May Chan - Academia.edu (original) (raw)

Papers by May Chan

2020 IEEE Aerospace Conference

Current plans for the exploration of Moon and Mars envision the use of telerobotic systems contro... more Current plans for the exploration of Moon and Mars envision the use of telerobotic systems controlled from orbiting laboratories. The advantage of telerobotics is that it combines the resilience, endurance and precision of robots with the inherent flexibility, anticipation and decision making capabilities of humans. The primary disadvantage of telerobotics is the communication time delay in the human-robot control loop. The delay can lead to a loss of situation awareness, an increase in operator work load, and an overall decrease in effectiveness and efficiency of the human-robot system. Most of the effects of the delay can be mitigated by the use of predictive displays, presenting the operator with a simulated system state. This paper presents current work on such a predictive display designed to support an operator in remote flight and landing of space robots and unmanned aerial vehicles. The Adaptable Human-Machine Interface was developed for hardware-in-the-loop laboratory experiments with a Parrot A.R. Drone 2.0 quadcopter as test case. Based on live video from two on-board cameras, attitude and velocity telemetry, and control inceptor deflection, the interface calculates a predicted flight path and attitude and presents it in a “tunnel in the sky” display. The graphical display itself was developed in the Unity3D game engine. The paper describes the implementation of the interface between Unity3D and the A.R. Drone, the dynamic model of the quadcopter, and the prediction algorithm. The paper also discusses the results of flight tests involving a number of test subjects and projects the path forward in the development of this technology.

A conference report for Code4Lib 2013 from the perspective of a cataloguer

Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control ... more Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control study ben-efitting from detailed exposure and genotyping data. Methods Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D3 measurement adjusted for season, age, sex, and body mass index. Results Adjusted analyses showed that vitamin D levels were sub-optimal especially in the sun-sensitive individu-als (-2.61 nmol/L, p = 0.03) and for inheritance of a genetic variant in the GC gene coding for the vitamin D-binding protein (-5.79 for heterozygotes versus wild type, p = \0.0001). Higher levels were associated with

Spectrography has been employed for the analysis of speech sounds in the last decades, and many s... more Spectrography has been employed for the analysis of speech sounds in the last decades, and many signi?cant discoveries about speech has been made using this technique. This poster will present techniques which are employed in spectrographic analysis of consonantal speech sounds in sociophonetic studies. The formant pro?les of various consonants as well as the question of how one particular ’consonant’ can be realised in di?erent ways will be explored. The aim is to uncover the acoustic properties of consonantal sounds which are signi?cant in explaining how speakers present their own identities and perceive those of others.

Molecular Genetics and Metabolism, 2021

This talk presents findings from a study on alveola rization in Hong Kong Cantonese, a phenomenon... more This talk presents findings from a study on alveola rization in Hong Kong Cantonese, a phenomenon whereby velar nasal –ŋ and velar stop –k syllable-final consonants are fronted to alveolar counterparts -n and -t respectively. Since one of the first descriptions on alveolarization (Bauer 1979), there have been a number of quantitative sociolinguistic studies on sound changes, particula rly of the syllable-initial consonants, in Cantonese (e.g. Yeung 1980; Bauer 1982; Pan 1982 ; Bourgerie 1990; and Ho 2004), but few studies have focused solely on alveolarizat ion of the syllable-final consonants (except two small-scale studies, Shum 1993 and Wong 2005). To address the question of how prevalent alveolarization is in present-day Hong Kong Cantonese, and to investigate the extent to which language-internal a nd –external factors correlate with alveolarization, I collected sociolinguistic interv iew data in 2010, from 30 native speakers of Hong Kong Cantonese, stratified accordi ng to age...

