bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary Dermal Melanoma: A Case Report
Authors: Weiss Amy , Christensen Rachel E. , Maghari Amin , Wassef Cindy 
Published: November 2021

Abstract:
Primary dermal melanoma (PDM) is defined as a primary melanoma tumor confined to the dermis, subcutis, or both, without epidermal involvement. The significant overlap of histopathological features in PDM and cutaneous metastatic melanoma makes diagnostic accuracy of PDM challenging. We present a case of a 48-year-old man with a nontender 1.5 × 1.5 cm subcutaneous nodule on the left leg, which had been present for years. Biopsy revealed a dermal tumor with melanocytic differentiation noted to be positive for SOX-10. Additional pathology findings included a high Ki-67 proliferation index and a loss of p16 expression. Pathology reports were consistent with primary tumor stage 4a, and the patient was referred to surgical oncology where examination and workup demonstrated no evidence of the residual lesion representing a metastasis from a primary site. As PDM is histologically indistinguishable from melanoma metastasis to the skin, clues including a history of an evolving subepidermal nodule and exclusion of previous or concurrent melanomas can assist in its accurate diagnosis. Currently, a consensus on the criteria, staging, and management of PDM does not exist. Poorly defined diagnostic criteria and general lack of awareness of PDM result in high rates of incorrect and late-stage diagnoses. This case report highlights the importance of physician familiarity with PDM to ensure accurate recognition, evidence-based management, and improved patient outcomes.
Poorly Differentiated Scrotal Carcinoma With Apocrine Immunophenotype
Authors: Kamanda Sonia , Epstein Jonathan I. , Osunkoya Adeboye O. , Cimino-Mathews Ashley , Argani Pedram , Sangüeza Martin , Plaza Jose Antonio , Matoso Andres 
Published: November 2021

Abstract:
Cutaneous carcinoma of the scrotum is rare with the most common type being squamous cell carcinoma. Here, we report 6 cases of poorly differentiated carcinoma with apocrine immunophenotype. Mean age at presentation was 68 years (range: 31–91 years). Clinical presentation included eczematous rash over mass, scrotal cyst, ulcerated mass, and mass. Tumor size ranged from 1.2 to 5.5 cm (average 2.5 cm). The tumors were solid with involvement of the dermis/hypodermis and composed of cords and nests of eosinophilic cells displaying nuclei with prominent nucleoli and surrounded by desmoplastic stroma. Focal squamous differentiation was evident in one case (17%). An intraductal component was seen in one case (17%). Pagetoid spread in the epidermis was seen in 3 cases. There was no morphologic evidence of apocrine differentiation. By immunohistochemistry, the tumor cells were positive for GCDFP-15 (n = 6/6), GATA3 (n = 6/6), CK7 (n = 5/5), AR (n = 4/4), and mammaglobin (n = 3/5). Five (83%) patients had metastases at diagnosis. Treatment included wide local excisions and inguinal lymph node dissection, followed by chemotherapy (gemcitabine, carboplatin; n = 3), trastuzumab/Lupron (n = 1), tamoxifen/Arimidex (n = 1), and radiotherapy (n = 1). Two patients (40%) were dead of disease, less than 2 years from diagnosis. Four patients developed metastases to lymph nodes, liver, bones, and lungs. Molecular analysis (n = 2) detected a HER-2 mutation in one and microsatellite instability in another. Although the presence of an intraepidermal pagetoid component could hint toward the diagnosis of invasive extramammary Paget disease, tumors without an intraepidermal component could be diagnostically challenging given the lack of morphologic evidence of apocrine differentiation.
The challenging screen detection of ovarian cancer in BRCA mutation carriers adhering to a 6-month follow-up program: results from a 6-years surveillance
Authors: Grandi Giovanni , Fiocchi Federica , Cortesi Laura , Toss Angela , Boselli Fausto , Sammarini Margaret , Sighinolfi Giovanna , Facchinetti Fabio 
Published: November 2021

Abstract

Objective:
Approximately 25% of ovarian cancer (OC) cases are related to an inherited predisposition. Genetic mutations for the oncosuppressor genes BRCA1 and 2 have the best-known linkage to a higher incidence of OC and breast cancer, in approximately 70% to 80% of hereditary OC cases. To provide the first comprehensive clinical description of screen-detected (SD) OCs during a 6-years surveillance of a cohort of young BRCA carriers and carriers who refuse risk-reducing salpingo-oophorectomy.

