BACKGROUND: Precancerous high-grade squamous intraepithelial lesion (HSIL), the current consensus terminology for anogenital squamous cell carcinoma in situ (SCCIS), often presents with distinctive histopathologic findings that may be a function of anatomic site or associated human papillomavirus infection.

METHODS: Fifty-six specimens of anogenital HSIL were compared with an equal number of specimens of SCCIS from non-anogenital sites in regard to the presence of parakeratosis, flag sign in the stratum corneum, compact stratum corneum, hypergranulosis, koilocytes, small blue cells, clonal populations of keratinocytes, pagetoid scatter of atypical keratinocytes, clear cell change, glassy red cytoplasm, pigmentation, nuclear/cytoplasmic(N/C) ratio >2/1, nuclear hyperchromasia, pleomorphic nuclei, mitotic figures, abnormal mitotic figures, dyskeratotic keratinocytes, involvement of skin appendages, acantholysis and amyloid deposition.

RESULTS: Hypergranulosis, koilocytes, small blue cells, pigmentation, nuclear hyperchromasia, dyskeratotic keratinocytes and amyloid deposition were more frequently noted in anogenital HSIL. Parakeratosis, clear cell change, pleomorphic nuclei, skin appendages involvement and acantholysis were strongly associated with non-anogenital location. There was no significant difference in the incidence of the remaining features.

CONCLUSION: The strongest predicators of an anogenital location included hypergranulosis, koilocytes, small blue cells and nuclear hyperchromasia. Pigmentation and amyloid deposition were also strongly associated with an anogenital location.

Viruses evade the innate immune response by suppressing the production or activity of cytokines such as type I interferons (IFNs). Here we report the discovery of a mechanism by which the SARS-CoV-2 virus coopts an intrinsic cellular machinery to suppress the production of the key immunostimulatory cytokine IFN-β. We reveal that the SARS-CoV-2 encoded nonstructural protein 2 (NSP2) directly interacts with the cellular GIGYF2 protein. This interaction enhances the binding of GIGYF2 to the mRNA cap-binding protein 4EHP, thereby repressing the translation of the

Our previous studies have implicated expression of the mitochondrial isoform of the arginase enzyme arginase 2 (A2) in neurovascular injury during ischemic retinopathies. The aim of this study was to characterize the specific involvement of A2 in retinal injury following optic nerve crush (ONC). To accomplish this, wild-type (WT) or A2 knockout (A2) mice were subjected to ONC injury. The contralateral eye served as sham control. Quantitative RT-PCR and western blot were used to evaluate mRNA and protein expression. Retinal ganglion cell (RGC) survival was assessed in retinal whole mounts. Axonal sprouting was determined by anterograde transport of Cholera Toxin B (CTB). These analyses showed increased A2 expression following ONC. Numbers of NeuN-positive neurons as well as Brn3a- and RBPMS-positive RGC were decreased in the WT retinas at 14 days after ONC as compared to the sham controls. This ONC-induced neuronal loss was diminished in the A2 retinas. Similarly, axonal degeneration was ameliorated by A2 deletion whereas axon sprouting was enhanced. Significant retinal thinning was also seen in WT retinas at 21 days after ONC, and this was blocked in A2 mice. Cell death studies showed an increase in TUNEL positive cells in the RGC layer at 5 days after ONC in the WT retinas, and this was attenuated by A2 deletion. ONC increased glial cell activation in WT retinas, and this was significantly reduced by A2 deletion. Western blotting showed a marked increase in the neurotrophin, brain derived neurotrophic factor (BDNF) and its downstream signaling in A2 retinas vs. WT after ONC. This was associated with increases in the axonal regeneration marker GAP-43 in A2 retinas. Furthermore, A2 retinas showed decreased NLRP3 inflammasome activation and lower interleukin (IL-) 1β/IL-18 levels as compared to WT retinas subjected to ONC. Collectively, our results show that deletion of A2 limits ONC-induced neurodegeneration and glial activation, and enhances axonal sprouting by a mechanism involving increases in BDNF and decreases in retinal inflammation. These data demonstrate that A2 plays an important role in ONC-induced retinal damage. Blockade of A2 activity may offer a therapeutic strategy for preventing vision loss induced by traumatic retinal injury.

