bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital Solitary Orbital Juvenile Xanthogranuloma. Report of a Case With Challenging Clinical and Microscopic Presentation
Authors: Nassereddine Hussein , Libert Jordan , Baldeschi Lelio , Van Eeckhout Pascal
Published: September 2023

Juvenile xanthogranuloma (JXG) is a benign cutaneous disorder. Extracutaneous mainly ophthalmic involvement is not uncommon, but congenital solitary forms are extremely rare. We report a case of a male newborn presenting for management of a left orbital mass discovered by prenatal ultrasonography. Magnetic resonance showed an orbital mass of 28-mm diameter with 5-mm intracranial extension through an enlarged superior orbital fissure. Fine-needle aspiration cytology and then an open biopsy were performed. Based on the clinical, morphological, immunohistochemical and molecular studies, a diagnosis of congenital solitary orbital JXG was made, and a wait-and-see strategy was decided. Juvenile xanthogranuloma is regarded as the most common form of non-Langerhans cell histiocytoses. Histiocytoses are rare disorders that were broadly divided into 3 categories, but recently a revised classification was proposed with categorization into 5 groups: the “L” (Langerhans) group, the “C” (cutaneous and mucocutaneous) group, the “M” (malignant) group, the “R” (Rosai-Dorfman disease; RDD) group, and the “H” (hemophagocytic lymphohistiocytosis and macrophage activation syndrome) group. In our case, clinical, histopathological, and radiological features along with molecular and immunohistochemical data are consistent with the diagnosis of JXG of the C group. In conclusion, JXG is capable of spontaneous regression, and for this, its management can be conservative.
Diagnostic Dilemma: Atypical Giant Cell Tumor of Bone Versus Primary Giant Cell Sarcoma
Authors: Shannon Tierney A. , Kelly Sean , Krause Katherine , Krauland Kevin J. , Lybeck Dustin
Published: September 2023

Giant cell tumors of bone (GCTBs) are rare tumors that are locally aggressive but benign. Malignant transformation is described after multiple resections, although more commonly after irradiation. However, there exists a rare variant of GCTB that is malignant in nature. We present a case of a 24-year-old man presenting with 6 weeks of thigh pain. Biopsy demonstrated a benign-appearing GCTB, and final pathology after intralesional curettage yielded the same diagnosis. At 12 weeks postoperatively, a biopsy was performed for a recurrence on imaging, and two independent pathologists confirmed a recurrent GCTB. Single-agent chemotherapy was initiated, yet the patient developed an enlarging soft tissue mass at the same location along with new pulmonary nodules. The patient underwent a third biopsy of the thigh mass as well as a pulmonary wedge resection. The diagnosis at this time was primary giant cell sarcoma of bone. The patient subsequently underwent osteosarcoma-based chemotherapy and above-knee amputation. At 14-month follow-up, patient was found to have biopsy-proven recurrent pulmonary metastatic disease. The differential diagnosis for giant cell rich tumors is broad, and it is often difficult to distinguish benign GCTB from their malignant counterparts. The importance of a multidisciplinary approach involving pathology, medical oncology, radiology, and orthopedic surgery is paramount in difficult and rare cases to establish the proper diagnosis and treatment plan.
Unsuspected Cirrhosis-Like Subtype of Hepatocellular Carcinoma in Explanted Liver: A Review
Authors: Gosse Matthew D. , Appelman Henry D.
Published: September 2023

Cirrhosis-like hepatocellular carcinoma is a rare subtype of hepatocellular carcinoma that is mostly diagnosed at time of liver transplantation or autopsy and is not clinically suspected preoperatively or premortem. This entity is characterized by numerous distinct neoplastic foci that arise within regenerative cirrhotic nodules. Knowledge of this subtype of HCC is important for comprehensive examination of explanted and autopsy liver specimens. The clinical presentation, gross, histology, and prognosis are discussed in this review.
ETV6-NTRK3–Positive Inflammatory Myofibroblastic Tumor of the Ileum: Report of an Infantile Case and Review of the Differential Diagnosis of Pediatric Intestinal Polypoid Lesions
Authors: Tanaka Mio , Terada Nanako , Yoshida Misa , Shinkai Masato , Tanaka Yukichi
Published: September 2023

We report a case of an intestinal polyp causing intussusception in a 2-month-old boy. The resected polyp was diagnosed by histology and immunohistochemistry as an anaplastic lymphoma kinase (ALK)–negative inflammatory myofibroblastic tumor (IMT), and the ETS variant 6 (ETV6)–neurotrophic receptor tyrosine kinase 3 (NTRK3) fusion gene was detected by reverse transcription–polymerase chain reaction. Recently, histologically definitive, ALK-negative IMTs possessing the ETV6-NTRK3 fusion gene have been reported. To the best of our knowledge, this is the first case of an intestinal IMT harboring ETV6-NTRK3. In the differential diagnosis of ALK-negative IMTs or spindle cell lesions showing considerably high cellularity, ETV6 rearrangement should be considered.
Unusual Human Papillomavirus–Related Neoplasms of the Head and Neck: A Case Series and Review of Literature
Authors: Devins Kyle M. , Baloch Zubair , LiVolsi Virginia
Published: September 2023