Methods:
A prospective cohort study in a university hospital describing 191 women with BRCA1 and 2 mutations adhering continuously to our surveillance between 2015 and 2020, including a 6-monthly evaluation of cancer antigen 125 (CA 125) with concomitant transvaginal ultrasound (TVUS) performed by a dedicated specialist. Main outcomes were tumor's laterality, CA 125 at diagnosis, TVUS and computed tomography (CT) findings.

Results:
Risk-reducing salpingo-oophorectomy was performed in 58/191 (30.4%) of mutation carriers during the study period (one OC case identified). Nine SD-OCs and no interval OCs were found in the remaining 133 women. OCs (FIGO stage I or II: 88.9%) occur mainly in BRCA 1 (77.8%), being bilateral in 85.7% BRCA 1 and unilateral in 100% BRCA 2. No lesions involved only the tubes: left ovaries/tubes were more frequently involved. We have described three new possible scenarios regarding imaging: 1) Evident cases (33.3%, TVUS and CT obvious for OC, CA 125 sensitivity: 100%), 2) Possible cases (55.6%, TVUS and CT are in general accordance, documenting new TVUS signs: increased solid pattern of the ovary with peripheral cortical small cysts, hypoechoic circular mass near the ovary, intraparenchymal small hyperechoic foci), and 3) Hidden cases (11.1%, the smallest lesion but the highest stage (IIIA2), with CA 125 44.2 U/mL and concomitant endometrial hyperplasia).

Conclusions:
Different diagnostic tools must integrate to ensure early diagnosis of OC in BRCA mutation carriers adhering to a follow-up program.
Factors Affecting Lower-pole Stretch after Breast Augmentation
Authors: Weniger Frederick G. , Barrero Carlos E. , Weidman Allan A. , Amarillo Sarah M. 
Published: November 2021

Background:
Breast augmentation surgical planning based on soft-tissue characteristics including the type of lower-pole pocket direction has been described. Objective outcome measures of the effects of some of these choices on postoperative lower-pole settling, including dual-plane dissection type, have been lacking.

Objective:
The aim of this study was to determine whether the type/extent of dual-plane dissection, patient age, or variables in breast implant characteristics affected implant–soft tissue dynamics of the lower pole of the breast enough to cause difference in implant settling during the postoperative period.

Methods:
Measurements of nipple-to-inframammary fold distance in primary breast augmentation patients were collected prospectively for 227 female primary breast augmentation patients during postoperative visits over an 8-year period. Changes in this distance during the postoperative period were evaluated for correlation with dual-plane dissection type, patient age, implant fill material, implant size, and implant profile.

Results:
Increasing dual-plane dissection type did demonstrate a trend toward greater postoperative lower-pole stretch. Only implant profile affected lower-pole stretch, with statistical significance shown in the ultrahigh-profile group. Age, implant fill material, and size of implant did not show any notable effect.

Conclusions:
Ultrahigh-profile implants cause significantly more lower-pole stretch postoperatively, whereas increasing dual-plane dissection type appears to have some effect as well. Age, implant material, and size of implant are of less importance over a 6-month period.
An Unoperated Crouzon Family Treated with Monobloc Distraction: Challenges and Lessons
Authors: Hart Justin , Lu Stephen , Gasteratos Konstantinos , Chaiyasate Kongkrit 
Published: November 2021

Background:
Crouzon syndrome (CS) is a rare form of craniosynostosis characterized by bicoronal craniosynostosis and facial features including severe midface hypoplasia, exophthalmos, and hypertelorism. Most patients are diagnosed and treated in early childhood; however, there are a few reports of Crouzon patients treated as adults with monobloc facial advancement. To our knowledge, this is the first report of a family affected by CS treated sequentially with monobloc facial advancement using combined internal and external distraction osteogenesis (rigid external distraction).

Methods:
We present a family from Jamaica (mother 47 years old, older daughter 17, and younger daughter 9) who were brought to our craniofacial clinic with stigmata of CS and no previous surgical intervention. Patients had bicoronal craniosynostosis and exorbitism, with varying severity, sequelae, and comorbidities. Here, we delineate our technique of monobloc distraction osteogenesis with advancement osteotomies using dual “push–pull” method, elevation of a split anteriorly based tunneled pericranial flap to seal off nasal cavity, and internal and external distraction.

