bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lagrange-NG: The next generation of Lagrange
Authors: Bettisworth Ben , Smith Stephen A , Stamatakis Alexandros 
Published: January 2023

Abstract
Computing ancestral ranges via the Dispersion Extinction and Cladogensis (DEC) model of biogeography is characterized by an exponential number of states relative to the number of regions considered. This is because the DEC model requires computing a large matrix exponential, which typically accounts for up to 80% of overall runtime. Therefore, the kinds of biogeographical analyses that can be conducted under the DEC model are limited by the number of regions under consideration. In this work, we present a completely redesigned efficient version of the popular tool Lagrange which is up to 49 times faster with multithreading enabled, and is also 26 times faster when using only one thread. We call this new version Lagrange-NG (Lagrange-Next Generation). The increased computational efficiency allows Lagrange-NG to analyze datasets with a large number of regions in a reasonable amount of time, up to 12 regions in approximately 18 min. We achieve these speedups using a relatively new method of computing the matrix exponential based on Krylov subspaces. In order to validate the correctness of Lagrange-NG, we also introduce a novel metric on range distributions for trees so that researchers can assess the difference between any two range inferences. Finally, Lagrange-NG exhibits substantially higher adherence to coding quality standards. It improves a respective software quality indicator as implemented in the SoftWipe tool from average (5.5; Lagrange) to high (7.8; Lagrange-NG). Lagrange-NG is freely available under GPL2. [Biogeography; Phylogenetics; DEC Model.]
Epidermotropic B-Cell Lymphoma: A Case of Secondary Cutaneous Splenic Marginal Zone B-Cell Lymphoma With Autoinvolutive and Recurrent Cutaneous Lesions
Authors: Rovira-López Roger , Gallardo Fernando , Salar Antonio , Colomo Lluis , Pujol Ramon M. 
Published: January 2023

Abstract:
An 84-year-old woman presented with a 3-month history of a papular rash on the trunk, abdomen, and back. Histopathological examination revealed atypical lymphoid deep and band-like dermal infiltrates with marked epidermotropism. Neoplastic cells expressed B-cell markers (CD20), and clonal immunoglobulin gene rearrangement was observed. A complete peripheral blood study revealed aberrant circulating villous lymphocytes with the expression of B-cell markers (CD20, CD22, and CD79a) and aberrant expression of CD5. A staging workup revealed discrete splenic enlargement and bone marrow and gastrointestinal tract involvement. Skin lesions regressed spontaneously several weeks after diagnosis. Throughout evolution, the patient developed scattered cutaneous nodules and generalized papulo-nodules showing either epidermotropic or nonepidermotropic atypical dermal lymphoid infiltrates. This case illustrates the observation of autoinvolutive and recurrent epidermotropic B-cell atypical cutaneous infiltrates as a characteristic feature of secondary cutaneous involvement in splenic marginal B-cell lymphoma. Previously reported cases of epidermotropic B-cell lymphoma have been reviewed. Concurrent and simultaneous observation of epidermotropic and nonepidermotropic lesions seems to indicate that epidermotropism is an important but nonconstant diagnostic feature of splenic marginal B-cell lymphoma.
Trichoepithelioma on the Finger: A Rare Location and Dermoscopic–Histopathologic Correlation
Authors: Mayo-Martínez Fátima , Moro Ruggero , Traves Victor , Llombart Beatriz , Requena Celia 
Published: January 2023

Abstract:
Trichoepithelioma is a benign adnexal neoplasm of follicular germinative cells, with bulbs, papillae, and sheaths of perifollicular connective tissue as signs of follicular differentiation. Accordingly, trichoepithelioma may arise in any hair-bearing location, mostly on the face. That is why trichoepithelioma cannot appear in glabrous skin, and, although the dorsum of the hands and feet are a hair-bearing area, acral location is exceptional. We report the first case of trichoepithelioma localized in the finger of a 79-year-old man. It was a brown-pink, firm, 7-mm diameter, solid papule on the dorsal aspect of his left index finger. The lesion was completely asymptomatic, and he remembered to have it for many years. We describe this case highlighting its rare anatomical location and correlate its dermoscopic features with the histopathological appearance.
Reactive Eccrine Syringofibroadenoma (ESFA) in Association With a Merkel Cell Carcinoma Excision Scar
Authors: Salah Haneen T. , Czelusta Adam J. , Sanchez Ramon L. 
Published: January 2023