Oropharyngeal squamous cell carcinoma accounts for the majority of human papillomavirus (HPV)–related neoplasms in the head and neck. However, recent studies have identified high-risk HPV in other, clinicopathologically distinct tumors in this region. We report a series of cases involving two unique HPV-mediated neoplasms. Human papillomavirus–related multiphenotypic sinonasal carcinoma is a locally aggressive tumor arising exclusively in the sinonasal tract with pathologic features reminiscent of high-grade adenoid cystic carcinoma. Ciliated adenosquamous carcinoma often presents as a unilateral neck mass and consists of admixed nonkeratinizing squamous cell carcinoma and glandular elements, which may be deceptively bland. Cilia are often present, which are traditionally associated with benignity and may lead to misdiagnosis as a benign branchial cleft cyst. In most cases, an oropharyngeal primary tumor is later identified. Despite aggressive features, both entities have a relatively favorable prognosis. These unusual tumors present unique diagnostic challenges that require particular attention to prevent misdiagnosis and mistreatment.
Clear Cell Tumor of the Maxilla With MAML2 and EWSR1 Gene Rearrangements: A True Hybrid or a Flourescence in Situ Hybridization Fumble?
Authors: Hamza Ameer , Yao Christopher M. K. L. , Lai Stephen Y. , Bell Diana
Published: September 2023

Clear cell odontogenic carcinoma and clear cell variant of mucoepidermoid carcinoma are rare and aggressive tumors that usually affect individuals in the fifth decade of life and have a predilection for the maxilla and mandible. Clear cell odontogenic carcinoma is characterized by EWSR1 gene rearrangement, whereas MAML 2 gene rearrangement is pathognomonic for mucoepidermoid carcinoma. Fluorescence in situ hybridization analysis for rearrangement of these genes can be extremely helpful in difficult cases when conventional histological distinction is not possible. Herein, we describe a unique case in which a 69-year-old man had an intraosseous maxillary tumor with clear cell morphology and fluorescence in situ hybridization analysis showing rearrangement of the MAML2 gene as well as a low-level rearrangement of the EWSR1 gene. In our opinion, this case represents a hybrid tumor harboring dual gene rearrangement.
Langerhans Cell Histiocytosis With Solitary Hepatic Involvement in an Adult Patient: Diagnosis, Transplantation, and Recurrence
Authors: Rush Natalia , Saxena Romil , Lin Jingmei
Published: September 2023

Langerhans cell histiocytosis (LCH) rarely involves the liver without systemic manifestations, especially in adult population. We describe an unusual case of LCH with solitary hepatic involvement. Histopathologic materials from both native and allograft specimens, including all biopsies, explant hepatectomies, and correlating clinical data accumulated over a 10-year interval, were reviewed. A 46-year-old woman presented with jaundice and pruritus. An initial workup including liver biopsy led to the diagnosis of antimitochondrial antibody–negative primary biliary cholangitis with advanced fibrosis. Within a year, the patient progressed to decompensated cirrhosis requiring transplantation. Her posttransplant course was complicated by frequent bouts of markedly elevated alkaline phosphatase and γ-glutamyl transferase with mild liver transaminases elevation. These abnormalities and the liver biopsy findings of bile duct injury and portal inflammation were thought to be acute cellular rejection. Her liver enzymes showed some improvement but never completely normalized on high-dose steroid and became elevated once the therapy stopped. Three years after transplantation, the diagnosis of LCH was established based on the histopathology and immunohistochemistry in the allograft biopsy. Four more years later, the patient lost the liver allograft and required a second transplantation. The explanted allograft revealed patchy distribution of the disease, confirming difficulty of LCH diagnosis on a liver biopsy without systemic involvement. For clinicians and pathologists, it is critical to exclude hepatic involvement by LCH before rending a diagnosis of antimitochondrial antibody–negative primary biliary cholangitis or small duct primary sclerosing cholangitis.
Adamantinoma of the Femur With High-Grade Epithelial and Sarcomatoid Components: Case Report and Review of the Literature
Authors: Sharifai Nima , Runyon R. Scott , Friedman Michael V. , Cipriano Cara A. , Chrisinger John S. A.
Published: September 2023

Adamantinomas are rare low-grade malignant bone tumors that are composed of epithelial cells set in an osteofibrous stroma. Osteofibrous dysplasia-like and classic forms are well known; however, sarcomatous transformation (dedifferentiation) is very rarely observed. We present the case of a 48-year-old woman who presented with a 5-cm proximal femoral lytic lesion at risk of pathologic fracture. Frozen-section evaluation demonstrated an intimate admixture of atypical squamous nests and spindle cells, consistent with metastatic sarcomatoid carcinoma, so prophylactic intramedullary nailing was completed. Postoperative clinical and radiologic evaluation failed to identify a primary carcinoma, and short-term follow-up demonstrated rapid tumor spread throughout the femur and thigh. The patient underwent hip disarticulation, and microscopic examination demonstrated areas of classic adamantinoma associated with both high-grade epithelial and sarcomatoid components. Diffuse metastatic spread was evident within seven months. Along with a description of this case, we review the clinical, radiographic, histologic, and immunophenotypic characteristics of the eight adamantinomas with high-grade sarcomatous transformation that have been previously reported in detail in the English literature, and discuss important considerations for differential diagnosis.
Intrahepatic Mass-Forming Extramedullary Hematopoiesis in a Patient With Sickle Cell Disease: Case Report and Literature Review
Authors: Al-Dalahmah Osama , De Michele Simona , Sperling David C. , O'Toole Kathleen M. , Iuga Alina C.
Published: September 2023