Results:
Our patients had favorable outcomes after reconstruction to reduce ocular symptoms and improve midface hypoplasia and aesthetic appearance. No intracranial injury, hardware/soft-tissue infection, hardware failure, or (new) loss of vision were encountered in 10 months follow-up.

Conclusions:
Dual “push–pull” monobloc distraction is safe and effective for a range of ages in CS; it allows good vector control, accommodates patient compliance, and allows early rigid external distraction device removal with sufficient time for consolidation. This surgery can be performed with highly satisfactory results.
Upper Lip Reconstruction Using Fujimori Gate Flap in an Electrical Burn Patient
Authors: Poncio Mar Aristeo G. , Nable-Aguilera Ma. Adela 
Published: November 2021

Summary:
The Fujimori gate flap has been known and used for reconstruction of defects resulting from oncologic surgery. In this case report, we describe how this flap was utilized in reconstructing the upper lip of a patient who experienced an electrical burn injury resulting in 70% tissue loss of the upper lip with exposed alveolar bone. A 22-year-old man presented to our institution with near total full-thickness burn over the upper lip, deep partial thickness burns over left upper lid, and superficial partial thickness burns over both malar areas, anterior chest, and both legs. He underwent full-thickness skin grafting of the left upper lid and upper cutaneous lip. After 3 weeks, a unilateral gate flap was performed. The flap was elevated with care to preserve the right angular artery and the Stensen’s duct. The flap was rotated 90 degrees medially and was sutured to the contralateral orbicularis oris, gingivobuccal mucosa, and to the rest of the upper cutaneous lip. The patient was followed up at 6 months and 1 year postoperatively. The flap was able to restore oral competence and enabled the patient to speak and chew with no difficulty. Patients suffering from high-voltage electrical burns, especially involving the mouth, present a challenging case for surgeons for reconstruction. Here, the goals of the reconstruction are to restore oral competence and ability to articulate, and still provide good appearance. A feasible and aesthetically acceptable flap providing good functional outcome is provided by the use of the unilateral Fujimori gate flap among patients suffering from high-voltage electrical burns of the oral cavity.
Accessible, Open-source Hardware and Process Designs for 3D Bioprinting and Culturing Channels Lined with iPSC-derived Vascular Endothelial Cells
Authors: Gross Andrew R , Santos Roberta S. , Sareen Dhruv 
Published: November 2021

AbstractIndirect bioprinting for cell culture requires the use of several technologies and techniques which currently prevent many researchers not specialized in electrical engineering or materials science from accessing these new tools. In this paper, a printer and all necessary associated hardware was developed and tested for the purpose of seeding human induced Pluripotent Stem Cell (iPSC)-derived endothelial cells (iECs) onto all surfaces of a fibringelatin channel. Immature iECs were seeded onto all channel surfaces and completed differentiation along channel walls. All required tools and methods, including engineering drawing, printable files, code, and hand-tool templates, have been provided with sufficient clarity to enable full, open-source replication of all technique employed.
Inhibition of SAR S-CoV-2 infection and replication by lactoferrin, MUC1 and α-lactalbumin identified in human breastmilk
Authors: Lai Xinyuan , Yu Yanying , Xian Wei , Ye Fei , Ju Xiaohui , Luo Yuqian , Dong Huijun , Zhou Yihua , Tan Wenjie , Zhuang Hui , Li Tong , Liu Xiaoyun , Ding Qiang , Xiang Kuanhui 
Published: November 2021

