaged 3.15 (N = 208, SD = 4.51) publications while in medical school and 8.1 publications during residency (N = 209, SD = 10.0). For h-index calculated at the end of residency, having dedicated medical school research time was the only statistically significant factor (coefficient = 2.96, P = 0.002).

Conclusions:

Plastic surgery residents published more often as first authors and overall during residency than medical school, indicating increased research involvement and leadership. The present study builds upon prior studies by confirming the importance of dedicated medical school research time and its lasting impact. Understanding the associations of academic factors with increased research productivity in residency is relevant for both applicants and programs evaluating residency candidates.
Thromboembolism in Cancer Patients With COVID-19 Infection Compared With Other Infections—A Case Series
Authors: Binkam Mounika , Greene John N. , Oehler Stephanie M. , Thai Christy , Holmström Björn
Published: October 2023

An increased risk of venous thromboembolism (VTE) with COVID-19 infection has been well documented, particularly in critically ill-hospitalized patients. The presence of cancer, in addition to several anticancer treatments, can further elevate the risk of VTE. The following case reports describe an increased risk of extensive thrombosis that can be seen with COVID-19 infection in cancer patients. We report 3 cases of pulmonary embolism and deep vein thrombosis in cancer patients with COVID-19 infection. All 3 cases are unique with the timeline of COVID-19 infection and diagnosis of VTE. The current pandemic has alerted the clinician to the potential increased risk for thrombus formation in cancer patients with COVID-19, even days to months after acute infection.
Fuchs endothelial corneal dystrophy masking an underlying postrefractive surgery ectasia
Authors: Gnanaraj Ramya , Taravella Michael , Davidson Richard
Published: October 2023

Introduction:

This article describes a case presenting Fuchs endothelial corneal dystrophy (FECD) masking an underlying postrefractive surgery ectasia.

Patient and Clinical Findings:

A 69-year-old woman presented in January 2022 with blurriness, halos, and glare in the left eye. Ocular history included a photorefractive keratectomy performed twice in her left eye in 2007 for hyperopic astigmatism. A diagnosis of asymptomatic Fuchs dystrophy was noted in 2010. She had acute decompensation of the cornea in the left eye because of FECD, and the first Descemet-stripping automated endothelial keratoplasty (DSAEK) with cataract surgery was performed in 2018.

Diagnosis, Intervention, and Clinical Findings:

The patient had a failed DSAEK graft in the left eye. A repeat DSAEK was performed in 2022, and 6 months postoperatively, the patient started showing signs of ectasia in the left eye. The authors believe the ectasia was preexisting but masked by the failed DSAEK graft and FECD and started showing after corneal deturgescence postoperatively.

Conclusions:

The presence of FECD and corneal ectasia can complicate diagnosis because of overlapping clinical and topographic features. This case highlights the importance of preoperative topography with epithelial/stromal thickness mapping in patients with a history of multiple refractive corneal procedures to consider the possibility of ectasia and prevent unforeseen outcomes and complications. Further research is necessary to determine standardized imaging techniques, particularly in cases of concurrent diseases.
Use of a Supplemental Feeding Tube Device and Breastfeeding at 4 Weeks
Authors: Penny Frances , Brownell Elizabeth A. , Judge Michelle , Marshall-Crim Mary , Cartagena Diana , McGrath Jacqueline M.
Published: October 2023

Background:

Mothers having difficulty breastfeeding their infants may use alternative supportive feeding methods. Although a supplemental feeding tube device is commonly used, efficacy for supporting sustained breastfeeding remains unknown.

Purpose:

To describe supplemental feeding tube device use by breastfeeding mothers as an alternative feeding method through exploration of associations between supplemental feeding tube device use and continued breastfeeding at 4 weeks of infant's age.

Method:

Forty mothers participated. They were interviewed during the birth hospitalization and at 4 weeks postpartum. Questions addressed use of supplemental feeding tube devices, breastfeeding issues, and continued breastfeeding relationships. We examined the relationship between LATCH scores at 2 to 3 days of life.

Results:

Breastfeeding mothers who chose to supplement with bottle-feeding instead of use of a supplemental feeding tube device were 30% less likely to continue breastfeeding at a medium/high/exclusive level.