Extramedullary hematopoiesis (EMH) is characterized by the expansion of hematopoietic tissue outside the bone marrow niche. It occurs when bone marrow function is insufficient and typically presents with generalized hepatosplenomegaly. We describe a rare case of mass-forming EMH that presented as two intrahepatic lesions, radiologically well-demarcated and nonenhancing on computed tomography. On magnetic resonance imaging, the lesions appeared T1 hypointense and T2 hyperintense with restricted diffusion. The lesions were discovered at the surgical workup for acute cholecystitis in a patient with previous history notable for sickle cell disease. Given the radiological concern for a neoplastic process, an ultrasound-guided biopsy was performed and diagnosed histologically as EMH. A review of the current literature detailing the common clinical, radiological, and pathological presentation of EMH is provided.
Pancreatic Panniculitis—Not Just a Skin Disease
Authors: Crimmins Jennifer M. , Russell Devin , Samulski Teresa Danielle , Ziemer Carolyn M. , Googe Paul B.
Published: September 2023

Pancreatic panniculitis is a rare sequela of pancreatic disease classically presenting with tender, erythematous subcutaneous nodules involving the lower extremities. Rarer associations include involvement of the marrow, intra-abdominal fat, intrathoracic fat, and the clinical finding of joint pain. We present the case of a patient who presented with a 1-year history of intermittent nausea, bloating, and anorexia with computed tomography scan findings of a complex pancreatic cystic lesion, omental findings concerning for carcinomatosis, and ascites. She developed tender, erythematous, and hyperpigmented subcutaneous nodules on bilateral lower extremities that were first noted on admission. Pancreatic biopsy revealed pancreatic pseudocyst and laboratory findings on admission were consistent with pancreatitis and pancreatic ascites. Laparoscopic omental biopsies revealed multifocal, nodular fat necrosis and associated inflammation with no carcinoma identified. Histologically similar to the omental biopsies, a punch biopsy of skin revealed lobular fat necrosis, inflammation, and basophilic stippling by calcium consistent with pancreatic panniculitis. Given the similar histologic findings in the skin and omentum in the setting of pancreatic ascites, her omental findings were attributed to pancreatic panniculitis. This case highlights the importance of recognizing that pancreatic panniculitis can present as a systemic disorder. We highlight the laparoscopic, dermatologic, laboratory, and biopsy findings of pancreatic panniculitis to demonstrate that the pathologic findings are similar in the various organs involved.
Glial Tumors
Authors: Welsh Cynthia
Published: September 2023

Glial tumors comprise the majority of primary intra-axial intracranial tumors. Since its introduction in 2016, the revised fourth edition of the World Health Organization (WHO) classification of central nervous system tumors has changed the diagnostic and therapeutic approach in glial tumors (WHO Classification of Tumours of the Central Nervous System [revised fourth edition]; Lyon, France: IARC; 2016). Diffuse gliomas (WHO grades II–IV) are now molecularly stratified based on isocitrate dehydrogenase 1 or 2 mutation status and classified according to 1p/19q codeletion status into astrocytic or oligodendroglial type. Updates now occur faster than new editions of the WHO classification can be prepared, so updates are being issued by way of journal articles from a Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (Brain Pathol 2019;29(4):469–472).
A Posterior Fossa Mass in a 6-Year-Old
Authors: Baker Tiffany G. , Smith Michael T.
Published: September 2023

Medulloblastoma is a high-grade embryonal tumor of the central nervous system arising in the infratentorium of patients of all ages with a peak incidence in childhood. Within the last decade, advances in molecular profiling of gene expression and epigenetics have advanced general understanding of previously perceived intertumoral heterogeneity. Currently, 4 subtypes of medulloblastoma are recognized: wingless (WNT)–activated, sonic hedgehog (SHH)–activated, and the non-WNT/non-SHH group, which combines groups 3 and 4. The new subgroups, which continue to evolve, have greatly complicated the process of rendering a pathologic diagnosis through integration of histopathologic and molecular data. The criterion-standard techniques for identifying these subgroups include gene expression and methylation profiling; however, such complicated and expensive laboratory techniques may not be accessible to all laboratories. Although recommendations for the approach to an integrated diagnosis have been made, no specific algorithm has been put forth. We present a case of pediatric medulloblastoma in which hematoxylin-eosin–stained tissue sections, reticulin special stain, immunohistochemistry, cytogenetics, and next-generation sequencing were implemented for the purpose of identifying subgroup and other markers of prognosis, such as TP53 mutation and MYC family member amplification. The discussion herein is aimed at reviewing current opinions on the integration of histomorphologic and molecular subgroups of medulloblastoma and providing a foundation for designing a practical and clinically meaningful approach to diagnosis.
Mass in the Meninges: Meningioma Types and Grades
Authors: Han Pengcheng , Smith Michael T.
Published: September 2023

Tumors of the meninges are common, probably the most common tumor of the cranial vault. Meningiomas arise from the arachnoid, but because the arachnoid and dura are frequently fused, they may appear to be of dural origin. Meningiomas frequently arise from the arachnoid cap cells, which are arachnoidal projections into dural sinuses for reabsorption of cerebrospinal fluid. This explains the frequency of meningiomas found along the dural sinuses. Meningiomas are considered benign, but recurrences are common. More frequent recurrences are found with the higher grades. Complete surgical removal is associated with a good prognosis. One study showed 20% recurrences within 20 years for meningiomas as a group (Surg Neurol 1986 26:461–469). Prognosis is closely related to surgical resection and tumor grade. This review summarizes grading in three case presentations.
A “Double-Hit” Translocation Sarcoma—First Report of the Co-occurrence of EWSR1-FLI1 and MTMR2-NTRK2 Fusion in a Small Round Blue Cell Sarcoma
Authors: Vargas Ana Cristina , Kurek Caroline , Bonar Fiona , Maclean Fiona , Qiu Min Ru , Boyle Richard , Brookwell Ross , Gill Anthony J.
Published: September 2023

