bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superficial Papular Neuroma: Two Cases of a Distinctive Dermal Neoplasm
Authors: Knittel Ronan , Paton David , Beer Trevor W. 
Published: October 2024

Abstract:
Superficial papular neuroma is a rare cutaneous spindle cell lesion, with only 5 cases reported in 2 studies. We document 2 additional cases in a 45-year-old man and a 43-year-old woman (the first case identified in a woman). Clinically, superficial papular neuromas appear as a single, non-specific papule on the head, neck, or back. Histologically, these lesions are within the papillary and superficial reticular dermis, with nerve-like structures composed of bland spindle-shaped cells intersecting normal tissue with mild reactive acanthosis. The cells are SOX10 positive with neurofilament protein staining multiple axons within. The nerve-like structures in this study were occasionally surrounded by a thin rim of CD34 positivity, with no epithelial membrane antigen staining, similar to normal sensory neurons. Superficial papular neuroma are rare benign neoplasms with no reports of recurrence, even when incompletely excised.
Comparative Bulk RNA-Seq Analysis of Poly-l-Lactic Acid Versus Calcium Hydroxylapatite Reveals a Novel, Adipocyte-Mediated Regenerative Mechanism of Action Unique to PLLA
Authors: Waibel Jill , Ziegler Mary , Nguyen Thu Q. , Le Jennifer H. T. D. , Qureshi Aamir , Widgerow Alan , Meckfessel Matthew 
Published: October 2024

BACKGROUND
Injectable biostimulators are widely used to improve facial aging signs. This study was performed to compare the genetic pathways affected by 2 different injectable biostimulators.

METHODS
Randomized 13-week study (n = 21) comparing gene expression after poly l-lactic acid (PLLA-SCA) and calcium hydroxylapatite (CaHA-R) injections (baseline [BL] and Day 28) as treatment of nasolabial fold wrinkles. Punch biopsy was performed at BL and day 90; RNA was isolated, gene expression was analyzed, and bulk RNA sequencing performed. Data from both pathways were studied using the Search Tool for Retrieval of Interacting Genes/Proteins and Reactome databases.

RESULTS
Analysis at Day 0 and Day 90 showed differing gene regulation for PLLA-SCA and CaHA-R (after accounting for minor differences at BL, p < .05 at Day 90 for 9–12 genes). PLLA-SCA uniquely correlates with genes involved in adipocyte regeneration, while CaHA-R did not affect these genes. Clinically, this could translate to healthy fat replacement with an enhanced effect beyond the improvement of the collagen structure and a longer-lasting effect with PLLA-SCA. Furthermore, the adipokines that appear to be upregulated are regenerative with a positive impact on skin health.

CONCLUSION
PLLA-SCA has a novel and unique signature, which supports a potential regenerative mechanism of action through its role in the modulation of adipocyte function.
Consensus Agreements on Regenerative Aesthetics: A Focus on Regenerative Biostimulation With Calcium Hydroxylapatite
Authors: Goldie Kate , Chernoff Greg , Corduff Niamh , Davies Owen , van Loghem Jani , Viscomi Bianca 
Published: October 2024

BACKGROUND
A growing population of patients is seeking treatments that not only affect their overlying features but also restore a more biologically youthful structure and function to the underlying tissue. These strategies are part of what is known as regenerative aesthetics (RA). As an emergent field, clarity regarding the precise definitions and aims of RA and methods to measure the regenerative capacity of RA treatments are lacking.

METHODS
A panel of 6 multidisciplinary experts discussed the foundational aspects of RA. Consensus statements covered aspects of RA including terminology, goals of treatment, treatment strategies, and biological benchmarks indicating regeneration. Consensus on a statement was defined as ≥75% agreement.

