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Background: There have been conflicting results about the association between Behçet's disease and smoking. Smoking has been reported to be a protective factor for Behçet's disease, whereas smoking may have a role in triggering Behçet's disease. Objectives: The aim of this study was to investigate the incidence of Behçet's disease in Korea according to smoking status using nationwide population data. Methods: We analysed clinical data from individuals 20 years of age and older who received a health examination arranged by the Korean national insurance programme between 2009 and 2012. The incidence of Behçet's disease was analysed according to smoking status reported by individuals during their health examination. Newly diagnosed cases of Behçet's disease were identified using claims data from baseline to the date of diagnosis or until 31 December 2016. Results: The risk of Behçet's disease was lower in current smokers compared with never‐smokers regardless of the amount and duration of smoking. The decreased risk of Behçet's disease in current smoker persisted after adjusting for age, sex, regular exercise, drinking status, BMI, diabetes mellitus, hypertension, and dyslipidaemia, history of stroke and/or history of ischaemic heart diseases. Limitations: Genetic susceptibility or family history of Behçet's disease was not considered. Conclusions: This study found a decreased incidence of Behçet's disease in current smokers compared with never‐smokers. Further investigation of the pathophysiology responsible for the negative association between smoking and Behçet's disease is needed. [ABSTRACT FROM AUTHOR]

Aims We investigated the roles of neuronal-derived nitric oxide (NO) in the modulation of spontaneous activity of mouse detrusor smooth muscle. Methods Detrusor smooth muscle strips were isolated from nNOS gene knock-out (nNOS−/−) mice and their wild type siblings (nNOS+/+). The properties of smooth muscle cells were assessed using intracellular electrophysiology and Ca2+ imaging by laser-scanning confocal microscopy. The effects of an nNOS inhibitor, 7-nitro indazole (7-NI) on electrically evoked contractility were assessed using nNOS+/+ mouse detrusor strips. Results In spontaneously active cells, the frequency of spontaneous action potentials (sAPs) and whole cell Ca2+ flashes in nNOS−/− preparations was lower than that in the nNOS+/+ preparations. The frequency of sAPs was enhanced by a nitric oxide donor, diethylamine NONOate sodium salt (NONOate; 100 µM), both when used alone and when the cGMP pathway was blocked by 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 10 µM). 7-NI (100 µM) significantly suppressed the electrically evoked contraction of mouse detrusor strips. Conclusions We suggest that neuronal-derived NO facilitates the generation of spontaneous activity via a cGMP-independent pathway, and consequently enhances the evoked contraction of detrusor. Dysregulation of nNOS containing nerves may underlie bladder pathologies. Neurourol. Urodynam. 31:572-578, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Investigates the synthesis of maturation-related wheat germ agglutinin binding glycoproteins in human corpus epididymis. Technique used in the synthesis; Role of GP-83 in sperm maturation; Significance of attachment and proliferation of cultured epididymal cells.

Investigates the glycoproteins in principal cells of corpus epididymis and the conjugation of molecules on caput sperm using co-cultures. General appearance of corpus epididymal cells; Site of synthesis and secretion of mutation-related glycoproteins; Effects of estradiol on the synthesis of tissue proteins and receptors.

Measures survival, growth rate, and initial egg complement of California red scale, Aonidiella aurantii, when reared on foliage and bark of four citrus cultivars in order to determine the extent that variation among citrus cultivars may introduce variation in the number and quality of scale for utilization by the introduced parasitoid Aphytis melinus.

