Serum haptoglobin and C-reactive protein in human skeletal fluorosis

Circulating levels of haptoglobin and C-reactive protein were studied in patients of skeletal fluorosis and compared with two types of controls. The first type of control included normal healthy individuals consuming water containing permissible levels of fluoride (up to 1 mg/L). The second type of control included individuals consuming water contaminated with fluoride (1.2-14.5 mg/L) but not exhibiting clinical manifestations of skeletal fluorosis. A significant increase in the levels of haptoglobin (p < 0.01) and C-reactive protein (p < 0.01) as well as a raised erythrocyte sedimentation rate were seen in patients of skeletal fluorosis as compared to both types of controls. The present study suggests the possibility of a subclinical inflammatory reaction occurring in patients with skeletal fluorosis

Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine

The zona pellucida (ZP) surrounding a mammalian oocyte mediates the initial recognition and binding of spermatozoon to oocyte in a relatively species-specific manner and plays an important role in the subsequent activation events during the fertilization process. The ZP comprises three biochemically and immunologically distinct glycoproteins termed ZP1, ZP2 and ZP3. The critical role of ZP glycoproteins in reproduction together with their tissue-specific nature have led to their being considered as potential candidate antigens for immunocontraception. Immunization of females with ZP glycoproteins leads to a block of fertility in several animal models. However, it is invariably associated with either a transient or an irreversible alteration in the cyclicity, hormonal profile and follicular development in the ovary. To overcome these problems, attempts are being made to delineate relevant 'B'cell epitopes on ZP proteins so as to design immunocontraceptive vaccines based on synthetic peptides devoid of oophoritogenic 'T' cell epitopes. Monoclonal antibodies capable of inhibiting the gamete interaction are being employed to delineate such regions. Additionally, DNA-recombinant technology has made it feasible to obtain, in reasonably large quantities, the ZP glycoproteins from human and non-human primates. Availability of sequence information of these zona proteins and the availability of recombinant antigens (devoid of other ovarian-associated proteins) will further help in understanding more precisely their functions during fertilization and make it feasible to undertake immunization studies to determine their prospects as immunogens for fertility regulation

Juniper Networks

draft-ashesh-bfd-stability-00.txt This document describes extensions to the Bidirectional Forwarding Detection (BFD) protocol to measure BFD stability. Specifically, it describes a mechanism for detection of BFD frame loss, of delays in frame transmitter and receiver engines, and of inter-frame delays that might explain issues with a BFD session. Requirements Languag

Feasibility of Adaptive Radiation Therapy for Human-Papilloma Virus-Positive Oropharyngeal Cancer Patients Using MR-Guided RT

Human-papilloma virus (HPV)-positive oropharyngeal cancer (OPC) is a potentially curable disease with a rising incidence in the United States. Despite improved radiation therapy (RT) techniques, toxicities remain a concern. Adaptive RT (ART) can reduce radiation to organs-at-risk (OARs) without sacrificing tumoricidal dose to target volumes, but there are barriers to routine implementation. These include (1) technical barriers to ART and (2) timing of ART for shrinking tumor volumes or changes in body contours (such as weight loss or contracture of OARs). Magnetic resonance (MR)-Linacs allow for frequent, online, and standardized plan adaption, made possible by improved visualization of tumors and OARs as well as an integrated planning system. This study aims to: (1) develop an ART workflow protocol using an online adapt-to-shape approach on our MR-Linac while (2) identifying barriers to performance (such as treatment times and the influence to quality of life) and (3) characterizing quantitative imaging biomarkers during RT. Sixteen eligible participants with non-metastatic HPV+ OPC will be enrolled. All participants will undergo simulation on our institution's MR-Linac. Participants will receive concurrent chemoRT with a dose prescription of 70 Gy in 35 fractions on the MR-Linac. ART planning will occur every 5th fraction of RT (i.e. the 6th, 11th, 16th, 21st, 26th, and 31st fractions). At 3-months follow-up, participants will undergo another MRI scan on the MR-Linac. The primary endpoint is to assess the accuracy of ART by (1) calculating the percent difference between initial and weekly ART plans and (2) confirming accuracy of deformable imaging registration. Secondary endpoints include (1) treatment times, calculated from guidelines set by the MR-Linac Consortium Head and Neck Tumor Site, as well as (2) quality of life measurements using study questionnaires (i.e. EORTC QLQs Core 30 and H&N43) at all study timepoints. As an exploratory endpoint, quantitative imaging biomarkers of tumor and nodal volume regression will be descriptively characterized. This study is a trial-in-progress and has not reached pre-specified endpoints for analysis. MR-Linacs are underutilized in the treatment of OPC patients, despite previous validation of clinically acceptable head and neck RT plans. For OPC patients, replanning is often static (i.e. at one timepoint), offline, and limited in standardization. This work will help clarify the role of MR-guided ART in HPV+ OPC: its feasibility, quality, and overall patient experience

Exploring Applications of Radiomics in Magnetic Resonance Imaging of Head and Neck Cancer: A Systematic Review