We report a case of a 51-year-old man with primary diagnosis of Ewing sarcoma confined to the soft tissue, associated with EWSR1-FLI1 gene fusion demonstrated by fluorescence in situ hybridization (FISH). Six years after the diagnosis, immunohistochemistry for NTRK (neurotrophic receptor tyrosine kinase 1–3) was performed on this tumor using 2 Pan-Trk rabbit monoclonal antibodies, A7H6R (Cell Signaling Technology, Danvers, Mass) and EPR17341 (Abcam, Cambridge, Mass). Both clones showed diffuse moderate to strong cytoplasmic expression including presence of nuclear stain. RNA sequencing demonstrated the co-occurrence of MTMR2-NTRK2, a novel gene fusion, in the same tumor block used for EWSR1 FISH testing. While FISH for NRK2 did not confirm gene rearrangement, an atypical signal pattern was identified. This case challenges the concept that NTRK fusions are mutually exclusive with other oncogenic drivers. The clinical course of this patient has also been unusual as the tumor has followed an indolent course with no evidence of recurrent or metastatic disease.
High-Grade Gliomas in Early Adulthood: A Case-Based Review of Current Molecular Diagnostic Considerations
Authors: Canbeldek Leyla , Ames Heather M.
Published: September 2023

High-grade gliomas in early adulthood (between the ages of 20 and 40 years) have a wide differential diagnosis that includes entities from childhood and late adulthood. These gliomas are increasingly defined by their molecular signatures, requiring a molecular-based workup that is informed by morphology and anatomy. Here we present four cases with four different diagnoses, some rare and some common, presenting with new brain lesions. This diagnostic process is informed by the 2016 World Health Organization guidelines, c-IMPACT Now updates, and the clinico-pathologic features shown by these high-grade tumors. Particularly, we focus on practical diagnostic decisions that may need to be made with limited tissue and/or limited on-site molecular resources.
The Tale of Two Hedgehogs: Central Nervous System Embryonal Tumor Diagnosis in 3 Acts
Authors: Drake Rosanna F. , Ames Heather M.
Published: September 2023

Primitive embryonal tumors of the central nervous system have undergone considerable evolution in their categorization in the past century—most rapidly in the past decade with the application of molecular pathology in diagnosis. This presents numerous practical considerations when encountering one of these tumors. One may need to utilize multiple techniques to come to a prognostically accurate and actionable diagnosis. We review two cases, both with the final diagnosis of “medulloblastoma, SHH activated and TP53 wild type (World Health Organization grade IV).” These diagnoses were each arrived upon using separate, valid approaches, with consideration of the histological differential diagnosis. Immunohistochemistry, next-generation sequencing, and methylation array analysis are each presented with practical considerations of when they are most useful.
When the Horse Has Stripes: Central Nervous System Blastomycosis Presenting as a Ring-Enhancing Lesion in an Immunocompetent Patient
Authors: Hardy Naomi , Markidan Janina , Luethy Paul M. , Ames Heather M.
Published: September 2023

A new, single, ring-enhancing lesion in the cortex of an immunocompetent individual has a broad differential diagnosis, although primary or metastatic malignancies are usually highest on the list. The presence of inflammation without overt malignancy, however, is cause for considerations that may require ancillary testing with fresh tissue and obtaining multiple frozen samples. Central nervous system (CNS) infection with blastomycosis is a rare but potentially fatal complication, with a mortality rate approaching 20% secondary to multiple factors including delay in presentation and diagnosis (Clin Infect Dis 2010;50:797–804). What makes CNS blastomycosis so difficult to diagnose, along with other rare fungal infections, is that it can masquerade as a primary neural tumor. Infectious etiologies should always be considered in ring-enhancing lesions that show inflammation, necrosis, and no significant glial atypia on frozen section. Here we describe a case in an otherwise healthy woman, who presented with seizures and was found to have a peripherally enhancing intraparenchymal lesion on imaging. Differential diagnosis, frozen-section management, histology, and microbiology in the workup of CNS blastomycosis are discussed.
Application of Antibiotic-Impregnated Polymethyl-Methacrylate Bone Cement for the Treatment of Infected Cranioplasties
Authors: Englar Kevin M. , Kordahi Anthony M. , Brandel Michael G. , Santiago-Dieppa David R. , Wali Arvin R. , Pham Martin , Barba David , Ciacci Joseph , Rechnic Mark
Published: September 2023

Background

Management of infected cranioplasty implants remains a surgical challenge. Surgical debridement, removal of the infected implant, and prolonged antibiotic therapy are part of the acute management. In addition, cranioplasty removal poses the risk of dural tear. Reconstruction of the cranial defect is usually delayed for several months to years, increasing the difficulty due to soft tissue contraction and scarring.

Objective

The aim of the study was to propose an alternative to delayed reconstruction in the face of infection with a dual purpose: treat the infection with a material which delivers antibiotic to the area (polymethyl-methacrylate antibiotic) and which functions as a temporary or permanent cranioplasty.