Results
Panelists emphasized the importance of natural, youthful tissue architecture and function including cellular and extracellular components. Replacement of a single biological component was not considered sufficient for an aesthetic treatment to be described as regenerative. Rather, the relative amounts, ratios, types, and organization are important to determine regenerative potential. Calcium hydroxylapatite is an example of an aesthetic injectable with evidence of regenerative capacity, as demonstrated by its ability to improve collagen type I/III ratios as well as induce the production of elastin and proteoglycans, which ultimately improve measures of skin quality.
Estrous cycle regulates cephalic mechanical sensitivity and sensitization of the trigemino-cervical complex in a female rat model of chronic migraine
Authors: Barnet Maxime , Descheemaeker Amelie , Favier Lea , Moisset Xavier , Schopp Julien , Dallel Radhouane , Artola Alain , Monconduit Lenaic , Antri Myriam 
Published: October 2024

Abstract
The higher incidence of migraines in women compared with men has led to the inclusion of female animals in pain research models. However, the critical role of the hormonal cycle is frequently overlooked, despite its clear correlation with migraine occurrences. In this study, we show in a rat model of migraine induced by repeated dural infusions of an inflammatory soup (IS) that a second IS (IS2) injection performed in proestrus/estrus (PE, high estrogen) female rats evokes higher cephalic mechanical hypersensitivities than when performed in metestrus/diestrus (MD, low estrogen) or ovariectomized (OV) rats. This hypersensitivity induced by IS2 correlates with increased c-Fos expression in outer lamina II (IIo) neurons located in the periorbital projection area of the trigemino-cervical complex (TCC), in PE only. Four IS (IS4) repetition induced an enlargement of c-Fos expression in adjacent territories areas in PE, but not MD or OV animals. Unexpectedly, c-Fos expression in locus coeruleus neurons does not potentiate after IS2 or IS4 injections. To examine the impacts of the hormonal cycle on the physiology of lamina IIo TCC neurons, we performed whole-cell patch-clamp recordings. Second inflammatory soup depolarizes neurons in PE and MD but not in OV rats and enhances excitatory synaptic inputs in PE animals to a greater extent compared with MD and OV rats. These findings show that central TCC sensitization triggered by meningeal nociceptor activation and the resulting cephalic hypersensitivity are modulated by the estrous cycle. This highlights the crucial need to account for not just sex, but also the female estrous cycle in pain research.
Time to Ring in the Body Checking, Head Contact, and Suspected Injury Rates in Youth Ringette: A Video-Analysis Study in Youth Ringette and Female Ice Hockey
Authors: Heming Emily E. , Kolstad Ash T. , West Stephen W. , Williamson Rylen A. , Sobry Alexandra J. , Cairo Alexis L. , Dennett Brooke , Russell Kelly , Goulet Claude , Emery Carolyn A. 
Published: October 2024

Objective:
To compare physical contacts (PCs), including head contacts (HCs), suspected concussion, and nonconcussion injury incidence rates between youth ringette and female ice hockey.

Design:
Cross-sectional.

Setting:
Alberta ice arenas.

Participants:
Players participating in 8 U16AA (ages 14-15 years) ringette and 8 U15AA (ages 13-14 years) female ice hockey games during the 2021 to 2022 season.

Assessment of Risk Factors:
Dartfish video-analysis software was used to analyze video recordings.

Main Outcome Measures:
Univariate Poisson regression analyses (adjusted for cluster by team-game, offset by game minutes) were used to estimate PCs (including HCs) and suspected injury (concussion and nonconcussion) and concussion-specific IRs and incidence rate ratios (IRRs) to compare sports. Proportions of all PCs that were body checks (level 4-5 trunk PC) and direct HCs (HC1) penalized were reported.

Results:
Ringette had a 2.6-fold higher rate of body checking compared with hockey (IRR = 2.63, 95% CI: 1.59-4.37). Ringette also had a 2-fold higher rate of HC1 compared with hockey (IRR = 2.08, 95% CI: 1.37-3.16). A 3.4-fold higher rate of suspected injury was found in ringette (IRR = 3.37, 95% CI: 1.40-8.15). There was no significant difference in suspected concussion IRs in ringette compared with hockey (IRR = 1.93, 95% CI: 0.43-8.74). Despite being prohibited in both sports, only a small proportion of body checks (Ringette = 18%; Hockey = 17%) and HC1 (Ringette = 6%; Hockey = 6%) were penalized.

