bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformed Follicular Lymphoma: The Role of the Pathologist in Aiding Therapeutic Decision Making
Authors: Pasion Jeremiah , El Chaer Firas , Rapoport Aaron , Dahiya Saurabh , Koka Rima 
Published: September 2023

Abstract
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma. Follicular lymphoma is generally an indolent disorder, and despite being incurable with standard chemotherapy, recent advances in treatment strategies have improved clinical outcomes and survival. Over time, FL could acquire additional genetic mutations and transform into diffuse large B-cell lymphoma, a more aggressive B-cell neoplasm, which markedly reduces survival. Treatment of transformed FL is based on combination chemotherapy and immunotherapy. Rituximab has changed the treatment landscape in FL. However, novel approaches to treatment of transformed FL are in development. Here, we present a case of FL with transformation to diffuse large B-cell lymphoma and review diagnostic modalities along with current and upcoming therapies, many of which require assessment of antigen expression patterns from the pathologist. In particular, we will highlight the role the pathologist plays in management decisions.
Spironolactone Bodies: An Interesting Pathological Phenomenon in Adrenal Aldosteronomas
Authors: Moore Edwina C. , Nguyen Jane , Magi-Galluzzi Cristina , Siperstein Allan 
Published: September 2023

Abstract
This is a case of a patient with Conn syndrome. We present a brief summary of his presentation, diagnostic work-up, operative management, and outcome. The association of spironolactone bodies (S bodies) with the use of spironolactone in patients with Conn syndrome is described. Furthermore, the incidence, pathophysiology, and histological characteristics or S bodies are reviewed. This case is educational as it provides a concise summary of the workup for adrenal aldosteronomas. Additionally, it highlights a rare and poorly understood pathological feature unique to this tumor type. Recognition of S bodies in a surgical specimen adds to diagnostic certainty and may avoid delay in pathological diagnosis or unnecessary investigations postoperatively.
Combined Erdheim-Chester Disease and Langerhans Cell Histiocytosis in the Lung: A Report of 2 Patients With Overlap Syndrome
Authors: Pires Yumay , Jokerst Clinton E. , Panse Prasad M. , Kipp Benjamin R. , Tazelaar Henry D. 
Published: September 2023

Abstract
Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis (LCH) are two rare diseases typically separated by clinical, radiologic, and histologic criteria. However, coexistence of both entities is rare, with fewer than 50 cases reported. Although there are reports of patients with LCH and ECD in the same organ, there have been no reported cases of the two diseases involving the lung. We report two cases of ECD-LCH “overlap syndrome” occurring in the lung. In both cases, the diagnoses were supported by typical immunohistochemical patterns, and in both cases, the BRAF V600E mutation was identified by next-generation sequencing and confirmed by droplet digital polymerase chain reaction. In neither case was either diagnosis suspected. The recognition of overlap histiocytoses is important. Although LCH and ECD may differ in treatment and prognosis, in some cases, such as the two patients reported here, they may have the same activating mutations and may be able to be treated with the same targeted therapy.
Bilateral Multifocal Warthin Tumors Mimicking Metastatic Papillary Thyroid Carcinoma: A Rare Case Posing a Diagnostic Challenge
Authors: Kulkarni Tanvee , Shah Snehal , Rane Swapnil , Mahajan Abhishek , Bal Munita , Vaish Richa , Patil Asawari 
Published: September 2023

AbstractWarthin tumor is the second most common benign tumor of parotid gland. It rarely may be multifocal and occur at extraparotid sites, most common being the cervical lymph nodes. Fine-needle aspirate cytology is diagnostic in most cases of parotid Warthin tumors; however, in extraparotid sites, the diagnosis can be challenging. The difficulty can be further amplified if there is a synchronous lesion in a visceral organ on radiology, raising the suspicion of a metastatic carcinoma. We report an unusual diagnostically challenging case of synchronous, bilateral, multifocal intraparotid and extraparotid Warthin tumors mimicking a metastatic papillary thyroid carcinoma. We also highlight the usefulness of intraoperative consultation in guiding appropriate management in such cases.
Pitfalls and Traps in Neuropathology
Authors: Smith Michael Timothy , Bruner Evelyn T. 
Published: September 2023

