Outcomes of SWI/SNF complex-deficient sinonasal carcinomas in a Southeast Asian cohort.

BACKGROUND: SWI/SNF complex-deficient sinonasal carcinomas are rare, genetically distinct, and aggressive entities. METHODS: SMARCB1 and SMARCA4 immunohistochemistry was retrospectively performed on a cohort of undifferentiated, poorly differentiated, and poorly defined sinonasal carcinomas. Survival outcomes were compared between SMARCB1/SMARCA4 (SWI/SNF complex)-deficient and -retained groups. RESULTS: Eight SWI/SNF complex-deficient (six SMARCB1-deficient, two SMARCA4-deficient) cases were identified among 47 patients over 12 years. Triple-modality treatment was more frequently utilized in SWI/SNF complex-deficient carcinomas than in SWI/SNF complex-retained carcinomas (71.4% vs. 11.8%, p = 0.001). After a median follow-up of 21.3 (IQR 9.9-56.0) months, SWI/SNF complex-deficient sinonasal carcinomas showed comparable recurrence rates (57.1% vs. 52.9%, p = 0.839), time-to-recurrence (7.3 [IQR 6.6-8.3] vs. 9.1 [IQR 3.9-17.4] months, p = 0.531), and overall survival (17.7 [IQR 11.8-67.0] vs. 21.6 [IQR 8.9-56.0] months, p = 0.835) compared to SWI/SNF complex-retained sinonasal carcinomas. CONCLUSION: Triple-modality treatment may improve survival in SWI/SNF complex-deficient sinonasal carcinomas.

Primary Epithelioid Angiosarcoma of the Submandibular Gland-A Case Report with Histology-Cytology Correlation and Comprehensive Molecular Analysis.

BACKGROUND: Angiosarcoma is a sarcoma that occurs in a range of tissue types, and only rarely in the salivary glands, showing a predilection for the parotid glands of older patients. Preoperative diagnosis may be challenging, especially on cytology, with significant morphological overlap with high-grade primary salivary gland carcinomas. The molecular alterations of this rare salivary gland neoplasm are also not well-characterized. METHODS AND RESULTS: We present a case of right submandibular gland swelling in a 73-year-old male. On fine needle aspiration, including immunohistochemical stains on cell block, the tumor was initially diagnosed as poorly differentiated carcinoma. Resection of the submandibular gland revealed epithelioid angiosarcoma. We performed molecular work-up of the tumor, utilizing targeted next-generation sequencing, DNA methylation profiling and fluorescence in-situ hybridization. Histopathologic assessment revealed an infiltrative tumor comprising solid sheets of epithelioid cells. The tumor cells formed haphazardly anastomosing vascular channels with intracytoplasmic lumina containing red blood cells. On immunohistochemistry, the tumor cells were positive for CD31, CD34 and ERG. Approximately 40% of the tumor cells showed nuclear expression of GATA3. A pathogenic TP53 R267W mutation was detected on next-generation sequencing. DNA methylation analysis did not cluster the tumor with any known sarcoma type. Copy number analysis showed possible MYC amplification and CDKN2A losses, although only the latter was confirmed on fluorescence in-situ hybridization. CONCLUSION: Epithelioid angiosarcoma is an important differential diagnosis to high-grade salivary gland carcinoma. In particular, GATA3 expression may be encountered in both angiosarcoma and high-grade salivary gland carcinomas and cause diagnostic confusion. Identification of TP53 mutations and CDKN2A losses suggest shared oncogenic pathways with soft tissue angiosarcomas, and should be further investigated.

Clinical performance of a prefabricated immunofluorescence assay for nasopharyngeal cancer screening.

BACKGROUND: Epstein-Barr virus (EBV) IgA serology for viral capsid antigen (VCA) and early antigen (EA) aids early detection of nasopharyngeal cancer (NPC), resulting in improved survival. We evaluated the diagnostic performance of a prefabricated immunofluorescent assay (IFA) for NPC screening in high-risk individuals. METHODS: Sera from 96 biopsy-proven patients with NPC diagnosed at the outpatient clinic and 96 healthy family members were tested for EBV-VCA IgA and EBV-EA IgA using the prefabricated IFA from EUROIMMUN (EI) and the traditional immunofluorescence method. RESULTS: The AUC of EI EBV-VCA IgA and EBV-EA IgA was 0.907 (95% confidence interval [CI]: 0.894-0.965) and 0.898 (95% CI: 0.848-0.947), respectively. Combined testing with the prefabricated assay at a threshold of VCA ≥1:320 or EA ≥1:10 showed 92.7% sensitivity and 81.2% specificity. Overall, the traditional EBV-EA IgA assay demonstrated the best accuracy (sensitivity 91.7% and specificity 96.9%) at a threshold of ≥1:5. CONCLUSION: While the traditional IFA method was more accurate, the prefabricated IFA test kit can be a useful tool for NPC screening in high-risk populations.