Conclusion:

Use of the supplemental feeding tube device may help avoid the potentially detrimental effect of bottle-feeding on continued breastfeeding.
Case Report: Branch Retinal Vein Occlusion Post mRNA SARS-CoV-2 (COVID-19) Vaccination
Authors: Lee Jing , Ong Kah Wei , Wan Abdul Halim Wan Haslina , Mohd Khialdin Safinaz , Yong Meng Hsien
Published: October 2023

Significance

Systemic thromboembolic complications are well documented to be associated with Coronavirus disease 2019 (COVID-19), however, there has been a growing number of reports regarding ocular complications stemming from COVID-19 vaccinations. This case illustrates a clear temporal and possible causal relationship of COVID-19 vaccination with an ocular microvascular disorder, namely retinal vein occlusion.

Purpose

To report a case of inferotemporal branch retinal vein occlusion after mRNA SARS-CoV-2 vaccination.

Case report

A middle-aged female developed right eye central scotoma two days after COVID-19 vaccination. She had transient hypertension during the first two days post-vaccination. A decrease in visual acuity (6/18) was documented. Initial retinal findings included flame-shaped hemorrhages and cotton wool spots along inferotemporal branch retinal vessels. Optical coherence tomography revealed right eye cystoid macular edema. Laboratory investigation revealed mildly raised erythrocyte sedimentation rate and C-reactive protein. Other systemic examinations were unremarkable. She was treated for right eye inferotemporal branch retinal vein occlusion with cystoid macular edema and was given intravitreal anti-vascular endothelial growth factor monthly in three doses. Her visual acuity improved to 6/6 with resolved cystoid macular edema.

Conclusions

This case illustrates a clear temporal and possible causal relationship between COVID-19 vaccination and retinal vein occlusion. Post vaccination transient hypertension, or the immunological and inflammatory response to the vaccine may have contributed to the venous occlusive event in this case. Eye care providers should remain aware of this possibility. The effectiveness of intravitreal anti-vascular endothelial growth for the treatment of macular edema secondary to branch retinal vein occlusion was demonstrated in this patient.
AI as a New Frontier in Contrast Media Research
Authors: Haubold Johannes , Hosch René , Jost Gregor , Kreis Felix , Forsting Michael , Pietsch Hubertus , Nensa Felix
Published: October 2023

Artificial intelligence (AI) techniques are currently harnessed to revolutionize the domain of medical imaging. This review investigates 3 major AI-driven approaches for contrast agent management: new frontiers in contrast agent dose reduction, the contrast-free question, and new applications. By examining recent studies that use AI as a new frontier in contrast media research, we synthesize the current state of the field and provide a comprehensive understanding of the potential and limitations of AI in this context. In doing so, we show the dose limits of reducing the amount of contrast agents and demonstrate why it might not be possible to completely eliminate contrast agents in the future. In addition, we highlight potential new applications to further increase the radiologist's sensitivity at normal doses. At the same time, this review shows which network architectures provide promising approaches and reveals possible artifacts of a paired image-to-image conversion. Furthermore, current US Food and Drug Administration regulatory guidelines regarding AI/machine learning–enabled medical devices are highlighted.
Incidental Detection of Parathyroid Adenoma on 18F-PSMA PET/CT
Authors: Broos Wouter A. M. , van der Zant Friso M. , Knol Remco J. J.
Published: October 2023

A 70-year-old man, diagnosed with prostate cancer, was referred to the Department of Nuclear Medicine for tumor staging with prostate-specific membrane antigen (PSMA) PET/CT. High PSMA uptake was observed in the prostate without PSMA-avid lymph nodes or distant metastases. Coincidentally, a PSMA-avid nodule was observed dorsal to the right thyroid lobe. A complementary 4-dimensional CT showed a round nodule of 18 mm with quick contrast enhancement well demarcated from its surroundings. Blood tests revealed elevated serum calcium and parathyroid hormone consistent with primary hyperparathyroidism. Subsequently, parathyroidectomy was performed, and histopathological examination of the nodule confirmed a parathyroid adenoma.
Atypical Presentation of Liver Metastases of Prostate Cancer in 68Ga-PSMA-11 PET/CT
Authors: Stanzel Susanne , Weitzer Friedrich , Janek Elmar , Plhak Elisabeth , Aigner Reingard M.
Published: October 2023

68Ga-PSMA-11 (68Ga–prostate-specific membrane antigen-11) PET/CT continues to have a great clinical value for staging in prostate cancer. Lymph nodes and bone are the most typical metastatic sites of prostate cancer, whereas liver metastases are rare and usually show focally increased tracer uptake in 68Ga-PSMA-11 PET/CT. Here, we present an 88-year-old man with histologically proven metastatic castration-resistant prostate cancer and extensive PSMA-negative liver metastases identified by 68Ga-PSMA-11 PET/CT. This finding is remarkable because the decreased liver uptake of 68Ga-PSMA-11 may resemble a primary hepatic tumor.
Peptide Receptor Radionuclide Therapy Performed Shortly After Administration of Long-Acting Octreotide
Authors: Low Han Chung , Tay Young Soon , Ong Simon Yew Kuang , Tham Wei Ying , Yan Sean Xuexian
Published: October 2023

