Antibody stabilization for thermally accelerated deep immunostaining.

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining.

Convergent dysbiosis of upper aerodigestive microbiota between patients with esophageal and oral cavity squamous cell carcinoma.

The bidirectional association between primary esophageal squamous cell carcinoma (ESCC) and oral cavity squamous cell carcinoma (OSCC) suggests common risk factors and oncogenic molecular processes but it is unclear whether these two cancers display similar patterns of dysbiosis in their upper aerodigestive microbiota (UADM). We conducted a case-control study to characterize the microbial communities in esophageal lavage samples from 49 ESCC patients and oral rinse samples from 91 OSCC patients using 16S rRNA V3-V4 amplicon sequencing. Compared with their respective non-SCC controls from the same anatomical sites, 32 and 45 discriminative bacterial genera were detected in ESCC and OSCC patients, respectively. Interestingly, 20 of them were commonly enriched or depleted in both types of cancer, suggesting a convergent niche adaptation of upper aerodigestive SCC-associated bacteria that may play important roles in the pathogenesis of malignancies. Notably, Fusobacterium, Selenomonas, Peptoanaerobacter and Peptostreptococcus were enriched in both ESCC and OSCC, whereas Streptococcus and Granulicatelia were commonly depleted. We further identified Fusobacterium nucleatum as the most abundant species enriched in the upper aerodigestive SCC microenvironment, and the higher relative abundances of Selenomonas danae and Treponema maroon were positively correlated with smoking. In addition, predicted functional analysis revealed several depleted (eg, lipoic acid and pyruvate metabolism) and enriched (eg, RNA polymerase and nucleotide excision repair) pathways common to both cancers. Our findings reveal a convergent dysbiosis in the UADM between patients with ESCC and OSCC, suggesting a shared niche adaptation of host-microbiota interactions in the pathogenesis of upper aerodigestive tract malignancies.

Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication-A Systematic Review.

Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.

Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with R/R TCL and NKTL were treated with standard dose ICE, dexamethasone 20mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose level (DL) 1, 2 and 3 were 40, 60 and 80mg respectively. Eleven patients with a median age of 60 were enrolled; 6 at DL1 and 5 at DL2. Patients had received a median of 2 (range 1-4) prior lines of treatment and 7 had primary refractory disease at study entry. Patients received a median of 3 cycles (range 1-6) of selinexor-DICE. The most common grade (G) 1/2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common G 3/4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed doselimiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the 10 evaluable patients, the overall and complete response rates were 91% and 82% respectively. The MTD of selinexor was 40mg when combined with DICE. The combination showed promising CR rates in patients with R/R TCL and NKTL but was poorly tolerated.

Recommendations for head and neck surgical oncology practice in a setting of acute severe resource constraint during the COVID-19 pandemic: an international consensus.

The speed and scale of the global COVID-19 pandemic has resulted in unprecedented pressures on health services worldwide, requiring new methods of service delivery during the health crisis. In the setting of severe resource constraint and high risk of infection to patients and clinicians, there is an urgent need to identify consensus statements on head and neck surgical oncology practice. We completed a modified Delphi consensus process of three rounds with 40 international experts in head and neck cancer surgical, radiation, and medical oncology, representing 35 international professional societies and national clinical trial groups. Endorsed by 39 societies and professional bodies, these consensus practice recommendations aim to decrease inconsistency of practice, reduce uncertainty in care, and provide reassurance for clinicians worldwide for head and neck surgical oncology in the context of the COVID-19 pandemic and in the setting of acute severe resource constraint and high risk of infection to patients and staff.