Abstract
Impediments to making a correct diagnosis are avoided, and complex administrative efforts are used to make those impediments less frequent. There are quality control procedures, patient safety initiatives, and endless meetings attempting to lessen medical errors. Pitfalls and traps are encountered daily by pathologists, and most are avoided. Artifacts produce traps created by cautery, physical crush, thick sections, and drying and are well known. Appropriate deferral, recuts, stains, and collegial consultations aid in error avoidance in these instances. Neuropathology has some pitfalls and traps that are encountered infrequently especially in the low neuropathology case load environment. Those traps are unfamiliar and treacherous for the unwary pathologist. This review describes five cases each with its special trap.
Delayed Presentation of Sagittal Suture Craniosynostosis
Authors: Modi Rishi N. , Belza Caitlyn C. , Kamel George N. , McKee Ryan M. , Carbullido Mary K. , Gosman Amanda A. 
Published: September 2023

Background
Sagittal craniosynostosis typically presents as dolichocephaly or less frequently as clinocephaly, a “saddle-shaped” phenotype. This project aimed to characterize clinically relevant differences between sagittal synostosis phenotypes and examine the etiology of the delay in presentation.

Methods
An institutional review board–approved retrospective review was performed from January 1999 to November 2018 at a single institution. Analyses examined correlations between subphenotype, time of presentation, minor suture fusion, developmental delay, and operative technique.

Results
One hundred sixty patients diagnosed with single-suture sagittal craniosynostosis were identified. A total of 30.6% had a saddle phenotype (n = 49) and 69.4% had dolichocephaly (n = 111). Patients with the saddle phenotype were more likely to present with a developmental delay and to have at least 1 minor suture fused than patients with dolichocephaly were. Patients with the saddle phenotype presented for surgery at an older age and were more likely to undergo open cranial vault repair, with increased blood loss, higher transfusion volume, and longer time.

Conclusions
This study highlights clinical differences in sagittal craniosynostosis phenotypes and shows that developmental delay is an initial presentation of the saddle phenotype. The saddle phenotype also correlated with fusion of the minor squamous and sphenoid sutures. The link between developmental delay and minor suture fusion was notable and should be explored with a larger sample size. Patients with saddle synostosis present for surgery at an older age than patients with dolichocephaly and therefore are more likely to receive open cranial vault repair, with a taxing intraoperative experience characterized by increased blood loss, increased transfusions, and longer operation time.
Analysis of Readmission and Complications After Repair of Orbital Fractures Using California's Office of Statewide Health Planning and Development Database
Authors: Chopra Christina S. , Neubauer Daniel C. , Hornacek Michael , Calvo Richard Y. , Segal Rachel , Reid Christopher M. , Martin Matthew J. , Gosman Amanda A. 
Published: September 2023

Background
Orbital fractures represent one of the most common trauma-related facial fractures and may present with a variety of concomitant injuries. Many factors including age, associated diagnoses, and fracture complications are important in determining surgical candidacy. We used a statewide database to determine the prevalence of orbital fractures, rates of surgical repair during initial admission, and early patient outcomes.

Methods
A longitudinal analysis of patients with orbital fracture was performed using California's Office of Statewide Health Planning and Development patient discharge database for admissions occurring between January 2015 and December 2018.
Patients were identified using International Classification of Diseases, Tenth Revision codes. The primary risk factor was surgical management of orbital fractures. The primary outcomes of interest were readmission requiring surgical management and complications of the fracture. Survival models were developed to evaluate the risk of a repair at readmission adjusting for relevant covariates.