We present a case of a 68-year-old man with metastatic small bowel neuroendocrine tumor who underwent 4 cycles of peptide receptor radionuclide therapy with 177Lu-DOTATATE. For his first 3 cycles, therapy was performed approximately 4 weeks after his last dose of octreotide LAR. Because of miscommunication in scheduling, his fourth cycle was performed only 48 hours after his last full dose of octreotide LAR. Despite this, we found that the tumoral uptake was not reduced at all, which may add to the increasing evidence on the nonnecessity of stopping somatostatin analogs before peptide receptor radionuclide therapy.
Intratumoral 99mTc-DPD Uptake on Bone Scintigraphy in a Patient With Invasive Micropapillary Breast Carcinoma: A Pathologic Review
Authors: Koh Namhee , Lee Kyoungyul , Oh Ha Yeun , Chun In Kook
Published: October 2023

Invasive micropapillary carcinoma (IMPC) is a rare and aggressive subtype of breast cancer with a poorer prognosis due to high local recurrence and lymphovascular invasion. Interestingly, IMPC often does not show suspicious patterns of calcifications related to malignancy on mammography. Therefore, the lack of suspicious calcifications makes it difficult to detect breast cancer on mammography. With only nonspecific calcifications on mammography, we observed an unusual intratumoral 99mTc-DPD uptake on whole-body bone scintigraphy in an IMPC breast cancer patient during the initial staging workup, and its characteristics were compared with mammographic findings and the postoperative pathologic features.
Galcanezumab in the Treatment of Migraine: A Narrative Review of Real-World Studies
Authors: Dell Agnello Grazia , Buzzoni Carlotta , Antenori Amalia , Torelli Federico , Altamura Claudia , Vernieri Fabrizio
Published: October 2023

Objectives

Randomized controlled trials (RCTs) have established the efficacy of galcanezumab, an antibody binding calcitonin gene-related peptide (CGRP) ligand, in the preventive treatment of migraine. The objective was to summarize real-world data evaluating galcanezumab in the preventive treatment of migraine, to complement RCT results with evidence observed in clinical practice.

Methods

A literature search was conducted to identify real-world studies evaluating galcanezumab in the treatment for patients with migraine.

Results

Twenty-five studies were identified; some only evaluated galcanezumab, and others used pooled data from multiple anti-CGRP antibodies. The studies recruited diverse patient populations, including patients who had failed multiple prior preventive therapies. Treatment was associated with significant reductions from baseline in monthly migraine days and monthly headache days by 4.3 to 12.9 and 3.1 to 13.9, respectively. These values were numerically greater than those reported in most galcanezumab RCTs. Significant decreases from baseline were evident within the first month of treatment, and efficacy was maintained throughout the follow-up periods, ranging from 3 to 12 months. Galcanezumab was also associated with improvements in other efficacy end points, including decreased headache pain intensity, reduction in analgesic use, and improvements in daily functioning and quality of life. Functionality scores, as assessed by the Migraine Disability Assessment Scale questionnaire, decreased by 27 to 75 points from baseline at 3 to 12 months. Galcanezumab was associated with a low discontinuation rate and higher rates of persistence compared with standard migraine preventive treatments.

Conclusions

The results provide complementary data that galcanezumab is effective across the diverse patient populations observed in routine clinical practice.
Remote Assessment of Real-World Surgical Safety Checklist Performance Using the OR Black Box: A Multi-Institutional Evaluation
Authors: Riley Max S , Etheridge James , Palter Vanessa , Zeh Herbert , Grantcharov Teodor , Kaelberer Zoey , Sonnay Yves , Smink Douglas S , Brindle Mary E , Molina George
Published: October 2023

BACKGROUND:

Large-scale evaluation of surgical safety checklist performance has been limited by the need for direct observation. The operating room (OR) Black Box is a multichannel surgical data capture platform that may allow for the holistic evaluation of checklist performance at scale.

STUDY DESIGN:

In this retrospective cohort study, data from 7 North American academic medical centers using the OR Black Box were collected between August 2020 and January 2022. All cases captured during this period were analyzed. Measures of checklist compliance, team engagement, and quality of checklist content review were investigated.