The role of tumor DNA as a diagnostic tool for head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) represents the most common type of head and neck cancer worldwide. However, despite advances in cancer care globally there has been little progress in HNSCC, with survival remaining static and slightly worse in laryngeal squamous cell carcinoma with 5 year survivals remaining at ∼50%. Conventional analysis of tissue through cytopathology or histopathology are the mainstay of diagnosis. Furthermore there are no useful biomarkers for disease diagnosis or surveillance. With recent technological advances, particularly in next generation sequencing, here we explore the application of tumor DNA for HNSCC diagnosis and surveillance, to improve surgical margin analysis and the potential use of molecular agents aiding in the imaging of HNSCC.

Early results of a safety and feasibility clinical trial of a novel single-port flexible robot for transoral robotic surgery.

The aim of this study was to describe the early results of a phase 1 safety and feasibility clinical trial of the first clinical use of a novel robot for transoral robotic surgery (TORS)-the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA). Study design of this study is prospective clinical trial. The methods used in this study are prospective innovation, development, exploration, assessment, and long-term study phase 1 clinical trial. Early results of six patients underwent TORS with the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA) demonstrate access the nasopharynx, oropharynx, larynx, and hypopharynx. There were no conversions of the robotic surgical system. There were no serious adverse events or adverse events related to the use of the robot at 30-day follow-up for all six patients. The early results of this safety and feasibility trial of the da Vinci SP (Intuitive Surgical Inc., Sunnyvale, CA, USA) clearly demonstrate that the device is safe and that it is feasible in performing TORS to access the nasopharynx, oropharynx, larynx, and hypopharynx.

Clinical subsets associated with different anti-aminoacyl transfer RNA synthetase antibodies and their association with coexisting anti-Ro52.

OBJECTIVE: To characterize clinical features of polymyositis/dermatomyositis (PM/DM) patients with different anti-aminoacyl transfer RNA synthetase (ARS) antibodies and their association with anti-Ro52. METHODS: Autoantibodies in sera from 97 Japanese patients (36 PM, 56 DM, and 5 clinically amyopathic DM), who satisfied Bohan and Peter or modified Sontheimer's criteria, were characterized by immunoprecipitation and enzyme-linked immunosorbent assay. Clinical information was from medical records. Features associated with different anti-ARS and anti-Ro52 antibodies were analyzed. RESULTS: The prevalence of anti-ARS was similar to other studies (Jo-1, 22%; EJ, 4%; OJ, 1%; PL-12, 1%), except for a high prevalence of anti-PL-7 (12%), which allowed us to characterize patients carrying this specificity. Serum creatine kinase >3000 IU/l was less common in anti-PL-7-positive patients (57%) than anti-Jo-1-positive patients (18%) (p = 0.0328) and was not found in anti-EJ-positive individuals. Interstitial lung disease was common in anti-ARS-positive patients (97%) (p < 0.0001 vs. 48% in anti-ARS-negative). Anti-Ro52 antibodies were frequently detected with anti-ARS (59%) (57% in anti-Jo-1, 67% in anti-PL-7) (vs. 21% in anti-ARS-negative, p < 0.0002). Anti-Ro52 was associated with overlap syndrome (26%) (vs. 7% in anti-Ro52-negative, p = 0.0119). CONCLUSIONS: Patients with different anti-ARS in combination with anti-Ro52 appear to be associated with distinctive clinical subsets.

Prevalence and clinical significance of anti-MDA5 antibodies in European patients with polymyositis/dermatomyositis.