Pigment Cell & Melanoma Research, 2021

Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biolo... more Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biology to query the role of host and tumour‐specific processes in defining the phenotype. Albumin level as a measure of systemic inflammation was predictive of fewer tumour‐infiltrating lymphocytes and poorer survival in the Leeds Melanoma Cohort. Ulcerated melanomas were thicker and more mitotically active (with corresponding transcriptomic upregulated cell cycle pathways). Sequencing identified tumoural p53 and APC mutations, and TUBB2B amplification as associated with the phenotype. Ulcerated tumours had perturbed expression of cytokine genes, consistent with protumourigenic inflammation and histological and transcriptomic evidence for reduced adaptive immune cell infiltration. Pathway/network analysis of multiomic data using neural networks highlighted a role for the β‐catenin pathway in the ulceration, linking genomic changes in the tumour to immunosuppression and cell proliferation. In summary, the data suggest that ulceration is in part associated with genomic changes but that host factors also predict melanoma death with evidence of reduced immune responses to the tumour.

Journal of Cutaneous Pathology, 2021

Background: Deviations from the classic melanocytic immunophenotype in melanoma can present a dia... more Background: Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas. Methods: Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score. Results: PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases. Conclusions: PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis.

Journal of Cutaneous Pathology, 2020

This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Journal of Clinical Oncology, 2020

We thank Hindié 1 for his interest in our study, 2 and we are happy to provide the clarifications... more We thank Hindié 1 for his interest in our study, 2 and we are happy to provide the clarifications requested. We agree that our nomogram has not been prospectively tested on unselected patients with thin melanoma. Although prospective testing is desirable, it would not be ethical to use unselected patients with stage T1 melanoma because sentinel node biopsy (SNB) would be overtreatment in most cases. Similarly, Hindié 1 notes that we did not test the nomogram on the two subgroups (of the development and validation cohorts) that did not receive SNB. Once again, it is precisely because these subgroups did not receive an SNB that nomogram performance could not be assessed. Thus, we did the only thing possible: assess outcomes after long follow-up, finding that foregoing SNB in these subgroups was justified post hoc.

Human Pathology, 2020

Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping micro... more Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping microscopic and immunophenotypic features. Improved understanding of molecular alterations in these tumors may provide diagnostic and therapeutic insights. We characterized 111 cutaneous sarcomatoid malignancies and their counterparts, including primary cutaneous angiosarcoma (n Z 7), atypical fibroxanthoma (AFX) (n Z 21), pleomorphic dermal sarcoma (PDS) (n Z 17), extracutaneous undifferentiated pleomorphic sarcoma (n Z 8), cutaneous leiomyosarcoma (LMS) (n Z 5), extracutaneous LMS (n Z 9), sarcomatoid squamous cell carcinoma (spindle cell squamous cell carcinoma) (S-SCC) (n Z 24), and conventional cutaneous squamous cell carcinoma (SCC) (n Z 20), by nextgeneration sequencing (NGS) using the StrataNGS panel for copy number variations, mutations, and/or fusions in more than 60 cancer-related genes. TP53 mutations were highly recurrent in most groups. Angiosarcoma displayed previously reported MYC amplifications, as well as CCND1 gains. RB1 mutations were relatively restricted to cutaneous LMS. As previously reported, PIK3CA mutations occurred in AFX, whereas RAS activation was more frequent in PDS. CDKN2A mutations were recurrent in AFX and S-SCC, whereas PDS displayed frequent CDKN2A deletion. S-SCC displayed mutational similarity to conventional SCC. BRCA1/2 mutations were specific to tumors with disease progression. In a subset, we detected potential driver events novel to these tumor types: activating mutations in IDH2 (PDS), MAP2K1 (angiosarcoma, PDS), and JAK1 (S-SCC) and copy gains in FGFR1 (angiosarcoma, S-SCC), KIT (AFX), MET (PDS), and PDGFRA (PDS). Our findings confirm and expand the spectrum of known genomic aberrations, including potential targetable drivers, in cutaneous sarcomatoid malignancies. In addition, certain events are relatively specific to particular tumors within this differential diagnosis and hence might be diagnostically informative.