Abstract:
Eccrine syringofibroadenoma (ESFA) is a rare benign skin adnexal lesion of the acrosyringium of eccrine sweat ducts. Reactive ESFA, a subtype of ESFA, is usually associated with non-neoplastic cutaneous dermatoses or neoplastic skin tumors. Clinically, the lesions can be solitary or multiple, pink, or skin-colored coalescing papules or nodules of variable sizes. Histopathologically, this tumor is composed of numerous anastomosing cords of monomorphic cuboidal epithelial cells with eccrine duct formation. The association of reactive ESFA with benign conditions, such as psoriasis, diabetic polyneuropathy, scars, and leprosy, has been reported. However, the association of reactive ESFA with malignant tumors is extremely rare, with very few cases reported in the literature. We present a case of a 72-year-old woman who developed reactive ESFA associated with Merkel cell carcinoma excision scar. The ESFA tumors developed in the area of the surgical graft 10 months after the Merkel cell carcinoma had been excised. New ESFA tumors have continued to appear in the scar on a yearly basis while, so far, has been no recurrence of the original tumor. However, the presence of new tumor growths in the area suggested the possibility of recurrence of the Merkel cell carcinoma. That possibility was enhanced by the fact that PET scans revealed hypermetabolic activity in the ESFA papules.
Transcription Factor HES-1: How Is the Expression of This Transcriptional Factor in Paucibacillary Leprosy Patients?
Authors: Serrano-Coll Héctor , Ospina-Gómez Juan Pablo , Salamanca Carolina , Restrepo Lina , Berbeo Katerine , Olarte Graciela , Cardona-Castro Nora 
Published: January 2023

Introduction:
Leprosy is an ancient and chronic infectious disease caused by 2 mycobacteria (Mycobacterium leprae and Mycobacterium lepromatosis). Recently, our research group observed that HES-1, an innate cellular component of the Notch signaling pathway, is related to the pathogenesis of leprosy. Therefore, it could be helpful in its detection.

Objective:
To determine the expression of HES-1 in the skin of patients with paucibacillary (PB) leprosy.

Methods:
A cross-sectional, descriptive, observational study was conducted. Forty-five skin samples from patients with leprosy were evaluated (30 samples from MB leprosy and 15 from PB leprosy) using immunohistochemistry of HES-1 and S-100.

Results:
PB leprosy biopsies revealed a reduction of HES-1 in 66.7% of the epidermis, 80% of the eccrine glands, and 62.5% of the hair follicles of these patients, with statistical differences in the control group (P < 0.0001). Besides, HES-1 showed similar utility to S-100 immunostaining in detecting the MB and PB leprosy.

Conclusions:
HES-1 is a transcriptional factor also reduced in PB patients' epidermis and skin appendages. Finally, our data show that HES-1 could be a biomarker in diagnosing PB and MB leprosy.
Determining the Association Between Melanomas and Fields of Melanocytic Dysplasia
Authors: Mata Douglas A. , Lian Christine G. , Hafeez Farhaan 
Published: January 2023

Abstract:
Some have proposed that melanomas in situ may be associated with fields of melanocytic dysplasia, particularly on sun-damaged skin, whereas others maintain that the atypical junctional melanocytic hyperplasia (MH) at the periphery of melanomas is simply background junctional MH of sun-damaged skin. The biological potential of atypical junctional MH at the periphery of melanomas is uncertain. We examined whether atypical junctional MH was intrinsic to the melanoma itself (ie, melanoma-associated field of melanocytic dysplasia) or was simply the predictable junctional MH associated with long-standing sun exposure. We retrospectively compared 106 cutaneous melanoma excisions without residual tumor with 105 nonmelanoma cutaneous tumor excisions (ie, basal cell or squamous cell carcinomas) without residual tumor. MH with atypia occurred significantly more frequently in melanoma than in nonmelanoma cutaneous tumor excisions (55.7% vs. 24.8%, P < 0.001). Solar elastosis occurred significantly less frequently in melanoma than in nonmelanoma cutaneous tumor excisions; 33.0% of melanoma excisions and 8.6% of nonmelanoma excision samples exhibited no solar elastosis, respectively (P < 0.001). After controlling for solar elastosis using multivariable linear regression, the association between MH with atypia and melanoma excisions remained significant (P < 0.001). Our results, therefore, demonstrate that melanomas were associated with atypical junctional MH that could not solely be accounted for by the extent of sun damage as measured by solar elastosis.
Primary Cutaneous Ewing Sarcoma of the Scalp With Metastasis to the Lung: An Unusual Manifestation During Pregnancy
Authors: Regmi Aayushma , Raouf Maryam , Mudaliar Kumaran M. , Speiser Jodi J. , Ananthanarayanan Vijayalakshmi 
Published: January 2023