We have integrated the low work function NiSi:Hf gate on high-κ LaAlO3 and on smart-cut Ge-on-insulator (SC-GOI) n-MOSFETs. At 1.4-nm equivalent oxide thickness, the NiSi:Hf-LaAlO3/SC-GOI n-MOSFET has comparable gate leakage current with the control Al gate on LaAlO3-Si MOSFETs that is ∼5 orders of magnitude lower than SiO2. In addition, the LaAlO3/SC-GOI n-MOSFET with a metal-like fully NiSi:Hf gate has high peak electron mobility of 398 cm²/Vs and 1.7 times higher than LaAlO3-Si devices. [ABSTRACT FROM AUTHOR]

High-κ Al2O3/Ge-on-insulator (GOI) n- and p-MOSFETs with fully silicided NiSi and germanided NiGe dual gates were fabricated. At 1.7-nm equivalent-oxide-thickness (EOT), the Al2O3-GOI with metal-like NiSi and NiGe gates has comparable gate leakage current with Al2O3-Si MOSFETs. Additionally, Al2O3-GOI C-MOSFETs with fully NiSi and NiGe gates show 1.94 and 1.98 times higher electron and hole mobility, respectively, than Al2 O3-Si devices, because the electron and hole effective masses of Ge are lower than those of Si. The process with maximum 500 °C rapid thermal annealing (RTA) is ideal for integrating metallic gates with high-κ to minimize interfacial reactions and crystallization of the high-κ material, and oxygen penetration in high-κ MOSFETs. [ABSTRACT FROM AUTHOR]

We have fabricated the fully silicided NiSi and germanided NiGe dual gates n- and p-MOSFETs on 1.9 nm thick SiO[sub 2] gate dielectric. The extracted work functions of fully NiSi and NiGe gates from thickness-dependent fiat band voltage were 4.55 and 5.2 eV respectively, which may provide possible wide work function tuning using NiSi[sub 1-x]Ge[sub x]. In additional to the lower gate current than Al gate n- and p-MOSFETs, the fully silicided NiSi and germanided NiGe gates MOSFETs show electron and hole mobilities close to universal mobility values with special advantage of process compatible to current VLSI fabrication line. [ABSTRACT FROM AUTHOR]

Studies examining ctDNA, a blood-based marker of tumor burden, have largely focused on its use as a prognostic and predictive biomarker. While patient reported outcomes are most often associated with treatment-related toxicities, tumor burden may also contribute to these symptoms, including pain. Approximately one third of patients (pts) who receive radiation (RT) to painful bone metastases (mets) do not experience pain relief, but few studies have identified predictors of response to palliative RT. We hypothesize that ctDNA will predict persistent pain in pts with metastatic breast cancer and could be used to predict response to palliative RT. Plasma was collected before and 3 months (mos) after RT in pts with stage IV HR+, HER2- breast cancer in the context of a multi-institutional Phase II study of palbociclib, hormone therapy (HT), and palliative RT [30 Gy in 10 fractions (fxns) or 20 Gy in 5 fxns] for bone mets. ctDNA was detected using Snapshot, an anchored multiplex assay that detects 28 clinically significant cancer genes. Pts were eligible if treated with HT and palbociclib for at least one cycle and had either painful bone mets or asymptomatic bone mets at risk for a clinical event. Response, the primary endpoint, was prespecified as either a 2-point decrease in maximum pain score on the Brief Pain Inventory in the irradiated site(s) 3 mos post RT or prevention of a clinical event (e.g., cord compression) among pts with asymptomatic disease. The relationship between ctDNA and response to palliative RT was examined. 35 pts completed baseline and 3-month post RT assessments. 27 were treated for painful bone mets. With concurrent palbociclib, 61% and 37% of pts received aromatase inhibitors and fulvestrant, respectively. Median age was 60 years (31-83). 25% of pts were non-Hispanic Black. 72% of pts received 5 fxn RT and 69% received RT to one bone region. 29 pts (83%) were responders [95% CI: 66%-93%, p=.003]. Median progression free survival (PFS) was 30.4 mos (1.3 - 44.0). Three-year PFS and overall survival were 45.6% and 67.2%, respectively. 41% and 39% of pts had detectable ctDNA prior to and 3 mos post RT, respectively. 39% of pts had stable or increased ctDNA proportions 3 mos post RT relative to baseline. Six pts, all of whom presented with painful bone mets, did not respond to palliative RT. 100% of pts (n=15) without detectable ctDNA before and after RT responded to palliative RT, while 39% of pts with stable or increased ctDNA 3 mos post RT had no pain relief to RT (p=0.005). Four pts with ctDNA at baseline had no detectable ctDNA after RT, and all responded to RT. Our multi-institutional Phase II trial is the first to demonstrate high rates of response to concurrent RT with palbociclib and HT and to evaluate ctDNA as a biomarker of pain and response to palliative RT in pts with metastatic breast cancer. Our novel findings indicate that ctDNA detection correlates with persistent pain, a patient reported symptom, and predicts the efficacy of palliative RT. [ABSTRACT FROM AUTHOR]