Methods

We reviewed the records of 3 consecutive patients who underwent single-stage polymethyl-methacrylate antibiotic salvage cranioplasty.

Results

All patients underwent debridement of infected tissue. Titanium mesh was placed over the bony defect. Polymethyl methacrylate impregnated with vancomycin and tobramycin was then spread over the plate and defect before closure. Patients also received extended treatment with systemic antimicrobials. Early outcomes have been encouraging for both cosmesis and treatment of infection.

Conclusions

Benefits of this treatment strategy include immediate reconstruction rather than staged procedures and delivery of high concentrations of antibiotics directly to the affected area in addition to systemic antibiotics.
Tissue Expander-Assisted Component Separation for Pediatric Abdominal Wall Reconstruction
Authors: Segal Rachel Marie , Wong Alvin , Zaldana-Flynn Michelle , Englar Kevin , Ewing Emily , Lance Samuel H. , Gosman Amanda A.
Published: September 2023

Background

Tissue expander-assisted component separation can be used to increase the amount of skin, muscle, and fascial components available for repair of congenital abdominal wall defects via a staged approach without the need for flap reconstruction. We present the largest case series to date using a tissue expander-assisted component separation technique for treatment of congenital abdominal wall defects in a pediatric patient population.

Methods

A retrospective chart review of 9 patients with large congenital abdominal wall defects not initially amenable to primary repair between 2009 and 2020 was performed. Patients first underwent placement of tissue expanders, followed by removal once they had reached a sufficient expander volume. Component separation, with and without mesh placement, was performed to achieve abdominal wall closure.

Results

The average age of patients at primary repair was 3.2 years (SD ±1.7 years). Eight patients (88.8%) had congenital omphalocele, and 1 patient (11.1%) had gastroschisis; none were amenable to primary repair. The average size of the defects before closure was 87.6 cm2 (SD = 33.6 cm2). Eighteen tissue expanders were placed in 9 patients, 72.2% of which were placed in the plane between the external and internal oblique muscles. Patients were seen in clinic an average of 6.8 times (SD, ±3.3 visits) for volume expansion into the tissue expander, receiving an average of 32.0 mL in each per visit. An average of 4.3 months (SD, ±1.8 months) elapsed between placement and removal of the expanders. At the time of tissue expander removal and abdominal wall closure, the defects ranged from 30 to 132 cm2 (mean, 54 cm2). All defects were successfully repaired using a component separation and bilateral fasciocutaneous flap advancement. Two patients (18.2%) experienced infection of the surgical site and seroma, both of which required debridement. One patient (9.1%) experienced partial thickness skin necrosis that was managed nonsurgically. The overall complication rate was 36.4%.

Conclusions

Omphalocele and gastroschisis can produce abdominal wall defects that are not amenable to primary repair. Staged reconstruction using tissue expander-assisted component separation is a safe and effective method of obtaining adequate local soft tissue to achieve primary closure.
Using the Disruptive Score to Identify Publications That Changed Plastic Surgery Practice
Authors: Neubauer Daniel C. , Blum Jessica D. , Labou Stephanie G. , Heskett Karen M. , Calvo Richard Y. , Reid Christopher M. , Martin Matthew J. , Gosman Amanda A.
Published: September 2023

Purpose

The impact of academic publications is often characterized by the total number of future citations. However, this metric does not adequately characterize the true impact in terms of changing practices or paradigms. A new metric called the “disruption score” (DS) has been developed and validated in nonsurgical publications. This study aims to use the DS to identify the most disruptive publications in plastic surgery.

The DS, a ratio of 2 numbers, varies between −1 and +1. Scores closer to −1 are developing papers that summarize the known literature while papers closer to +1 are disruptive—they result in a paradigm shift in the field of study.

Methods

A search was performed for all articles from 1954 to 2014 in the following journals: Plastic and Reconstructive Surgery; Aesthetic Surgery Journal; Journal of Plastic, Reconstructive, and Aesthetic Surgery; Annals of Plastic Surgery; Aesthetic Plastic Surgery; Clinics in Plastic Surgery; and Plastic Surgery. The disruptive score was calculated for each article.

The top 100 papers ranked by DS were examined and any editorials/viewpoints, publications with less than 26 citations, or less than 3 references were excluded because of their subjective nature and smaller academic contribution. The remaining 64 publications were analyzed for topic, study type, and citation count.

Results

A total of 32,622 articles were found with a DS range from 0.385 to 0.923. The mean score of the top 64 articles was 0.539 with an average citation count of 195 and 9 references. Plastic and Reconstructive Surgery had the most disruptive papers with 50. There were no randomized controlled trials with a majority of the studies being technical descriptions or case series.