RESULTS:

Data from 7,243 surgical procedures were evaluated. A time-out was performed during most surgical procedures (98.4%, n = 7,127), whereas a debrief was performed during 62.3% (n = 4,510) of procedures. The mean percentage of OR staff who paused and participated during the time-out and debrief was 75.5% (SD 25.1%) and 54.6% (SD 36.4%), respectively. A team introduction (performed 42.6% of the time) was associated with more prompts completed (31.3% vs 18.7%, p < 0.001), a higher engagement score (0.90 vs 0.86, p < 0.001), and a higher percentage of team members who ceased other activities (80.3% vs 72%, p < 0.001) during the time-out.

CONCLUSIONS:

Remote assessment using OR Black Box data provides useful insight into surgical safety checklist performance. Many items included in the time-out and debrief were not routinely discussed. Completion of a team introduction was associated with improved time-out performance. There is potential to use OR Black Box metrics to improve intraoperative process measures.
Environment-driven trends in fish larval abundance predict fishery recruitment in two temperate reef congeners: Mechanisms and implications for fishery recovery under a changing ocean
Authors: Mason Erica T. Jarvis , Watson William , Ward Eric J. , Thompson Andrew R. , Semmens Brice X.
Published: October 2023

Environmental and biological processes acting on fish larvae can drive fishery cohort strength, but predictive ability oftentimes falls short, and larval abundance is generally considered more useful as a proxy for spawning biomass. Under a changing ocean, studies that relate environmental covariates, larval abundance, and fishery recruitment are worthy of continued research, especially in data-limited contexts. We focus on a popular, recreational-only, multispecies saltwater bass fishery (genusParalabrax)whose population status and recovery potential are uncertain. We used 54 years of ichthyoplankton data (1963-2016) and a species distribution model to 1) deconstruct species-specific standardized indices of larval abundance, 2) test these indices as indicators of adult stock status or predictors of future fishery recruitment, and 3) evaluate spatiotemporal trends in their population dynamics relative to environmental variables. Contrary to expectation, species-specific larval abundance predicted future catch, with recent elevated larval abundance suggesting imminent fishery recovery. Additionally, we identified strong relationships with environmental variables, thereby providing additional tools for predicting fishery recruitment and anticipating population change. Our findings paint a path forward for improving estimates of current and future fishery status under changing natural and anthropogenic influences and the incorporation of ecosystem considerations into fishery management.
Physiological Profiles of Male and Female CrossFit®Athletes
Authors: Hodžić Deni , D’Hulst Gommaar , Leuenberger Rahel , Arnet Janik , Westerhuis Elena , Roth Ralf , Schmidt-Trucksäss Arno , Knaier Raphael , Wagner Jonathan
Published: October 2023

Objective

To 1) establish extensive physiological profiles of highly-trained CrossFit athletes using gold-standard tests and 2) investigate which physiological markers best correlate with CrossFit®Open performance.

Methods

This study encompassed sixty participants (30 males and 30 females), all within the top 5% of the CrossFit®Open, including 7 CrossFit®Semi-finalists and 3 Games finalists. Isokinetic dynamometers were employed to measure maximum isometric and isokinetic leg and trunk strength. Countermovement jump height and maximum isometric mid-thigh pull strength were assessed on a force plate. V□O2peakwas measured by a cardiopulmonary exercise test, while critical power and W’ were evaluated during a 3-minute all-out test, both on a cycle ergometer.

Results

Male and female athletes’ median (IQR) V□O2peakwas 4.64 (4.43, 4.80) and 3.21 (3.10, 3.29) (L·min-1), critical power 314.5 (285.9, 343.6) and 221.3 (200.9, 238.9) (W) and mid-thigh pull 3158 (2690, 3462) and 2035 (1728, 2347) (N). Linear regression analysis shows strong evidence for associations between different anthropometric variables and CrossFit®Open performance in men and women, whereas for markers of cardiorespiratory fitness such as V□O2peakthis was only true for women but not men. Conventional laboratory evaluations of strength, however, manifest minimal evidence for associations with Open performance across both sexes.