Conclusions:
Higher rates of body checking, HC1, and suspected injuries were found in ringette compared with female ice hockey. Body checking and HC1 were rarely penalized, despite rules disallowing them in both sports. Future research should consider other youth age groups.
“Mini Brain” Appearance in Spinal Metastasis From Type A Thymoma Detected by 18F-FDG PET/CT
Authors: Dong Youwen 
Published: October 2024

Abstract
A 66-year-old man presented with persistent dull pain in the lower back for over 7 months. An expansile lytic lesion in the L4 vertebral body showed a characteristic “mini brain” appearance on MRI, which is highly suggestive of plasmacytoma. 18F-FDG PET/CT scan revealed increased FDG uptake in the L4 lesion, with an additional finding of a mass in the anterior mediastinum that showed mild FDG uptake. Lumbar surgery and complete resection of the anterior mediastinum tumor confirmed spinal metastatic type A thymoma, which was classified as p-T1aN0M1b, stage IVb. The patient’s condition improved postsurgery and chemotherapy, with long-term follow-up necessary due to recurrence risk.
Metastatic Mucinous Adenocarcinoma of Unknown Origin Showing 68Ga-DOTATATE Uptake
Authors: Filizoglu Nuh , Ozguven Salih , Dede Fuat , Turoglu Halil Turgut , Erdil Tanju Yusuf 
Published: October 2024

Abstract
Although the use of 18F-FDG PET/CT is well established in the evaluation of adenocarcinoma, the performance of 18F-FDG PET/CT in mucinous adenocarcinoma is not consistent. 68Ga-DOTATATE uptake can be observed in some non-neuroendocrine tumors as a result of tumor blood flow and somatostatin receptor expression at different levels. For this reason, 68Ga-DOTATATE PET/CT may have a prospective role in the evaluation of mucinous adenocarcinoma. However, there is no published case of mucinous adenocarcinoma with 68Ga-DOTATATE uptake. We present a unique case of metastatic mucinous adenocarcinoma of unknown origin on 68Ga-DOTATATE PET/CT.
Explainable machine-learning model to classify culprit calcified carotid plaque in embolic stroke of undetermined source
Authors: Sakai Yu , Kim Jiehyun , Phi Huy Q , Hu Andrew C , Balali Pargol , Guggenberger Konstanze V , Woo John H , Bos Daniel , Kasner Scott E , Cucchiara Brett L , Saba Luca , Huang Zhi , Haehn Daniel , Song Jae W 
Published: October 2024

AbstractBackgroundEmbolic stroke of undetermined source (ESUS) may be associated with carotid artery plaques with <50% stenosis. Plaque vulnerability is multifactorial, possibly related to intraplaque hemorrhage (IPH), lipid-rich-necrotic-core (LRNC), perivascular adipose tissue (PVAT), and calcification morphology. Machine-learning (ML) approaches in plaque classification are increasingly popular but often limited in clinical interpretability by black-box nature. We apply an explainable ML approach, using noncalcified plaque components and calcification features with SHapley Additive exPlanations (SHAP) framework to classify calcified carotid plaques as culprit/non-culprit.MethodsIn this retrospective cross-sectional study, patients with unilateral anterior circulation ESUS who underwent neck CT angiography and had calcific carotid plaque were analyzed. Calcification-level features were derived from manual segmentations. Plaque-level features were assessed by a neuroradiologist blinded to stroke-side and by semi-automated software. Calcifications/plaques were classified as culprit if ipsilateral to stroke-side. Eight baseline ML models were compared. Three CatBoost models were trained: Plaque-level, Calcification-level, and Combined. SHAP was incorporated to explain model decisions.Results70 patients yielded 116 calcific carotid plaques (60 ipsilateral to stroke; 270 calcifications (146 ipsilateral)). 17 plaque-level and 15 calcification-level features were extracted. Baseline CatBoost model outperformed other models. Combined model achieved test AUC 0.77 (95% CI: 0.59-0.92), accuracy 0.82 (95% CI: 0.71 - 0.91), mean cross-validation AUC 0.78. Plaque-level and calcification-level models performed lower (AUC 0.41 95% CI: 0.15-0.68, 0.60 95% CI 0.44-0.76). Combined model utilized five features: plaque thickness, IPH/LRNC volume ratio, PVAT volume, calcification minimum density, and total calcification volume over mean density ratio. Plaque thickness was most important feature based on SHAP values, with potential threshold at >2.6 mm.ConclusionsML model trained with noncalcified plaque and calcification features can classify culprit calcific carotid plaque with greater accuracy than models trained using only plaque-level or calcification-level features. Model using clinically interpretable features with SHAP framework provides explanations for its decisions and allows identification of potential thresholds for high-risk features.Abstract FigureGraphic AbstractOverall design of our study.
Improving Accuracy of Somatic Mutation Profiling in Large Epidemiologic Studies: Addressing Cases without Matched Normal Samples
Authors: Arora Arshi , Luo Li , Kostrzewa Caroline E. , Reiner Allison , Seshan Venkatraman , Ernstoff Marc S. , Edmiston Sharon N. , Conway Kathleen , Gorlov Ivan , Busam Klaus , Orlow Irene , Hernando Eva , Thomas Nancy E. , Berwick Marianne , Begg Colin B. , Shen Ronglai ,   InterMEL
Published: October 2024