Background and Aims: Gastric peroral endoscopic myotomy (G-POEM) has been regarded as a novel and minimally invasive therapy for refractory gastroparesis. This study reports the long-term outcomes and possible predictive factors for successful outcomes after G-POEM in an Asian population.

Methods: This is a retrospective single-centre study of 16 patients who underwent G-POEM for refractory gastroparesis from August 2016 to October 2017. This study included 11 males and 5 females; in addition, 13 patients had postsurgical gastroparesis, and 3 patients had diabetes. The patients included had severe and refractory gastroparesis, as indicated by a Gastroparesis Cardinal Symptom Index (GCSI) score ≥20, and evidence of a delay on gastric emptying scintigraphy (GES). The primary outcome parameter was an assessment of the long-term clinical efficacy of the procedure. The secondary outcome parameter was the detection of possible predictive factors for success and the determination of cut-off values for such predictors.

Results: Technical success was achieved in 100% of the patients, with a mean procedure time of 45.25±12.96 min. The long-term clinical response was assessed in all patients during a median follow-up of 14.5 months. Clinical success was achieved in 13 (81.25%) patients. There was a significant reduction in the GCSI scores and GES values after the procedure compared to the baseline values, with values of <0.0001 and 0.012, respectively. Univariate regression analysis showed that the GCSI and GES had significant associations with the future clinical outcomes of the patients, but this finding was not confirmed in multivariate analysis. A GCSI cut-off score of ≤30 had a high sensitivity and a negative predictive value (NPV) of 100% for predicting a successful procedure. GES (half emptying time ≤221.6 min and 2-hour retention ≤78.6%) had a high specificity and a positive predictive value (PPV) of 100%.

Conclusions: G-POEM is a safe and effective treatment option with a long-term efficacy of 81.6%. GCSI and GES could serve as good predictive measures.

For the solar photovoltaic (PV) system to operate efficiently, it is necessary to effectively establish an equivalent model of PV cell and extract the relevant unknown model parameters accurately. This paper introduces a new metaheuristic algorithm, i.e., gaining-sharing knowledge based algorithm (GSK) to solve the solar PV model parameter extraction problem. This algorithm simulates the process of knowledge acquisition and sharing in the human life cycle and is with strong competitiveness in solving optimization problems. It includes two significant phases. The first phase is the beginner–intermediate or junior acquisition and sharing stage, and the second phase is the intermediate–expert or senior acquisition and sharing stage. In order to verify the effectiveness of GSK, it is applied to five PV models including the single diode model, double diode model, and three PV modules. The influence of population size on the algorithm performance is empirically investigated. Besides, it is further compared with some other excellent metaheuristic algorithms including basic algorithms and advanced algorithms. Among the five PV models, the root mean square error values between the measured data and the calculated data of GSK are 9.8602E−04 ± 2.18E−17, 9.8280E−04 ± 8.72E−07, 2.4251E−03 ± 1.04E−09, 1.7298E−03 ± 6.25E−18, and 1.6601E−02 ± 1.44E−16, respectively. The results show that GSK has overall better robustness, convergence, and accuracy.

Dielectric constant (ε, epsilon) is one of the basic physical parameters for materials, determining the response of materials to electromagnetic waves or electrical field; its value is generally positive. In fact, dielectric constant can also be negative, regarded as supernormal performance to some degree. The negative dielectric property has become research hotspot as an essential key for constructing metamaterials, showing unique and exotic electromagnetic properties not existing in naturally occurring materials, such as negative refraction, perfect troubles, and reverse Doppler effect. Recently, the feasibility is demonstrated to achieve negative dielectric property in conventional heterogeneous composites rather than periodic artificial arrays; drawing great attention from researchers in material science and engineering, many advances have been made and can promote the development of metamaterials and conventional electromagnetic functional materials. Here, we reviewed the recent advances in negative dielectric property designed in some heterogeneous composites, including metal composites, carbon composites, ceramic composites, conducting polymer. Besides, various strategies, including designing different microstructures, changing the working temperatures, choosing flexible matrix or fillers, electro-magnetic coupling, were summarized to precisely adjust negative dielectric property. Finally, the question unsolved and perspectives about negative dielectric property are put forward; we expect to shed light on the mechanism of negative dielectric property as well as its relationship with the material design in composition and microstructure.