Conclusions

This study provides the first detailed insights into the physiology of high-performing CrossFit®athletes and informs training optimization. Further the results emphasize the advantage of athletes with shorter limbs and suggests potential modifications to Open workout designs to level the playing field for athletes across different anthropometrics characteristics.
Myocardial Elasticity Imaging Correlates with Histopathology in a Model of Anthracycline-Induced Cardiotoxicity
Authors: Miller Caroline E. , Jordan Jennifer H. , Thomas Alexandra , Friday Sarah R. , Meléndez Giselle C. , Weis Jared A.
Published: October 2023

Background

There is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker for cardiac decline. Biomarker strategies are of particular interest in cardio-oncology due to cardiotoxic effects of anti-neoplastic therapies, particularly anthracycline-based chemotherapeutics. Current clinical methods for diagnosing cardiotoxicity are too coarse to identify cardiac decline early enough for meaningful therapeutic intervention, or too cumbersome for clinical implementation.

Methods

Utilizing changes in myocardial elasticity as a biomarker for subclinical cardiac decline, we developed a biomechanical model-based elasticity imaging methodology (BEIM) to estimate spatial maps of left ventricle (LV) myocardial elasticity. In this study, we employ this methodology to assess changes in LV elasticity in a non-human primate model of doxorubicin-induced cardiotoxicity. Cardiac magnetic resonance imaging of five African Green monkeys was acquired at baseline prior to doxorubicin administration, 6-weeks, and 15-weeks after final doxorubicin dose and histopathological samples of the LV were taken at 15-weeks after final doxorubicin dose. Spatial elasticity maps of the mid-short axis plane of the LV were estimated at each image acquisition. Global and regional LV elasticity were calculated and changes between imaging time points was assessed. LV elasticity at baseline and final time point were compared to cardiomyocyte size and collagen volume fraction measurements calculated from histopathological staining of archived tissue bank samples and study endpoint tissue samples utilizing Pearson’s correlation coefficients.

Results

We identify significant changes in LV elasticity between each imaging time point both globally and regionally. We also demonstrate strong correlation between LV elasticity and cardiomyocyte size and collagen volume fraction measurements. Results indicate that LV elasticity estimates calculated using BEIM correlate with histopathological changes that occur due to doxorubicin administration, validating LV elasticity solutions and providing significant promise for use of BEIM to non-invasively elucidate cardiac injury.

Conclusions

This methodology can show progressive changes in LV elasticity and has potential to be a more sensitive indicator of elasticity changes than current clinical measures of cardiotoxicity. LV elasticity may provide a valuable biomarker for cardiotoxic effects of anthracycline-based chemotherapeutics and cardiac disease detection.
Genetic ablation of neuronal mitochondrial calcium uptake halts Alzheimer’s disease progression
Authors: Jadiya Pooja , Kolmetzky Devin W. , Tomar Dhanendra , Thomas Manfred , Cohen Henry M. , Khaledi Salman , Garbincius Joanne F. , Hildebrand Alycia N. , Elrod John W.
Published: October 2023

Alzheimer’s disease (AD) is characterized by the extracellular deposition of amyloid beta, intracellular neurofibrillary tangles, synaptic dysfunction, and neuronal cell death. These phenotypes correlate with and are linked to elevated neuronal intracellular calcium (iCa2+) levels. Recently, our group reported that mitochondrial calcium (mCa2+) overload, due to loss ofmCa2+efflux capacity, contributes to AD development and progression. We also noted proteomic remodeling of the mitochondrial calcium uniporter channel (mtCU) in sporadic AD brain samples, suggestive of alteredmCa2+uptake in AD. Since the mtCU is the primary mechanism for Ca2+uptake into the mitochondrial matrix, inhibition of the mtCU has the potential to reduce or preventmCa2+overload in AD. Here, we report that neuronal-specific loss of mtCU-dependentmCa2+uptake in the 3xTg-AD mouse model of AD reduced Aβ and tau-pathology, synaptic dysfunction, and cognitive decline. Knockdown ofMcuin a cellular model of AD significantly decreased matrix Ca2+content, oxidative stress, and cell death. These results suggest that inhibition of neuronalmCa2+uptake is a novel therapeutic target to impede AD progression.
Divergent changes in PBN excitability in a mouse model of neuropathic pain
Authors: Torruella-Suárez María L , Neugebauer Benjamin , Flores-Felix Krystal , Keller Asaf , Carrasquillo Yarimar , Cramer Nathan
Published: October 2023

The transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino–parabrachio–amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus. Usingex vivoslice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitability relative to shams. In contrast, quiescent PBN neurons from cuff mice were less excitable than those from shams. Despite an increase in excitability in a subset of PBN neurons, the presence of after-discharges frequently observedin vivowere largely absentex vivoin both injury models. However, GABAB-mediated presynaptic inhibition of GABAergic terminals is enhanced in PBN neurons after CCI-ION. These data suggest that the amplified activity of PBN neurons observed in rodent models of chronic pain arise through a combination of changes in firing properties and network excitability.