Abstract:
A 32-year-old G2P1L1 (5 months pregnant) woman presented with a 3-month history of a slow-growing cystic lesion on her scalp vertex. Similar lesions in the exact location were excised twice in the past with a diagnosis of trichilemmal carcinoma (TC). A biopsy of the scalp lesion showed morphology and immunoprofile consistent with previously diagnosed TC. Staging PET/CT demonstrated a 4.7 cm right upper lobe lung, and a subsequent lung biopsy showed a small, round blue-cell tumor with necrosis, morphologically identical to the prior biopsies from the scalp. Considering the unusual clinical course of TC, a lung biopsy was sent for next-generation sequencing that showed EWSR1-FLI1 (type1) fusion. Additionally, CD99 immunostaining revealed uniform cytoplasmic and membranous staining in the tumor cells. The previous scalp excision specimen was also sent for mutation analysis, which showed EWSR1-FLI1 fusion. In conjunction with clinical history and histological and molecular findings, a definitive diagnosis of primary cutaneous Ewing sarcoma (PCES) with local recurrence and metastasis to the lung was made. We present a case of PCES, which was previously misdiagnosed and treated as TC. This case emphasizes the importance of CD99 in the initial screening of cutaneous small round blue-cell tumors to avoid misdiagnosis from other morphological overlaps. Also, despite its rarity, PCES should be included in the differential diagnosis of small, round, blue cell tumors at cutaneous sites. Our case also exemplifies common biases in medical decision-making, including premature closure and anchoring bias which can result in misdiagnosis or diagnostic delay and associated delay in appropriate management.
Staged Excision of Lentigo Maligna of the Head and Neck: Assessing Surgical Excision Margins With Melan A, SOX10, and PRAME Immunohistochemistry
Authors: de Wet Johann , Plessis Pieter J. du , Schneider Johann W. 
Published: January 2023

Background:
Staged excision has emerged as a superior treatment option for lentigo maligna (LM) of the head and neck when compared with conventional wide local excision. Assessing surgical excision margins for remaining LM poses a diagnostic challenge.

Objectives:
To determine whether immunohistochemical (IHC) staining with SOX10 and preferentially expressed antigen in melanoma (PRAME) aids in diagnosing LM on excision margins compared with conventional hematoxylin and eosin and Melan A IHC staining.

Methods:
This study included cases of LM of the head and neck treated with staged excision. Histological findings were reviewed according to standard criteria for the diagnosis of LM and compared with the results after IHC staining for Melan A, SOX10, and PRAME.

Results:
The cohort consisted of 35 sections. Based on hematoxylin and eosin and Melan A IHC staining, 23 sections were diagnosed as LM by the initial pathologist. Further staining with SOX10 IHC showed only 8 to be consistent with a diagnosis of LM and 9 revealing features of actinic melanocyte hyperplasia. PRAME was positive in 5 of the 8 cases of LM and negative in all 9 cases of actinic melanocyte hyperplasia (P = 0.009). The presence of melanocyte nests (P = 0.29) and pagetoid spread (P = 0.003) was the most reliable histological findings distinguishing LM from its mimics.

Conclusion:
SOX10 is a more specific and sensitive marker for melanocytes when assessing for LM on excision margins compared with Melan A. The addition of PRAME can be useful to confirm or exclude the diagnosis in challenging cases.
Complete Femoral Osteonecrosis in the Setting of Myelodysplastic Syndrome
Authors: Kargar Samani Isaac , Akachar Yassin , Krug Bruno 
Published: January 2023