BackgroundRadiomics has been widely investigated for non-invasive acquisition of quantitative textural information from anatomic structures. While the vast majority of radiomic analysis is performed on images obtained from computed tomography, magnetic resonance imaging (MRI)-based radiomics has generated increased attention. In head and neck cancer (HNC), however, attempts to perform consistent investigations are sparse, and it is unclear whether the resulting textural features can be reproduced. To address this unmet need, we systematically reviewed the quality of existing MRI radiomics research in HNC.MethodsLiterature search was conducted in accordance with guidelines established by Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Electronic databases were examined from January 1990 through November 2017 for common radiomic keywords. Eligible completed studies were then scored using a standardized checklist that we developed from Enhancing the Quality and Transparency of Health Research guidelines for reporting machine-learning predictive model specifications and results in biomedical research, defined by Luo et al. (1). Descriptive statistics of checklist scores were populated, and a subgroup analysis of methodology items alone was conducted in comparison to overall scores.ResultsSixteen completed studies and four ongoing trials were selected for inclusion. Of the completed studies, the nasopharynx was the most common site of study (37.5%). MRI modalities varied with only four of the completed studies (25%) extracting radiomic features from a single sequence. Study sample sizes ranged between 13 and 118 patients (median of 40), and final radiomic signatures ranged from 2 to 279 features. Analyzed endpoints included either segmentation or histopathological classification parameters (44%) or prognostic and predictive biomarkers (56%). Liu et al. (2) addressed the highest number of our checklist items (total score: 48), and a subgroup analysis of methodology checklist items alone did not demonstrate any difference in scoring trends between studies [Spearman’s ρ = 0.94 (p < 0.0001)].ConclusionAlthough MRI radiomic applications demonstrate predictive potential in analyzing diverse HNC outcomes, methodological variances preclude accurate and collective interpretation of data

KRAS mutation status in the prediction of pancreatic tumor response after neoadjuvant systemic therapy and magnetic resonance-guided SBRT

709 Background: Stereotactic body radiotherapy (SBRT) has been incorporated into multi-modality treatment of locally advanced and borderline resectable pancreatic ductal adenocarcinoma (PDAC). For non-metastatic inoperable PDAC patients (pts) who receive magnetic resonance-guided SBRT (MRgSBRT), baseline features that predict for treatment response remain unsettled. In localized PDAC, multiple studies have investigated the KRAS oncogene as a prognostic factor with mixed findings. In this single institution retrospective study of PDAC pts treated with MRgSBRT, we hypothesized that KRAS mutation status would be predictive of meaningful clinical outcomes. Methods: From an IRB approved dataset of PDAC pts treated with MRgSBRT between 2016 and 2022, 39 pts with non-metastatic inoperable pancreatic cancer, known KRAS mutation status, ≥ 3 months of neoadjuvant systemic therapy (NST), and at least 3 months post-RT follow up were extracted for analysis. Baseline demographics, tumor and treatment characteristics, and clinical endpoints including conversion to resectability, best imaging response per RECIST v1.1, pathologic response (PR) per TRG-CAP, and overall survival (OS) after MRgSBRT were collected. Objective response (ORR) on both imaging and pathology was defined as complete response (CR) + partial response (PR); disease control (DC) was defined as CR + PR + stable disease (SD). Logistic regression was used to assess correlation between baseline variables and ORR. Cox proportional hazard models were utilized to determine association with OS. Results: Out of 39 pts, 21 (53%) were KRAS-mutated (KRAS-mt) and 18 (47%) were KRAS wild-type (KRAS-wt). Median age was 62, 54% were male, only 1 pt had ECOG > 1, and CA 19-9 at diagnosis was 197. Median duration of NST was 9 cycles, and common agents included Gemcitabine and Abraxane (21%); FOLFIRINOX (28%); a combination of the two regimens (41%); or other NSTs (10%). Median MRgSBRT dose fractionation was 50 Gy (range 35 – 50) in 5 fractions; all fractions underwent adaptive optimization. Thirty pts (77%) experienced DC on imaging, 16 (43%) had ORR, and 12 (31%) were converted to resectable following MRgSBRT. Cohort median OS was 12.3 months, and pts who had surgery had a non-significant median OS advantage (18 vs 12 months; p=0.19). KRAS-mt was associated with worse ORR (p=0.04; AUC=0.73) and decreased OS (HR: 2.15; p=0.03). In a clinical model incorporating baseline characteristics (age, ECOG, radiographic staging, CA 19-9 level, and KRAS), only KRAS predicted OS (HR: 3.02 for KRAS-mt; p=0.01). KRAS-mt status was also predictive of OS among pts who underwent surgery (HR: 5.24 for KRAS-mt; p=0.04). Conclusions: For localized PDAC pts inoperable at diagnosis who received NST followed by MRgSBRT, KRAS was the only significant predictor of ORR and OS, highlighting the need for further treatment intensification in KRAS-mt pts