Significance Statement

Hyperactivity of neurons in the parabrachial nucleus (PBN) is causally linked to exaggerated pain behaviors in rodent models of chronic pain but the underlying mechanisms remain unknown. Using two mouse models of neuropathic pain, we show the intrinsic properties of PBN neurons are largely unaltered following injury. However, subsets of PBN neurons become more excitable and GABABreceptor mediated suppression of inhibitory terminals is enhanced after injury. Thus, shifts in network excitability may be a leading factor in injury induced potentiation of PBN activity.
Numerical simulation and analysis of droplet formation within an amphiphilic particle
Authors: Song Xinpei , Destgeer Ghulam
Published: October 2023

An instrument-free particle-templated droplet formation can be achieved upon simple mixing of amphiphilic particles with aqueous and oil phases in a well plate by using a common lab pipette. Here, a two-dimensional, two-phase flow model was established using a finite element method to mimic the droplet formation within a concentric amphiphilic particle, which consisted of an outer hydrophobic layer and an inner hydrophilic layer. Immiscible water and oil phases selectively interacted with the hydrophilic and hydrophobic layers of the particle, respectively, to form an isolated aqueous compartment within a cavity. Three extreme models were also simulated, including completely hydrophilic, completely hydrophobic, and oppositely amphiphilic particle, which indicated that a right order of the particle layers was necessary to capture the droplet inside the cavity. Moreover, we performed a systematic study of particle-templated droplet formation by varying the individual layer thicknesses of particle, particle height, interfacial tension between water and oil, contact angle of interface with different surfaces, velocity of incoming oil media, and distance between neighboring particles. The volume fraction of water droplet trapped within the target cavity region was calculated to characterize the droplet formation. Our work will help to optimize the particle fabrication process, predict the experiment droplet formation, and explain the physical mechanism underlying compartmentalization phenomena.
Scalable distance-based phylogeny inference using divide-and-conquer
Authors: Arvestad Lars
Published: October 2023

Distance-based methods for inferring evolutionary trees are important subroutines in computational biology, sometimes as a first step in a statistically more robust phylogenetic method. The most popular method is Neighbor Joining, mainly to to its relatively good accuracy, but Neighbor Joining has a cubic time complexity, which limits its applicability on larger datasets. Similar but faster algorithms have been suggested, but the overall time complexity remains essentially cubic as long as the input is a distance matrix. This paper investigates a randomized divide-and-conquer heuristic,dnctree, which selectively estimates pairwise sequence distances and infers a tree by connecting increasingly large subtrees. The divide-and-conquer approach avoids computing all pairwise distances and thereby saves both time and memory. The time complexity is at worst quadratic, and seems to scale likeO(nlgn) on average. A simple Python implementation,dnctree, available on GitHub and PyPI.org, has been tested and we show that it is a scalable solution. In fact, it is applicable to very large datasets even as plain Python program.
Reassessing the Role of Foot Power in Human Gait
Authors: Yetman Quinn , Welte Lauren , Shimizu Aidan , Rainbow Michael J
Published: October 2023

The foot acts as the primary interface to the ground during bipedal locomotion. It absorbs and returns energy over stance as the longitudinal arch deforms and recoils. The term ‘arch recoil’ evokes the concept that the foot’s returned energy directly propels the centre of mass forward by lifting the talus. However, recent work has shown that arch recoil does not directly drive the body forward; instead, it lowers and posteriorly tilts the talus, putting it into a more favourable position for upright gait. Here, we aim to supply a kinetic explanation for this mechanism. We applied the unified deformable power approach to highly accurate talus kinematics from biplanar videoradiography and force plate measurements to measure the power absorbed/produced by the foot. We coupled these measurements with a simple mathematical model that allowed us to restrict rotation and linear actuation of the talus caused by the recoil of the arch to demonstrate that positive foot power primarily contributes to posteriorly tilting the talus. This suggests the role of positive foot power during propulsion is to keep the talocrural surface in a more favourable position for upright gait rather than directly propelling the centre of mass forwards. These findings highlight that arch mobility during push-off is critical for allowing the ankle to directly propel the body forward and upward during the propulsive phase of gait.
Designing efficient randstrobes for sequence similarity analyses
Authors: Karami Moein , Mohammadi Aryan Soltani , Martin Marcel , Ekim Barış , Shen Wei , Guo Lidong , Xu Mengyang , Pibiri Giulio Ermanno , Patro Rob , Sahlin Kristoffer
Published: October 2023