OBJECTIVES: Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease characterised by skin and muscle inflammation, internal organ involvement and serum disease-specific autoantibodies. The recently identified anti-MDA5 (melanoma differentiation-associated gene 5) antibodies are associated with clinically amyopathic DM (CADM), rapidly progressive interstitial lung disease, severe skin manifestations, and poor prognosis. Our objective was to examine the clinical significance of anti-MDA5 antibodies in a cohort of European Caucasian patients with PM/DM, considering that data on anti-MDA5 serology are limited to Asian and US cohorts. METHODS: Sera from 76 consecutive adult Italian patients with PM/DM were analysed by immunoprecipitation (IP) of 35S-methionine radiolabelled HeLa and K562 cell extracts, ELISA using recombinant MDA5 protein and IP-Western Blot using rabbit anti-MDA5 antibodies. Clinical associations of anti-MDA5 antibody positive patients were analysed. RESULTS: Anti-MDA5 antibodies were identified in 5/76 (7%) PM/DM cases and all 5 cases were CADM; anti-MDA5 was the second most common autoantibody in DM after anti-MJ/NXP-2, found in 24% of cases. Compared to 29 anti-MDA5 (-) DM, anti-MDA5 (+) patients have more typical DM skin disease (digit pulp/periungual lesions, Gottron's papules, heliotrope rash) (p=ns). Interstitial lung disease was observed in 3/5 anti-MDA5 (+) patients but only 14% of anti-MDA5 (-) cases (p=0.048). CONCLUSIONS: Our study on European patients with PM/DM confirms that anti-MDA5 antibodies are not uncommon. All anti-MDA5 (+) cases are affected by CADM with typical skin disease, while rapidly progressive pulmonary involvement was diagnosed only in one case. Further studies in larger cohorts are necessary to define the clinical significance of anti-MDA5 antibodies in European PM/DM.

The Ability of Physical Performance Measures to Identify Fall Risk in Older Adults Living With Dementia: A Systematic Review and Meta-Analysis.

OBJECTIVES: To determine whether physical performance measures commonly used in clinical settings can discriminate fallers from nonfallers and predict falls in older adults with dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Older adults with dementia residing in the community, hospitals, and residential care facilities. METHODS: MEDLINE, Embase, PsycINFO, CINAHL, SPORTDiscus, the Cochrane Library, and the PEDro databases were searched from inception until December 27, 2023 (PROSPERO registration number: CRD42022303670). Retrospective or prospective studies that evaluated the associations between physical performance measures and falls in older adults with dementia were included. A random effects model was used to calculate the standardized mean difference (SMD) and 95% CI for each physical performance measure between fallers and nonfallers. Sensitivity analyses were conducted on the longitudinal studies to determine the ability of physical performance measures to predict future falls. RESULTS: Twenty-eight studies were included in this review (n = 3542). The 5-time chair stand test [SMD = 0.23 (0.01, 0.45)], the Berg Balance Scale [SMD = -0.52 (-0.87, -0.17)], postural sway when standing on the floor [SMD = 0.25 (0.07, 0.43)] and on a foam surface [SMD = 0.45 (0.25, 0.66)], and the Short Physical Performance Battery total score [SMD = -0.46 (-0.66, -0.27)] could discriminate fallers from nonfallers. Sensitivity analyses showed that gait speed could predict future falls in longitudinal cohort studies [SMD = -0.29 (-0.49, -0.08)]. Subgroup analyses showed that gait speed [SMD = -0.21 (-0.38, -0.05)] and the Timed Up and Go test [SMD = 0.54 (0.16, 0.92)] could identify fallers staying in residential care facilities or hospitals. CONCLUSIONS AND IMPLICATIONS: The 5-time chair stand test, the Berg Balance Scale, postural sway when standing on the floor and a foam surface, and the Short Physical Performance Battery can be used to predict falls in older adults with dementia. Gait speed and the Timed Up and Go test can be used to predict falls in institutionalized older adults with dementia. Clinicians are recommended to use these physical performance measures to assess fall risk in older adults with dementia.

Radiofrequency ablation compared to surgery for thyroid nodules: A case for office based treatment.