To introduce an ultrasound-based method for evaluating long-term radiation-induced parotid gland toxicity in head and neck cancer (HNC) patients. The method integrates ultrasound radiomics analysis of the parotid gland with machine learning techniques. A cohort of 56 patients who had previously undergone radiotherapy for HNC was enrolled during routine follow-up visits (median: 25 months, range: 12 -87 months) when each participant underwent a sagittal ultrasound scan of the parotid glands, using a conventional scanner equipped with a linear probe (10 MHz). The scan duration is less than 5 minutes. Manual contours of the parotid glands were delineated on the B-mode images, and subsequently, radiomic features, were extracted. These features encompassed first-order histogram, second-order gray level and gray tone features. Patient self-assessment questionnaires rated saliva consistency and mouth dryness on a 0-3 scale. Correlations between extracted radiomic features, mean radiation dose, and toxicity outcomes were analyzed. Six machine learning models classified toxicity into none/mild versus moderate/severe, evaluated via area under the curve of the receiver operating characteristic curve (AUC-ROC), accuracy, precision, and sensitivity with three-fold cross-validation. Significant correlations (p < 0.05) were found between 34 radiomic features and mean dose (6.4 – 61.8 Gy). Notable features included Difference Variance of the gray-level co-occurrence matrix (Pearson correlation coefficient: 0.54, p < 0.01). For saliva consistency toxicity, 53 significant features were identified, with Root Mean Squared (Spearman correlation coefficient: 0.50, p < 0.01) being prominent. Mouth dryness showed 18 significant features, with Large Area Emphasis being notable (Spearman correlation coefficient: 0.30, p = 0.01). Table 1 presents the performance of the top machine learning models in classifying none/mild versus moderate/severe toxicities. Ultrasound radiomics combined with machine learning effectively assesses long-term radiation-induced parotid toxicity in HNC radiotherapy, highlighting clear associations between radiomic features, radiation dose, and toxicity outcomes. This imaging method offers potential for improved patient care through enhanced monitoring and management of radiation-induced parotid toxicity. [ABSTRACT FROM AUTHOR]

Abstract: High mobility channel materials such as Ge and compound semiconductors (CS) show promise for future generation MOSFETs. The challenge is to integrate these materials with a Si substrate and create good interfaces in the devices. Here we show dislocation-free CSOI and Ge-on-insulator (GOI) devices with good characteristics. The InAlAs/InGaAs/InAlAs-OI on Si MESFETs shows a mobility of 8100cm2/Vs. To reduce the leakage current an Al2O3/InGaAs MOSFET was fabricated. Good 451cm2/Vs mobility was obtained, higher than the 340cm2/Vs of GOI MOSFETs. However the marginally better mobility than GOI and 18X lower mobility than MESFETs indicate that the soft phonon scattering, high-κ interface scattering and process variations are challenges for CS MOSFETs. In contrast, the GOI CMOS provides a simpler process and significantly higher electron and hole mobilities than its Si counterparts. [Copyright &y& Elsevier]