Substrings of lengthk, commonly referred to ask-mers, play a vital role in sequence analysis, reducing the search space by providing anchors between queries and references. However,k-mers are limited to exact matches between sequences. This has led to alternative constructs, such as spacedk-mers, that can match across substitutions. We recently introduced a class of new constructs,strobemers, that can match across substitutions and smaller insertions and deletions.Randstrobes, the most sensitive strobemer proposed in [18], has been incorporated into several bioinformatics applications such as read classification, short read mapping, and read overlap detection. Randstrobes are constructed by linking togetherk-mers in a pseudo-random fashion and depend on a hash function, alink function, and a comparator for their construction. Recently, we showed that the more random this linking appears (measured in entropy), the more efficient the seeds for sequence similarity analysis. The level of pseudo-randomness will depend on the hashing, linking, and comparison operators. However, no study has investigated the efficacy of the underlying operators to produce randstrobes.

In this study, we propose several new construction methods. One of our proposed methods is based on a Binary Search Tree (BST), which lowers the time complexity and practical runtime to other methods for some parametrizations. To our knowledge, we are also the first to describe and study the types of biases that occur during construction. We designed three metrics to measure the bias. Using these new evaluation metrics, we uncovered biases and limitations in previous methods and showed that our proposed methods have favorable speed and sampling uniformity to previously proposed methods. Lastly, guided by our results, we change the seed construction in strobealign, a short-read mapper, and find that the results change substantially. Also, we suggest combining the two versions to improve accuracy for the shortest reads in our evaluated datasets. Our evaluation highlights sampling biases that can occur and provides guidance on which operators to use when implementing randstrobes.
Endocannabinoids and their receptors modulate endometriosis pathogenesis and immune response
Authors: Lingegowda Harshavardhan , Zutautas Katherine B , Wei Yuhong , Yolmo Priyanka , Sisnett Danielle J , McCallion Alison , Koti Madhuri , Tayade Chandrakant
Published: October 2023

Endometriosis (EM), characterized by the presence of endometrial-like tissue outside the uterus, is the leading cause of chronic pelvic pain and infertility in females of reproductive age. Despite its high prevalence, the molecular mechanisms underlying EM pathogenesis remain poorly understood. The endocannabinoid system (ECS) is known to influence several cardinal features of this complex disease including pain, vascularization, and overall lesion survival, but the exact mechanisms are not known. Utilizing CNR1 knockout (k/o), CNR2 k/o and wild type (WT) mouse models of EM, we reveal contributions of ECS and these receptors in disease initiation, progression, and immune modulation. Particularly, we identified EM-specific T cell dysfunction in the CNR2 k/o mouse model of EM. We also demonstrate the impact of decidualization- induced changes on ECS components, and the unique disease-associated transcriptional landscape of ECS components in EM. Imaging Mass Cytometry (IMC) analysis revealed distinct features of the microenvironment between CNR1, CNR2, and WT genotypes in the presence or absence of decidualization. This study, for the first time provides an in-depth analysis of the involvement of the ECS in EM pathogenesis and lays the foundation for the development of novel therapeutic interventions to alleviate the burden of this debilitating condition.
Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain
Authors: Cornelssen Carena , Payne Allison , Parker Dennis , Alexander Matthew , Merrill Robb , Senthilkumar Sharayu , Christensen Jacob , Wilcox Karen S. , Odéen Henrik , Rolston John D.
Published: October 2023

Objective

High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.

Methods

The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.

Results

Comparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.
KmerSV: a visualization and annotation tool for structural variants using Human Pangenome derived k-mers
Authors: Meng Qingxi , Ji Hanlee P. , Lee HoJoon
Published: October 2023

KmerSV is a visualization and annotation tool for structural variants (SVs). It can be applied to assembly contigs or long-read sequences. Using k-mers it rapidly generates images and provides genome features of SVs. As an important feature, it utilizes the new Human Pangenome reference which provide haploid specific assemblies, addresses limitations in prior references and improves the discovery of SVs.