Journal of Bacteriology, 1974

The bisulfite reductase (P582) from Desulfotomaculum nigrificans was purified to homogeneity as j... more The bisulfite reductase (P582) from Desulfotomaculum nigrificans was purified to homogeneity as judged by polyacrylamide gel electrophoresis. By colorimetric methods of analysis, the products of bisulfite reduction by this enzyme were determined to be trithionate, thiosulfate, and sulfide. Of these, trithionate was consistently found to be the major product, whereas the latter two were formed in lesser quantities. When [35S]bisulfite was incorporated as substrate, no labeled sulfide was detected. Furthermore, when trithionate and thiosulfate were isolated from reaction mixtures and chemically degraded, 35S was found in all three sulfur atoms of trithionate; however, only the inner sulfur atom of thiosulfate was radioactive. From these data we conclude that the bisulfite reductase of D. nigrificans reduces bisulfite to trithionate and that thiosulfate and sulfide are endogenous side products of the reaction.

Journal of Cutaneous Pathology, 2018

This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Journal of Bacteriology, 1973

Spin-labeling studies were conducted to elucidate the rigidity and viscosity of the membrane of a... more Spin-labeling studies were conducted to elucidate the rigidity and viscosity of the membrane of a facultative thermophilic bacillus. By employing nitroxide stearate probes, it was observed that this fatty acid was incorporated into the membrane fraction. Electron spin resonance spectroscopy indicated that cells grown at 55 C contained a membrane which was more rigid and viscous than the membrane from cells grown at 37 C.

Journal of Clinical Oncology, 2020

PURPOSE Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Region... more PURPOSE Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status f...

Trends in Anaesthesia and Critical Care, 2020

Modern Pathology, 2019

Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its ... more Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (<8) prioritized somatic mutations, and lacked an ultraviolet (UV) signature. The most recurrent mutation was TP53 inactivation in four (22%) tumors. Frame-preserving insertions affecting the kinase domain of JAK1 were detected in three (17%) cases, and were nonoverlapping with TP53 mutations. Seven (39%) cases demonstrated copy number gain of at least one oncogene. By immunohistochemistry, p53 expression was significantly higher in microcystic adnexal carcinomas with TP53 mutations compared with those without such mutations and syringomas. Similarly, phospho-STAT3 expression was significantly higher in microcystic adnexal carcinomas harboring JAK1 kinase insertions compared with those with wild-type JAK1 and syringomas. In conclusion, microcystic adnexal carcinomas are molecularly heterogeneous tumors, with inactivated p53 or activated JAK/STAT signaling in a subset. Unlike most other nonmelanoma skin cancers involving sun-exposed areas, most microcystic adnexal carcinomas lack evidence of UV damage, and hence likely originate from a relatively photo-protected progenitor population in the dermis. These findings have implications for the biology, diagnosis, and treatment of microcystic adnexal carcinomas, including potential for therapeutic targeting of p53 or the JAK/STAT pathway in advanced tumors.

Clinical Cancer Research, 2019

Purpose: Previously identified transcriptomic signatures have been based on primary and metastati... more Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10−8 to 10−4) but showed a significant interaction with AJCC stage (P = 0.04) and did n...

American Journal of Surgical Pathology, 2019

Diagnosis of calciphylaxis is crucial, yet its distinction from other vascular diseases can be ch... more Diagnosis of calciphylaxis is crucial, yet its distinction from other vascular diseases can be challenging. Although vascular calcification and thrombosis are hallmarks of calciphylaxis, the incidence and patterns of these features in other vascular diseases have not been well characterized. The specificity of fine calcium deposits in vessel walls (identifiable on von Kossa [VK] stain only) and other extravascular calcifications is not entirely clear. We retrospectively examined the clinicopathologic features in calciphylaxis (n = 27), gangrene and viable skin at amputation margin (n = 20 each), chronic stasis (n = 22), and thrombotic vasculopathy (n = 19) to identify useful discriminators. Calcification of subcutaneous small vessels appreciable on hematoxylin and eosin stain was relatively specific for calciphylaxis, although sensitivity was low (56%). VK detected fine calcium deposits in vessel walls not appreciable on hematoxylin and eosin, however, specificity was limited by frequent finding of similar deposits in peripheral artery disease. Combining calcium deposits detected by VK and thrombosis of subcutaneous small vessels resulted in optimal sensitivity (85%) and specificity (88%) for calciphylaxis. Similar observations applied to medium-sized vessel calcification. Calcification of eccrine gland basement membranes, elastic fibers, and perineurium did not effectively distinguish calciphylaxis from other groups. Diffuse dermal angiomatosis was exclusively found in calciphylaxis in this study. In conclusion, VK is useful in enhancing the detection of vascular calcification and avoiding the false-negative diagnosis, but this finding requires concomitant subcutaneous small vessel thrombosis to support a diagnosis of calciphylaxis. Diffuse dermal angiomatosis should increase suspicion for underlying calciphylaxis and prompt deeper sampling in the appropriate clinical setting.