AbstractIdeally, detection of somatic mutations in a tumor is accomplished using a patient-matched sample of normal cells as the benchmark. In this way somatic mutations can be distinguished from rare germline mutations. In large retrospective studies, archival tissue collection can pose challenges in obtaining samples of normal DNA. In this article we propose a protocol that improves somatic mutation analysis in the absence of a matched normal sample. The method was motivated by the InterMEL study, a large-scale epidemiologic investigation involving multiomic, multi-institutional genomic profiling of 1000 primary melanoma samples. The key insight for accomplishing improved mutation calling is the fact that germline mutations should produce a variant allele frequency (VAF) of around 50%. While a similar VAF of 50% would also be expected for somatic mutations in pure tumor samples, typically the tumor purity is much less than 50%, resulting in a considerably lower VAF. Making use of a technique that can simultaneously estimate both tumor purity and VAF from tumor-only samples we have developed a method for better distinguishing somatic versus germline variants. Based on 137 melanomas from the InterMEL Study with matched normal tissue to provide a gold standard we show that the conventional pipeline using a panel of (unmatched) normal samples has a false positive rate of 15.6% and a false negative rate of 3.5%. Our new technique improves these error rates to 6.4% and 2.1%, respectively.
Genetic diversity and population structure of pedunculate oaks (Quercus robur) in Wytham Woods
Authors: Hung Tin Hang , Formaggia Elias , Morley Lucy , Kirby Keith , Salguero-Gómez Roberto , Sheldon Ben C. , MacKay John J. 
Published: October 2024

SummaryGenetic diversity is fundamental for adaptation to changing environments. It is particularly important in forest trees because of their significant role in nature’s contribution to people. However, their genetic diversity has been significantly changed by human activities in the past centuries.This paper investigates a focal site, the Wytham Woods, one of the most researched woodlands on Earth, and presents a population genetic study on pedunculate oaks (Quercus robur), a keystone species in the ecosystem. We characterised 210 trees with Genotyping by Sequencing (GbS) and quantified levels of genetic diversity across stands with different histories and management regimes.We detected only a weak population structure within the 218,567 SNPs, such that most genetic variation occurred within but not among stands, which included semi-natural woodland areas and plantations aged between 200 to 50 years ago. We also observed little difference in observed and expected heterozygosity among stand types, but detected some inbreeding in the youngest plantation. We discovered 26,174 SNPs (11.98%) that were highly differentiated and under potential selection.We suggest that the life history traits of oak contribute to its resistance against genetic erosion, which is also observed in beeches, spruces, and pines. Preference for oaks as a timber tree and the tendency to use local seed source might have resulted in the homogeneous population structure. However, tree-to-tree differences may harbour variation in putative adaptive loci. Our study contributes crucial baseline information on for conservation and management of human-modified woodlands, in addition to supporting long-term ecological studies on many other species, which depend on this keystone oak species.Societal Impact StatementOur study highlights the importance of monitoring and preserving genetic diversity in forest trees, particularly in keystone species like pedunculate oaks. Human activities, including land use changes and forestry practices, could influence their genetic diversity and potentially alter nature’s contribution to people. We demonstrate how understanding the genetic structure of oaks in stands ranging from semi-natural to plantations could (1) shed light on the natural history and the consequence of human activities in Wytham Woods, (2) support the many continuing, long-term ecological studies including adaptational potential in the oak population, and (3) be translated for other co-occurring species and other woodlands for effective genetic monitoring at large.
Cancer-cell-derived cGAMP limits the activity of tumor-associated CD8+T cells
Authors: Herbst Michael , Köksal Hakan , Brunn Silvan , Zanetti Dominik , Domocos Ioana , De Stefani Viola , Pereira Paulo , Nater Marc , Cecconi Virginia , van den Broek Maries 
Published: October 2024