Results
Of the 67,408 facial fractures included in our study, 8.7% (n = 5872) were diagnosed with orbital fractures. Among this population, 18.4% (n = 1082) underwent surgical repair during their initial admission. Patients were primarily male (71.1%; n = 4,173) and presented in a nonurgent fashion (93.7%; n = 5501). Less than half (42.8%) of patients with an urgent presentation and 16.8% of patients with a nonurgent presentation underwent repair. Centers of Medicaid & Medicare Services guidelines dictated presentation classification. Repair was associated with a significantly higher survival outcome. Orbital fractures were more frequently repaired in the setting of concomitant zygomatic, nasal, and LeFort I–III fractures. Increased risk in complications was observed in all concomitant fracture groups, and there existed a decreased risk of postsurgical complications in these same cohorts.

Conclusions
Although most orbital fractures were managed nonoperatively, our analysis found that rates of repair for orbital floor, maxillary, and zygomatic fractures were greater than for other facial fractures. Concomitant fractures were associated with an increased hazard ratio for complications. Although low in prevalence overall, the most often observed postoperative complications in this population were diplopia, glaucoma, and blindness/low vision.
Elevation, drainage, and spatially heterogeneous vulnerability of tidal marshes to sea level rise
Authors: Qi Man , Gedan Keryn 
Published: September 2023

AbstractMarsh plants regulate marsh surface elevation through organic matter accumulation and sediment capturing, thus feedback loops and relationships between vegetation and marsh elevation form the basis of numerical models that estimate and predict marsh vulnerability to Sea Level Rise (SLR). However, with interior portions of shallow-sloping microtidal marshes suffering much more extensive inundation relative to edge marshes, it is necessary to identify factors in addition to elevation that create spatial heterogeneity in flood vulnerability. Here we studied the influence of drainage on vulnerability of the marsh interior and the marsh edge. Specifically, we compared the deviation ofin situobserved hydrological metrics for surface (hydroperiod, daily inundation duration) and subsurface (soil saturation index, or SSI) soil levels of interior and edge marsh from expected values estimated using elevation and tidal regime alone. We further analyzed the bias that hydrological deviation introduced to marsh vulnerability estimation using growth response curves of typical marsh macrophytes to hydroperiod. We found that the water table fluctuation was attenuated from marsh edge to interior, which resulted in a higher sensitivity of interior marsh to elevation deficiency. At the brim of marsh collapse in the marsh interior, hydroperiod and SSI increased dramatically; they were 20-50% higher than at the same elevation at the marsh edge, which greatly reduces the window of opportunity for interior marsh plant communities to adapt to SLR. Our findings demonstrate the importance of drainage in explaining spatial patterns in vulnerability across the marsh platform, which should be considered in future empirical studies and numerical simulations to develop practical tools for coastal management.
Simultaneous Native Mass Spectrometry Analysis of Single and Double Mutants to Probe Lipid Binding to Membrane Proteins
Authors: Jayasekera Hiruni S. , Mohona Farhana Afrin , Ewbank Megan , Marty Michael T. 
Published: September 2023

AbstractLipids are critical modulators of membrane protein structure and function. However, it is challenging to investigate the thermodynamics of protein-lipid interactions because lipids can simultaneously bind membrane proteins at different sites with different specificities. Here, we developed a native mass spectrometry (MS) approach using single and double mutants to measure the relative energetic contributions of specific residues on Aquaporin Z (AqpZ) toward cardiolipin (CL) binding. We first mutated potential lipid-binding residues on AqpZ, and mixed mutant and wild-type proteins together with CL. By using native MS to simultaneously resolve lipid binding to the mutant and wild-type proteins in a single spectrum, we directly determined the relative affinities of CL binding, thereby revealing the relative Gibbs free energy change for lipid binding caused by the mutation. Comparing different mutants revealed that the W14 contributes to the tightest CL binding site, with R224 contributing to a lower affinity site. Using double mutant cycling, we investigated the synergy between W14 and R224 sites on CL binding. Overall, this novel native MS approach provides unique insights into lipid binding to specific sites on membrane proteins.
Long-read transcript sequencing identifies differential isoform expression in the entorhinal cortex in a transgenic model of tau pathology
Authors: Leung Szi Kay , Jeffries Aaron R , Castanho Isabel , Bamford Rosemary A , Moore Karen , Dempster Emma L , Brown Jonathan T , Ahmed Zeshan , O’Neill Paul , Hannon Eilis , Mill Jonathan 
Published: September 2023