2020 IEEE Aerospace Conference

Current plans for the exploration of Moon and Mars envision the use of telerobotic systems contro... more Current plans for the exploration of Moon and Mars envision the use of telerobotic systems controlled from orbiting laboratories. The advantage of telerobotics is that it combines the resilience, endurance and precision of robots with the inherent flexibility, anticipation and decision making capabilities of humans. The primary disadvantage of telerobotics is the communication time delay in the human-robot control loop. The delay can lead to a loss of situation awareness, an increase in operator work load, and an overall decrease in effectiveness and efficiency of the human-robot system. Most of the effects of the delay can be mitigated by the use of predictive displays, presenting the operator with a simulated system state. This paper presents current work on such a predictive display designed to support an operator in remote flight and landing of space robots and unmanned aerial vehicles. The Adaptable Human-Machine Interface was developed for hardware-in-the-loop laboratory experiments with a Parrot A.R. Drone 2.0 quadcopter as test case. Based on live video from two on-board cameras, attitude and velocity telemetry, and control inceptor deflection, the interface calculates a predicted flight path and attitude and presents it in a “tunnel in the sky” display. The graphical display itself was developed in the Unity3D game engine. The paper describes the implementation of the interface between Unity3D and the A.R. Drone, the dynamic model of the quadcopter, and the prediction algorithm. The paper also discusses the results of flight tests involving a number of test subjects and projects the path forward in the development of this technology.

A conference report for Code4Lib 2013 from the perspective of a cataloguer

Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control ... more Background We report the determinants of serum levels of vitamin D in a UK melanoma case–control study ben-efitting from detailed exposure and genotyping data. Methods Sun exposure, supplemental vitamin D, and SNPs reported to be associated with serum levels were assessed as predictors of a single serum 25-hydroxyvitamin D3 measurement adjusted for season, age, sex, and body mass index. Results Adjusted analyses showed that vitamin D levels were sub-optimal especially in the sun-sensitive individu-als (-2.61 nmol/L, p = 0.03) and for inheritance of a genetic variant in the GC gene coding for the vitamin D-binding protein (-5.79 for heterozygotes versus wild type, p = \0.0001). Higher levels were associated with

Spectrography has been employed for the analysis of speech sounds in the last decades, and many s... more Spectrography has been employed for the analysis of speech sounds in the last decades, and many signi?cant discoveries about speech has been made using this technique. This poster will present techniques which are employed in spectrographic analysis of consonantal speech sounds in sociophonetic studies. The formant pro?les of various consonants as well as the question of how one particular ’consonant’ can be realised in di?erent ways will be explored. The aim is to uncover the acoustic properties of consonantal sounds which are signi?cant in explaining how speakers present their own identities and perceive those of others.