SUMMARYUsing a mouse tumor model with inducible cancer-cell-intrinsic cGAS expression, we show that cancer-cell-derived cGAMP is essential and sufficient to trigger a sustained type I interferon response within the tumor microenvironment. This led to improved CD8+T cell-dependent tumor restriction. However, cGAMP limits the proliferation, survival, and function of STING-expressing but not of STING-deficient CD8+T cells.In vivo, STING deficiency in CD8+T cells enhanced tumor restriction. Consequently, cancer-cell-derived cGAMP both drives and limits the anti-tumor potential of CD8+T cells. Mechanistically, T cell-intrinsic STING is associated with pro-apoptotic and antiproliferative gene signatures. Our findings suggest that STING signaling acts as a checkpoint in CD8+T cells that balances tumor immunity.Graphical abstract
Epistasis and cryptic QTL identified using modified bulk segregant analysis of copper resistance in budding yeast
Authors: Buzby Cassandra , Plavskin Yevgeniy , Sartori Federica M.O. , Tong Qiange , Vail Janessa K. , Siegal Mark L. 
Published: October 2024

AbstractThe contributions of genetic interactions to natural trait variation are challenging to estimate experimentally, as current approaches for detecting epistasis are often underpowered. Powerful mapping approaches such as bulk segregant analysis, wherein individuals with extreme phenotypes are pooled for genotyping, obscure epistasis by averaging over genotype combinations. To accurately characterize and quantify epistasis underlying natural trait variation, we have engineered strains of the budding yeastSaccharomyces cerevisiaeto enable crosses where one parent’s chromosome is fixed while the rest of the chromosomes segregate. These crosses allow us to use bulk segregant analysis to identify quantitative trait loci (QTL) whose effects depend on alleles on the fixed parental chromosome, indicating a genetic interaction with that chromosome. Our method, which we term epic-QTL (forepistatic-with-chromosomeQTL) analysis, can thus identify interaction loci with high statistical power. Here we perform epic-QTL analysis of copper resistance with chromosome I or VIII fixed in a cross between divergent naturally derived strains. We find seven loci that interact significantly with chromosome VIII and none that interact with chromosome I, the smallest of the 16 budding yeast chromosomes. Each of the seven interactions alters the magnitude, rather than the direction, of an additive QTL effect. We also show that fixation of one source of variation — in this case chromosome VIII, which contains the large-effect QTL mapping toCUP1— increases power to detect the contributions of other loci to trait differences.Author SummaryMost traits of interest that vary in populations are determined by multiple genetic factors, as well as by environmental variation and random chance. These influences may combine in complicated ways, for example when the effect of one genetic variant depends on genetic variants elsewhere in the genome. Such dependencies are difficult to identify and characterize because testing many possible combinations of influences reduces statistical power. We address this challenge by combining bulk segregant analysis, a robust method for detecting effects of individual genetic variants averaged across genetic backgrounds, with chromosome fixation in budding yeast. This approach allows us to detect gene-variant effects that depend on the fixed chromosome with statistical power comparable to that achieved when detecting background-independent effects. Applying the approach to copper sulfate resistance, we identify and characterize interaction effects and, by removing one source of variation (a single yeast chromosome), improve detection of background-independent effects as well.
Machine learning models reveal environmental and genetic factors associated with the plant circadian clock
Authors: Reynolds Connor , Colmer Joshua , Rees Hannah , Khajouei Ehsan , Rusholme-Pilcher Rachel , Kudoh Hiroshi , Dodd Antony N. , Hall Anthony 
Published: October 2024

AbstractThe circadian clock of plants contributes to their survival and fitness. However, understanding clock function at the transcriptome level and its response to the environment requires assaying across high resolution time-course experiments. Generating these datasets is labour-intensive, costly and, in most cases, performed under tightly controlled laboratory conditions. To overcome this barrier, we have developed ChronoGauge: an ensemble model which can reliably estimate the endogenous circadian time of plants using the expression of a handful of time-indicating genes within a single time-pointed transcriptomic sample. ChronoGauge can predict a plant’s circadian time with high accuracy across unseenArabidopsisbulk RNA-seq and microarray samples, and can be further applied across samples in non-model species, including field samples. Finally, we demonstrate how ChronoGauge can be applied to test hypotheses regarding the response of the circadian transcriptome to specific genotypes or environmental conditions.