Objective: We aim to evaluate the safety and effectiveness of radiofrequency ablation (RFA) for benign thyroid nodules by ENT surgeons and to compare it to conventional hemithyroidectomy in the public healthcare, operating theater contained setting. Methods: 50 patients who underwent a single session of RFA for symptomatic benign thyroid nodules in Prince of Wales Hospital and Tseung Kwan O Hospital in Hong Kong from 2020 to 2022 were evaluated. Objective outcomes including nodule volume, volume reduction rate (VRR) and complications were recorded. Subjective response in the form of a 0-10 point scale for patient symptoms including obstructive, cosmetic, pain and satisfaction scores were collected. Results: Significant reduction in mean VRR was found at 3, 6 and 12 months post treatment, accompanied by a significant reduction in the mean obstructive and cosmetic symptom scores. Comparing with conventional hemithyroidectomy, the RFA group had a significantly shorter mean procedure time and lower rate of complications. Estimated cost to patient for RFA was found to be less than half of that of hemithyroidectomy. Conclusion: RFA is a safe and effective treatment modality for benign thyroid nodules by ENT surgeons with advantages of being a scarless local anesthetic procedure with shorter procedure time, lower complication rate and lower cost to patient compared to hemithyroidectomy. In Hong Kong, where most of the population is treated in the public sector, there are limited resources, often with high caseload burden and long operation waiting times. Therefore, RFA is an office-based treatment that serves as a valuable alternative to hemithyroidectomy for benign nodules, especially in lower resource settings. Level of evidence: 3.

Reactive postural adjustment in response to predictable and unpredictable perturbations in healthy adults: A comparison between swayback, hyperlordotic and erect postures.

BACKGROUND: Promoting an erect posture in standing has been advocated to offer superior protection to the spine when compared to hyperlordotic and swayback postures. RESEARCH QUESTION: Do postural adjustments towards external perturbation differ between erect, hyperlordotic and swayback postures? If so, which posture offers better protection to lumbar spine? METHODS: Forty-four healthy adults received top-down perturbations under unpredictable (without visual-and-auditory input) and predictable (with visual-and-auditory input) conditions in three simulated postures: erect, hyperlordotic, and swayback. Postural adjustments namely the centre of pressure parameters, joint angle onsets, and neuromuscular responses measured by muscle onsets and co-contraction between muscle pairs upon the perturbation were compared using the two-way repeated measures ANOVA. Post-hoc analysis with Bonferroni correction was conducted to identify the between-posture differences for the respective postural adjustment parameters. RESULTS: Path length, ellipse area and average velocity of centre of pressure were significantly greater under unpredictable condition as compared to predictable condition (p < 0.001). Significant between-posture difference was detected in centre of pressure path length (p < 0.035), pelvic tilt onset (p < 0.038) and all muscle co-contraction indexes (p < 0.001). Post-hoc analysis revealed significantly smaller centre of pressure path length in erect posture as compared to hyperlordotic and swayback postures (p < 0.01) under unpredictable conditions. Significantly greater co-contraction indexes of lumbar multifidus and erector spinae, and internal oblique and lumbar multifidus were found in hyperlordotic as compared to erect and swayback postures (p < 0.05). SIGNIFICANCE: Compared to erect posture, adoption of hyperlordotic and swayback postures altered the contributions of the active and passive subsystems of the spine that regulates postural control upon external perturbations. Such differences in neuromuscular control may lessen the capacity of the human spine to withstand loading and shear forces. Prospective studies are required to validate if habitually adopted hyperlordotic and swayback postures contribute to an earlier/ higher prevalence of spinal dysfunctions.

A Safety and Feasibility Trial of Ultrasound-Guided Radiofrequency Ablation of Parotid Warthin's Tumor.