Molecular Genetics and Metabolism, 2021

This talk presents findings from a study on alveola rization in Hong Kong Cantonese, a phenomenon... more This talk presents findings from a study on alveola rization in Hong Kong Cantonese, a phenomenon whereby velar nasal –ŋ and velar stop –k syllable-final consonants are fronted to alveolar counterparts -n and -t respectively. Since one of the first descriptions on alveolarization (Bauer 1979), there have been a number of quantitative sociolinguistic studies on sound changes, particula rly of the syllable-initial consonants, in Cantonese (e.g. Yeung 1980; Bauer 1982; Pan 1982 ; Bourgerie 1990; and Ho 2004), but few studies have focused solely on alveolarizat ion of the syllable-final consonants (except two small-scale studies, Shum 1993 and Wong 2005). To address the question of how prevalent alveolarization is in present-day Hong Kong Cantonese, and to investigate the extent to which language-internal a nd –external factors correlate with alveolarization, I collected sociolinguistic interv iew data in 2010, from 30 native speakers of Hong Kong Cantonese, stratified accordi ng to age...

Pigment Cell & Melanoma Research, 2021

Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biolo... more Microscopic ulceration is an independent predictor of melanoma death. Here, we used systems biology to query the role of host and tumour‐specific processes in defining the phenotype. Albumin level as a measure of systemic inflammation was predictive of fewer tumour‐infiltrating lymphocytes and poorer survival in the Leeds Melanoma Cohort. Ulcerated melanomas were thicker and more mitotically active (with corresponding transcriptomic upregulated cell cycle pathways). Sequencing identified tumoural p53 and APC mutations, and TUBB2B amplification as associated with the phenotype. Ulcerated tumours had perturbed expression of cytokine genes, consistent with protumourigenic inflammation and histological and transcriptomic evidence for reduced adaptive immune cell infiltration. Pathway/network analysis of multiomic data using neural networks highlighted a role for the β‐catenin pathway in the ulceration, linking genomic changes in the tumour to immunosuppression and cell proliferation. In summary, the data suggest that ulceration is in part associated with genomic changes but that host factors also predict melanoma death with evidence of reduced immune responses to the tumour.

Journal of Cutaneous Pathology, 2021

Background: Deviations from the classic melanocytic immunophenotype in melanoma can present a dia... more Background: Deviations from the classic melanocytic immunophenotype in melanoma can present a diagnostic challenge. PAX8 and PAX2 are common markers for renal or Müllerian differentiation. While most PAX8+ or PAX2+ carcinomas are seldom confused with melanoma, some cases may show a more ambiguous immunophenotype, especially when MiTF family altered renal cell carcinoma (MiTF-RCC) is in the differential diagnosis. Neither PAX8 nor PAX2 expression has been reported in melanoma to date. We aimed to better characterize PAX8, PAX2, and cytokeratin immunoreactivity in a large series of melanomas. Methods: Tissue microarrays consisting of 263 melanomas were immunostained for PAX8, PAX2, and cytokeratin and graded by an h-score. Results: PAX8 expression was seen in 7.9% of melanomas and was significantly associated with spindle cytomorphology. PAX2 was positive in one (0.4%) melanoma. Cytokeratin positivity was seen in three (1.2%) cases and was associated with metastases. Conclusions: PAX8 is expressed in a subset of melanomas and may be strong/extensive. As PAX8 positivity does not exclude a diagnosis of melanoma, it should be used in conjunction with other immunohistochemical markers, such as cytokeratin and PAX2, when melanoma, MiTF-RCC, and other PAX8+ tumors are in the differential diagnosis.

Journal of Cutaneous Pathology, 2020

This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Journal of Clinical Oncology, 2020

We thank Hindié 1 for his interest in our study, 2 and we are happy to provide the clarifications... more We thank Hindié 1 for his interest in our study, 2 and we are happy to provide the clarifications requested. We agree that our nomogram has not been prospectively tested on unselected patients with thin melanoma. Although prospective testing is desirable, it would not be ethical to use unselected patients with stage T1 melanoma because sentinel node biopsy (SNB) would be overtreatment in most cases. Similarly, Hindié 1 notes that we did not test the nomogram on the two subgroups (of the development and validation cohorts) that did not receive SNB. Once again, it is precisely because these subgroups did not receive an SNB that nomogram performance could not be assessed. Thus, we did the only thing possible: assess outcomes after long follow-up, finding that foregoing SNB in these subgroups was justified post hoc.