Conclusions

There are many ways to measure academic success, but there are fewer ways to measure the impact of academic contributions. The DS is a novel measurement that can demonstrate when an article results in a paradigm shift as opposed to just total citation count. When applied to the plastic surgery literature, the DS demonstrates that technical innovation and creativity are the most academically impactful. Future evaluations of academic success should include the DS to measure the quality of academic contributions.
Land use configuration shapes climate change risk to gallery forests in a savannah ecosystem
Authors: Schulte to Bühne Henrike , Tobias Joseph A. , Durant Sarah M. , Pettorelli Nathalie
Published: September 2023

Interactions between anthropogenic pressures make it difficult to predict biodiversity change and plan conservation interventions. Climate change is expected to drive widespread ecological change in the tropics over the coming decades, but it is unclear where and when these changes are going to intensify, or reduce, the impacts of additional pressures from human land use. To address this uncertainty, we apply a novel risk assessment framework to show how land use configuration modifies risks arising from climate change to gallery forests, an important vegetation type in tropical savannahs. Our analysis shows that the spatial distribution of climate change (specifically, change in annual rainfall) interacts with the spatial distribution of land use (specifically, cropland), as well as the biophysical context of the study site (the W-Arly-Pendjari transboundary protected area in West Africa), to shape the risk that changes in rainfall pose to gallery forests in the region. Due to the pathways by which rainfall change and land use interact, risks are especially elevated in core protected areas, warranting particular attention from conservation managers. Overall, our work illustrates how unexpected patterns in risks can arise through interactions between pressures on biodiversity, highlighting the importance of considering mechanistic pathways for predicting biodiversity outcomes under multifacetted global environmental change.
TSWIFT, a novel method for iterative staining of embedded and mounted human brain sections
Authors: Porter Corey M , Truttmann Matthias C.
Published: September 2023

Comprehensive characterization of protein networks in mounted brain tissue represents a major challenge in brain and neurodegenerative disease research. In this study, we develop a simple staining method, called TSWIFT, to iteratively stain pre-mounted formalin fixed, paraffin embedded (FFPE) brain sections, thus enabling high-dimensional sample phenotyping. We show that TSWIFT conserves tissue architecture and allows for relabeling a single mounted FFPE sample more than 10 times, even after prolonged storage at 4 °C. Using TSWIFT, we profile the abundance and localization of the HSP70 family chaperones HSC70 (HSPA8) and BiP (HSPA5) in mounted human brain tissue. Our results establish TSWIFT as an efficient method to obtain integrated high-dimensional knowledge of cellular proteomes by analyzing mounted FFPE human brain tissue.
NSD1 supports cell growth and regulates autophagy in HPV-negative head and neck squamous cell carcinoma
Authors: Topchu Iuliia , Bychkov Igor , Gursel Demirkan , Makhov Petr , Boumber Yanis
Published: September 2023

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Despite advances in therapeutic management and immunotherapy, the five-year survival rate for head and neck cancer remains at ∼66% of all diagnosed cases. A better definition of drivers of HPV-negative HNSCC that are targetable points of tumor vulnerability could lead to significant clinical advances. NSD1 is a histone methyltransferase which catalyzes histone H3 lysine 36 di-methylation (H3K36me2); mutations inactivating NSD1 have been linked to improved outcomes in HNSCC. In this study, we show that NSD1 induces H3K36me2levels in HNSCC, and that the depletion of NSD1 reduces HNSCC of cell growthin vitroandin vivo. We also find that NSD1 strongly promotes activation of the Akt/mTORC1 signaling pathway. NSD1 depletion in HNSCC induces an autophagic gene program activation, causes accumulation of the p62 and LC3B-II proteins, and decreases the autophagic signaling protein ULK1 at both protein and mRNA levels. Reflecting these signaling defects, knockdown of NSD1 disrupts autophagic flux in HNSCC cells. Taken together, these data identify positive regulation of Akt/mTORC1 signaling and autophagy as novel NSD1 functions in HNSCC, suggesting that NSD1 may be of value as a therapeutic target in this cancer.
Cardiomyocyte-specific Loss of Glutamyl-prolyl-tRNA Synthetase Leads to Disturbed Protein Homeostasis and Dilated Cardiomyopathy
Authors: Wu Jiangbin , Hollinger Jared , Bonanno Emily , Jiang Feng , Yao Peng
Published: September 2023

Glutamyl-prolyl-tRNA synthetase (EPRS1), an aminoacyl-tRNA synthetase (ARS) ligating glutamic acid and proline to their corresponding tRNAs, plays an essential role in decoding proline codons during translation elongation. The physiological function of EPRS1 in cardiomyocytes (CMs) and the potential effects of CM-specific loss of EPRS1 remain unknown. Here, we found that heterozygousEprs1knockout in CMs does not cause any significant changes in CM hypertrophy induced by pressure overload, while homozygous knockout leads to dilated cardiomyopathy, heart failure, and lethality at around 1 month afterEprs1deletion. Transcriptomic profiling of early-stageEprs1knockout hearts suggests a significantly decreased expression of multiple ion channel genes and an increased gene expression in proapoptotic pathways and integrated stress response. Proteomic analysis shows decreased protein expression of multi-aminoacyl-tRNA synthetase complex components, fatty acid, and branched-chain amino acid metabolic enzymes, as well as a compensatory increase in cytosolic translation machine-related proteins. Immunoblot analysis indicated that multiple proline-rich proteins were reduced at the early stage, which might contribute to cardiac dysfunction ofEprs1knockout mice. Taken together, this study demonstrates the physiological and molecular outcome of loss-of-function of EPRS1in vivoand provides valuable insights into the potential side effects on CMs resulting from the EPRS1-targeting therapeutic approach.
Bering:joint cell segmentation and annotation for spatial transcriptomics with transferred graph embeddings
Authors: Jin Kang , Zhang Zuobai , Zhang Ke , Viggiani Francesca , Callahan Claire , Tang Jian , Aronow Bruce J. , Shu Jian
Published: September 2023