Primary Parotid Carcinomas (PPC) comprise a wide array of histologies, each with varying propensity for local invasion and cervical nodal involvement. Upfront surgical excision of the primary tumor constitutes the standard of care for PPC, but there exists little consensus regarding management of the clinically negative neck (cN0). We conducted a clinicopathologic correlative analysis of the National Cancer Database (NCDB) to identify predictors of occult nodal involvement in PPC to guide elective neck management. The NCDB was queried for adults diagnosed from 2010-2020 with cN0M0 PPC who underwent adequate surgical resection (defined as subtotal to radical parotidectomy with >/=18 nodes examined) without pre-surgical treatment. Pathologic T-classification, tumor size, histology, grade, lymphovascular space invasion (LVSI), gender, and age at diagnosis were specified a priori as variables of interest. The primary outcome, occult nodal positivity (i.e. cN0 but pN+), was assessed by univariable (UVA) and multivariable (MVA) logistic regression, depicted as odds ratios (OR) and corresponding 95% confidence intervals (95%CI) with a prespecified threshold for statistical significance of p< 0.05. Recursive partitioning analysis (RPA) was then performed to hierarchically categorize patients according to occult nodal disease risk. From an initial 51,663 patients with PPC 1,899 met inclusion criteria and were included for analysis, of whom 1,047 (55.1%) had occult nodal involvement. By UVA, the incidence of occult nodal positivity was significantly higher with male sex; age 51 and older; high grade; pT2 status or greater; histology of adenocarcinoma, salivary duct carcinoma, or carcinoma ex-PA; tumor size >2cm; and LVSI. On MVA, tumor size, age, and gender were no longer significantly associated with occult nodal involvement; however, LVSI (OR 8.3, 95%CI 6.3-10.8), carcinoma ex-pleomorphic adenoma (OR 3.6, 95%CI 1.7-7.7), adenocarcinoma (OR 3.5, 95%CI 2.2-5.5), salivary duct carcinoma (OR 3.62, 95%CI 2.2-6.1), pT3 (OR 1.9, 95%CI 1.1-3.3), pT4 (OR 3.1, 95%CI 1.8-5.4), and high grade (OR 2.7, 95%CI 2.0-3.5) remained significant. On RPA evaluating LVSI, histology, pT, and grade, LVSI was the strongest predictor of occult nodal involvement (87% if LVSI+ vs 32% if LVSI–). LVSI appears to supersede tumor histology, grade, size, and pT status as the strongest risk factor for occult nodal involvement in PPC. To our knowledge, this is the largest series to evaluate this pathologic feature. Further research into this heretofore underappreciated risk factor and its implications for management of the cN0 neck is warranted. [ABSTRACT FROM AUTHOR]

Proton therapy is highly sensitive to anatomical changes and setup variations in head-and-neck (HN) treatments. To address this issue, proton centers often acquire patient CT images weekly to monitor patient anatomical changes during the treatment course and perform offline plan adaptation when needed. However, offline adaptation cannot fully account for daily setup variations or the anatomical changes occurring with high frequency. There are a few groups endeavoring to develop advanced technologies to enable online adaptive proton therapy (APT). However, the necessity of online APT remains controversial, as it is unknown that whether online APT will significantly improve treatment quality and outcomes compared to offline APT. The purpose of this study is to estimate the clinical potential of online APT in the management of HN cancers in relation to the current offline APT. Our retrospective study was conducted with four HN patients (35 fractions per patient), who had been treated with intensity modulated proton therapy and had offline adaptation once or twice during their treatment courses. Synthetic CT (sCT) images were generated from 140 daily CBCT images for us to recalculate the dose of the treatment plan in patient's actual treatment anatomy for each treatment fraction and adapt the plan when warranted. These adaptations were assumed to be performed online before treatment delivery to mimic an online APT course. Accumulative doses were calculated for both courses using the CBCT-based sCT images of every fraction for us to compare the target coverage, organ at risk (OAR) sparing, tumor control probability (TCP) and normal tissue complication probability (NTCP). An in-house script was developed to semi-automate this process in a commercial treatment planning system to facilitate our study. All patients would benefit from online APT to different extents. For the first patient, with OAR doses comparable to the actual offline course, the retrospective online APT course improved dose coverages of the three CTVs from 95.2%, 98.64% and 89.53% to 98.88%, 99.81%, 98.97%, which would lead to a 4.52% improvement in TCP. Similarly, online APT would yield a 2.66% improvement in TCP for the second patient. For the third patient, with comparable CTV dose coverages, the mean doses of right parotid and oral cavity were decreased from 29.52 Gy relative biological effectiveness (RBE) and 41.89 Gy RBE to 22.16 Gy RBE and 34.61 Gy RBE, leading to a reduce of 1.67% and 3.40% in NTCP. The mean dose of right parotid was decreased from 21.71 Gy RBE to 19.37 Gy RBE for the last patient, leading to a reduce of 0.73% in NTCP. Our results showed that online APT could better maintain the treatment plan quality than offline APT for all the four patients, despite their significant anatomical changes. Future investigation will focus on collecting more patient data to obtain statistically significant results and help identify the patients to whom the online APT will be of most benefit. [ABSTRACT FROM AUTHOR]