AbstractThe global pandemic of COVID-19 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection confers great threat to the public health. Human breastmilk is an extremely complex with nutritional composition to nourish infants and protect them from different kinds of infection diseases and also SARS-CoV-2 infection. Previous studies have found that breastmilk exhibited potent antiviral activity against SARS-CoV-2 infection. However, it is still unknown which component(s) in the breastmilk is responsible for its antiviral activity. Here, we identified Lactoferrin (LF), MUC1 and α-Lactalbumin (α-LA) from human breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and in vitro confirmation that inhibited SARS-CoV-2 infection and analyzed their antiviral activity using the SARS-CoV-2 pseudovirus system and transcription and replication-competent SARS-CoV-2 virus-like-particles (trVLP) in the Huh7.5, Vero E6 and Caco-2-N cell lines. Additionally, we found that LF and MUC1 could inhibit viral attachment, entry and post-entry replication, while α-LA just inhibit viral attachment and entry. Importantly, LF, MUC1 and α-LA possess potent antiviral activities towards not only wild-type but also variants such as B.1.1.7 (alpha), B.1.351 (beta), P.1 (gamma) and B.1.617.1 (kappa). Moreover, LF from other species (e.g., bovine and goat) is still capable of blocking viral attachment to cellular heparan sulfate. Taken together, our study provided the first line of evidence that human breastmilk components (LF, MUC1 and α-LA) are promising therapeutic candidates warranting further development or treatingVID-19 given their exceedingly safety levels.
WY14643 Increases Herpesvirus Replication Independently of PPARα Expression and Inhibits IFNβ Production
Authors: Tao Lili , Dryden Phillip , Lowe Alexandria , Wang Guoxun , Dozmorov Igor , Chang Tyron , Reese Tiffany A. 
Published: November 2021

AbstractPeroxisome proliferator activated receptor (PPAR) agonists are commonly used to treat metabolic disorders in humans because they regulate fatty acid oxidation and cholesterol metabolism. In addition to their roles in controlling metabolism, PPAR agonists also regulate inflammation and are immunosuppressive in models of autoimmunity. We aimed to test whether activation of PPARα with clinically relevant ligands could impact herpesvirus infection using the model strain murine gammaherpesvirus-68. We found that PPARα agonists WY14643 and fenofibrate increased herpesvirus replication in vitro. In vivo, WY14643 increased viral replication and caused lethality in mice. Unexpectedly, these effects proved independent of PPARα. Investigating the mechanism of action for WY14643, we found that it suppresses production of type I interferon by inhibiting stimulator of interferon (STING), which lies downstream of the cytoplasmic DNA sensor cGAS. Thus, WY14643 regulates interferon downstream of cytoplasmic DNA recognition and increases herpesvirus replication in a PPARα-independent manner. Taken together, our data indicate that caution should be employed when using PPARα agonists in immuno-metabolic studies, as they can have off-target effects on viral replication.ImportancePPAR agonists are used clinically to treat both metabolic and inflammatory disorders. Because viruses are known to rewire host metabolism to their own benefit, the intersection of immunity, metabolism, and virology is an important research area. Our article is an important contribution to this field because for two reasons. First, it shows a role for PPARα agonists in altering virus detection by cells. Second, it shows that PPARα agonists can affect virus replication in a manner unrelated to their expected genetic function. This knowledge is valuable for anyone seeking to use PPARα agonists as a research tool.
Nuclear activation in dual-durotaxing cells on a matrix with cell-scale stiffness-heterogeneity
Authors: Kidoaki Satoru , Ebata Hiroyuki , Moriyama Kosuke , Kuboki Thasaneeya , Tsuji Yukie , Sawada Rumi , Sasaki Saori , Okuda Tatsuya , Hamano Kosuke , Kawano Takahito , Yamamoto Aki , Kono Ken , Tanaka Kazusa 
Published: November 2021

AbstractLiving organisms are typically composed of various tissues with microscopic cell-scale stiffness-heterogeneity, in which some cells receive dynamically fluctuating mechanical stimuli from the heterogeneous extracellular milieu during long-term movement. Although intracellular stress dynamics (ISD), which are closely related to the regulation of cell functions such as proliferation and differentiation, can be characteristically modulated in cells migrating on a matrix with stiffness-heterogeneity, it has been unclear how the mode of fluctuation of ISD affects cell functions. In the present study, we demonstrate that mesenchymal stem cells (MSCs) dual-durotaxing (i.e., both forward and reverse durotaxis) on microelastically-patterned gels with stiff triangular domains markedly amplify the fluctuation of ISD, nuclear shape, and the spatial distribution of chromatins, which makes the cells remain far from tensional equilibrium. We provide evidence that amplified chromatin fluctuation in the dual-durotaxing MSCs can cause activation of cellular vigor and maintenance of the stemness.
Genetic dietary adaptation in Neandertal, Denisovan and Sapiens revealed by gene copy number variation
Authors: Vicedomini Riccardo , Righetti Niccolò , Polit Lélia , Condemi Silvana , Longo Laura , Carbone Alessandra 
Published: November 2021