Availability and implementation

KmerSV is implemented in Python and available at github.com/sgtc-stanford/kmerSV
Edge Community Entropy is a Novel Neural Correlate of Aging and Moderator of Fluid Cognition
Authors: Shankar Anita , Tanner Jacob , Mao Tianrui , Betzel Richard , Prakash Ruchika Shaurya
Published: October 2023

Decreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogues of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of nodal specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. Global entropy uniquely covaried with age when controlling for network segregation. Importantly, relationships between both metrics and fluid cognition were age-dependent, although entropy’s relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level.
Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells
Authors: Liu Haibo , Caliz Amada D. , Learnard Heather , Koupenova Milka , Keaney John F. , Kant Shashi , Zhu Lihua Julie , Vertii Anastassiia
Published: October 2023

Inflammatory stresses underlie endothelial dysfunction and contribute to the development of chronic cardiovascular disorders such as atherosclerosis and vascular fibrosis. The initial transcriptional response of endothelial cells to pro-inflammatory cytokines such as TNF-alpha is well established. However, very few studies uncover the effects of inflammatory stresses on chromatin architecture. We used integrative analysis of ATAC-seq and RNA-seq data to investigate chromatin alterations in human endothelial cells in response to TNF-alpha and febrile-range heat stress exposure. Multi-omics data analysis suggests a correlation between the transcription of stress-related genes and endothelial dysfunction drivers with chromatin regions exhibiting differential accessibility. Moreover, microscopy identified the dynamics in the nuclear organization, specifically, the changes in a subset of heterochromatic nucleoli-associated chromatin domains, the centromeres. Upon inflammatory stress exposure, the centromeres decreased association with nucleoli in a p38-dependent manner and increased the number of transcripts from pericentromeric regions. Overall, we provide two lines of evidence that suggest chromatin alterations in vascular endothelial cells during inflammatory stresses.
Translating electrophysiological signatures of awareness into thalamocortical mechanisms by inverting systems-level computational models across arousal states
Authors: Medel Vicente , Muller Eli J. , Munn Brandon R. , Casey Cameron , Sanders Robert D. , Shine James M.
Published: October 2023

While consciousness never fades during wakefulness, there is a paradoxical coexistence of consciousness during dreaming states. It’s also possible for sensory awareness to be either present or absent when awakened from seemingly-identical states of sedation and anaesthesia. Traditionally, these states have been characterised in terms of their electroencephalographic neural correlates, however, without clear underlying neurobiological mechanisms. To bridge this gap, we invert a validated neural mass model of the corticothalamic system using scalp EEG collected during nonlinear transitions in conscious experience and sensory awareness across varying depths of dexmedetomidine sedation. We found that a decline in conscious experience and sensory awareness with dexmedetomidine was associated with a decrease in the engagement of excitatory thalamocortical loop resonances, along with an increase in inhibitory intrathalamic loop gains. These findings shed light into the neural mechanisms of conscious experience and sensory awareness, and explain how it fades across arousal states, bridging the gap between the neural correlates of consciousness and its underlying systems-level thalamocortical mechanisms.
Ecological tradeoffs lead to complex evolutionary trajectories and sustained diversity on dynamic fitness landscapes
Authors: Amado André , Bank Claudia
Published: October 2023

The course and outcome of evolution are critically determined by the fitness landscape, which maps genotype to fitness. Most theory has considered static fitness landscapes or fitness landscapes that fluctuate according to abiotic environmental changes. In the presence of biotic interactions between coexisting genotypes, the fitness landscape becomes dynamic and frequency-dependent.

Here, we introduce a fitness landscape model that incorporates ecological interactions between individuals in a population. In the model, fitness is determined by individuals competing for resources according to a set of traits they possess. An individual’s genotype determines the trait values through a Rough Mount Fuji fitness landscape model, allowing for tunable epistasis (i.e., non-additive gene interaction) and trait correlations (i.e., whether there are tradeoffs or synergies in the ability to use resources). Focusing on the effects of epistasis and trait correlations, we quantify the resulting eco-evolutionary dynamics under simulated Wright-Fisher dynamics (i.e., including genetic drift, mutation, and selection under the assumption of a constant population size) on the dynamics fitness landscape in comparison with a similar, static, fitness landscape model without ecological interactions.

Whereas the non-ecological model ultimately leads to the maintenance of one main geno-type in the population, evolution in the ecological model can lead to the long-term coexistence of several genotypes at intermediate frequencies across much of the parameter range. Including ecological interactions increases steady-state diversity whenever the trait correlations are not too strong. However, strong epistasis can hinder coexistence, and additive genotype-phenotype maps yield the highest haplotype diversity at the steady state. Interestingly, we frequently observe long-term coexistence also in the absence of induced trade-offs in the ability to consume resources.

In summary, our simulation study presents a new dynamic fitness landscape model that highlights the complex eco-evolutionary consequences of a (finite) genotype-phenotype-fitness map in the presence of biotic interactions.