DNA methylation, an important type of epigenetic modification in humans, participates in crucial cellular processes, such as embryonic development, X-inactivation, genomic imprinting and chromosome stability. Several platforms have been developed to study genome-wide DNA methylation. Many investigators in the field have chosen the Illumina Infinium HumanMethylation microarray for its ability to reliably assess DNA methylation following sodium bisulfite conversion. Here, we analyzed methylation profiles of 489 adult males and 357 adult females generated by the Infinium HumanMethylation450 microarray. Among the autosomal CpG sites that displayed significant methylation differences between the two sexes, we observed a significant enrichment of cross-reactive probes co-hybridizing to the sex chromosomes with more than 94% sequence identity. This could lead investigators to mistakenly infer the existence of significant autosomal sex-associated methylation. Using sequence identity cutoffs derived from the sex methylation analysis, we concluded that 6% of the array probes can potentially generate spurious signals because of co-hybridization to alternate genomic sequences highly homologous to the intended targets. Additionally, we discovered probes targeting polymorphic CpGs that overlapped SNPs. The methylation levels detected by these probes are simply the reflection of underlying genetic polymorphisms but could be misinterpreted as true signals. The existence of probes that are cross-reactive or of target polymorphic CpGs in the Illumina HumanMethylation microarrays can confound data obtained from such microarrays. Therefore, investigators should exercise caution when significant biological associations are found using these array platforms. A list of all cross-reactive probes and polymorphic CpGs identified by us are annotated in this paper.

EpCAM (epithelial cell adhesion molecule) is a cell surface molecule that is known to be highly expressed in colon and other epithelial carcinomas. EpCAM is involved in cell-to-cell adhesion and has been the target of antibody therapy in several clinical trials. To assess the value of EpCAM as a novel target for breast cancer gene therapy, we performed real-time reverse transcription-PCR to quantify the level of EpCAM mRNA expression in normal breast tissue and primary and metastatic breast cancers. We found that EpCAM is overexpressed 100-to 1000-fold in primary and metastatic breast cancer. Silencing EpCAM gene expression with EpCAM short interfering RNA (siRNA) resulted in a 35-80% decrease in the rate of cell proliferation in four different breast cancer cell lines. EpCAM siRNA treatment decreased cell migration by 91.8% and cell invasion by 96.4% in the breast cancer cell line MDA-MB-231 in vitro. EpCAM siRNA treatment was also associated with an increase in the detergent-insoluble protein fraction of E-cadherin, ␣-catenin, and ␤-catenin, consistent with the known biology of EpCAM as a regulator of cell adhesion. Our hypothesis is that modulation of EpCAM expression can affect cell migration, invasion, and proliferation by enhancing E-cadherinmediated cell-to-cell adhesion. These data provide compelling evidence that EpCAM is a potential novel target for breast cancer gene therapy and offer insights into the mechanisms associated with EpCAM gene silencing.

Sacroiliac joint (SIJ) pain is an underappreciated source of mechanical low back pain, affecting between 15 and 30% of individuals with chronic, nonradicular pain. Predisposing factors for SIJ pain include true and apparent leg length discrepancy, older age, inflammatory arthritis, previous spine surgery, pregnancy and trauma. Compared with facet-mediated and discogenic low back pain, individuals with SIJ pain are more likely to report a specific inciting event, and experience unilateral pain below L5. Owing in part to its size and heterogeneity, the pain referral patterns of the SIJ are extremely variable. Although no single physical examination or historical feature can reliably identify a painful SIJ, studies suggest that a battery of three or more provocation tests can predict response to diagnostic blocks. Evidence supports both intra- and extra-articular causes for SIJ pain, with clinical studies demonstrating intermediate-term benefit for both intra- and extra-articular steroid injections. In those who fail to experience sustained relief from SIJ injections, radiofrequency denervation may provide significant relief lasting up to 1 year. This review covers all aspects of SIJ pain, with the treatment section being primarily focused on procedural interventions.

Abstract Background It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for. Methods To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period. Results In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization. Conclusions The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.

high photoluminescence quantum yield (PLQY), wide wavelength tunability, and high color purity, [4][5][6] they have been attractive for light-emitting diode (LED) applications. Since the first demonstration of perovskite LEDs in 2014, [7] the device external quantum efficiency (EQE) has risen rapidly from 0.1% [7] to ≈20%, [2,4,8] and the efficiency enhancements are mainly attributed to passivation and compositional engineering, [2,8] improved charge balance by optimization of device structure, [9] and efficient light extraction. [4] More recently, these materials are considered as optical gain medium for lasers. In 2014, the first amplified spontaneous emission (ASE) was observed from CH 3 NH 3 PbI 3 thin films with a threshold of 12 µJ cm −2 and a gain of 250 cm −1 , which is ascribed to the large absorption coefficient, low bulk defect density, and slow Auger recombination rate. [10] These ASE threshold and gain values are comparable to the state of art gain media such as colloidal quantum dots [11] and organic thin films. [12] Since then, optically pumped lasers have been demonstrated based on various microcavity structures such as Fabry-Pérot cavities, [13,14] distributed feedback (DFB) gratings, [3,15] and whispering gallery cavities. [16] The flexibility of fabricating hybrid perovskite lasers using solution-processed methods enables large-scale production and is attractive for the realization of on-chip integration of photonic circuits. [17] Quasi-2D perovskites, which are also known as Ruddlesden-Popper (RP) perovskites, are mixed phases of 2D and 3D nanocrystals. In the mixture, 2D domains exhibit quantumwell-like electronic properties with strong exciton binding energy due to the reduced dimensionality. [18] Typically, the 2D perovskite (A') 2 A n−1 B n X 3n+1 domains consist of multilayers of BX 6 octahedra separated by intercalating ammonium cations A', which is too large to fit into the crystal structure and hinder the growth of 3D ABX 3 crystals (A = methylammonium (MA + ), formamidinium (FA + ), or Cs + , B = Pb 2+ , and X = I − , Br − , Cl − ). As a result, the number of layers determine the bandgap of 2D quantum-well-like domains. [19] Different from 3D perovskites, thin films of qausi-2D perovskites typically contain a mixture of domains with different layers. Within such inhomogenous Quasi-2D Ruddlesden-Popper halide perovskites with a large exciton binding energy, self-assembled quantum wells, and high quantum yield draw attention for optoelectronic device applications. Thin films of these quasi-2D perovskites consist of a mixture of domains having different dimensionality, allowing energy funneling from lower-dimensional nanosheets (high-bandgap domains) to 3D nanocrystals (low-bandgap domains). High-quality quasi-2D perovskite (PEA) 2 (FA) 3 Pb 4 Br 13 films are fabricated by solution engineering. Grazing-incidence wide-angle X-ray scattering measurements are conducted to study the crystal orientation, and transient absorption spectroscopy measurements are conducted to study the charge-carr...