Single-cell spatial transcriptomics such asin-situhybridization or sequencing technologies can provide subcellular resolution that enables the identification of individual cell identities, locations, and a deep understanding of subcellular mechanisms. However, accurate segmentation and annotation that allows individual cell boundaries to be determined remains a major challenge that limits all the above and downstream insights. Current machine learning methods heavily rely on nuclei or cell body staining, resulting in the significant loss of both transcriptome depth and the limited ability to learn latent representations of spatial colocalization relationships. Here, we proposeBering, a graph deep learning model that leverages transcript colocalization relationships for joint noise-aware cell segmentation and molecular annotation in 2D and 3D spatial transcriptomics data. Graph embeddings for the cell annotation are transferred as a component of multi-modal input for cell segmentation, which is employed to enrich gene relationships throughout the process. To evaluate performance, we benchmarkedBeringwith state-of-the-art methods and observed significant improvement in cell segmentation accuracies and numbers of detected transcripts across various spatial technologies and tissues. To streamline segmentation processes, we constructed expansive pre-trained models, which yield high segmentation accuracy in new data through transfer learning and self-distillation, demonstrating the generalizability ofBering.
A multivariate outcome test of covariance
Authors: Boetto Christophe , Frouin Arthur , Henches Léo , Auvergne Antoine , Suzuki Yuka , Patin Etienne , Bredon Marius , Chiu Alec ,   Milieu Interieur Consortium, Sankararaman Sriram , Zaitlen Noah , Kennedy Sean P. , Quintana-Murci Lluis , Duffy Darragh , Sokol Harry , Aschard Hugues
Published: September 2023

Multivariate analysis is becoming central in studies investigating high-throughput molecular data, yet, some important features of these data are seldom explored. Here, we present MANOCCA (Multivariate Analysis of Conditional CovAriance), a powerful method to test for the effect of a predictor on the covariance matrix of a multivariate outcome. The proposed test is by construction orthogonal to tests based on the mean and variance, and is able to capture effects that are missed by both approaches. We first compare the performances of MANOCCA with existing correlation-based methods and show that MANOCCA is the only test correctly calibrated in simulation mimicking omics data. We then investigate the impact of reducing the dimensionality of the data using principal component analysis when the sample size is smaller than the number of pairwise covariance terms analysed. We show that, in many realistic scenarios, the maximum power can be achieved with a limited number of components. Finally, we apply MANOCCA to 1,000 healthy individuals from the Milieu Interieur cohort, to assess the effect of health, lifestyle and genetic factors on the covariance of two sets of phenotypes, blood biomarkers and flow cytometry-based immune phenotypes. Our analyses identify significant associations between multiple factors and the covariance of both omics data.
Integrated genomics provides insights for the evolution of the polyphosphate accumulation trait ofCa.Accumulibacter
Authors: Xie Xiaojing , Deng Xuhan , Chen Liping , Yuan Jing , Chen Hang , Wei Chaohai , Liu Xianghui , Wuertz Stefan , Qiu Guanglei
Published: September 2023

CandidatusAccumulibacter plays a major role in enhanced biological phosphorus removal (EBPR), but the key genomic elements in metagenome assembled genomes enabling their phosphorus cycling ability remain unclear. Pangenome analyses were performed to systematically compare the genomic makeup ofCa.Accumulibacter and non-Ca. Accumulibacter members within the Rhodocyclaceae family. Metatranscriptomic analyses of an enrichment culture ofCa.Accumulibacter clade IIC strain SCUT-2 were performed to investigate gene transcription characteristics in a typical anaerobic-aerobic cycle. Two hundred ninety-eight core genes were shown to be obtained byCa.Accumulibacter at their least common ancestor. One hundred twenty-four of them were acquired via horizontal gene transfer (HGT) based on best-match analysis against the NCBI database. Fourty-four laterally derived genes were actively transcribed in a typical EBPR cycle, including the polyphosphate kinase 2 (PPK2) gene. Genes in the phosphate regulon (Pho) were poorly transcribed. Via a systematical analysis of the occurrences of these genes in closely relatedDechloromonas-polyphosphate accumulating organisms (PAOs) andPropionivibrio-non-PAOs, a Pho dysregulation hypothesis is proposed to explain the mechanism of EBPR. It states that the PhoU acquired by HGT fails in regulating the high-affinity phosphate transport (Pst) system. To avoid phosphate poisoning, the laterally acquired PPK2 is employed to condense excess phosphate into polyphosphate. Alternatively, genes encoding PhoU and PPK2 are obtained from different donor bacteria, leading to unmatched phosphate concentration thresholds for their activation/inactivation. PPK2 tends to reduce the intracellular phosphate to concentration levels perceived by PhoU as low-phosphate states. PhoU is not activated to turn off the Pst system, resulting in continuous phosphate uptake. In conclusion, based on integrated genomic analyses, the HGT ofphoU andppk2 and the resultant Pho dysregulation may have triggered the development and evolution of the P cycling trait inCa.Accumulibacter.
Distinct T Cell Receptor (TCR) gene segment usage and MHC-restriction between foetal and adult thymus
Authors: Rowell Jasmine , Lau Ching-In , Ross Susan , Yanez Diana C. , Peña Oscar A. , Chain Benny , Crompton Tessa
Published: September 2023

Here we sequenced rearranged TCRβ and TCRα chain sequences in CD4+CD8+ double positive (DP), CD4+CD8-single positive (SP4) and CD4-CD8+ (SP8) thymocyte populations from the foetus and young adult mouse. We found that life-stage had a greater impact on TCRβ and TCRα gene segment usage than cell-type. Foetal repertoires showed bias towards 3’TRAV and 5’TRAJ rearrangements in all populations, whereas adult repertoires used more 5’TRAV gene segments, suggesting that progressive TCRα rearrangements occur less frequently in foetal DP cells. When we synchronised young adult DP thymocyte differentiation by hydrocortisone treatment the new recovering DP thymocyte population showed more foetal-like 3’TRAV and 5’TRAJ gene segment usage. In foetus we identified less influence of MHC-restriction on α-chain and β-chain combinatorial VxJ usage and CDR1xCDR2 (V region) usage in SP compared to adult, indicating weaker impact of MHC-restriction on the foetal TCR repertoire.