AbstractDietary adaptation involves evolving an efficient system to digest food available in an ecosystem. The diet of archaic humans is traditionally reconstructed by isotopic analyses of human remains combined with the faunal assemblages found on the sites, and, recently, from metagenomic analyses of dental calculus. Here, we propose a new computational approach to find the genetic basis for human dietary adaptation. We searched 15 genomes from Neandertal, Denisovan and Early Sapiens for food digestion genes that tend to have more or fewer copies than the modern human reference genome. We identify 50 genes, including 10 gene clusters, with discernible copy number variation (CNV) trends at the population level, from an analysis of the full set of 20,000 human genes. The genomic variation of 19 of these genes shows how metabolic pathways for carbohydrates, lipids, liver lipids and brown fat in archaic humans adapted to metabolize food from animal or plant sources. The remaining 31 genes are all highly expressed in tissues of the digestive apparatus and are involved in immune response, environmental response and obesity. Analysis of the CNV profiles, compared to 64 modern human individuals belonging to distinct ethnic groups in Eurasia, Africa, Oceania, suggests thatHomo sapiensmay have had an evolutionary advantage compared to Neandertal and Denisovan in adapting to cold and temperate ecosystems.Significance StatementUnderstanding dietary strategies and foraging behaviors of past populations are among the goals of paleoanthropological and prehistoric studies. Based on a new computational approach, we seek for the genetic basis for human dietary adaptation. Gene copy number variation (CNV) is a major type of structural genome variation that we used as indicator of efficient metabolic processes for food digestion. By analysing billions of short sequences from 15 archaic human genomes and 64 modern human ones, across the full set of 20,000 human genes, we identify 50 genes whose population-wide discernable CNV trends point to lipid metabolism as being crucial for Neandertal, the efficiency in carbohydrate metabolism for Sapiens’ diet, and the importance of lipid metabolism and brown fat metabolism for both Neandertal and early Sapiens compared to modern humans.Preprint availability:an early version, where the CNV analysis of ancient genomes was conducted on the human reference genome hg19, was deposited on BioRxiv on November 2, 2021 (DOI:10.1101/2021.10.30.466563). The current version, which utilises CNV estimates based on the human reference genome hg38 and includes comparisons with modern human populations, was deposited in BioRxiv in November 2024.
Proteomics reveals unique identities of human TGF-β-induced and thymus-derived CD4+ regulatory T cells
Authors: Mensink Mark , Schrama Ellen , Cuadrado Eloy , van den Biggelaar Maartje , Amsen Derk , de Kivit Sander , Borst Jannie 
Published: November 2021

AbstractThe CD4+ regulatory T (Treg) cell lineage, as defined by FOXP3 expression, comprises thymus-derived (t)Treg cells and peripherally induced (p)Treg cells. In human, naïve tTreg cells can be isolated from blood, while effector tTreg and pTreg cells cannot be purified reliably for lack of cell surface markers. As a model for Treg cells, studies often employ TGF-β-induced (i)Treg cells generated from CD4+ conventional T (Tconv) cells in vitro. Here, we describe the relationship of iTreg cells to tTreg and Tconv cells, as optimally purified from human blood. Proteomic analysis revealed that each of these cell populations has a unique protein expression pattern before and after CD3/CD28-mediated activation. iTreg cells had limited overlap in protein expression with tTreg cells and exhibited markedly differential expression of proteins involved in signal transduction and metabolism. Whereas iTreg and Tconv cells responded strongly to CD3/CD28-mediated activation, tTreg cells showed a modest response, which reflects their adaptations in signal transduction pathways. As a benchmark, we used a previously defined proteomic signature that discerns ex vivo naïve and effector Treg cells from Tconv cells and includes conserved Treg cell properties. This Treg cell core signature was largely absent in iTreg cells, as exemplified by STAT4 expression that may contribute to pro-inflammatory functions. In addition, we used a proteomic signature that distinguishes ex vivo effector Treg cells from Tconv cells and naïve Treg cells. This effector Treg cell signature was partially present in iTreg cells, indicating that they do have protein expression features in common with ex vivo effector Treg cells. In conclusion, iTreg cells are distinct from tTreg cells and largely lack the Treg cell core proteomic signature, indicating that caution is warranted when using iTreg cells as a model for Treg cell populations found in vivo.