Human Pathology, 2020

Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping micro... more Sarcomas on photodamaged skin vary in prognosis and management, but can display overlapping microscopic and immunophenotypic features. Improved understanding of molecular alterations in these tumors may provide diagnostic and therapeutic insights. We characterized 111 cutaneous sarcomatoid malignancies and their counterparts, including primary cutaneous angiosarcoma (n Z 7), atypical fibroxanthoma (AFX) (n Z 21), pleomorphic dermal sarcoma (PDS) (n Z 17), extracutaneous undifferentiated pleomorphic sarcoma (n Z 8), cutaneous leiomyosarcoma (LMS) (n Z 5), extracutaneous LMS (n Z 9), sarcomatoid squamous cell carcinoma (spindle cell squamous cell carcinoma) (S-SCC) (n Z 24), and conventional cutaneous squamous cell carcinoma (SCC) (n Z 20), by nextgeneration sequencing (NGS) using the StrataNGS panel for copy number variations, mutations, and/or fusions in more than 60 cancer-related genes. TP53 mutations were highly recurrent in most groups. Angiosarcoma displayed previously reported MYC amplifications, as well as CCND1 gains. RB1 mutations were relatively restricted to cutaneous LMS. As previously reported, PIK3CA mutations occurred in AFX, whereas RAS activation was more frequent in PDS. CDKN2A mutations were recurrent in AFX and S-SCC, whereas PDS displayed frequent CDKN2A deletion. S-SCC displayed mutational similarity to conventional SCC. BRCA1/2 mutations were specific to tumors with disease progression. In a subset, we detected potential driver events novel to these tumor types: activating mutations in IDH2 (PDS), MAP2K1 (angiosarcoma, PDS), and JAK1 (S-SCC) and copy gains in FGFR1 (angiosarcoma, S-SCC), KIT (AFX), MET (PDS), and PDGFRA (PDS). Our findings confirm and expand the spectrum of known genomic aberrations, including potential targetable drivers, in cutaneous sarcomatoid malignancies. In addition, certain events are relatively specific to particular tumors within this differential diagnosis and hence might be diagnostically informative.

Journal of Bacteriology, 1974

The bisulfite reductase (P582) from Desulfotomaculum nigrificans was purified to homogeneity as j... more The bisulfite reductase (P582) from Desulfotomaculum nigrificans was purified to homogeneity as judged by polyacrylamide gel electrophoresis. By colorimetric methods of analysis, the products of bisulfite reduction by this enzyme were determined to be trithionate, thiosulfate, and sulfide. Of these, trithionate was consistently found to be the major product, whereas the latter two were formed in lesser quantities. When [35S]bisulfite was incorporated as substrate, no labeled sulfide was detected. Furthermore, when trithionate and thiosulfate were isolated from reaction mixtures and chemically degraded, 35S was found in all three sulfur atoms of trithionate; however, only the inner sulfur atom of thiosulfate was radioactive. From these data we conclude that the bisulfite reductase of D. nigrificans reduces bisulfite to trithionate and that thiosulfate and sulfide are endogenous side products of the reaction.

Journal of Cutaneous Pathology, 2018

This is the author manuscript accepted for publication and has undergone full peer review but has... more This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Journal of Bacteriology, 1973

Spin-labeling studies were conducted to elucidate the rigidity and viscosity of the membrane of a... more Spin-labeling studies were conducted to elucidate the rigidity and viscosity of the membrane of a facultative thermophilic bacillus. By employing nitroxide stearate probes, it was observed that this fatty acid was incorporated into the membrane fraction. Electron spin resonance spectroscopy indicated that cells grown at 55 C contained a membrane which was more rigid and viscous than the membrane from cells grown at 37 C.

Journal of Clinical Oncology, 2020

PURPOSE Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Region... more PURPOSE Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB. PATIENTS AND METHODS The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status f...