AbstractIncreasing evidence suggests that alternative splicing plays an important role in Alzheimer’s disease (AD), a devastating neurodegenerative disorder involving the intracellular aggregation of hyperphosphorylated tau. We used long-read cDNA sequencing to profile transcript diversity in the entorhinal cortex of wild-type (WT) and transgenic (TG) mice harboring a mutant form of human tau. Whole transcriptome profiling showed that previously reported gene-level expression differences between WT and TG mice reflect changes in the abundance of specific transcripts. Ultradeep targeted long-read cDNA sequencing of genes implicated in AD revealed hundreds of novel isoforms and identified specific transcripts associated with the development of tau pathology. Our results highlight the importance of differential transcript usage, even in the absence of gene-level expression alterations, as a mechanism underpinning gene regulation in the development of neuropathology. Our transcript annotations and a novel informatics pipeline for the analysis of long-read transcript sequencing data are provided as a resource to the community.
Differential evolution of cooperative traits in aggregative multicellular bacteriumMyxococcus xanthusdriven by varied population bottleneck sizes
Authors: Kalathera Jyotsna , Patel Vishwa , Pande Samay 
Published: September 2023

AbstractRepeated population bottlenecks influence the evolution and maintenance of cooperation1,2. However, it remains unclear whether bottlenecks select all cooperative traits expressed by an organism or only a subset of them.Myxococcus xanthus, a social bacterium, displays multiple cooperative traits, including growth, predation, sporulation in multicellular fruiting bodies, and germination3–6. Using laboratory evolution experiment, we investigated the effect of repeated stringent versus relaxed population bottlenecks on the evolution of these four cooperative traits when they were all under selection. We found that only fruiting body formation and growth were positively selected under the stringent regimen, while the other two traits were negatively selected. The pattern was reversed in the relaxed regimen. Additionally, the relaxed regimen led to a significant increase in fitness when competed against ancestors across the entire lifecycle, whereas the stringent treatment did not change competitive fitness. Genomic analysis revealed that mutations in σ54interacting protein and DNA-binding response regulator protein are linked with the changes observed in stringent and relaxed regimens respectively. Further, similar trade-offs are also seen among natural populations ofM. xanthus. Overall, we demonstrate that different bottleneck sizes drive the evolution of lifecycles in distinct manners, driven by trade-offs between cooperative life history traits.
Bayesian analysis of resting-state temporal low-γ power in children with phonemic decoding deficits and certain comorbidities
Authors: Lasnick Oliver , Hancock Roeland , Hoeft Fumiko 
Published: September 2023

AbstractDyslexia (decoding-based reading disorder, or RD) is a common learning disorder affecting a large proportion of the population. One theory of the origins of reading deficits is a language network which cannot effectively ‘entrain’ to speech, with cascading effects on the development of phonological skills. Low-gamma (low-γ, 30-45 Hz) neural activity is thought to correspond to tracking at phonemic rates in speech. The main goals of the current study were to investigate temporal low-γ band-power during rest in a sample of children and adolescents with and without RD. We used a Bayesian statistical approach, which has become increasingly popular in the field for its ability to quantify the relative likelihood of competing hypotheses. We examined whether (1) resting-state temporal low-γ power was attenuated in the left temporal region in those with RD; (2) low-γ power covaried with individual performance in reading skills; (3) low-γ temporal lateralization was atypical in the group with RD. Results did not support the hypothesized effects of RD status and poor phonemic decoding ability on left hemisphere low-γ power or lateralization: post-hoc tests revealed that the lack of atypicality in the RD group was not due to the inclusion of those with comorbid attentional deficits. However, post-hoc tests also revealed a specific left-dominance for low-γ rhythms in the RDs only when participants with attentional deficits were excluded. We also observed an inverse relationship between phonemic decoding and left-lateralization in the controls, such that those with better decoding skills were less likely to show left-lateralization, contrary to our expectations. We discuss these unexpected findings in the context of prior theoretical frameworks on temporal sampling, and suggest that our null findings in resting-state EEG may reflect the importance of real-time language processing to evoke gamma rhythms in the phonemic range during childhood and adolescence.
Tracing endogenous proteins in living cells through electrotransfer of mRNA encoding chromobodies
Authors: Juncker Théo , Richert Ludovic , Masson Murielle , Chatton Bruno , Donzeau Mariel 
Published: September 2023