Abstract
A 76-year-old man was diagnosed with a hematological neoplasm combining myelodysplastic and myeloproliferative characteristics back in July 2021. Five months after the diagnosis, his condition got more severe when the blasts rose up to 14%, so he was started on hypomethylating agent–based therapy. A few weeks later, the patient was hospitalized after developing fever and a pain in the right thigh. To exclude any source of occult infection, an 18F-FDG PET/CT was performed. FDG PET/CT showed a complete lack of metabolism in the right femur. An MRI and a biopsy confirmed the suspected diagnosis of osteonecrosis.
MACROPHAGE SWITCHING: POLARIZATION AND MOBILIZATION AFTER TRAUMA
Authors: Hoteit Lara , Loughran Patricia , Haldeman Shannon , Reiser Danielle , Alsaadi Nijmeh , Andraska Elizabeth , Bonaroti Jillian , Srinivasan Amudan , Williamson Kelly M. , Alvikas Jurgis , Steinman Richard , Keegan Joshua , Lederer James A. , Scott Melanie , Neal Matthew D. , Seshadri Anupamaa 
Published: January 2023

ABSTRACT

Introduction: Trauma alters the immune response in numerous ways, affecting both the innate and adaptive responses. Macrophages play an important role in inflammation and wound healing following injury. We hypothesize that macrophages mobilize from the circulation to the site of injury and secondary sites after trauma, with a transition from proinflammatory (M1) shortly after trauma to anti-inflammatory (M2) at later time points. Methods: C57Bl6 mice (n = 6/group) underwent a polytrauma model using cardiac puncture/hemorrhage, pseudofemoral fracture, and liver crush injury. The animals were killed at several time points: uninjured, 24 h, and 7 days. Peripheral blood mononuclear cells, spleen, liver nonparenchymal cells, and lung were harvested, processed, and stained for flow cytometry. Macrophages were identified as CD68+; M1 macrophages were identified as iNOS+; M2 macrophages as arginase 1+. Results: We saw a slight presence of M1 macrophages at baseline in peripheral blood mononuclear cells (6.6%), with no significant change at 24 h and 7 days after polytrauma. In contrast, the spleen has a larger population of M1 macrophages at baseline (27.7%), with levels decreasing at 24 h and 7 days after trauma (20.6% and 12.6%, respectively). A similar trend is seen in the lung where at baseline 14.9% of CD68+ macrophages are M1, with subsequent continual decrease reaching 8.7% at 24 h and 4.4% at 7 days after polytrauma. M1 macrophages in the liver represent 14.3% of CD68+ population in the liver nonparenchymal cells at baseline. This percentage increases to 20.8% after trauma and decreases at 7 days after polytrauma (13.4%). There are few M2 macrophages in circulating peripheral blood mononuclear cells and in spleen at baseline and after trauma. The percentage of M2 macrophages in the lungs remains constant after trauma (7.2% at 24 h and 9.2% at 7 days). In contrast, a large proportion of M2 macrophages are seen in the liver at baseline (36.0%). This percentage trends upward and reaches 45.6% acutely after trauma and drops to 21.4% at 7 days. The phenotypic changes in macrophages seen in the lungs did not correlate with a functional change in the ability of the macrophages to perform oxidative burst, with an increase from 2.0% at baseline to 22.1% at 7 days after polytrauma (P = 0.0258). Conclusion: Macrophage phenotypic changes after polytrauma are noted, especially with a decrease in the lung M1 phenotype and a short-term increase in the M2 phenotype in the liver. However, macrophage function as measured by oxidative burst increased over the time course of trauma, which may signify a change in subset polarization after injury not captured by the typical macrophage phenotypes.
High proportion of Ugandans with pre-pandemic SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell responses
Authors: Namuniina Annemarie , Muyanja Enoch S , Biribawa Victoria M , Okech Brenda A , Ssemaganda Aloysious , Price Matt A , Hills Nancy , Nanteza Ann , Bagaya Bernard Ssentalo , Weiskopf Daniela , Riou Catherine , Reynolds Steven J , Galwango Ronald M , Redd Andrew D 
Published: January 2023