A Novel Ear Impression-Taking Method Using Structured Light Imaging and Machine Learning: A Pilot Proof of Concept Study with Patients' Feedback on Prototype.

INTRODUCTION: Taking an ear impression is a minimally invasive procedure. A review of existing literature suggests that contactless methods of scanning the ear have not been developed. We proposed to establish a correlation between external ear features with the ear canal and with this proof of concept to develop a prototype and an algorithm for capturing and predicting ear canal information. METHODS: We developed a novel prototype using structured light imaging to capture external images of the ear. Using a large database of existing ear impression images obtained by traditional methods, correlation analyses were carried out and established. A deep neural network was devised to build a predictive algorithm. Patients undergoing hearing aid evaluation undertook both methods of ear impression-taking. We evaluated their subjective feedback and determined if there was a close enough objective match between the images obtained from the impression techniques. RESULTS: A prototype was developed and deployed for trial, and most participants were comfortable with this novel method of ear impression-taking. Partial matching of the ear canal could be obtained from the images taken, and the predictive algorithm applied for a few sample images was within good standard of error with proof of concept established. DISCUSSION: Further studies are warranted to strengthen the predictive capabilities of the algorithm and determine optimal prototype imaging positions so that sufficient ear canal information can be obtained for three-dimensional printing. Ear impression-taking may then have the potential to be automated, with the possibility of same-day three-dimensional printing of the earmold to provide timely access.

The effects of acute social ostracism on subsequent snacking behavior and future body mass index in children.

BACKGROUND/OBJECTIVES: Ostracism may lead to increased food intake, yet it is unclear whether greater reactivity to ostracism contributes to higher body mass index (BMI). We investigated whether children who exhibited greater stress to social exclusion subsequently consume more energy and whether this predicts BMI 6- and 18-months later. SUBJECTS/METHODS: Children (8.5 years-old) (N = 262, males = 50.4%; Chinese = 58.4%) completed a laboratory-based manipulation of social exclusion (the Cyberball task) prior to an ad-libitum snack. Heart rate variability (HRV) was measured during the inclusion and exclusion conditions and proportionate changes were calculated as a physiological measure of exclusion-related stress. Social anxiety and social-emotional assets were also measured as moderators. RESULTS: Greater stress (as measured physiologically or by self-report) did not directly, or indirectly via energy intake, predict later BMI (at 9- and 10-years). However, among children reporting higher social anxiety, greater stress as measured by proportionate changes in HRV was associated with increased energy intake (B = 532.88, SE = 226.49, t(255) = 2.35, [CI95 = 86.85,978.92]). A significant moderated mediation was also observed (index: (b = 0.01, bootSE = 0.01, [CI95 = 0.001, 0.036]), such that among children reporting higher social anxiety, greater stress from social exclusion predicted increased energy intake from a subsequent snack, which in turn predicted higher BMI 1.5 years later. CONCLUSION: This prospective study suggests that a pattern of greater snack intake in response to heightened vulnerability to the effects of ostracism may contribute to increases in child BMI scores.

Lexicon for classifying ear-canal shapes.

The ear canal is usually described as an S-shaped funnel. In attempting to classify ear-canal shapes obtained from point clouds digitized from molds of 300 ears, the problem of designing criteria for distinguishing and organizing the canal shapes arose. In this work, we extracted features inspired by the S-shape characteristic (critical point, maximum, minimum, twist, writhe, translation, rotation) and, through them, introduced 14 types of ear-canal shapes. This classification allowed comparison of ears within a type and of ears between different types. It expanded our range of descriptors of canal shapes and unlocked perspectives for applications.

Teleconsultation Perceptions of Medical and Radiation Oncologists in the COVID-19 and Post-COVID-19 Era: A National Survey in the Philippines.