AbstractChromobodies made of nanobodies fused to fluorescent proteins are powerful tools for targeting and tracing intracellular proteins in living cells. Typically, this is achieved by transfecting plasmids encoding the chromobodies. However, an excess of unbound chromobody relative to the endogenous antigen can result in high background fluorescence in live cell imaging. Here, we overcome this problem by using mRNA encoding chromobodies. Our approach allows one to precisely control the amount of chromobody expressed inside the cell by adjusting the amount of transfected mRNA. To challenge our method, we evaluate three chromobodies targeting intracellular proteins of different abundance and cellular localization, namely lamin A/C, Dnmt1 and actin. We demonstrate that expression of chromobodies in living cells by transfection of tuned amounts of the corresponding mRNAs allows the accurate tracking of their cellular targets by time-lapse fluorescence microscopy.
Autophagy contributes to homeostasis in esophageal epithelium where high autophagic vesicle content marks basal cells with limited proliferation and enhanced self-renewal potential
Authors: Klochkova Alena , Karami Adam L. , Fuller Annie D. , Parham Louis R. , Panchani Surali R. , Natarajan Shruthi , Jackson Jazmyne L. , Mu Anbin , Tan Yinfei , Cai Kathy Q. , Klein-Szanto Andres J. , Muir Amanda B. , Tétreault Marie-Pier , Hamilton Kathryn E. , Whelan Kelly A. 
Published: September 2023

AbstractBackground & AimsAutophagy has been demonstrated to play roles in esophageal pathologies both benign and malignant. Here, we aim to define the role of autophagy in esophageal epithelium under homeostatic conditions.MethodsWe generated tamoxifen-inducible, squamous epithelial-specificAtg7(autophagy related 7) conditional knockout mice to evaluate effects on esophageal homeostasis and response to the carcinogen 4-nitroquinoline 1-oxide (4NQO) using histological and biochemical analyses. We FACS sorted esophageal basal cells based upon fluorescence of the autophagic vesicle (AV)-identifying dye Cyto-ID, then subjected these cells to transmission electron microscopy, image flow cytometry, 3D organoid assays, RNA-Sequencing (RNA-Seq), and cell cycle analysis. 3D organoids were subjected to passaging, single cell (sc) RNA-Seq, cell cycle analysis, and immunostaining.ResultsGenetic autophagy inhibition in squamous epithelium resulted in increased proliferation of esophageal basal cells. Esophageal basal cells with high AV level (Cyto-IDHigh) displayed limited organoid formation capability upon initial plating but passaged more efficiently than their counterparts with low AV level (Cyto-IDLow). RNA-Seq suggested increased autophagy in Cyto- IDHighesophageal basal cells along with decreased cell cycle progression, the latter of which was confirmed by cell cycle analysis. scRNA-Seq of 3D organoids generated by Cyto-IDLowand Cyto- IDHighcells identified expansion of 3 cell populations, enrichment of G2/M-associated genes, and aberrant localization of cell cycle-associated genes beyond basal cell populations in the Cyto- IDHighgroup. Ki67 expression was also increased in organoids generated by Cyto-IDHighcells, including in cells beyond the basal cell layer. Squamous epithelial-specific autophagy inhibition induced significant weight loss in mice treated with 4NQO that further displayed perturbed epithelial tissue architecture.ConclusionsHigh AV level identifies esophageal epithelium with limited proliferation and enhanced self-renewal capacity that contributes to maintenance of the esophageal proliferation- differentiation gradientin vivo.