AbstractThe estimated mortality rate of the SARS-CoV-2 pandemic varied greatly around the world with multiple countries in East, Central, and West Africa having significantly lower rates of COVID-19 related fatalities than many resource-rich nations with significantly earlier wide-spread access to life-saving vaccines. One possible reason for this lower mortality could be the presence of pre-existing cross-reactive immunological responses in these areas of the world. To explore this hypothesis, stored peripheral blood mononuclear cells (PBMC) from Ugandans collected from 2015-2017 prior to the COVID-19 pandemic (n=29) and from hospitalized Ugandan COVID-19 patients (n=3) were examined using flow-cytometry for the presence of pre-existing SARS-CoV-2 cross-reactive CD4+ and CD8+ T-cell populations using four T-cell epitope mega pools. Of pre-pandemic participants, 89.7% (26/29) had either CD4+ or CD8+, or both, SARS-CoV-2 specific T-cell responses. Specifically, CD4+ T-cell reactivity (72.4%) and CD8+ T-cell reactivity (65.5%) were relatively similar, and 13 participants (44.8%) had both types of cross-reactive types of T-cells present. There were no significant differences in response by sex in the population. The rates of cross-reactive T-cell populations in these Ugandans is higher than previous estimates from resource-rich countries like the United States (20-50% reactivity). It is unclear what role, if any, this cross-reactivity played in decreasing COVID-19 related mortality in Uganda and other African countries, but does suggest that a better understanding of global pre-existing immunological cross-reactivity could be an informative data of epidemiological intelligence moving forward.
Increased TCR signaling in regulatory T cells is disengaged from TCR affinity
Authors: Jing Yi , Kong Yuelin , Allard Denise , Liu Baoyu , Kolawole Elizabeth , Sprouse Maran , Evavold Brian , Bettini Matthew , Bettini Maria 
Published: January 2023

SummaryFoxp3+ regulatory T cells (Tregs) are capable suppressors of aberrant self-reactivity. However, TCR affinity and specificities that support Treg function, and how these compare to autoimmune T cells remain unresolved. In this study, we used antigen agnostic and epitope-focused analyses to compare TCR repertoires of regulatory and effector T cells that spontaneously infiltrate pancreatic islets of non-obese diabetic mice. We show that effector and regulatory T cell-derived TCRs possess similar wide-ranging reactivity for self-antigen. Treg-derived TCRs varied in their capacity to confer optimal protective function, and Treg suppressive capacity was in part determined by effector TCR affinity. Interestingly, when expressing the same TCR, Tregs showed higher Nur77-GFP expression than Teffs, suggesting Treg-intrinsic ability to compete for antigen. Our findings provide a new insight into TCR-dependent and independent mechanisms that regulate Treg function and indicate a TCR-intrinsic insufficiency in tissue-specific Tregs that may contribute to the pathogenesis of type 1 diabetes.
Regulation ofPYR/PYL/RCARABA receptors mRNA stability: involvement of miR5628 in decay ofPYL6mRNA
Authors: Vieira João G. P. , Duarte Gustavo T. , Barrera-Rojas Carlos H. , Matiolli Cleverson C. , Viana Américo J. C. , Canesin Lucas E. D. , Vicentini Renato , Nogueira Fabio T. S. , Vincentz Michel 
Published: January 2023

ABSTRACTHormone signaling fine-tuning involves feedback regulatory loops. Abscisic acid (ABA) plays key functions in development and tolerance to abiotic stress. ABA is sensed by the PYR/PYL/RCAR receptors and it also represses their gene expression. Conversely, ABA inducesPP2Cphosphatases expression, which are negative regulators of the ABA signaling pathway. This feedback regulatory scheme is likely important for the modulation of ABA signal transduction. Here, we provide a new insight into the mechanisms underlying the ABA-induced negative control ofPYR/PYL/RCARexpression inArabidopsis thaliana. The strong and sustained repression ofPYR/PYL/RCARsrevealed by ABA time course treatment defines the regulation of receptors genes as an important step in resetting the ABA signaling pathway. Transcription inhibition by cordycepin showed that destabilization ofPYL1/4/5/6mRNA is involved in ABA-induced repression of these genes. Furthermore, genetic evidence indicated that decapping may play a role inPYL4/5/6mRNAs decay. In addition, we provide evidence that theArabidopsis-specificmicroRNA5628 (miR5628), which is transiently induced by the ABA core signaling pathway, guides the cleavage ofPYL6transcript in response to ABA. After cleavage, the resulting RISC 5’- and 3’-cleaved fragments ofPYL6mRNA may be degraded by exoribonuclease XRN4. MiR5628 is an evolutionary novelty that may contribute, with decapping and XRN4 activities, to enhancePYL6mRNA degradation. Thus, control of stability ofPYR/PYL/RCARtranscripts is an important step in maintaining homeostasis of ABA signaling.One Sentence SummaryAttenuation of ABA signaling involves destabilization ofPYL1/4/5/6transcripts. ABA core signaling induces miR5628 expression to enhancePYL6mRNA degradation in conjunction with decapping and XRN4 activities.