The foetal TCRβ repertoire was less diverse, less evenly distributed, with fewer non-template insertions, and all foetal populations contained more clonotypic expansions than adult. The differences between the foetal and adult thymus TCR repertoires are consistent with the foetal thymus producing αβT-cells with properties and functions that are distinct from adult T-cells: their repertoire is less governed by MHC-restriction, with preference for particular gene segment usage, less diverse with more clonotypic expansions, and more closely encoded by genomic sequence.
Breeding alters females’ social positions by changing dominance dynamics
Authors: Dehnen Tobit , Nyaguthii Brendah , Cherono Wismer , Boogert Neeltje J. , Farine Damien R.
Published: September 2023

Agonistic and affiliative interactions with group members dictate individuals’ access to resources, and investment in competing for resources is often traded off with other needs. For example, reproductive investment can reduce body condition and, thereby, an individual’s ability to win future agonistic interactions. However, group members may also alter their behaviour towards reproductive individuals, such as becoming more or less aggressive. Here, we investigated the social consequences of reproduction in female vulturine guineafowlAcryllium vulturinum, a plural breeder in which females disperse and are subordinate to males. We found opposing patterns for breeders’ within- and between-sex dominance interactions from before to after breeding. Specifically, while breeding females became far less likely to win dominance interactions with non-breeding females after breeding than before breeding, they received considerably fewer male aggressions than non-breeding females after breeding. Using agent-based models, we then show that hierarchies inferred using the Percolation and Conductance method are robust to such variation in interaction rates, while other common methods may be prone to systematically overestimating or underestimating particular individuals’ hierarchy positions. Our study highlights reproduction as a driver of dominance dynamics, and illustrates how the study of dominance may benefit from considering variation in interaction rates.
Phosphatidylinositol (PI) Lipids Modulate the Binding of Tau Fibrils on Lipid Bilayers
Authors: Chowdhury Unmesh D. , Paul Arnav , Bhargava B. L.
Published: September 2023

Phosphatidylinositol (PI) lipids play a crucial role as a vital lipid component in cell membrane domain formation, contributing to cell signaling. In this study, we investigate the impact of PI lipids on the conformational dynamics of tubulin-associated unit (tau) fibrils through multiscale modelling. While prior experimental work by the Lecomte group has demonstrated the influence of PI lipids on the morphology and secondary structure of tau fragments, a detailed molecular understanding of the binding mechanism between tau and PI-incorporated lipids remains absent. Our molecular dynamics (MD) simulations reveal the intricate molecular mechanisms governing tau binding to PI-incorporated bilayers. Specifically, we conduct MD simulations on lipid patches containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (PC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (PG), enabling us to explore conformational changes in the R3–R4 section of tau fibrils. Control simulations are conducted on pure lipid patches without tau fibrils, as well as on tau fibrils within bulk water. Our findings demonstrate that PI-incorporated lipids exhibit a stronger affinity for binding to tau fibrils compared to pure PC/PG lipids. All-atom simulations highlight the potential docking sites for PI headgroups at positively charged residues (Lysine, Arginine) on the tau surface. Moreover, the aggregation of PI lipids facilitates tau binding to the membrane. These results not only enhance our comprehension of the disruption of PI-incorporated bilayers, but also shed light on the stability of the tau over the PI containing bilayers.
PMTPred: Machine Learning Based Prediction of Protein Methyltransferases using the Composition of k-spaced Amino Acid Pairs
Authors: Yadav Arvind Kumar , Gupta Pradeep Kumar , Singh Tiratha Raj
Published: September 2023

Protein methyltransferases (PMTs) are a group of enzymes that help to catalyze the transfer of a methyl group to its substrates. These enzymes play an important role in epigenetic regulation and are able to methylate various substrates with DNA, RNA, protein, and smallmolecule secondary metabolites. Dysregulation of methyltransferases is involved in different types of human cancers. However, in light of the well-recognized significance of PMTs, it becomes crucial to have reliable and fast methods for identifying these proteins. In the present work, we propose a machine-learning-based method for the identification of PMTs. Various sequence-based features were calculated and prediction models were develped using different machine-learning methods. A ten-fold cross-validation technique was used for model training. The SVM-based CKSAAP model gave the best prediction and achieved the highest accuracy of 87.94% with balance sensitivity (88.8%) and specificity (87.11%) with MCC of 0.759 and AUROC of 0.945. Also, SVM performed better than the compared deep learning algorithms for the prediction of PMTs. Finally, the best model was implemented in standalone software of PMTPred to facilitate the prediction of PMTs. The PMTPred achieved 86.50% prediction accuracy with 82.33% sensitivity, 90.67% specificity and ROC value 0.939 on the blind dataset. The standalone software of PMTPred is freely available for download athttps://github.com/ArvindYadav7/PMTPredfor research and academic use.