Trends in Anaesthesia and Critical Care, 2020

Modern Pathology, 2019

Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its ... more Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (<8) prioritized somatic mutations, and lacked an ultraviolet (UV) signature. The most recurrent mutation was TP53 inactivation in four (22%) tumors. Frame-preserving insertions affecting the kinase domain of JAK1 were detected in three (17%) cases, and were nonoverlapping with TP53 mutations. Seven (39%) cases demonstrated copy number gain of at least one oncogene. By immunohistochemistry, p53 expression was significantly higher in microcystic adnexal carcinomas with TP53 mutations compared with those without such mutations and syringomas. Similarly, phospho-STAT3 expression was significantly higher in microcystic adnexal carcinomas harboring JAK1 kinase insertions compared with those with wild-type JAK1 and syringomas. In conclusion, microcystic adnexal carcinomas are molecularly heterogeneous tumors, with inactivated p53 or activated JAK/STAT signaling in a subset. Unlike most other nonmelanoma skin cancers involving sun-exposed areas, most microcystic adnexal carcinomas lack evidence of UV damage, and hence likely originate from a relatively photo-protected progenitor population in the dermis. These findings have implications for the biology, diagnosis, and treatment of microcystic adnexal carcinomas, including potential for therapeutic targeting of p53 or the JAK/STAT pathway in advanced tumors.

Clinical Cancer Research, 2019

Purpose: Previously identified transcriptomic signatures have been based on primary and metastati... more Purpose: Previously identified transcriptomic signatures have been based on primary and metastatic melanomas with relatively few American Joint Committee on Cancer (AJCC) stage I tumors, given difficulties in sampling small tumors. The advent of adjuvant therapies has highlighted the need for better prognostic and predictive biomarkers, especially for AJCC stage I and stage II disease. Experimental Design: A total of 687 primary melanoma transcriptomes were generated from the Leeds Melanoma Cohort (LMC). The prognostic value of existing signatures across all the AJCC stages was tested. Unsupervised clustering was performed, and the prognostic value of the resultant signature was compared with that of sentinel node biopsy (SNB) and tested as a biomarker in three published immunotherapy datasets. Results: Previous Lund and The Cancer Genome Atlas signatures predicted outcome in the LMC dataset (P = 10−8 to 10−4) but showed a significant interaction with AJCC stage (P = 0.04) and did n...

American Journal of Surgical Pathology, 2019

Diagnosis of calciphylaxis is crucial, yet its distinction from other vascular diseases can be ch... more Diagnosis of calciphylaxis is crucial, yet its distinction from other vascular diseases can be challenging. Although vascular calcification and thrombosis are hallmarks of calciphylaxis, the incidence and patterns of these features in other vascular diseases have not been well characterized. The specificity of fine calcium deposits in vessel walls (identifiable on von Kossa [VK] stain only) and other extravascular calcifications is not entirely clear. We retrospectively examined the clinicopathologic features in calciphylaxis (n = 27), gangrene and viable skin at amputation margin (n = 20 each), chronic stasis (n = 22), and thrombotic vasculopathy (n = 19) to identify useful discriminators. Calcification of subcutaneous small vessels appreciable on hematoxylin and eosin stain was relatively specific for calciphylaxis, although sensitivity was low (56%). VK detected fine calcium deposits in vessel walls not appreciable on hematoxylin and eosin, however, specificity was limited by frequent finding of similar deposits in peripheral artery disease. Combining calcium deposits detected by VK and thrombosis of subcutaneous small vessels resulted in optimal sensitivity (85%) and specificity (88%) for calciphylaxis. Similar observations applied to medium-sized vessel calcification. Calcification of eccrine gland basement membranes, elastic fibers, and perineurium did not effectively distinguish calciphylaxis from other groups. Diffuse dermal angiomatosis was exclusively found in calciphylaxis in this study. In conclusion, VK is useful in enhancing the detection of vascular calcification and avoiding the false-negative diagnosis, but this finding requires concomitant subcutaneous small vessel thrombosis to support a diagnosis of calciphylaxis. Diffuse dermal angiomatosis should increase suspicion for underlying calciphylaxis and prompt deeper sampling in the appropriate clinical setting.