PURPOSE: The study reports on the current perception of medical and radiation oncologists regarding teleconsultation in the Philippines. Before the COVID-19 pandemic, the adoption of telemedicine was not widespread. With movement restrictions imposed during the pandemic, physicians were compelled to use telemedicine. It is uncertain whether physicians will still adopt its use in practice in the post-COVID-19 era. This study gives insight into the possible adaptation of this mode of consultation in the future, especially in areas with limited health care resources. MATERIALS AND METHODS: We conducted a national survey among medical oncologists and radiation oncologists in the Philippines. A 43-item online survey was developed, validated, and administered to the oncologists. The demographics and data from categorical questions were reported as frequencies and percentages. RESULTS: A total of 142 responses were gathered from 82 medical oncologists and 60 radiation oncologists. There was agreement among participants that, during the pandemic, teleconsultation could be used for the first visit, diagnostic workup request, treatment explanation, follow-up care, and chronic disease management. There was disagreement whether cancer diagnosis disclosure and cancer prognosis revelation could be performed via teleconsultation, and there was agreement that emergency consultation and physical examination would warrant a face-to-face consultation. After the COVID-19 pandemic, 78.7% intend to continue using teleconsultation except for emergency consultations, first visits, physical examination, diagnosis disclosure, and cancer prognosis revelation. CONCLUSION: Teleconsultation was perceived by oncologists as an acceptable method of providing cancer care during and after the COVID-19 pandemic. Oncologists also intend to use teleconsultation in the post-COVID-19 era in certain aspects of patient care.

Endometrial stem/progenitor cells in menstrual blood and peritoneal fluid of women with and without endometriosis.

RESEARCH QUESTION: Are endometrial stem/progenitor cells shed into uterine menstrual blood (UMB) and the peritoneal cavity in women with and without endometriosis during menstruation? DESIGN: Women with (n = 32) and without endometriosis (n = 29) at laparoscopy (total 61), carried out during the menstrual (n = 41) and non-menstrual phase (n = 20) were recruited. The UMB, peritoneal fluid and peripheral blood were analysed by clonogenicity assay and flow cytometry to quantify the concentrations of endometrial clonogenic cells, SUSD2+ mesenchymal stem cells (eMSC) and N-cadherin+ epithelial progenitor cells (eEPC). RESULTS: Clonogenic endometrial cells, eMSC and eEPC were found in most UMB samples at similar concentrations in women with and without endometriosis. In contrast, 62.5% of women with endometriosis and 75.0% without (controls) had clonogenic cells in peritoneal fluid samples during menses. The eMSC were present in the peritoneal fluid of 76.9% of women with endometriosis and 44.4% without, and eEPC were found in the peritoneal fluid of 60.0% of women with and 25.0% without endometriosis during menses. Median clonogenic, eMSC and eEPC concentrations in peritoneal fluid were not significantly different between groups. More clonogenic cells persisted beyond the menstrual phase in the peritoneal fluid of women with endometriosis (menstrual 119/ml [0-1360/ml] versus non-menstrual 8.5/ml [0-387/ml]; P = 0.277) compared with controls (menstrual 76.5/ml [1-1378/ml] versus non-menstrual 0/ml [0-14/ml]; P = 0.0362). No clonogenic endometrial cells were found in peripheral blood. CONCLUSIONS: Clonogenic endometrial cells, SUSD2+ eMSC and N-cadherin+ eEPC are present in UMB and the peritoneal fluid of women with and without endometriosis. Further study of the function of these cells may shed light on the cellular origins of endometriosis.

Stopping or reducing dietary fiber intake reduces constipation and its associated symptoms.

AIM: To investigate the effect of reducing dietary fiber on patients with idiopathic constipation. METHODS: Sixty-three cases of idiopathic constipation presenting between May 2008 and May 2010 were enrolled into the study after colonoscopy excluded an organic cause of the constipation. Patients with previous colon surgery or a medical cause of their constipation were excluded. All patients were given an explanation on the role of fiber in the gastrointestinal tract. They were then asked to go on a no fiber diet for 2 wk. Thereafter, they were asked to reduce the amount of dietary fiber intake to a level that they found acceptable. Dietary fiber intake, symptoms of constipation, difficulty in evacuation of stools, anal bleeding, abdominal bloating or abdominal pain were recorded at 1 and 6 mo. RESULTS: The median age of the patients (16 male, 47 female) was 47 years (range, 20-80 years). At 6 mo, 41 patients remained on a no fiber diet, 16 on a reduced fiber diet, and 6 resumed their high fiber diet for religious or personal reasons. Patients who stopped or reduced dietary fiber had significant improvement in their symptoms while those who continued on a high fiber diet had no change. Of those who stopped fiber completely, the bowel frequency increased from one motion in 3.75 d (± 1.59 d) to one motion in 1.0 d (± 0.0 d) (P < 0.001); those with reduced fiber intake had increased bowel frequency from a mean of one motion per 4.19 d (± 2.09 d) to one motion per 1.9 d (± 1.21 d) on a reduced fiber diet (P < 0.001); those who remained on a high fiber diet continued to have a mean of one motion per 6.83 d (± 1.03 d) before and after consultation. For no fiber, reduced fiber and high fiber groups, respectively, symptoms of bloating were present in 0%, 31.3% and 100% (P < 0.001) and straining to pass stools occurred in 0%, 43.8% and 100% (P < 0.001). CONCLUSION: Idiopathic constipation and its associated symptoms can be effectively reduced by stopping or even lowering the intake of dietary fiber.