OBJECTIVE: To determine if ultrasound-guided (USG) radiofrequency ablation (RFA) of Parotid Warthin's tumor under local anesthesia is a safe and effective procedure. STUDY DESIGN: Safety and feasibility study. SETTING: Tertiary academic medical center. METHODS: This is an IDEAL phase 2a trial in a tertiary referral center. Twenty patients with Parotid Warthin's tumor were recruited. RFA was done between September and December 2021 for all 20 patients using a CoATherm AK-F200 machine with a disposable, 18G × 7 mm radiofrequency electrode. Results and follow-up statistics were compared with a historic sample of patients with parotid Warthin's tumor who underwent parotidectomy between 2019 and 2021 in the same center. RESULTS: Nineteen patients were included in the analysis as 1 patient dropped out after 4 weeks of follow-up. The mean age for the RFA group was 67 years old with most of them being male smokers. At a median of 45 weeks (44-47 weeks) postprocedure there was a 7.48 mL (68.4%) volume reduction compared to baseline. Three patients had transient facial nerve (FN) paresis, 1 recovered within hours, and the other 2 by 12 weeks follow-up. Three patients had great auricular nerve numbness; 1 patient had infected hematoma treated in an out-patient manner. Compared to a historic cohort of parotidectomy patients for Warthin's tumor, there was no significant difference in FN paresis and other minor complications between the 2 treatment modalities. CONCLUSION: The current analysis suggests that USG RFA of Warthin's Tumor is a safe alternative to parotidectomy with shorter operative time and length of stay.

Comparison of da Vinci Single Port vs Si Systems for Transoral Robotic-Assisted Surgery: A Review With Technical Insights.

Importance: Transoral robot-assisted surgery (TORS) continues to have a major role in the treatment of oropharyngeal cancer. As new iterations of robotic technology are increasingly utilized, it is important to share learning experiences and clinical outcomes data, to optimize technical efficiency and clinical care. Observations: This was a retrospective review of a large academic institution's initial clinical use of the da Vinci Single Port (SP) compared with the da Vinci Si (Si) system. A total of 205 TORS cases were reviewed: 109 in the SP group (November 22, 2018, through September 30, 2020), and 96 in the Si group (January 1, 2016, through November 12, 2018). Both groups had comparable operative times, rates of postoperative pharyngeal hemorrhage, length of hospital stay, and duration of nasogastric feeding tube use. There was no difference in pathological characteristics, rates of positive margins, or indications for or time to initiation of adjuvant therapy between the groups. The collective experience of 6 faculty members-who have trained 139 TORS surgeons for the SP system rollout-was compiled to provide a summary of learning experiences and technical notes on safe and efficient operation of the SP system. Conclusions and Relevance: This Review found that the functional and oncologic outcomes were comparable between TORS cases performed with the Si and SP systems, and they had similar complication rates. Recognized advantages of the SP over the Si system include the availability of bipolar-energized instruments, a usable third surgical arm, and improved camera image quality.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

Changes in the Incidence and Human Papillomavirus-Positive Portion of Oropharyngeal Squamous Cell Carcinoma in Hong Kong.

The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010-2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016-2020 vs. 40.4% (19/47) in 2010-2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers.

Integrative analysis reveals associations between oral microbiota dysbiosis and host genetic and epigenetic aberrations in oral cavity squamous cell carcinoma.

Dysbiosis of the human oral microbiota has been reported to be associated with oral cavity squamous cell carcinoma (OSCC) while the host-microbiota interactions with respect to the potential impact of pathogenic bacteria on host genomic and epigenomic abnormalities remain poorly studied. In this study, the mucosal bacterial community, host genome-wide transcriptome and DNA CpG methylation were simultaneously profiled in tumors and their adjacent normal tissues of OSCC patients. Significant enrichment in the relative abundance of seven bacteria species (Fusobacterium nucleatum, Treponema medium, Peptostreptococcus stomatis, Gemella morbillorum, Catonella morbi, Peptoanaerobacter yurli and Peptococcus simiae) were observed in OSCC tumor microenvironment. These tumor-enriched bacteria formed 254 positive correlations with 206 up-regulated host genes, mainly involving signaling pathways related to cell adhesion, migration and proliferation. Integrative analysis of bacteria-transcriptome and bacteria-methylation correlations identified at least 20 dysregulated host genes with inverted CpG methylation in their promoter regions associated with enrichment of bacterial pathogens, implying a potential of pathogenic bacteria to regulate gene expression, in part, through epigenetic alterations. An in vitro model further confirmed that Fusobacterium nucleatum might contribute to cellular invasion via crosstalk with E-cadherin/ß-catenin signaling, TNFα/NF-κB pathway and extracellular matrix remodeling by up-regulating SNAI2 gene, a key transcription factor of epithelial-mesenchymal transition (EMT). Our work using multi-omics approaches explored complex host-microbiota interactions and provided important insights into genetic and functional basis in OSCC tumorigenesis, which may serve as a precursor for hypothesis-driven study to better understand the causational relationship of pathogenic bacteria in this deadly cancer.