Primary Parotid Carcinomas (PPC) comprise a wide array of histologies, each with varying propensity for local invasion and cervical nodal involvement. Upfront surgical excision of the primary tumor constitutes the standard of care for PPC, but there exists little consensus regarding management of the clinically negative neck (cN0). We conducted a clinicopathologic correlative analysis of the National Cancer Database (NCDB) to identify predictors of occult nodal involvement in PPC to guide elective neck management. The NCDB was queried for adults with a first malignant diagnosis of cN0M0 cancer of the parotid who underwent adequate surgical resection (defined as subtotal to radical parotidectomy with ³18 nodes examined) without pre-surgical treatment. Pathologic T-classification, tumor size, histology, grade, lymphovascular space invasion (LVSI), gender, and age at diagnosis were specified a priori as variables of interest. The primary outcome, occult nodal positivity (i.e. cN0 but pN+), was assessed by univariable (UVA) and multivariable (MVA) logistic regression analysis, depicted as odds ratios (OR) and corresponding 95% confidence intervals (95% CI) with a prespecified threshold for statistical significance of p £0.05. Recursive partitioning analysis (RPA) was subsequently performed to categorize patients according to their calculated risk of occult nodal disease. From an initial cohort of 41,445 patients with PPC 978 met inclusion criteria and were included for analysis, of whom 331 (33.8%) had occult nodal involvement. By UVA, the incidence of occult nodal positivity was significantly higher in male patients, those aged 72 and older, patients with high grade disease, pT4 classification, adenocarcinoma histology, a >4cm tumor, and those with positive LVSI. On MVA, tumor size, age, and gender were no longer significantly associated with occult nodal involvement; however, LVSI (OR 6.1, 95% CI 4.3-8.8), carcinoma ex-pleomorphic adenoma (OR 5.6, 95% CI 2.1-14.8), adenocarcinoma (OR 5.1, 95% CI 2.6-9.9), salivary duct (OR 4.0, 95% CI 1.8-8.6), or mucoepidermoid (OR 2.3, 95% CI 1.2-4.3) histology, pT3 (OR 2.0, 95% CI 1.1-3.7) or pT4 (OR 3.9, 95% CI 2.1-7.3) status, and high grade (OR 2.0, 95% CI 1.4-3.0) remained significant. LVSI, histology, pT status, and grade were further evaluated with RPA, which identified LVSI as the strongest predictor of occult nodal involvement (57.1% vs 42.9%, p <0.01). LVSI appears to supersede tumor histology, grade, size, and pT status as the strongest risk factor for occult nodal involvement in PPC. To our knowledge, this is the largest series to evaluate this pathologic feature. Further research into this heretofore underappreciated risk factor and its implications for management of the cN0 neck is warranted. [ABSTRACT FROM AUTHOR]