Changes in culture expanded human amniotic epithelial cells: implications for potential therapeutic applications.

Human amniotic epithelial cells (hAEC) isolated from term placenta have stem cell-like properties, differentiate into tissue specific cells and reduce lung and liver inflammation and fibrosis following transplantation into disease models established in mice. These features together with their low immunogenicity and immunosuppressive properties make hAEC an attractive source of cells for potential therapeutic applications. However, generation of large cell numbers required for therapies through serial expansion in xenobiotic-free media may be a limiting factor. We investigated if hAEC could be expanded in xenobiotic-free media and if expansion altered their differentiation capacity, immunophenotype, immunosuppressive properties and production of immunomodulatory factors. Serial expansion in xenobiotic-free media was limited with cumulative cell numbers and population doubling times significantly lower than controls maintained in fetal calf serum. The epithelial morphology of primary hAEC changed into mesenchymal-stromal like cells by passage 4-5 (P4-P5) with down regulation of epithelial markers CK7, CD49f, EpCAM and E-cadherin and elevation of mesenchymal-stromal markers CD44, CD105, CD146 and vimentin. The P5 hAEC expanded in xenobiotic-free medium differentiated into osteocyte and alveolar epithelium-like cells, but not chondrocyte, hepatocyte, α- and ß-pancreatic-like cells. Expression of HLA Class IA, Class II and co-stimulatory molecules CD80, CD86 and CD40 remained unaltered. The P5 hAEC suppressed mitogen stimulated T cell proliferation, but were less suppressive compared with primary hAEC at higher splenocyte ratios. Primary and P5 hAEC did not secrete the immunosuppressive factors IL-10 and HGF, whereas TGF-ß1 and HLA-G were reduced and IL-6 elevated in P5 hAEC. These findings suggest that primary and expanded hAEC may be suitable for different cellular therapeutic applications.

The mesenchymal stem cell antigen MSCA-1 is identical to tissue non-specific alkaline phosphatase.

We have recently identified 2 distinct CD271(bright)MSCA-1(dim)CD56(+) and CD271(bright)MSCA-1(bright)CD56(-) MSC subsets in primary femur-derived bone marrow (BM), which differ in their expression pattern and morphology as well as in their clonogenic and differentiation capacity. Here, we show that MSCA-1 is identical to tissue non-specific alkaline phosphatase (TNAP), an ectoenzyme known to be expressed at high levels in liver, bone, and kidney as well as in embryonic stem (ES) cells. SDS-PAGE of WERI-RB-1 cell lysate and supernatant from phosphatidylinositol-specific phospholipase C (PI-PLC)-treated WERI-RB-1 cells resulted in the appearance of a prominent 68-kDa band. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDITOF MS) sequence analysis revealed TNAP-specific peptides. Screening of the MSCA-1-specific antibody W8B2 on HEK-293 cells transfected with the full-length coding sequence of TNAP showed specific reactivity with transfected but not with parent cell line. In addition, TNAP-specific mRNA expression was selectively detected in the transfectant line. In agreement with these findings, enzymatic activity of TNAP was exclusively detected in sorted MSCA-1(+) BM cells but not in the MSCA-1(-) negative fraction. Surface marker analysis revealed coexpression of the embryonic marker SSEA-3 but not SSEA-4, TRA-1-60, and TRA-1-81. In endometrium, TNAP is expressed at intermediate levels on CD146(+) cells and at high levels in the luminal space of glandular epithelia. Our results demonstrate that TNAP is a selective marker for the prospective isolation of BM-derived MSC and MSC-like cells in endometrium.