The Jefferson Laboratory community recently joined the dark sector search program with different, complementary efforts: APEX, HPS, DarkLight, and BDX. These fixed-target, electron-beam experiments ...are designed to search for Dark Matter in the mass range 10 MeV/c2 - 1 GeV/c2, the so-called "light Dark Matter" region. Each experiment is optimized to look for a specific light Dark Matter signal signature. In this paper, after a brief introduction to the light Dark Matter hypothesis, I present the four experiments, describing their scientific goal, the measurement setup, and the obtained or expected results.
This systematic review aimed to examine whether the incidence of osteonecrosis differed between patients who have dental extractions before or after radiotherapy (RT). The reported incidence of ...osteoradionecrosis (ORN) of the jaws following RT to the head and neck varies widely in the literature. Currently, for patients with head and neck cancer there are no universally accepted guidelines on the optimal timing of dental surgery relative to RT to minimise incident ORN. A literature review was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria. A search of PubMed, EMBASE, Evidence-Based Medicine, and Web of Science databases targeted literature published up to and including 10 April 2020. Two independent reviewers assessed studies for eligibility against inclusion criteria. An assessment of bias was conducted for each of the included studies and relevant data extracted. A meta-analysis was undertaken using the statistical methods described. Twenty-four of 708 studies were included. They were heterogeneous and included a wide variation of RT methods, head and neck malignancies, and comorbidities. While some concluded that the incidence of ORN was dependent on the timing of dental extractions in relation to RT, with regard to the risk of its development, others reported additional factors such as age, comorbidities, extent of surgical resection, and dose and field of radiation, as more important predictors than timing. In many there was consistent lack of detail around the timing of dental procedures in relation to the delivery of RT. From 21 studies including 36,294 patients, of whom 14,389 had extractions before RT, the pooled incidence of ORN was 5.5% (95% CI: 2.1% to 10.1%). Significant heterogeneity was found in Cochran’s Q-test (p<0.001) and Higgins I2=98.0%. From 21 studies including 37,805 patients, of whom 6030 had extractions after RT, the pooled incidence of ORN was 5.3% (95% CI: 2.9% to 8.2%). Significant heterogeneity was found in Cochran’s Q-test (p<0.001) and Higgins I2=80.0%. There was no statistically significant difference between these two groups (random-effects model Q=0.12, p=0.73). Large, longitudinal studies with a priori-specified methods are needed to identify, recruit, and prospectively follow patients with head and neck cancer for the onset of ORN after dental surgery. This will allow clinical guidelines to be established to assist clinicians to plan treatment when extractions are indicated in patients undergoing RT to the head and neck.
This paper describes the design and performance of a compact detector, BDX-MINI, that incorporates all features of a concept that optimized the detection of light dark matter in the MeV-GeV mass ...range produced by electrons in a beam dump. It represents a reduced version of the future BDX experiment expected to run at JLAB. BDX-MINI was exposed to penetrating particles produced by a 2.176 GeV electron beam incident on the beam dump of Hall A at Jefferson Lab. The detector consists of 30.5 kg of PbWO
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crystals with sufficient material following the beam dump to eliminate all known particles except neutrinos. The crystals are read out using silicon photomultipliers. Completely surrounding the detector are a passive layer of tungsten and two active scintillator veto systems, which are also read out using silicon photomultipliers. The design was validated and the performance of the robust detector was shown to be stable during a six month period during which the detector was operated with minimal access.
The large number of diseases occurring when desmosome constituents are impaired provides striking evidence for the key role of desmosomes in maintaining tissue integrity. A detailed understanding of ...the molecular alterations causing desmosomal dysfunction has, in turn, underpinned the development of novel diagnostic tools. This has salient clinical implications for dentists and oral medicine practitioners because the majority of desmosomal diseases affect the oral cavity. In the present article, we review the autoimmune, infectious, genetic, and neoplastic diseases that target the desmosome, with particular emphasis on clinical manifestations, diagnostic pathways, and relevant laboratory investigations.
The interrelationship between malignant epithelium and the underlying stroma is of fundamental importance in tumour development and progression. In the present study, we used cancer-associated ...fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), tumours that are characterized by the loss of genes such as TP53 and p16
and with extensive loss of heterozygosity, together with CAFs from their more genetically stable (GS) counterparts that have wild-type TP53 and p16
and minimal loss of heterozygosity (GS-OSCC). Using a systems biology approach to interpret the genome-wide transcriptional profile of the CAFs, we show that transforming growth factor-β (TGF-β) family members not only had biological relevance in silico but also distinguished GU-OSCC-derived CAFs from GS-OSCC CAFs and fibroblasts from normal oral mucosa. In view of the close association between TGF-β family members, we examined the expression of TGF-β1 and TGF-β2 in the different fibroblast subtypes and showed increased levels of active TGF-β1 and TGF-β2 in CAFs from GU-OSCC. CAFs from GU-OSCC, but not GS-OSCC or normal fibroblasts, induced epithelial-mesenchymal transition and down-regulated a broad spectrum of cell adhesion molecules resulting in epithelial dis-cohesion and invasion of target keratinocytes in vitro in a TGF-β-dependent manner. The results demonstrate that the TGF-β family of cytokines secreted by CAFs derived from genotype-specific oral cancer (GU-OSCC) promote, at least in part, the malignant phenotype by weakening intercellular epithelial adhesion.
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