Prevalence and sociodemographic correlates of antinuclear antibodies in the United States.

OBJECTIVE: To estimate the prevalence, types, and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANAs) in the US. METHODS: We conducted a cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey 1999-2004. ANAs were assessed by indirect immunofluorescence. In ANA-positive individuals, cellular staining patterns were determined, and specific autoantibody reactivities were assessed by immunoprecipitation. RESULTS: The ANA prevalence in the US population of individuals ages 12 years and older was 13.8% (95% confidence interval [95% CI] 12.2-15.5%). ANA prevalence increased with age (P=0.01), and ANAs were more prevalent among females than males (17.8% versus 9.6%; P<0.001), with the female-to-male ratio peaking at 40-49 years of age. ANA prevalence was modestly higher in African Americans compared with whites (age-adjusted prevalence odds ratio [POR] 1.30, 95% CI 1.00-1.70). Remarkably, ANAs were less common in overweight and obese individuals (age-adjusted POR 0.74) than in persons of normal weight. No significant associations of ANA with education, family income, alcohol use, smoking history, serum levels of cotinine, or C-reactive protein were observed. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns were seen in 21.8%, and nucleolar patterns were seen in 6.1%; the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). CONCLUSION: These findings suggest that more than 32 million persons in the US have ANAs, and that the prevalence is higher among females, older individuals, African Americans, and those with a normal body weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.

Autoantibodies to Argonaute 2 (Su antigen).

Like many other classical autoantibodies in systemic rheumatic diseases, anti-Su antibodies were originally defined by the double immunodiffusion assay in the early 80s. However, despite its high prevalence, only a few reports on anti-Su were published in the following years and the progress in characterizing the target antigens and clinical significance was slow, probably due to its inconsistent or poor reactivity in other standard immunoassays. In 2006 the target antigen was identified as the microRNA (miRNA)-binding protein Argonaute 2 (Ago2). Ago2 is a key component of the RNA-induced silencing complex enriched in cytoplasmic foci called GW bodies. Due to preferential reactivity of human autoantibodies with native antigens, immunoprecipitation is the only method to reliably detect anti-Su/Ago2 antibodies. Anti-Su/Ago2 does not appear to have disease specificity since it is found in 10-20% of patients with various rheumatic diseases, including systemic lupus erythematosus, scleroderma, polymyositis/dermatomyositis, and Sjögren's syndrome, as well as apparently healthy individuals at lower prevalence. The clinical significance and the mechanism of production of anti-Su/Ago2 remains to be clarified.

A case of congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma mimicking a carotid body tumor.

Ectopic parathyroid adenomas can be encountered during four gland explorations, but nearly 80% of adenomas are localized with ultrasound and sestamibi imaging. Ectopic adenomas are thought to arise from abnormal migration during development. As a cervical congenital anomaly, common carotid artery agenesis is an extremely rare anomaly characterized by separate origins of the internal and external carotid arteries directly from the aortic arch. Here we present a case of a 75 year old man with primary hyperparathyroidism who was found to have congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma within the parapharyngeal space, which mimicked a carotid body tumor based on location and imaging. The successful identification and resection of the ectopic parathyroid adenoma presented here demonstrate the importance of preoperative imaging studies to allow appropriate operative planning as well as the utility of intraoperative parathyroid hormone assay in predicting cure during surgery.